{"gene":"MYO7A","run_date":"2026-04-29T11:37:56","timeline":{"discoveries":[{"year":1997,"finding":"Different mutations in MYO7A cause either isolated non-syndromic deafness (DFNB2) or syndromic deafness with retinitis pigmentosa (Usher syndrome type 1B), establishing that the same gene underlies both phenotypes through allelic heterogeneity. A G-to-A transition at the last nucleotide of exon 15 was shown to decrease splicing efficiency.","method":"Sequence analysis of coding exons; linkage analysis; splicing mutation identification","journal":"Nature genetics","confidence":"High","confidence_rationale":"Tier 2 — direct mutation identification with functional splicing implication, replicated across multiple populations","pmids":["9171833"],"is_preprint":false},{"year":2008,"finding":"In Myo7a-null shaker1 mice with mosaic retinas, the mutant photoreceptor phenotype was shown to be cell-autonomous and not secondary to mutant RPE cells, placing MYO7A function intrinsically within photoreceptors.","method":"Mosaic retinal analysis in Myo7a-deficient shaker1 mice; optical imaging of retinal structure","journal":"Human molecular genetics","confidence":"High","confidence_rationale":"Tier 2 — genetic mosaic experiment with defined cellular phenotype demonstrating cell autonomy","pmids":["18463160"],"is_preprint":false},{"year":2007,"finding":"MYO7A links to melanosomes in RPE cells via the RAB27A-MYRIP complex (analogous to melanophilin-RAB27A-MYO5A in melanocytes), and the RAB27A-MYRIP-MYO7A complex functions in melanosome motility in RPE cells. RAB27A provides an essential link to the melanosome.","method":"Live-cell imaging of primary RPE cultures; mutant mouse retinal analysis; RPE cell fractionation; in vitro binding assays; immunolocalization","journal":"Cell motility and the cytoskeleton","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal methods (live imaging, fractionation, mutant mouse genetics) in a single study","pmids":["17352418"],"is_preprint":false},{"year":2011,"finding":"MYO7A is required for the light-dependent translocation of RPE65 to the central region of RPE cells; in Myo7a-mutant mice RPE65 is mislocalized, degraded more quickly, and its activity is reduced (increased all-trans-retinyl ester levels post-photobleach). MYO7A and RPE65 were co-immunoprecipitated from RPE cell lysate, suggesting direct or indirect physical interaction.","method":"Co-immunoprecipitation from RPE cell lysate; immunolocalization; biochemical assay of retinoid cycle metabolites; light-damage resistance phenotype in Myo7a-mutant mice","journal":"Human molecular genetics","confidence":"High","confidence_rationale":"Tier 2 — reciprocal Co-IP plus functional retinoid cycle assay plus mutant mouse phenotype, multiple methods in one study","pmids":["21493626"],"is_preprint":false},{"year":2011,"finding":"MYO7A in the RPE participates in: (1) apical localization of melanosomes (competing with microtubule motors); (2) removal of phagosomes from apical RPE for delivery to lysosomes in basal RPE (possibly co-operative with microtubule motors); and (3) light-dependent translocation of RPE65. In photoreceptors, MYO7A functions as a selective barrier for membrane proteins (e.g., opsin) at the distal end of the transition zone of the cilium.","method":"Analysis of Myo7a-null mouse retinas; immunolocalization; functional assays in RPE and photoreceptor cells","journal":"Biochemical Society transactions","confidence":"High","confidence_rationale":"Tier 2 — synthesis of multiple experimental studies using Myo7a-null mice with defined cellular phenotypes","pmids":["21936790"],"is_preprint":false},{"year":2009,"finding":"Near-infrared autofluorescence (NIR-AF) of the posterior eye originates predominantly from melanosomes in RPE and choroid. In Myo7a-null mouse RPE, melanosomes (NIR-AF signal) are absent from apical processes, directly correlating with previously described melanosome localization defects due to loss of MYO7A.","method":"Spectral deconvolution confocal microscopy of ex vivo mouse retinas; scanning laser ophthalmoscopy in USH1B patients; purified RPE melanosome spectroscopy","journal":"Investigative ophthalmology & visual science","confidence":"High","confidence_rationale":"Tier 2 — direct imaging with functional correlation in Myo7a-null tissue and human patients","pmids":["19324852"],"is_preprint":false},{"year":2016,"finding":"MYO7A (the mammalian ortholog of Drosophila CRINKLED) binds to and regulates CASPASE-8, acting as a substrate adaptor that recruits kinase substrates to caspases for cleavage, thereby modulating RIPK1>CASPASE-8 non-apoptotic signaling.","method":"Co-immunoprecipitation; genetic epistasis in Drosophila; functional caspase signaling assays; biochemical cleavage assays","journal":"Nature communications","confidence":"Medium","confidence_rationale":"Tier 2/3 — Co-IP and functional signaling assays for mammalian MYO7A/CASPASE-8; primary evidence from Drosophila ortholog with mammalian confirmation","pmids":["26960254"],"is_preprint":false},{"year":2016,"finding":"MYO7A forms a protein complex with PDZD7 (a paralog of USH1C/harmonin and DFNB31/whirlin) in stereocilia membrane fractions, as identified by mass spectrometry from enriched stereocilia membranes. MYO7A and PDZD7 interact in tissue-culture cells and co-localize to the ankle-link region of stereocilia in wild-type but not in Myo7a mutant mice.","method":"Stereocilia membrane fraction isolation; mass spectrometry proteomics; co-immunoprecipitation in tissue-culture cells; immunolocalization in wild-type and Myo7a mutant mouse hair cells","journal":"eLife","confidence":"High","confidence_rationale":"Tier 2 — MS-identified complex from native tissue + Co-IP in cells + localization dependent on Myo7a, multiple orthogonal methods","pmids":["27525485"],"is_preprint":false},{"year":2004,"finding":"A missense mutation (p.R853C) in the fifth IQ motif (IQ5) of MYO7A impairs calmodulin (CaM) binding, causing autosomal dominant hearing loss (DFNA11). Functional assay in vascular smooth muscle cells showed that wild-type IQ5 constitutively binds CaM at all physiologically relevant Ca2+ concentrations, while the mutant IQ5 does not.","method":"Expression of MYO7A IQ5-containing peptides in smooth muscle cells of microarteries; calmodulin-dependent vasoconstriction assay; functional CaM binding assessment","journal":"Human mutation","confidence":"Medium","confidence_rationale":"Tier 2 — functional assay in physiological cellular environment demonstrating impaired CaM binding; single lab, single method","pmids":["15300860"],"is_preprint":false},{"year":2004,"finding":"A missense mutation (p.N458I) in the motor domain of MYO7A is predicted by molecular modeling (based on Dictyostelium myosin II heavy chain structure) to disrupt ATP/ADP binding and impair the myosin power-stroke, providing a structural mechanism for DFNA11 dominant hearing loss.","method":"Molecular modeling of MYO7A motor domain; sequence analysis; linkage analysis","journal":"Human genetics","confidence":"Low","confidence_rationale":"Tier 4 — computational/structural prediction only, no direct biochemical validation","pmids":["15221449"],"is_preprint":false},{"year":2013,"finding":"The p.R668H mutation in the motor domain of MYO7A significantly reduces actin-activated ATPase activity, demonstrating that the motor domain mutation impairs the enzymatic function of myosin VIIA, causing DFNA11 hearing loss.","method":"Actin-activated ATPase activity assay (NADH oxidation rate) comparing wild-type and p.R668H mutant myosin VIIA protein","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 1 — direct in vitro enzymatic assay with mutant protein; single lab","pmids":["23383098"],"is_preprint":false},{"year":2008,"finding":"A DFNB2 allele (p.E1716del) in the tail domain of MYO7A retains the ability to localize correctly to hair cell stereocilia in transfected mouse hair cells, whereas a USH1B allele (equivalent GFP-myosin VIIa) does not localize properly to stereocilia, explaining why different mutations cause phenotypes of differing severity.","method":"GFP-tagged cDNA expression constructs with engineered mutations transfected into mouse hair cells; immunolocalization of GFP-myosin VIIa in stereocilia","journal":"Human mutation","confidence":"Medium","confidence_rationale":"Tier 2 — direct localization experiment in native hair cells with functional consequence; single lab","pmids":["18181211"],"is_preprint":false},{"year":2010,"finding":"A missense mutation in the exon 16 last nucleotide (c.1935G>A) in MYO7A enhances exclusion of exon 16 through partial impairment of the adjacent donor splice site without completely abolishing exon inclusion, causing a milder retinopathy than full USH1B. Minigene splicing assay confirmed the effect.","method":"Lymphoid RNA analysis; splicing minigene transfection assay; structural prediction of molecular model","journal":"Molecular vision","confidence":"Medium","confidence_rationale":"Tier 1/2 — minigene splicing assay directly demonstrated the splice-site effect; single lab","pmids":["21031134"],"is_preprint":false},{"year":2025,"finding":"MYO7A is essential for structural integrity and long-term maintenance of hair bundles in mature cochlear hair cells, distinct from its role in setting the resting open probability of MET channels. Postnatal deletion of Myo7a progressively reduces hair-bundle stiffness and MET current amplitude without initially affecting resting open probability, and increases vulnerability to noise-induced damage. RNA-sequencing identified downregulation of stereociliary genes indicating indirect compensatory mechanisms.","method":"Postnatal conditional Myo7a deletion (Cre-mediated); MET current electrophysiology; hair-bundle stiffness measurements; auditory threshold measurements (ABR); scanning electron microscopy; RNA-sequencing","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 1/2 — conditional KO with multiple orthogonal functional and structural readouts, mechanistic distinction from resting open probability established","pmids":["39746042"],"is_preprint":false},{"year":2011,"finding":"Mutations in multiple splicing sites in MYO7A (c.2283-1G>T and c.5856G>A) abolish consensus splice sites, producing exon skipping. This was demonstrated by hybrid minigene assay.","method":"Hybrid minigene splicing assay; bioinformatic splice prediction","journal":"Clinical genetics","confidence":"Medium","confidence_rationale":"Tier 1 — functional minigene assay; single lab","pmids":["20497194"],"is_preprint":false},{"year":2010,"finding":"Null mutation of Ush1c (harmonin) does not alter the cytoplasmic distribution of Myo7a in cochlear hair cells, demonstrating that harmonin is not required for Myo7a localization to the cytoplasm, though harmonin loss mislocalized Pcdh15 and Sans.","method":"Immunolocalization in Ush1c knockout mouse cochlea; morphological analysis of cochlear sections","journal":"International journal of experimental pathology","confidence":"Medium","confidence_rationale":"Tier 2 — direct localization experiment in KO mouse; single lab, single method","pmids":["21156003"],"is_preprint":false},{"year":2003,"finding":"Double homozygous Myo7a/Myo15 mutant mice show a superimposition of single mutant stereocilia phenotypes without epistatic interaction, and Myo7a heterozygosity does not modify the Myo15 hearing phenotype, indicating that Myo7a and Myo15 function in distinct pathways for stereocilia development.","method":"Genetic crosses to generate double mutant mice; hearing threshold measurement; scanning electron microscopy of stereocilia","journal":"Human molecular genetics","confidence":"Medium","confidence_rationale":"Tier 2 — genetic epistasis using double mutants with defined stereocilia phenotype; single study","pmids":["12966030"],"is_preprint":false},{"year":2016,"finding":"CRISPR/Cas9 correction of a MYO7A mutation (c.4118C>T) in patient-derived iPSCs restored normal stereocilia-like protrusion organization and electrophysiological function in derived hair cell-like cells, confirming MYO7A's role in stereocilia bundle assembly.","method":"CRISPR/Cas9 gene correction; iPSC differentiation to hair cell-like cells; morphological and electrophysiological analysis","journal":"Stem cells translational medicine","confidence":"Medium","confidence_rationale":"Tier 2 — genetic rescue with functional and morphological readouts; single lab","pmids":["27013738"],"is_preprint":false},{"year":2023,"finding":"In vivo AAV9-Myo7a gene delivery to shaker-1 (Myo7a mutant) mice rescued IHC mechanoelectrical transducer function, reestablished the normal adult synaptic profile of IHCs (preventing aberrant axosomatic cholinergic efferent contacts), and improved hearing, demonstrating that MYO7A function in IHCs is required for maintaining normal efferent synaptic organization.","method":"In vivo AAV-Myo7a gene delivery; functional MET current recording; immunofluorescence of efferent synapses; auditory brainstem response measurements","journal":"JCI insight","confidence":"Medium","confidence_rationale":"Tier 2 — in vivo gene rescue with defined synaptic and functional phenotypes; single lab","pmids":["39641274"],"is_preprint":false}],"current_model":"MYO7A encodes an unconventional actin-based motor protein that functions in multiple cell types: in cochlear and vestibular hair cells it is essential for stereocilia bundle structural integrity, mechanoelectrical transducer channel function, and tip-link/ankle-link region organization (interacting with PDZD7 and binding calmodulin via IQ motifs to regulate motor activity); in the retinal pigment epithelium it drives apical melanosome localization via a RAB27A-MYRIP-MYO7A complex, mediates phagosome trafficking to lysosomes, and enables light-dependent translocation of the visual cycle enzyme RPE65 (with which it physically interacts); and in photoreceptors it acts as a selective barrier for membrane proteins (e.g., opsin) at the ciliary transition zone, with loss-of-function mutations in MYO7A causing Usher syndrome type 1B (deaf-blindness) or non-syndromic hearing loss depending on allelic severity."},"narrative":{"teleology":[{"year":1997,"claim":"Establishing that the same gene underlies both isolated deafness and syndromic deaf-blindness resolved whether these were genetically distinct disorders and revealed allelic heterogeneity as the basis of phenotypic spectrum.","evidence":"Mutation screening of MYO7A coding exons in DFNB2 and USH1B families; identification of a splicing mutation at exon 15","pmids":["9171833"],"confidence":"High","gaps":["Mechanism by which specific mutation types produce syndromic versus non-syndromic phenotypes was not explained","No protein-level functional consequence demonstrated"]},{"year":2003,"claim":"Demonstrating non-epistatic interaction between Myo7a and Myo15 established that these two unconventional myosins operate in independent pathways for stereocilia development, narrowing the possible mechanistic role of each.","evidence":"Double homozygous Myo7a/Myo15 mutant mice; hearing thresholds and scanning electron microscopy","pmids":["12966030"],"confidence":"Medium","gaps":["No direct biochemical substrates or binding partners identified for either myosin in this context","Observation limited to developmental phenotype"]},{"year":2004,"claim":"Showing that a disease-causing IQ5 mutation abolishes constitutive calmodulin binding provided the first evidence that CaM-mediated regulation of the MYO7A lever arm is required for hearing function.","evidence":"Expression of IQ5 peptides in smooth muscle cells; calmodulin-dependent vasoconstriction functional assay","pmids":["15300860"],"confidence":"Medium","gaps":["Assay performed in smooth muscle cells, not in hair cells","Effect on motor processivity or force generation not directly measured"]},{"year":2007,"claim":"Identification of the RAB27A–MYRIP–MYO7A tripartite complex on melanosomes defined the molecular mechanism by which MYO7A captures and transports melanosomes in RPE cells.","evidence":"Live-cell imaging of primary RPE cultures; mutant mouse retinal analysis; cell fractionation; in vitro binding assays","pmids":["17352418"],"confidence":"High","gaps":["Whether MYO7A acts as a processive transporter or a tether on melanosomes was not resolved","Contribution of other motors to the same cargo not fully delineated"]},{"year":2008,"claim":"Mosaic retinal analysis proved that the MYO7A photoreceptor phenotype is cell-autonomous, ruling out the hypothesis that photoreceptor defects are secondary to RPE dysfunction and establishing a direct photoreceptor role.","evidence":"Mosaic retinal analysis in Myo7a-deficient shaker1 mice","pmids":["18463160"],"confidence":"High","gaps":["Molecular target or cargo of MYO7A within photoreceptors not identified","Whether the RPE and photoreceptor functions synergize in disease progression remained unclear"]},{"year":2008,"claim":"Demonstrating that a DFNB2 tail-domain mutant retains stereocilia targeting while a USH1B mutant does not provided a molecular explanation for allele-severity correlations in human disease.","evidence":"GFP-tagged MYO7A constructs with engineered mutations transfected into mouse hair cells; immunolocalization","pmids":["18181211"],"confidence":"Medium","gaps":["Only two alleles tested","Biochemical basis of targeting failure not identified"]},{"year":2011,"claim":"Discovery that MYO7A physically associates with RPE65 and is required for its light-dependent translocation revealed an unexpected role for an actin motor in the visual retinoid cycle.","evidence":"Co-immunoprecipitation from RPE lysates; retinoid metabolite assays; immunolocalization in Myo7a mutant mice","pmids":["21493626"],"confidence":"High","gaps":["Whether the MYO7A–RPE65 interaction is direct or bridged by an adaptor was not resolved","Structural basis of the interaction unknown"]},{"year":2011,"claim":"A unified functional model placed MYO7A in three distinct RPE trafficking pathways (melanosome positioning, phagosome clearance, RPE65 translocation) plus a ciliary-gate role in photoreceptors, consolidating disparate observations.","evidence":"Synthesis of Myo7a-null mouse retinal phenotypes; immunolocalization and functional assays","pmids":["21936790"],"confidence":"High","gaps":["Mechanism of selective membrane-protein gating at the ciliary transition zone not defined at molecular level","Whether the gate function is motor-dependent or scaffold-dependent was not tested"]},{"year":2013,"claim":"Direct measurement of reduced actin-activated ATPase activity for the R668H motor-domain mutant provided the first biochemical proof that disease mutations impair the enzymatic motor cycle of MYO7A.","evidence":"Purified wild-type vs. R668H MYO7A; NADH-coupled ATPase assay","pmids":["23383098"],"confidence":"Medium","gaps":["Motility or force-generation measurements not performed","Single mutant tested; generalizability to other motor-domain mutations not shown"]},{"year":2016,"claim":"Identification of MYO7A–PDZD7 complex by mass spectrometry from native stereocilia membranes, confirmed by co-IP and co-localization, established a new scaffold partner at the ankle-link region linking MYO7A to broader Usher-network organization.","evidence":"Stereocilia membrane proteomics; co-immunoprecipitation in cells; immunolocalization in WT and Myo7a mutant mouse hair cells","pmids":["27525485"],"confidence":"High","gaps":["Functional consequence of disrupting the MYO7A–PDZD7 interaction specifically was not tested","Whether PDZD7 is a cargo or a scaffold for MYO7A was not distinguished"]},{"year":2016,"claim":"Evidence that MYO7A binds and modulates CASPASE-8 in a non-apoptotic RIPK1 signaling pathway expanded MYO7A function beyond sensory-cell trafficking to signaling scaffold roles.","evidence":"Co-IP; genetic epistasis in Drosophila crinkled mutants; caspase signaling assays with mammalian confirmation","pmids":["26960254"],"confidence":"Medium","gaps":["Mammalian MYO7A–CASPASE-8 interaction not validated by reciprocal IP in native tissue","Physiological relevance in sensory cells not demonstrated","Mechanism of substrate recruitment to caspases incompletely defined"]},{"year":2023,"claim":"AAV-mediated Myo7a gene rescue in shaker-1 mice restored MET function and corrected aberrant efferent synaptic organization, revealing that MYO7A in inner hair cells is required to maintain the normal adult synaptic configuration.","evidence":"In vivo AAV9-Myo7a delivery; MET current recordings; efferent synapse immunofluorescence; ABR measurements","pmids":["39641274"],"confidence":"Medium","gaps":["Whether the synaptic phenotype is a direct consequence of MET dysfunction or an independent MYO7A function was not resolved","Long-term durability of rescue not assessed"]},{"year":2025,"claim":"Postnatal conditional deletion demonstrated that MYO7A is continuously required for hair-bundle stiffness and MET current maintenance in mature hair cells, separable from setting the resting open probability of MET channels.","evidence":"Postnatal Cre-mediated Myo7a deletion; MET electrophysiology; hair-bundle stiffness measurements; ABR; SEM; RNA-seq","pmids":["39746042"],"confidence":"High","gaps":["Direct molecular target through which MYO7A maintains bundle stiffness not identified","RNA-seq changes are correlative; causal downstream pathways not established"]},{"year":null,"claim":"Major open questions include the structural basis of MYO7A processivity and force generation along stereocilia actin, the molecular identity of cargoes gated at the photoreceptor ciliary transition zone, and whether the MYO7A–CASPASE-8 signaling axis operates in sensory cells in vivo.","evidence":"","pmids":[],"confidence":"Low","gaps":["No high-resolution structure of full-length MYO7A","No reconstituted in vitro motility with native cargoes","Ciliary transition-zone gating mechanism molecularly undefined"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140657","term_label":"ATP-dependent activity","supporting_discovery_ids":[10,8]},{"term_id":"GO:0003774","term_label":"cytoskeletal motor activity","supporting_discovery_ids":[10,13]},{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[10,13]}],"localization":[{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[7,13]},{"term_id":"GO:0005929","term_label":"cilium","supporting_discovery_ids":[4,1]},{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[7]}],"pathway":[{"term_id":"R-HSA-9709957","term_label":"Sensory Perception","supporting_discovery_ids":[0,13,18]},{"term_id":"R-HSA-9609507","term_label":"Protein localization","supporting_discovery_ids":[2,3,4]},{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[2,4]}],"complexes":["RAB27A-MYRIP-MYO7A melanosome transport complex","MYO7A-PDZD7 ankle-link complex"],"partners":["PDZD7","RAB27A","MYRIP","RPE65","CALM1","CASP8"],"other_free_text":[]},"mechanistic_narrative":"MYO7A encodes an unconventional myosin motor protein essential for mechanosensory and visual functions, with loss-of-function mutations causing Usher syndrome type 1B (deaf-blindness) or non-syndromic hearing loss (DFNB2/DFNA11) depending on allelic severity [PMID:9171833]. In cochlear hair cells, MYO7A maintains stereocilia bundle structural integrity and stiffness, sustains mechanoelectrical transducer (MET) channel function, and organizes the ankle-link region through interaction with PDZD7; postnatal loss progressively reduces hair-bundle stiffness and MET current amplitude and increases noise vulnerability [PMID:27525485, PMID:39746042]. In retinal pigment epithelium, MYO7A drives apical melanosome positioning via a RAB27A–MYRIP–MYO7A transport complex, facilitates phagosome trafficking to lysosomes, and mediates light-dependent translocation of the visual cycle enzyme RPE65, with which it physically associates; in photoreceptors it acts cell-autonomously as a selective barrier for membrane proteins at the ciliary transition zone [PMID:17352418, PMID:21493626, PMID:18463160, PMID:21936790]. Motor activity is regulated by calmodulin binding to IQ motifs, and disease-causing motor-domain mutations directly impair actin-activated ATPase activity [PMID:15300860, PMID:23383098]."},"prefetch_data":{"uniprot":{"accession":"Q13402","full_name":"Unconventional myosin-VIIa","aliases":[],"length_aa":2215,"mass_kda":254.4,"function":"Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Their highly divergent tails bind to membranous compartments, which are then moved relative to actin filaments. In the retina, plays an important role in the renewal of the outer photoreceptor disks. Plays an important role in the distribution and migration of retinal pigment epithelial (RPE) melanosomes and phagosomes, and in the regulation of opsin transport in retinal photoreceptors. In the inner ear, plays an important role in differentiation, morphogenesis and organization of cochlear hair cell bundles. Involved in hair-cell vesicle trafficking of aminoglycosides, which are known to induce ototoxicity (By similarity). Motor protein that is a part of the functional network formed by USH1C, USH1G, CDH23 and MYO7A that mediates mechanotransduction in cochlear hair cells. Required for normal hearing","subcellular_location":"Cytoplasm; Cytoplasm, cell cortex; Cytoplasm, cytoskeleton; Synapse","url":"https://www.uniprot.org/uniprotkb/Q13402/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/MYO7A","classification":"Not Classified","n_dependent_lines":7,"n_total_lines":1208,"dependency_fraction":0.005794701986754967},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/MYO7A","total_profiled":1310},"omim":[{"mim_id":"619749","title":"VEZATIN, ADHERENS JUNCTIONS TRANSMEMBRANE PROTEIN; VEZT","url":"https://www.omim.org/entry/619749"},{"mim_id":"612723","title":"PLECKSTRIN HOMOLOGY DOMAIN-CONTAINING PROTEIN, FAMILY H, MEMBER 2; PLEKHH2","url":"https://www.omim.org/entry/612723"},{"mim_id":"611790","title":"MYOSIN VIIA- AND RAB-INTERACTING PROTEIN; MYRIP","url":"https://www.omim.org/entry/611790"},{"mim_id":"609254","title":"SENIOR-LOKEN SYNDROME 5; SLSN5","url":"https://www.omim.org/entry/609254"},{"mim_id":"607696","title":"USH1 PROTEIN NETWORK COMPONENT SANS; USH1G","url":"https://www.omim.org/entry/607696"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"adrenal gland","ntpm":36.6}],"url":"https://www.proteinatlas.org/search/MYO7A"},"hgnc":{"alias_symbol":["NSRD2"],"prev_symbol":["USH1B","DFNB2","DFNA11"]},"alphafold":{"accession":"Q13402","domains":[{"cath_id":"-","chopping":"678-697_737-887","consensus_level":"medium","plddt":73.583,"start":678,"end":887},{"cath_id":"3.10.20.90","chopping":"1258-1351","consensus_level":"medium","plddt":80.8979,"start":1258,"end":1351},{"cath_id":"1.20.80.10","chopping":"1357-1471","consensus_level":"high","plddt":84.7676,"start":1357,"end":1471},{"cath_id":"2.30.29.30","chopping":"1494-1523_1568-1597","consensus_level":"medium","plddt":80.5962,"start":1494,"end":1597},{"cath_id":"1.25.40.530","chopping":"1714-1726_1745-1901","consensus_level":"medium","plddt":86.9511,"start":1714,"end":1901},{"cath_id":"3.10.20.90","chopping":"1902-1977","consensus_level":"medium","plddt":85.8092,"start":1902,"end":1977},{"cath_id":"1.20.80.10","chopping":"2002-2111","consensus_level":"medium","plddt":89.4795,"start":2002,"end":2111},{"cath_id":"2.30.29.30","chopping":"2113-2215","consensus_level":"medium","plddt":79.6562,"start":2113,"end":2215},{"cath_id":"2.30.30","chopping":"9-60","consensus_level":"high","plddt":77.8746,"start":9,"end":60}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q13402","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q13402-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q13402-F1-predicted_aligned_error_v6.png","plddt_mean":77.25},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=MYO7A","jax_strain_url":"https://www.jax.org/strain/search?query=MYO7A"},"sequence":{"accession":"Q13402","fasta_url":"https://rest.uniprot.org/uniprotkb/Q13402.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q13402/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q13402"}},"corpus_meta":[{"pmid":"9171833","id":"PMC_9171833","title":"The autosomal recessive isolated deafness, DFNB2, and the Usher 1B syndrome are allelic defects of the myosin-VIIA gene.","date":"1997","source":"Nature genetics","url":"https://pubmed.ncbi.nlm.nih.gov/9171833","citation_count":329,"is_preprint":false},{"pmid":"1478677","id":"PMC_1478677","title":"Linkage of Usher syndrome type I gene (USH1B) to the long arm of chromosome 11.","date":"1992","source":"Genomics","url":"https://pubmed.ncbi.nlm.nih.gov/1478677","citation_count":143,"is_preprint":false},{"pmid":"24568220","id":"PMC_24568220","title":"Dual adeno-associated virus vectors result in efficient in vitro and in vivo expression of an oversized gene, MYO7A.","date":"2014","source":"Human gene therapy methods","url":"https://pubmed.ncbi.nlm.nih.gov/24568220","citation_count":113,"is_preprint":false},{"pmid":"18463160","id":"PMC_18463160","title":"Usher syndromes due to MYO7A, PCDH15, USH2A or GPR98 mutations share retinal disease mechanism.","date":"2008","source":"Human molecular genetics","url":"https://pubmed.ncbi.nlm.nih.gov/18463160","citation_count":95,"is_preprint":false},{"pmid":"23344065","id":"PMC_23344065","title":"Retinal gene therapy with a large MYO7A cDNA using adeno-associated virus.","date":"2013","source":"Gene therapy","url":"https://pubmed.ncbi.nlm.nih.gov/23344065","citation_count":93,"is_preprint":false},{"pmid":"18181211","id":"PMC_18181211","title":"Mutation spectrum of MYO7A and evaluation of a novel nonsyndromic deafness DFNB2 allele with residual function.","date":"2008","source":"Human mutation","url":"https://pubmed.ncbi.nlm.nih.gov/18181211","citation_count":89,"is_preprint":false},{"pmid":"19074810","id":"PMC_19074810","title":"Disease boundaries in the retina of patients with Usher syndrome caused by MYO7A gene mutations.","date":"2008","source":"Investigative ophthalmology & visual science","url":"https://pubmed.ncbi.nlm.nih.gov/19074810","citation_count":81,"is_preprint":false},{"pmid":"14648237","id":"PMC_14648237","title":"Progressive hearing loss and increased susceptibility to noise-induced hearing loss in mice carrying a Cdh23 but not a Myo7a mutation.","date":"2003","source":"Journal of the Association for Research in Otolaryngology : JARO","url":"https://pubmed.ncbi.nlm.nih.gov/14648237","citation_count":78,"is_preprint":false},{"pmid":"8776602","id":"PMC_8776602","title":"A gene for a dominant form of non-syndromic sensorineural deafness (DFNA11) maps within the region containing the DFNB2 recessive deafness gene.","date":"1996","source":"Human molecular genetics","url":"https://pubmed.ncbi.nlm.nih.gov/8776602","citation_count":71,"is_preprint":false},{"pmid":"19324852","id":"PMC_19324852","title":"Retinal pigment epithelium defects in humans and mice with mutations in MYO7A: imaging melanosome-specific autofluorescence.","date":"2009","source":"Investigative ophthalmology & visual science","url":"https://pubmed.ncbi.nlm.nih.gov/19324852","citation_count":68,"is_preprint":false},{"pmid":"21873662","id":"PMC_21873662","title":"Retinal disease course in Usher syndrome 1B due to MYO7A mutations.","date":"2011","source":"Investigative ophthalmology & visual science","url":"https://pubmed.ncbi.nlm.nih.gov/21873662","citation_count":67,"is_preprint":false},{"pmid":"11222540","id":"PMC_11222540","title":"Electroretinographic anomalies in mice with mutations in Myo7a, the gene involved in human Usher syndrome type 1B.","date":"2001","source":"Investigative ophthalmology & visual science","url":"https://pubmed.ncbi.nlm.nih.gov/11222540","citation_count":66,"is_preprint":false},{"pmid":"27013738","id":"PMC_27013738","title":"Genetic Correction of Induced Pluripotent Stem Cells From a Deaf Patient With MYO7A Mutation Results in Morphologic and Functional Recovery of the Derived Hair Cell-Like Cells.","date":"2016","source":"Stem cells translational medicine","url":"https://pubmed.ncbi.nlm.nih.gov/27013738","citation_count":66,"is_preprint":false},{"pmid":"12121736","id":"PMC_12121736","title":"Stereocilia defects in waltzer (Cdh23), shaker1 (Myo7a) and double waltzer/shaker1 mutant mice.","date":"2002","source":"Hearing research","url":"https://pubmed.ncbi.nlm.nih.gov/12121736","citation_count":62,"is_preprint":false},{"pmid":"21936790","id":"PMC_21936790","title":"The many different cellular functions of MYO7A in the retina.","date":"2011","source":"Biochemical Society transactions","url":"https://pubmed.ncbi.nlm.nih.gov/21936790","citation_count":60,"is_preprint":false},{"pmid":"21901789","id":"PMC_21901789","title":"Whole-exome sequencing identifies ALMS1, IQCB1, CNGA3, and MYO7A mutations in patients with Leber congenital amaurosis.","date":"2011","source":"Human mutation","url":"https://pubmed.ncbi.nlm.nih.gov/21901789","citation_count":53,"is_preprint":false},{"pmid":"21493626","id":"PMC_21493626","title":"The Usher 1B protein, MYO7A, is required for normal localization and function of the visual retinoid cycle enzyme, RPE65.","date":"2011","source":"Human molecular genetics","url":"https://pubmed.ncbi.nlm.nih.gov/21493626","citation_count":53,"is_preprint":false},{"pmid":"11889386","id":"PMC_11889386","title":"Phenotype of DFNA11: a nonsyndromic hearing loss caused by a myosin VIIA mutation.","date":"2002","source":"The Laryngoscope","url":"https://pubmed.ncbi.nlm.nih.gov/11889386","citation_count":52,"is_preprint":false},{"pmid":"12112664","id":"PMC_12112664","title":"Mutations in myosin VIIA (MYO7A) and usherin (USH2A) in Spanish patients with Usher syndrome types I and II, respectively.","date":"2002","source":"Human mutation","url":"https://pubmed.ncbi.nlm.nih.gov/12112664","citation_count":47,"is_preprint":false},{"pmid":"27525485","id":"PMC_27525485","title":"PDZD7-MYO7A complex identified in enriched stereocilia membranes.","date":"2016","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/27525485","citation_count":44,"is_preprint":false},{"pmid":"15221449","id":"PMC_15221449","title":"Identification and molecular modelling of a mutation in the motor head domain of myosin VIIA in a family with autosomal dominant hearing impairment (DFNA11).","date":"2004","source":"Human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/15221449","citation_count":43,"is_preprint":false},{"pmid":"15389316","id":"PMC_15389316","title":"A Myo7a mutation cosegregates with stereocilia defects and low-frequency hearing impairment.","date":"2004","source":"Mammalian genome : official journal of the International Mammalian Genome Society","url":"https://pubmed.ncbi.nlm.nih.gov/15389316","citation_count":42,"is_preprint":false},{"pmid":"16470552","id":"PMC_16470552","title":"Mutation profile of the MYO7A gene in Spanish patients with Usher syndrome type I.","date":"2006","source":"Human mutation","url":"https://pubmed.ncbi.nlm.nih.gov/16470552","citation_count":40,"is_preprint":false},{"pmid":"15300860","id":"PMC_15300860","title":"Impaired calmodulin binding of myosin-7A causes autosomal dominant hearing loss (DFNA11).","date":"2004","source":"Human mutation","url":"https://pubmed.ncbi.nlm.nih.gov/15300860","citation_count":34,"is_preprint":false},{"pmid":"20132242","id":"PMC_20132242","title":"Variable hearing impairment in a DFNB2 family with a novel MYO7A missense mutation.","date":"2010","source":"Clinical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/20132242","citation_count":33,"is_preprint":false},{"pmid":"24831256","id":"PMC_24831256","title":"Novel and recurrent MYO7A mutations in Usher syndrome type 1 and type 2.","date":"2014","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/24831256","citation_count":32,"is_preprint":false},{"pmid":"21150918","id":"PMC_21150918","title":"Novel missense mutations in MYO7A underlying postlingual high- or low-frequency non-syndromic hearing impairment in two large families from China.","date":"2010","source":"Journal of human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/21150918","citation_count":32,"is_preprint":false},{"pmid":"9070921","id":"PMC_9070921","title":"The genomic structure of the gene defective in Usher syndrome type Ib (MYO7A).","date":"1997","source":"Genomics","url":"https://pubmed.ncbi.nlm.nih.gov/9070921","citation_count":30,"is_preprint":false},{"pmid":"12966030","id":"PMC_12966030","title":"Myo15 function is distinct from Myo6, Myo7a and pirouette genes in development of cochlear stereocilia.","date":"2003","source":"Human molecular genetics","url":"https://pubmed.ncbi.nlm.nih.gov/12966030","citation_count":29,"is_preprint":false},{"pmid":"17352418","id":"PMC_17352418","title":"Analysis of the linkage of MYRIP and MYO7A to melanosomes by RAB27A in retinal pigment epithelial cells.","date":"2007","source":"Cell motility and the cytoskeleton","url":"https://pubmed.ncbi.nlm.nih.gov/17352418","citation_count":29,"is_preprint":false},{"pmid":"24199935","id":"PMC_24199935","title":"Natural history and retinal structure in patients with Usher syndrome type 1 owing to MYO7A mutation.","date":"2013","source":"Ophthalmology","url":"https://pubmed.ncbi.nlm.nih.gov/24199935","citation_count":28,"is_preprint":false},{"pmid":"26960254","id":"PMC_26960254","title":"The unconventional myosin CRINKLED and its mammalian orthologue MYO7A regulate caspases in their signalling roles.","date":"2016","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/26960254","citation_count":27,"is_preprint":false},{"pmid":"19375528","id":"PMC_19375528","title":"Molecular screening of deafness in Algeria: high genetic heterogeneity involving DFNB1 and the Usher loci, DFNB2/USH1B, DFNB12/USH1D and DFNB23/USH1F.","date":"2009","source":"European journal of medical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/19375528","citation_count":27,"is_preprint":false},{"pmid":"31824252","id":"PMC_31824252","title":"A Novel Mouse Model of MYO7A USH1B Reveals Auditory and Visual System Haploinsufficiencies.","date":"2019","source":"Frontiers in neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/31824252","citation_count":26,"is_preprint":false},{"pmid":"16449806","id":"PMC_16449806","title":"Identification of a novel mutation in the myosin VIIA motor domain in a family with autosomal dominant hearing loss (DFNA11).","date":"2006","source":"Audiology & neuro-otology","url":"https://pubmed.ncbi.nlm.nih.gov/16449806","citation_count":26,"is_preprint":false},{"pmid":"34391192","id":"PMC_34391192","title":"Rare coding variants involving MYO7A and other genes encoding stereocilia link proteins in familial meniere disease.","date":"2021","source":"Hearing research","url":"https://pubmed.ncbi.nlm.nih.gov/34391192","citation_count":25,"is_preprint":false},{"pmid":"25558175","id":"PMC_25558175","title":"MYO7A and USH2A gene sequence variants in Italian patients with Usher syndrome.","date":"2014","source":"Molecular vision","url":"https://pubmed.ncbi.nlm.nih.gov/25558175","citation_count":23,"is_preprint":false},{"pmid":"11992483","id":"PMC_11992483","title":"Searching for evidence of DFNB2.","date":"2002","source":"American journal of medical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/11992483","citation_count":22,"is_preprint":false},{"pmid":"20844544","id":"PMC_20844544","title":"Mutation analysis of the MYO7A and CDH23 genes in Japanese patients with Usher syndrome type 1.","date":"2010","source":"Journal of human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/20844544","citation_count":22,"is_preprint":false},{"pmid":"35710827","id":"PMC_35710827","title":"CRISPR/Cas9 editing of the MYO7A gene in rhesus macaque embryos to generate a primate model of Usher syndrome type 1B.","date":"2022","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/35710827","citation_count":21,"is_preprint":false},{"pmid":"23383098","id":"PMC_23383098","title":"Identification and functional study of a new missense mutation in the motor head domain of myosin VIIA in a family with autosomal dominant hearing impairment (DFNA11).","date":"2013","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/23383098","citation_count":21,"is_preprint":false},{"pmid":"25605753","id":"PMC_25605753","title":"Gene Therapy for the Retinal Degeneration of Usher Syndrome Caused by Mutations in MYO7A.","date":"2015","source":"Cold Spring Harbor perspectives in medicine","url":"https://pubmed.ncbi.nlm.nih.gov/25605753","citation_count":20,"is_preprint":false},{"pmid":"16639269","id":"PMC_16639269","title":"Cochleovestibular and ocular features in a Dutch DFNA11 family.","date":"2006","source":"Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology","url":"https://pubmed.ncbi.nlm.nih.gov/16639269","citation_count":18,"is_preprint":false},{"pmid":"22898263","id":"PMC_22898263","title":"Next-generation sequencing identifies a novel compound heterozygous mutation in MYO7A in a Chinese patient with Usher Syndrome 1B.","date":"2012","source":"Clinica chimica acta; international journal of clinical chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/22898263","citation_count":18,"is_preprint":false},{"pmid":"37693946","id":"PMC_37693946","title":"Dual-AAV vector-mediated expression of MYO7A improves vestibular function in a mouse model of Usher syndrome 1B.","date":"2023","source":"Molecular therapy. Methods & clinical development","url":"https://pubmed.ncbi.nlm.nih.gov/37693946","citation_count":17,"is_preprint":false},{"pmid":"21031134","id":"PMC_21031134","title":"Reinforcement of a minor alternative splicing event in MYO7A due to a missense mutation results in a mild form of retinopathy and deafness.","date":"2010","source":"Molecular vision","url":"https://pubmed.ncbi.nlm.nih.gov/21031134","citation_count":17,"is_preprint":false},{"pmid":"26968074","id":"PMC_26968074","title":"Novel compound heterozygous mutations in MYO7A gene associated with autosomal recessive sensorineural hearing loss in a Chinese family.","date":"2016","source":"International journal of pediatric otorhinolaryngology","url":"https://pubmed.ncbi.nlm.nih.gov/26968074","citation_count":16,"is_preprint":false},{"pmid":"35453549","id":"PMC_35453549","title":"Clinical Heterogeneity Associated with MYO7A Variants Relies on Affected Domains.","date":"2022","source":"Biomedicines","url":"https://pubmed.ncbi.nlm.nih.gov/35453549","citation_count":14,"is_preprint":false},{"pmid":"34948090","id":"PMC_34948090","title":"The Study of a 231 French Patient Cohort Significantly Extends the Mutational Spectrum of the Two Major Usher Genes MYO7A and USH2A.","date":"2021","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/34948090","citation_count":13,"is_preprint":false},{"pmid":"20497194","id":"PMC_20497194","title":"Functional analysis of splicing mutations in MYO7A and USH2A genes.","date":"2011","source":"Clinical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/20497194","citation_count":13,"is_preprint":false},{"pmid":"39746042","id":"PMC_39746042","title":"MYO7A is required for the functional integrity of the mechanoelectrical transduction complex in hair cells of the adult cochlea.","date":"2025","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/39746042","citation_count":13,"is_preprint":false},{"pmid":"38594301","id":"PMC_38594301","title":"The prevalence and clinical features of MYO7A-related hearing loss including DFNA11, DFNB2 and USH1B.","date":"2024","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/38594301","citation_count":12,"is_preprint":false},{"pmid":"24194196","id":"PMC_24194196","title":"Analysis of two Arab families reveals additional support for a DFNB2 nonsyndromic phenotype of MYO7A.","date":"2013","source":"Molecular biology reports","url":"https://pubmed.ncbi.nlm.nih.gov/24194196","citation_count":12,"is_preprint":false},{"pmid":"29400105","id":"PMC_29400105","title":"Identification of a MYO7A mutation in a large Chinese DFNA11 family and genotype-phenotype review for DFNA11.","date":"2018","source":"Acta oto-laryngologica","url":"https://pubmed.ncbi.nlm.nih.gov/29400105","citation_count":12,"is_preprint":false},{"pmid":"33671976","id":"PMC_33671976","title":"Spectrum of MYO7A Mutations in an Indigenous South African Population Further Elucidates the Nonsyndromic Autosomal Recessive Phenotype of DFNB2 to Include Both Homozygous and Compound Heterozygous Mutations.","date":"2021","source":"Genes","url":"https://pubmed.ncbi.nlm.nih.gov/33671976","citation_count":11,"is_preprint":false},{"pmid":"27729122","id":"PMC_27729122","title":"Compound heterozygous MYO7A mutations segregating Usher syndrome type 2 in a Han family.","date":"2016","source":"International journal of pediatric otorhinolaryngology","url":"https://pubmed.ncbi.nlm.nih.gov/27729122","citation_count":11,"is_preprint":false},{"pmid":"31097876","id":"PMC_31097876","title":"A missense mutation in MYO7A is associated with bilateral deafness and vestibular dysfunction in the Doberman pinscher breed.","date":"2019","source":"Canadian journal of veterinary research = Revue canadienne de recherche veterinaire","url":"https://pubmed.ncbi.nlm.nih.gov/31097876","citation_count":11,"is_preprint":false},{"pmid":"33576163","id":"PMC_33576163","title":"Genotype-phenotype correlation in patients with Usher syndrome and pathogenic variants in MYO7A: implications for future clinical trials.","date":"2021","source":"Acta ophthalmologica","url":"https://pubmed.ncbi.nlm.nih.gov/33576163","citation_count":11,"is_preprint":false},{"pmid":"18667942","id":"PMC_18667942","title":"In search of the DFNA11 myosin VIIA low- and mid-frequency auditory genetic modifier.","date":"2008","source":"Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology","url":"https://pubmed.ncbi.nlm.nih.gov/18667942","citation_count":10,"is_preprint":false},{"pmid":"17093394","id":"PMC_17093394","title":"Two Finnish USH1B patients with three novel mutations in myosin VIIA.","date":"2006","source":"Molecular vision","url":"https://pubmed.ncbi.nlm.nih.gov/17093394","citation_count":10,"is_preprint":false},{"pmid":"21156003","id":"PMC_21156003","title":"Analysis of subcellular localization of Myo7a, Pcdh15 and Sans in Ush1c knockout mice.","date":"2010","source":"International journal of experimental pathology","url":"https://pubmed.ncbi.nlm.nih.gov/21156003","citation_count":10,"is_preprint":false},{"pmid":"26469752","id":"PMC_26469752","title":"A Founder Mutation in MYO7A Underlies a Significant Proportion of Usher Syndrome in Indigenous South Africans: Implications for the African Diaspora.","date":"2015","source":"Investigative ophthalmology & visual science","url":"https://pubmed.ncbi.nlm.nih.gov/26469752","citation_count":10,"is_preprint":false},{"pmid":"37586294","id":"PMC_37586294","title":"Expression of two major isoforms of MYO7A in the retina: Considerations for gene therapy of Usher syndrome type 1B.","date":"2023","source":"Vision research","url":"https://pubmed.ncbi.nlm.nih.gov/37586294","citation_count":9,"is_preprint":false},{"pmid":"28472130","id":"PMC_28472130","title":"Novel compound heterozygous MYO7A mutations in Moroccan families with autosomal recessive non-syndromic hearing loss.","date":"2017","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/28472130","citation_count":9,"is_preprint":false},{"pmid":"22219650","id":"PMC_22219650","title":"Novel mutations of MYO7A and USH1G in Israeli Arab families with Usher syndrome type 1.","date":"2011","source":"Molecular vision","url":"https://pubmed.ncbi.nlm.nih.gov/22219650","citation_count":9,"is_preprint":false},{"pmid":"29511501","id":"PMC_29511501","title":"The first case of NSHL by direct impression on EYA1 gene and identification of one novel mutation in MYO7A in the Iranian families.","date":"2018","source":"Iranian journal of basic medical sciences","url":"https://pubmed.ncbi.nlm.nih.gov/29511501","citation_count":9,"is_preprint":false},{"pmid":"28802369","id":"PMC_28802369","title":"The first sporadic case of DFNA11 identified by next-generation sequencing.","date":"2017","source":"International journal of pediatric otorhinolaryngology","url":"https://pubmed.ncbi.nlm.nih.gov/28802369","citation_count":8,"is_preprint":false},{"pmid":"29416772","id":"PMC_29416772","title":"Identification of a novel MYO7A mutation in Usher syndrome type 1.","date":"2017","source":"Oncotarget","url":"https://pubmed.ncbi.nlm.nih.gov/29416772","citation_count":8,"is_preprint":false},{"pmid":"25080338","id":"PMC_25080338","title":"Novel compound heterozygous mutations in MYO7A Associated with Usher syndrome 1 in a Chinese family.","date":"2014","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/25080338","citation_count":8,"is_preprint":false},{"pmid":"29942180","id":"PMC_29942180","title":"Severe retinal degeneration at an early age in Usher syndrome type 1B associated with homozygous splice site mutations in MYO7A gene.","date":"2017","source":"Saudi journal of ophthalmology : official journal of the Saudi Ophthalmological Society","url":"https://pubmed.ncbi.nlm.nih.gov/29942180","citation_count":8,"is_preprint":false},{"pmid":"29605349","id":"PMC_29605349","title":"Utility of whole exome sequencing in the diagnosis of Usher syndrome: Report of novel compound heterozygous MYO7A mutations.","date":"2018","source":"International journal of pediatric otorhinolaryngology","url":"https://pubmed.ncbi.nlm.nih.gov/29605349","citation_count":8,"is_preprint":false},{"pmid":"30826590","id":"PMC_30826590","title":"Identification of four novel mutations in MYO7A gene and their association with nonsyndromic deafness and Usher Syndrome 1B.","date":"2019","source":"International journal of pediatric otorhinolaryngology","url":"https://pubmed.ncbi.nlm.nih.gov/30826590","citation_count":8,"is_preprint":false},{"pmid":"28731162","id":"PMC_28731162","title":"A homozygous MYO7A mutation associated to Usher syndrome and unilateral auditory neuropathy spectrum disorder.","date":"2017","source":"Molecular medicine reports","url":"https://pubmed.ncbi.nlm.nih.gov/28731162","citation_count":7,"is_preprint":false},{"pmid":"17960123","id":"PMC_17960123","title":"Analysis of MYO7A in a Moroccan family with Usher syndrome type 1B: novel loss-of-function mutation and non-pathogenicity of p.Y1719C.","date":"2007","source":"Molecular vision","url":"https://pubmed.ncbi.nlm.nih.gov/17960123","citation_count":7,"is_preprint":false},{"pmid":"23559863","id":"PMC_23559863","title":"Novel compound heterozygous mutations in MYO7A in a Chinese family with Usher syndrome type 1.","date":"2013","source":"Molecular vision","url":"https://pubmed.ncbi.nlm.nih.gov/23559863","citation_count":7,"is_preprint":false},{"pmid":"31320737","id":"PMC_31320737","title":"Retinal findings in pediatric patients with Usher syndrome Type 1 due to mutations in MYO7A gene.","date":"2019","source":"Eye (London, England)","url":"https://pubmed.ncbi.nlm.nih.gov/31320737","citation_count":7,"is_preprint":false},{"pmid":"23237960","id":"PMC_23237960","title":"An Usher syndrome type 1 patient diagnosed before the appearance of visual symptoms by MYO7A mutation analysis.","date":"2012","source":"International journal of pediatric otorhinolaryngology","url":"https://pubmed.ncbi.nlm.nih.gov/23237960","citation_count":7,"is_preprint":false},{"pmid":"30881389","id":"PMC_30881389","title":"Novel deleterious mutation in MYO7A, TH and EVC2 in two Pakistani brothers with familial deafness.","date":"2019","source":"Pakistan journal of medical sciences","url":"https://pubmed.ncbi.nlm.nih.gov/30881389","citation_count":6,"is_preprint":false},{"pmid":"28451532","id":"PMC_28451532","title":"Screening of Myo7A Mutations in Iranian Patients with Autosomal Recessive Hearing Loss from West of Iran.","date":"2017","source":"Iranian journal of public health","url":"https://pubmed.ncbi.nlm.nih.gov/28451532","citation_count":6,"is_preprint":false},{"pmid":"38884554","id":"PMC_38884554","title":"Multicentric Longitudinal Prospective Study in a European Cohort of MYO7A Patients: Disease Course and Implications for Gene Therapy.","date":"2024","source":"Investigative ophthalmology & visual science","url":"https://pubmed.ncbi.nlm.nih.gov/38884554","citation_count":6,"is_preprint":false},{"pmid":"39641274","id":"PMC_39641274","title":"In vivo AAV9-Myo7a gene rescue restores hearing and cholinergic efferent innervation in inner hair cells.","date":"2024","source":"JCI insight","url":"https://pubmed.ncbi.nlm.nih.gov/39641274","citation_count":5,"is_preprint":false},{"pmid":"33955556","id":"PMC_33955556","title":"A natural knockout of the MYO7A gene leads to pre-weaning mortality in pigs.","date":"2021","source":"Animal genetics","url":"https://pubmed.ncbi.nlm.nih.gov/33955556","citation_count":5,"is_preprint":false},{"pmid":"9761396","id":"PMC_9761396","title":"Map refinement of the Usher syndrome type 1B gene, MYO7A, relative to 11q13.5 microsatellite markers.","date":"1998","source":"Clinical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/9761396","citation_count":5,"is_preprint":false},{"pmid":"33976695","id":"PMC_33976695","title":"Next-Generation Sequencing Identifies Pathogenic Variants in HGF, POU3F4, TECTA, and MYO7A in Consanguineous Pakistani Deaf Families.","date":"2021","source":"Neural plasticity","url":"https://pubmed.ncbi.nlm.nih.gov/33976695","citation_count":5,"is_preprint":false},{"pmid":"10447383","id":"PMC_10447383","title":"Identification of three novel mutations in the MYO7A gene.","date":"1999","source":"Human mutation","url":"https://pubmed.ncbi.nlm.nih.gov/10447383","citation_count":5,"is_preprint":false},{"pmid":"36164746","id":"PMC_36164746","title":"Novel compound heterozygous synonymous and missense variants in the MYO7A gene identified by next-generation sequencing in a Chinese family with nonsyndromic hearing loss.","date":"2022","source":"Journal of clinical laboratory analysis","url":"https://pubmed.ncbi.nlm.nih.gov/36164746","citation_count":4,"is_preprint":false},{"pmid":"30612476","id":"PMC_30612476","title":"Lower expression of prestin and MYO7A correlates with menopause-associated hearing loss.","date":"2019","source":"Climacteric : the journal of the International Menopause Society","url":"https://pubmed.ncbi.nlm.nih.gov/30612476","citation_count":4,"is_preprint":false},{"pmid":"15592175","id":"PMC_15592175","title":"Genetic analysis of a four generation Indian family with Usher syndrome: a novel insertion mutation in MYO7A.","date":"2004","source":"Molecular vision","url":"https://pubmed.ncbi.nlm.nih.gov/15592175","citation_count":4,"is_preprint":false},{"pmid":"29287847","id":"PMC_29287847","title":"Targeted next generation sequencing identified a novel mutation in MYO7A causing Usher syndrome type 1 in an Iranian consanguineous pedigree.","date":"2017","source":"International journal of pediatric otorhinolaryngology","url":"https://pubmed.ncbi.nlm.nih.gov/29287847","citation_count":4,"is_preprint":false},{"pmid":"26309859","id":"PMC_26309859","title":"Phenotype of Usher syndrome type II assosiated with compound missense mutations of c.721 C>T and c.1969 C>T in MYO7A in a Chinese Usher syndrome family.","date":"2015","source":"International journal of ophthalmology","url":"https://pubmed.ncbi.nlm.nih.gov/26309859","citation_count":4,"is_preprint":false},{"pmid":"33835720","id":"PMC_33835720","title":"Novel dilated cardiomyopathy associated to Calreticulin and Myo7A gene mutation in Usher syndrome.","date":"2021","source":"ESC heart failure","url":"https://pubmed.ncbi.nlm.nih.gov/33835720","citation_count":4,"is_preprint":false},{"pmid":"32428919","id":"PMC_32428919","title":"The p.R206C Mutation in MYO7A Leads to Autosomal Dominant Nonsyndromic Hearing Loss.","date":"2020","source":"ORL; journal for oto-rhino-laryngology and its related specialties","url":"https://pubmed.ncbi.nlm.nih.gov/32428919","citation_count":3,"is_preprint":false},{"pmid":"31997689","id":"PMC_31997689","title":"Investigation of MYO15A and MYO7A Mutations in Iranian Patients with Nonsyndromic Hearing Loss.","date":"2020","source":"Fetal and pediatric pathology","url":"https://pubmed.ncbi.nlm.nih.gov/31997689","citation_count":3,"is_preprint":false},{"pmid":"34979615","id":"PMC_34979615","title":"[Identifications of the novel mutants on MYO7A in a family with non-syndromic hereditary deafness].","date":"2022","source":"Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology head and neck surgery","url":"https://pubmed.ncbi.nlm.nih.gov/34979615","citation_count":3,"is_preprint":false},{"pmid":"34192699","id":"PMC_34192699","title":"Putative Digenic GJB2/MYO7A Inheritance of Hearing Loss Detected in a Patient with 48,XXYY Klinefelter Syndrome.","date":"2021","source":"Human heredity","url":"https://pubmed.ncbi.nlm.nih.gov/34192699","citation_count":3,"is_preprint":false},{"pmid":"10425080","id":"PMC_10425080","title":"Identification of three novel mutations in the MYO7A gene.","date":"1999","source":"Human mutation","url":"https://pubmed.ncbi.nlm.nih.gov/10425080","citation_count":3,"is_preprint":false},{"pmid":"36630074","id":"PMC_36630074","title":"Identification of novel missense mutation related with non-syndromic sensorineural deafness, DFNA11 in korean family by NGS.","date":"2023","source":"Genes & genomics","url":"https://pubmed.ncbi.nlm.nih.gov/36630074","citation_count":2,"is_preprint":false},{"pmid":"37727480","id":"PMC_37727480","title":"Autosomal dominant non-syndromic hearing loss caused by a novel mutation in MYO7A: A case report and review of the literature.","date":"2023","source":"World journal of clinical cases","url":"https://pubmed.ncbi.nlm.nih.gov/37727480","citation_count":2,"is_preprint":false},{"pmid":"28688563","id":"PMC_28688563","title":"A novel mutation in the MYO7A gene is associated with Usher syndrome type 1 in a Chinese family.","date":"2017","source":"International journal of pediatric otorhinolaryngology","url":"https://pubmed.ncbi.nlm.nih.gov/28688563","citation_count":2,"is_preprint":false},{"pmid":"17702415","id":"PMC_17702415","title":"[Gene mapping for autosomal dominant nonsyndromic hearing loss DFNA11].","date":"2007","source":"Zhonghua er bi yan hou tou jing wai ke za zhi = Chinese journal of otorhinolaryngology head and neck surgery","url":"https://pubmed.ncbi.nlm.nih.gov/17702415","citation_count":2,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":47554,"output_tokens":4512,"usd":0.105171},"stage2":{"model":"claude-opus-4-6","input_tokens":7982,"output_tokens":3193,"usd":0.179602},"total_usd":0.284773,"stage1_batch_id":"msgbatch_012ZiiCUBfB62NCTQd4Bk1Jo","stage2_batch_id":"msgbatch_01Xuqq9aUHoQouS7UVGZNStZ","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1997,\n      \"finding\": \"Different mutations in MYO7A cause either isolated non-syndromic deafness (DFNB2) or syndromic deafness with retinitis pigmentosa (Usher syndrome type 1B), establishing that the same gene underlies both phenotypes through allelic heterogeneity. A G-to-A transition at the last nucleotide of exon 15 was shown to decrease splicing efficiency.\",\n      \"method\": \"Sequence analysis of coding exons; linkage analysis; splicing mutation identification\",\n      \"journal\": \"Nature genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — direct mutation identification with functional splicing implication, replicated across multiple populations\",\n      \"pmids\": [\"9171833\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"In Myo7a-null shaker1 mice with mosaic retinas, the mutant photoreceptor phenotype was shown to be cell-autonomous and not secondary to mutant RPE cells, placing MYO7A function intrinsically within photoreceptors.\",\n      \"method\": \"Mosaic retinal analysis in Myo7a-deficient shaker1 mice; optical imaging of retinal structure\",\n      \"journal\": \"Human molecular genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — genetic mosaic experiment with defined cellular phenotype demonstrating cell autonomy\",\n      \"pmids\": [\"18463160\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"MYO7A links to melanosomes in RPE cells via the RAB27A-MYRIP complex (analogous to melanophilin-RAB27A-MYO5A in melanocytes), and the RAB27A-MYRIP-MYO7A complex functions in melanosome motility in RPE cells. RAB27A provides an essential link to the melanosome.\",\n      \"method\": \"Live-cell imaging of primary RPE cultures; mutant mouse retinal analysis; RPE cell fractionation; in vitro binding assays; immunolocalization\",\n      \"journal\": \"Cell motility and the cytoskeleton\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (live imaging, fractionation, mutant mouse genetics) in a single study\",\n      \"pmids\": [\"17352418\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"MYO7A is required for the light-dependent translocation of RPE65 to the central region of RPE cells; in Myo7a-mutant mice RPE65 is mislocalized, degraded more quickly, and its activity is reduced (increased all-trans-retinyl ester levels post-photobleach). MYO7A and RPE65 were co-immunoprecipitated from RPE cell lysate, suggesting direct or indirect physical interaction.\",\n      \"method\": \"Co-immunoprecipitation from RPE cell lysate; immunolocalization; biochemical assay of retinoid cycle metabolites; light-damage resistance phenotype in Myo7a-mutant mice\",\n      \"journal\": \"Human molecular genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal Co-IP plus functional retinoid cycle assay plus mutant mouse phenotype, multiple methods in one study\",\n      \"pmids\": [\"21493626\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"MYO7A in the RPE participates in: (1) apical localization of melanosomes (competing with microtubule motors); (2) removal of phagosomes from apical RPE for delivery to lysosomes in basal RPE (possibly co-operative with microtubule motors); and (3) light-dependent translocation of RPE65. In photoreceptors, MYO7A functions as a selective barrier for membrane proteins (e.g., opsin) at the distal end of the transition zone of the cilium.\",\n      \"method\": \"Analysis of Myo7a-null mouse retinas; immunolocalization; functional assays in RPE and photoreceptor cells\",\n      \"journal\": \"Biochemical Society transactions\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — synthesis of multiple experimental studies using Myo7a-null mice with defined cellular phenotypes\",\n      \"pmids\": [\"21936790\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"Near-infrared autofluorescence (NIR-AF) of the posterior eye originates predominantly from melanosomes in RPE and choroid. In Myo7a-null mouse RPE, melanosomes (NIR-AF signal) are absent from apical processes, directly correlating with previously described melanosome localization defects due to loss of MYO7A.\",\n      \"method\": \"Spectral deconvolution confocal microscopy of ex vivo mouse retinas; scanning laser ophthalmoscopy in USH1B patients; purified RPE melanosome spectroscopy\",\n      \"journal\": \"Investigative ophthalmology & visual science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — direct imaging with functional correlation in Myo7a-null tissue and human patients\",\n      \"pmids\": [\"19324852\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"MYO7A (the mammalian ortholog of Drosophila CRINKLED) binds to and regulates CASPASE-8, acting as a substrate adaptor that recruits kinase substrates to caspases for cleavage, thereby modulating RIPK1>CASPASE-8 non-apoptotic signaling.\",\n      \"method\": \"Co-immunoprecipitation; genetic epistasis in Drosophila; functional caspase signaling assays; biochemical cleavage assays\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2/3 — Co-IP and functional signaling assays for mammalian MYO7A/CASPASE-8; primary evidence from Drosophila ortholog with mammalian confirmation\",\n      \"pmids\": [\"26960254\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"MYO7A forms a protein complex with PDZD7 (a paralog of USH1C/harmonin and DFNB31/whirlin) in stereocilia membrane fractions, as identified by mass spectrometry from enriched stereocilia membranes. MYO7A and PDZD7 interact in tissue-culture cells and co-localize to the ankle-link region of stereocilia in wild-type but not in Myo7a mutant mice.\",\n      \"method\": \"Stereocilia membrane fraction isolation; mass spectrometry proteomics; co-immunoprecipitation in tissue-culture cells; immunolocalization in wild-type and Myo7a mutant mouse hair cells\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — MS-identified complex from native tissue + Co-IP in cells + localization dependent on Myo7a, multiple orthogonal methods\",\n      \"pmids\": [\"27525485\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"A missense mutation (p.R853C) in the fifth IQ motif (IQ5) of MYO7A impairs calmodulin (CaM) binding, causing autosomal dominant hearing loss (DFNA11). Functional assay in vascular smooth muscle cells showed that wild-type IQ5 constitutively binds CaM at all physiologically relevant Ca2+ concentrations, while the mutant IQ5 does not.\",\n      \"method\": \"Expression of MYO7A IQ5-containing peptides in smooth muscle cells of microarteries; calmodulin-dependent vasoconstriction assay; functional CaM binding assessment\",\n      \"journal\": \"Human mutation\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — functional assay in physiological cellular environment demonstrating impaired CaM binding; single lab, single method\",\n      \"pmids\": [\"15300860\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"A missense mutation (p.N458I) in the motor domain of MYO7A is predicted by molecular modeling (based on Dictyostelium myosin II heavy chain structure) to disrupt ATP/ADP binding and impair the myosin power-stroke, providing a structural mechanism for DFNA11 dominant hearing loss.\",\n      \"method\": \"Molecular modeling of MYO7A motor domain; sequence analysis; linkage analysis\",\n      \"journal\": \"Human genetics\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 — computational/structural prediction only, no direct biochemical validation\",\n      \"pmids\": [\"15221449\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"The p.R668H mutation in the motor domain of MYO7A significantly reduces actin-activated ATPase activity, demonstrating that the motor domain mutation impairs the enzymatic function of myosin VIIA, causing DFNA11 hearing loss.\",\n      \"method\": \"Actin-activated ATPase activity assay (NADH oxidation rate) comparing wild-type and p.R668H mutant myosin VIIA protein\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 — direct in vitro enzymatic assay with mutant protein; single lab\",\n      \"pmids\": [\"23383098\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"A DFNB2 allele (p.E1716del) in the tail domain of MYO7A retains the ability to localize correctly to hair cell stereocilia in transfected mouse hair cells, whereas a USH1B allele (equivalent GFP-myosin VIIa) does not localize properly to stereocilia, explaining why different mutations cause phenotypes of differing severity.\",\n      \"method\": \"GFP-tagged cDNA expression constructs with engineered mutations transfected into mouse hair cells; immunolocalization of GFP-myosin VIIa in stereocilia\",\n      \"journal\": \"Human mutation\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — direct localization experiment in native hair cells with functional consequence; single lab\",\n      \"pmids\": [\"18181211\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"A missense mutation in the exon 16 last nucleotide (c.1935G>A) in MYO7A enhances exclusion of exon 16 through partial impairment of the adjacent donor splice site without completely abolishing exon inclusion, causing a milder retinopathy than full USH1B. Minigene splicing assay confirmed the effect.\",\n      \"method\": \"Lymphoid RNA analysis; splicing minigene transfection assay; structural prediction of molecular model\",\n      \"journal\": \"Molecular vision\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1/2 — minigene splicing assay directly demonstrated the splice-site effect; single lab\",\n      \"pmids\": [\"21031134\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"MYO7A is essential for structural integrity and long-term maintenance of hair bundles in mature cochlear hair cells, distinct from its role in setting the resting open probability of MET channels. Postnatal deletion of Myo7a progressively reduces hair-bundle stiffness and MET current amplitude without initially affecting resting open probability, and increases vulnerability to noise-induced damage. RNA-sequencing identified downregulation of stereociliary genes indicating indirect compensatory mechanisms.\",\n      \"method\": \"Postnatal conditional Myo7a deletion (Cre-mediated); MET current electrophysiology; hair-bundle stiffness measurements; auditory threshold measurements (ABR); scanning electron microscopy; RNA-sequencing\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1/2 — conditional KO with multiple orthogonal functional and structural readouts, mechanistic distinction from resting open probability established\",\n      \"pmids\": [\"39746042\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"Mutations in multiple splicing sites in MYO7A (c.2283-1G>T and c.5856G>A) abolish consensus splice sites, producing exon skipping. This was demonstrated by hybrid minigene assay.\",\n      \"method\": \"Hybrid minigene splicing assay; bioinformatic splice prediction\",\n      \"journal\": \"Clinical genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 — functional minigene assay; single lab\",\n      \"pmids\": [\"20497194\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Null mutation of Ush1c (harmonin) does not alter the cytoplasmic distribution of Myo7a in cochlear hair cells, demonstrating that harmonin is not required for Myo7a localization to the cytoplasm, though harmonin loss mislocalized Pcdh15 and Sans.\",\n      \"method\": \"Immunolocalization in Ush1c knockout mouse cochlea; morphological analysis of cochlear sections\",\n      \"journal\": \"International journal of experimental pathology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — direct localization experiment in KO mouse; single lab, single method\",\n      \"pmids\": [\"21156003\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"Double homozygous Myo7a/Myo15 mutant mice show a superimposition of single mutant stereocilia phenotypes without epistatic interaction, and Myo7a heterozygosity does not modify the Myo15 hearing phenotype, indicating that Myo7a and Myo15 function in distinct pathways for stereocilia development.\",\n      \"method\": \"Genetic crosses to generate double mutant mice; hearing threshold measurement; scanning electron microscopy of stereocilia\",\n      \"journal\": \"Human molecular genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — genetic epistasis using double mutants with defined stereocilia phenotype; single study\",\n      \"pmids\": [\"12966030\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"CRISPR/Cas9 correction of a MYO7A mutation (c.4118C>T) in patient-derived iPSCs restored normal stereocilia-like protrusion organization and electrophysiological function in derived hair cell-like cells, confirming MYO7A's role in stereocilia bundle assembly.\",\n      \"method\": \"CRISPR/Cas9 gene correction; iPSC differentiation to hair cell-like cells; morphological and electrophysiological analysis\",\n      \"journal\": \"Stem cells translational medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — genetic rescue with functional and morphological readouts; single lab\",\n      \"pmids\": [\"27013738\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"In vivo AAV9-Myo7a gene delivery to shaker-1 (Myo7a mutant) mice rescued IHC mechanoelectrical transducer function, reestablished the normal adult synaptic profile of IHCs (preventing aberrant axosomatic cholinergic efferent contacts), and improved hearing, demonstrating that MYO7A function in IHCs is required for maintaining normal efferent synaptic organization.\",\n      \"method\": \"In vivo AAV-Myo7a gene delivery; functional MET current recording; immunofluorescence of efferent synapses; auditory brainstem response measurements\",\n      \"journal\": \"JCI insight\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — in vivo gene rescue with defined synaptic and functional phenotypes; single lab\",\n      \"pmids\": [\"39641274\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"MYO7A encodes an unconventional actin-based motor protein that functions in multiple cell types: in cochlear and vestibular hair cells it is essential for stereocilia bundle structural integrity, mechanoelectrical transducer channel function, and tip-link/ankle-link region organization (interacting with PDZD7 and binding calmodulin via IQ motifs to regulate motor activity); in the retinal pigment epithelium it drives apical melanosome localization via a RAB27A-MYRIP-MYO7A complex, mediates phagosome trafficking to lysosomes, and enables light-dependent translocation of the visual cycle enzyme RPE65 (with which it physically interacts); and in photoreceptors it acts as a selective barrier for membrane proteins (e.g., opsin) at the ciliary transition zone, with loss-of-function mutations in MYO7A causing Usher syndrome type 1B (deaf-blindness) or non-syndromic hearing loss depending on allelic severity.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"MYO7A encodes an unconventional myosin motor protein essential for mechanosensory and visual functions, with loss-of-function mutations causing Usher syndrome type 1B (deaf-blindness) or non-syndromic hearing loss (DFNB2/DFNA11) depending on allelic severity [PMID:9171833]. In cochlear hair cells, MYO7A maintains stereocilia bundle structural integrity and stiffness, sustains mechanoelectrical transducer (MET) channel function, and organizes the ankle-link region through interaction with PDZD7; postnatal loss progressively reduces hair-bundle stiffness and MET current amplitude and increases noise vulnerability [PMID:27525485, PMID:39746042]. In retinal pigment epithelium, MYO7A drives apical melanosome positioning via a RAB27A–MYRIP–MYO7A transport complex, facilitates phagosome trafficking to lysosomes, and mediates light-dependent translocation of the visual cycle enzyme RPE65, with which it physically associates; in photoreceptors it acts cell-autonomously as a selective barrier for membrane proteins at the ciliary transition zone [PMID:17352418, PMID:21493626, PMID:18463160, PMID:21936790]. Motor activity is regulated by calmodulin binding to IQ motifs, and disease-causing motor-domain mutations directly impair actin-activated ATPase activity [PMID:15300860, PMID:23383098].\",\n  \"teleology\": [\n    {\n      \"year\": 1997,\n      \"claim\": \"Establishing that the same gene underlies both isolated deafness and syndromic deaf-blindness resolved whether these were genetically distinct disorders and revealed allelic heterogeneity as the basis of phenotypic spectrum.\",\n      \"evidence\": \"Mutation screening of MYO7A coding exons in DFNB2 and USH1B families; identification of a splicing mutation at exon 15\",\n      \"pmids\": [\"9171833\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism by which specific mutation types produce syndromic versus non-syndromic phenotypes was not explained\", \"No protein-level functional consequence demonstrated\"]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"Demonstrating non-epistatic interaction between Myo7a and Myo15 established that these two unconventional myosins operate in independent pathways for stereocilia development, narrowing the possible mechanistic role of each.\",\n      \"evidence\": \"Double homozygous Myo7a/Myo15 mutant mice; hearing thresholds and scanning electron microscopy\",\n      \"pmids\": [\"12966030\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No direct biochemical substrates or binding partners identified for either myosin in this context\", \"Observation limited to developmental phenotype\"]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"Showing that a disease-causing IQ5 mutation abolishes constitutive calmodulin binding provided the first evidence that CaM-mediated regulation of the MYO7A lever arm is required for hearing function.\",\n      \"evidence\": \"Expression of IQ5 peptides in smooth muscle cells; calmodulin-dependent vasoconstriction functional assay\",\n      \"pmids\": [\"15300860\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Assay performed in smooth muscle cells, not in hair cells\", \"Effect on motor processivity or force generation not directly measured\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Identification of the RAB27A–MYRIP–MYO7A tripartite complex on melanosomes defined the molecular mechanism by which MYO7A captures and transports melanosomes in RPE cells.\",\n      \"evidence\": \"Live-cell imaging of primary RPE cultures; mutant mouse retinal analysis; cell fractionation; in vitro binding assays\",\n      \"pmids\": [\"17352418\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether MYO7A acts as a processive transporter or a tether on melanosomes was not resolved\", \"Contribution of other motors to the same cargo not fully delineated\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Mosaic retinal analysis proved that the MYO7A photoreceptor phenotype is cell-autonomous, ruling out the hypothesis that photoreceptor defects are secondary to RPE dysfunction and establishing a direct photoreceptor role.\",\n      \"evidence\": \"Mosaic retinal analysis in Myo7a-deficient shaker1 mice\",\n      \"pmids\": [\"18463160\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular target or cargo of MYO7A within photoreceptors not identified\", \"Whether the RPE and photoreceptor functions synergize in disease progression remained unclear\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Demonstrating that a DFNB2 tail-domain mutant retains stereocilia targeting while a USH1B mutant does not provided a molecular explanation for allele-severity correlations in human disease.\",\n      \"evidence\": \"GFP-tagged MYO7A constructs with engineered mutations transfected into mouse hair cells; immunolocalization\",\n      \"pmids\": [\"18181211\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Only two alleles tested\", \"Biochemical basis of targeting failure not identified\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Discovery that MYO7A physically associates with RPE65 and is required for its light-dependent translocation revealed an unexpected role for an actin motor in the visual retinoid cycle.\",\n      \"evidence\": \"Co-immunoprecipitation from RPE lysates; retinoid metabolite assays; immunolocalization in Myo7a mutant mice\",\n      \"pmids\": [\"21493626\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether the MYO7A–RPE65 interaction is direct or bridged by an adaptor was not resolved\", \"Structural basis of the interaction unknown\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"A unified functional model placed MYO7A in three distinct RPE trafficking pathways (melanosome positioning, phagosome clearance, RPE65 translocation) plus a ciliary-gate role in photoreceptors, consolidating disparate observations.\",\n      \"evidence\": \"Synthesis of Myo7a-null mouse retinal phenotypes; immunolocalization and functional assays\",\n      \"pmids\": [\"21936790\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism of selective membrane-protein gating at the ciliary transition zone not defined at molecular level\", \"Whether the gate function is motor-dependent or scaffold-dependent was not tested\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Direct measurement of reduced actin-activated ATPase activity for the R668H motor-domain mutant provided the first biochemical proof that disease mutations impair the enzymatic motor cycle of MYO7A.\",\n      \"evidence\": \"Purified wild-type vs. R668H MYO7A; NADH-coupled ATPase assay\",\n      \"pmids\": [\"23383098\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Motility or force-generation measurements not performed\", \"Single mutant tested; generalizability to other motor-domain mutations not shown\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Identification of MYO7A–PDZD7 complex by mass spectrometry from native stereocilia membranes, confirmed by co-IP and co-localization, established a new scaffold partner at the ankle-link region linking MYO7A to broader Usher-network organization.\",\n      \"evidence\": \"Stereocilia membrane proteomics; co-immunoprecipitation in cells; immunolocalization in WT and Myo7a mutant mouse hair cells\",\n      \"pmids\": [\"27525485\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Functional consequence of disrupting the MYO7A–PDZD7 interaction specifically was not tested\", \"Whether PDZD7 is a cargo or a scaffold for MYO7A was not distinguished\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Evidence that MYO7A binds and modulates CASPASE-8 in a non-apoptotic RIPK1 signaling pathway expanded MYO7A function beyond sensory-cell trafficking to signaling scaffold roles.\",\n      \"evidence\": \"Co-IP; genetic epistasis in Drosophila crinkled mutants; caspase signaling assays with mammalian confirmation\",\n      \"pmids\": [\"26960254\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mammalian MYO7A–CASPASE-8 interaction not validated by reciprocal IP in native tissue\", \"Physiological relevance in sensory cells not demonstrated\", \"Mechanism of substrate recruitment to caspases incompletely defined\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"AAV-mediated Myo7a gene rescue in shaker-1 mice restored MET function and corrected aberrant efferent synaptic organization, revealing that MYO7A in inner hair cells is required to maintain the normal adult synaptic configuration.\",\n      \"evidence\": \"In vivo AAV9-Myo7a delivery; MET current recordings; efferent synapse immunofluorescence; ABR measurements\",\n      \"pmids\": [\"39641274\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether the synaptic phenotype is a direct consequence of MET dysfunction or an independent MYO7A function was not resolved\", \"Long-term durability of rescue not assessed\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Postnatal conditional deletion demonstrated that MYO7A is continuously required for hair-bundle stiffness and MET current maintenance in mature hair cells, separable from setting the resting open probability of MET channels.\",\n      \"evidence\": \"Postnatal Cre-mediated Myo7a deletion; MET electrophysiology; hair-bundle stiffness measurements; ABR; SEM; RNA-seq\",\n      \"pmids\": [\"39746042\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct molecular target through which MYO7A maintains bundle stiffness not identified\", \"RNA-seq changes are correlative; causal downstream pathways not established\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Major open questions include the structural basis of MYO7A processivity and force generation along stereocilia actin, the molecular identity of cargoes gated at the photoreceptor ciliary transition zone, and whether the MYO7A–CASPASE-8 signaling axis operates in sensory cells in vivo.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No high-resolution structure of full-length MYO7A\", \"No reconstituted in vitro motility with native cargoes\", \"Ciliary transition-zone gating mechanism molecularly undefined\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140657\", \"supporting_discovery_ids\": [10, 8]},\n      {\"term_id\": \"GO:0003774\", \"supporting_discovery_ids\": [10, 13]},\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [10, 13]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [7, 13]},\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [4, 1]},\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [7]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-9709957\", \"supporting_discovery_ids\": [0, 13, 18]},\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [2, 3, 4]},\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [2, 4]}\n    ],\n    \"complexes\": [\n      \"RAB27A-MYRIP-MYO7A melanosome transport complex\",\n      \"MYO7A-PDZD7 ankle-link complex\"\n    ],\n    \"partners\": [\n      \"PDZD7\",\n      \"RAB27A\",\n      \"MYRIP\",\n      \"RPE65\",\n      \"CALM1\",\n      \"CASP8\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}