Affinage

USH2A

Usherin · UniProt O75445

Length
5202 aa
Mass
575.6 kDa
Annotated
2026-04-28
100 papers in source corpus 20 papers cited in narrative 20 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

USH2A encodes usherin, a large transmembrane protein with extensive extracellular laminin and fibronectin type III repeat domains that functions as an obligatory scaffold within the USH2 multiprotein complex (with ADGRV1, whirlin/WHRN, PDZD7, and SANS) at the periciliary membrane of photoreceptors and the ankle-link complex of cochlear hair cell stereocilia (PMID:20502675, PMID:26401052, PMID:28137943). Loss of any single USH2 complex member destabilizes the entire complex and disrupts protein trafficking through the connecting cilium in photoreceptors and stereociliary bundle integrity in hair cells, causing progressive retinal degeneration and sensorineural hearing loss (Usher syndrome type 2A) (PMID:20502675, PMID:15015129). USH2A protein stability is regulated by ADGRV1-mediated suppression of WHRN phosphorylation, which controls WDSUB1 E3-ligase-dependent ubiquitination of usherin; pathogenic ADGRV1 mutations release this brake, leading to usherin degradation (PMID:37066759). Usherin is also expressed in terminal Schwann cells of Meissner's corpuscles, where it is required for normal vibrotactile mechanoreceptor sensitivity (PMID:33288907).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1999 Medium

    Identification of USH2A as a laminin/fibronectin-domain extracellular matrix protein linked domain structure to disease: the Cys759Phe mutation in the fifth LE domain caused recessive RP without hearing loss, establishing that specific domain lesions determine clinical outcome.

    Evidence Mutation analysis and domain prediction in RP families

    PMID:10775529

    Open questions at the time
    • No biochemical validation of domain function
    • Short isoform only; full gene structure unknown
  2. 2004 Medium

    Discovery of the long transmembrane isoform (isoform b) resolved how a secreted ECM-like protein could function as a cell-surface receptor/scaffold: the extended protein contains a transmembrane domain and a C-terminal PDZ-binding motif, and mutations in the novel exons cause combined hearing loss and RP.

    Evidence Gene cloning and mutation screening across exons 22–73

    PMID:15015129

    Open questions at the time
    • No direct protein biochemistry confirming membrane insertion
    • PDZ-binding partner identity not yet determined
  3. 2006 High

    The first identification of usherin's direct binding partners — whirlin (WHRN) and VLGR1 — established usherin as part of a PDZ scaffold-organized multiprotein complex at photoreceptor connecting cilia, synapses, and cochlear hair cells.

    Evidence Yeast two-hybrid and co-immunoprecipitation with co-localization by immunohistochemistry

    PMID:16434480

    Open questions at the time
    • Stoichiometry and assembly order unknown
    • No structural data on the ternary complex
  4. 2010 High

    Knockout mouse studies demonstrated that USH2A, ADGRV1, and WHRN form an obligatory complex: loss of any one member destabilized and mislocalized all others at the periciliary membrane, directly linking complex integrity to photoreceptor survival.

    Evidence Multiple USH2 KO mouse models with immunofluorescence, Western blot, and ERG

    PMID:20502675

    Open questions at the time
    • Mechanism of mutual stabilization unknown
    • Whether complex disruption causes degeneration through trafficking defects versus structural failure unresolved
  5. 2011 High

    AAV-mediated whirlin re-expression in whirlin-KO photoreceptors recruited USH2A and ADGRV1 back to the periciliary membrane, placing whirlin upstream of usherin localization and establishing a hierarchy within USH2 complex assembly.

    Evidence AAV subretinal injection in Whrn-KO mice with immunofluorescence and immunoelectron microscopy

    PMID:21212183

    Open questions at the time
    • Whether whirlin directly chaperones usherin transport or merely anchors it at the destination unknown
    • Rescue of photoreceptor degeneration not fully demonstrated
  6. 2011 High

    Characterization of splicing mutations (deep-intronic and splice-site variants) revealed that many USH2A pathogenic alleles act through aberrant mRNA processing rather than simple protein truncation, opening therapeutic avenues for splice correction.

    Evidence Patient nasal epithelial cell RNA analysis and minigene splice assays for c.7595-2144A>G and other variants

    PMID:20497194 PMID:22009552

    Open questions at the time
    • In vivo splicing consequences in retinal tissue not directly assessed
    • Quantitative contribution of aberrant transcripts versus normal transcripts unknown
  7. 2015 High

    Systematic comparison of USH2 protein contributions to the cochlear ankle-link complex showed that ADGRV1 is the most critical organizer and that individual USH2 proteins make distinct, non-redundant contributions to stereociliary bundle morphogenesis and auditory function.

    Evidence Multiple USH2 KO mouse models with scanning electron microscopy and auditory testing

    PMID:26401052

    Open questions at the time
    • Molecular basis for differential contributions of USH2A versus ADGRV1 at ankle links unresolved
    • Direct extracellular interactions between USH2A and ADGRV1 ectodomains not characterized
  8. 2017 High

    SANS (USH1G) was identified as a direct interactor of usherin, bridging the USH1 and USH2 protein networks into a ternary USH1/USH2 complex; pathogenic USH1G mutations disrupt this complex, explaining the phenotypic overlap between Usher syndrome types.

    Evidence Yeast two-hybrid, co-IP, proximity ligation assay, and immunohistochemistry in rodent and human retina

    PMID:28137943

    Open questions at the time
    • Structural basis of USH1–USH2 bridging interaction unknown
    • Functional consequence of USH1/USH2 complex disruption in photoreceptors not directly shown in this study
  9. 2017 High

    Myosin VIIa was shown to be indispensable for USH2 complex assembly at cochlear ankle links but dispensable in photoreceptors, establishing tissue-specific mechanisms of USH2 complex organization.

    Evidence USH1 mutant mice with immunofluorescence and FLAG pull-down

    PMID:28031293

    Open questions at the time
    • Identity of the motor/transport system for USH2 complex in photoreceptors unknown
    • Whether myosin VIIa directly transports usherin or facilitates its retention unresolved
  10. 2019 High

    Usherin was localized to terminal Schwann cells of Meissner's corpuscles and shown to be required for vibrotactile mechanoreceptor sensitivity, extending usherin function beyond the retina and cochlea to somatosensory mechanotransduction.

    Evidence Immunohistochemistry in human/mouse skin, Ush2a-KO mouse electrophysiology, and psychophysical testing in USH2A patients

    PMID:33288907

    Open questions at the time
    • Molecular mechanism by which usherin contributes to mechanoreceptor function unknown
    • Whether the USH2 complex is present in Schwann cells not determined
  11. 2019 High

    Exon skipping strategies demonstrated that usherin protein lacking the exon 13-encoded region retains function: CRISPR deletion of mouse exon 12 restored cochlear structure and hearing, and morpholino-induced skipping in zebrafish rescued retinal function, validating a therapeutic concept.

    Evidence CRISPR exon deletion in mice with ABR; morpholino exon skipping in zebrafish with ERG

    PMID:31884594 PMID:33895329

    Open questions at the time
    • Long-term durability of exon-skipping rescue not established
    • Whether exon 13-deleted usherin fully recapitulates all wild-type functions unknown
  12. 2023 High

    The molecular mechanism controlling usherin stability was elucidated: ADGRV1 suppresses WHRN phosphorylation via local cAMP-PKA signaling; phosphorylated WHRN recruits the E3 ligase WDSUB1, which ubiquitinates and destabilizes USH2A, explaining how ADGRV1 loss-of-function leads to usherin degradation.

    Evidence Adgrv1 knock-in mice, yeast two-hybrid, FlAsH-BRET, NMR, ubiquitination assays, and MET recordings

    PMID:37066759

    Open questions at the time
    • Specific ubiquitination sites on USH2A not mapped
    • Whether deubiquitinating enzymes counteract WDSUB1 activity unknown
    • Pathway validated primarily in cochlear context; retinal applicability not directly shown
  13. 2023 Medium

    Multi-exon skipping strategies (exon pairs 30–31 and 39–40) and non-viral episomal full-length USH2A cDNA delivery both restored usherin expression and USH2 complex localization in zebrafish, broadening the therapeutic toolkit for the oversized USH2A gene.

    Evidence CRISPR exon deletion in zebrafish, ASO-mediated exon skipping in vitro, S/MAR episomal vector injection in zebrafish

    PMID:37313440 PMID:37337429

    Open questions at the time
    • Long-term efficacy and safety of episomal vectors in mammalian retina not tested
    • Functional rescue (ERG) not shown for multi-exon or episomal approaches
    • Delivery efficiency in human photoreceptors unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural basis of usherin's extracellular interactions, the precise cargo trafficking role of the USH2 complex at the connecting cilium, and whether pharmacological stabilization of usherin (e.g., by inhibiting WDSUB1) can prevent retinal degeneration remain unresolved.
  • No high-resolution structure of usherin or the USH2 complex
  • Cargo molecules trafficked by the USH2 periciliary complex not identified
  • No pharmacological intervention targeting the WDSUB1-usherin degradation axis tested in vivo

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 4 GO:0098631 cell adhesion mediator activity 1
Localization
GO:0005886 plasma membrane 4 GO:0005929 cilium 3 GO:0031012 extracellular matrix 2
Pathway
R-HSA-9709957 Sensory Perception 4 R-HSA-392499 Metabolism of proteins 1
Partners
ADGRV1MYO7APDZD7SANSWDSUB1WHRN
Complex memberships
USH1/USH2 ternary complexUSH2 complex (ankle-link complex)

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 USH2A encodes usherin, a protein with laminin epidermal growth factor-like (LE) domains and fibronectin type III repeats characteristic of extracellular matrix/basal lamina proteins; missense mutations within the fifth LE domain (Cys759Phe) cause recessive retinitis pigmentosa without hearing loss, establishing domain-function relationships Direct DNA sequencing, mutation analysis, protein domain prediction American journal of human genetics Medium 10775529
2004 The long isoform of USH2A encodes a transmembrane protein (usherin isoform b) with an extracellular domain containing a Laminin N-terminal domain, laminin G repeats, 28 fibronectin type III repeats, a transmembrane region, and a C-terminal intracellular PDZ-binding motif; pathogenic mutations in the novel exons 22–73 cause both hearing loss and retinitis pigmentosa Gene cloning, exon identification, expression profiling, mutation analysis American journal of human genetics Medium 15015129
2006 Whirlin (DFNB31/USH2D) directly associates with USH2A isoform b (usherin) and VLGR1b; this ternary complex co-localizes at photoreceptor synaptic regions, connecting cilia, and outer limiting membrane, and at cochlear outer hair cell synaptic regions, identifying usherin as a component of a PDZ scaffold-organized periciliary/synaptic interactome Yeast two-hybrid, co-immunoprecipitation, immunohistochemistry, confocal microscopy Human molecular genetics High 16434480
2010 The N-terminal PDZ domains of the whirlin long isoform mediate assembly of a multi-protein USH2 complex that includes usherin (USH2A) and VLGR1; this complex localizes to the periciliary membrane complex (PMC) in photoreceptors. Loss of any single USH2 protein disrupts normal localization of all USH2 proteins and causes protein destabilization, establishing that the three USH2 proteins form an obligatory functional complex in vivo Targeted gene knockout mice, immunofluorescence, Western blot, electroretinography, histology PLoS genetics High 20502675
2011 AAV-mediated whirlin transgene expression in whirlin knockout photoreceptors recruits USH2A and VLGR1 back to the periciliary membrane complex, restoring the USH2 protein complex; this demonstrates that whirlin is upstream of USH2A localization in photoreceptors AAV subretinal injection, immunofluorescence, immunoelectron microscopy, Western blot, electroretinography Investigative ophthalmology & visual science High 21212183
2011 A deep-intronic mutation in USH2A (c.7595-2144A>G) creates a pseudoexon (PE40) insertion into the mature transcript, generating a premature stop codon and a predicted truncated nonfunctional usherin protein; confirmed by RNA analysis from nasal cells and minigene assay RNA analysis from patient nasal epithelial cells, minigene splice assay, sequencing Human mutation High 22009552
2014 The common c.2299delG mutation in USH2A exon 13 disrupts an exonic splicing enhancer and creates an exonic splicing silencer, leading to aberrant splicing of exons 12–13 in addition to the predicted frameshift; shown by RT-PCR in patient nasal epithelial cells RT-PCR from patient nasal epithelial cells, bioinformatics splice prediction Experimental eye research Medium 24607488
2016 Antisense oligonucleotides targeting the PE40 splice acceptor site and exonic splice enhancer regions of USH2A pre-mRNA significantly correct aberrant splicing caused by the deep-intronic c.7595-2144A>G mutation in patient fibroblasts and a minigene assay AON treatment in patient-derived fibroblasts, minigene splice assay Molecular therapy. Nucleic acids High 27802265
2017 SANS (USH1G) directly interacts with usherin (USH2A) and both assemble into a ternary USH1/USH2 complex together with whirlin (USH2D) via mutual interactions; the complex localizes to the periciliary region, inner segment, and synapses of rodent and human photoreceptors, and pathogenic mutations in USH1G disrupt this complex Yeast two-hybrid, co-immunoprecipitation, proximity ligation assay, immunohistochemistry, mutagenesis Human molecular genetics High 28137943
2017 Myosin VIIa (USH1B) is indispensable for USH2 complex (USH2A/ADGRV1/WHRN/PDZD7) assembly at ankle links in cochlear hair cells, indicating a transport/anchoring role; however, myosin VIIa is not required for USH2 complex assembly in photoreceptors, demonstrating tissue-specific differences in USH2 complex organization USH1 mutant mice, immunofluorescence, FLAG pull-down assay Human molecular genetics High 28031293
2015 USH2A proteins (USH2A, ADGRV1, WHRN, PDZD7) assemble into the ankle link complex (ALC) at cochlear hair cell stereociliary bundles; individual USH2 proteins make distinct contributions to ALC assembly during development, with ADGRV1 being the most critical, and loss of individual proteins leads to variable stereociliary morphological and functional defects correlating with ALC disruption severity Multiple USH2 KO mouse models, immunofluorescence, scanning electron microscopy, auditory function testing Human molecular genetics High 26401052
2018 Knockout of ush2a in zebrafish causes disruption of fibronectin assembly at the retinal basement membrane, weakening cell adhesion, along with progressive rod-then-cone photoreceptor degeneration; upregulation of Ush1b and Ush1c expression was observed when Ush2a was absent TALEN-generated ush2a-/- zebrafish, ERG, histology, immunohistochemistry, Western blot Human genetics Medium 30242501
2019 USH2A (usherin) protein is expressed in terminal Schwann cells within Meissner's corpuscles in fingertip skin (not in sensory neurons); loss of USH2A reduces mechanoreceptor vibration sensitivity of rapidly adapting mechanoreceptors, and patients with biallelic USH2A mutations have specific impairment in vibrotactile touch perception Immunohistochemistry, Ush2a-/- mouse electrophysiology, human psychophysical testing Nature neuroscience High 33288907
2021 Morpholino-induced skipping of ush2a exon 13 in zebrafish ush2armc1 mutants restores production of a shortened usherin protein (usherinΔexon13) and completely rescues retinal function, demonstrating that an usherin protein lacking the exon 13-encoded region is functional Zebrafish morpholino exon skipping, ERG, Western blot, immunohistochemistry Molecular therapy : the journal of the American Society of Gene Therapy High 33895329
2019 CRISPR/Cas9-based deletion of mouse Ush2a exon 12 (ortholog of human exon 13) produces a shortened Ush2a-ΔEx12 protein that localizes correctly in the cochlea and, when expressed on an Ush2a null background, restores impaired hair cell structure and auditory function CRISPR/Cas9 exon deletion in mice, immunohistochemistry, auditory brainstem response testing Advances in experimental medicine and biology High 31884594
2023 ADGRV1 inhibits WHRN phosphorylation through regional cAMP-PKA signaling; phosphorylated WHRN recruits the E3 ligase WDSUB1 (identified by yeast two-hybrid), which ubiquitinates USH2A in a WHRN phosphorylation-dependent manner, regulating USH2A stability; the deafness-associated ADGRV1 Y6236fsX1 mutation fails to inhibit WHRN phosphorylation, leading to increased USH2A ubiquitination and destabilization Adgrv1 Y6236fsX1 knock-in mice, yeast two-hybrid, FlAsH-BRET assay, NMR spectrometry, mutagenesis, ubiquitination assays, stereocilia imaging, MET recordings Advanced science (Weinheim, Baden-Wurttemberg, Germany) High 37066759
2023 S/MAR non-viral episomal vectors carrying full-length USH2A cDNA (15.6 kb) drive persistent usherin expression in patient-derived fibroblasts and, after injection into ush2au507 zebrafish, rescue Usher 2 complex localization in photoreceptors for up to 12 months, demonstrating that full-length usherin can restore the USH2 complex in vivo S/MAR plasmid transfection, Western blot, immunofluorescence, zebrafish microinjection Molecular therapy : the journal of the American Society of Gene Therapy Medium 37337429
2011 Splice-site variants in USH2A (c.1841-2A>G, c.2167+5G>A, c.5298+1G>C) abolish consensus splice sites and produce exon skipping; c.2167+5G>A additionally activates a cryptic donor splice site; demonstrated by hybrid minigene assays Hybrid minigene splice assay, bioinformatics Clinical genetics Medium 20497194
2002 USH2A mRNA is expressed specifically in the outer nuclear layer of the retina (photoreceptors) in rat, mouse, and human, and in cochlea; during rat retinal development, expression appears in the neuroepithelium at embryonic day 17, establishing the cellular source of usherin in the primary disease-affected tissues In situ hybridization, gene cloning, radiation hybrid mapping Genomics Medium 12160733
2023 Excision of USH2A exon pairs 30-31 or 39-40 using CRISPR-Cas9 in zebrafish restores usherin expression in the retina and rescues photopigment mislocalization; ASO-induced dual exon skipping achieves the same in vitro, demonstrating that protein domain-oriented multi-exon skipping maintains a functional usherin CRISPR-Cas9 zebrafish exon deletion, immunohistochemistry, in vitro ASO assay Molecular therapy. Nucleic acids Medium 37313440

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Missense mutation in the USH2A gene: association with recessive retinitis pigmentosa without hearing loss. American journal of human genetics 219 10775529
2004 Identification of 51 novel exons of the Usher syndrome type 2A (USH2A) gene that encode multiple conserved functional domains and that are mutated in patients with Usher syndrome type II. American journal of human genetics 167 15015129
2006 The DFNB31 gene product whirlin connects to the Usher protein network in the cochlea and retina by direct association with USH2A and VLGR1. Human molecular genetics 156 16434480
2010 Novel mutations in the long isoform of the USH2A gene in patients with Usher syndrome type II or non-syndromic retinitis pigmentosa. Journal of medical genetics 142 20507924
2021 Antisense oligonucleotide-based treatment of retinitis pigmentosa caused by USH2A exon 13 mutations. Molecular therapy : the journal of the American Society of Gene Therapy 123 33895329
2016 Antisense Oligonucleotide-based Splice Correction for USH2A-associated Retinal Degeneration Caused by a Frequent Deep-intronic Mutation. Molecular therapy. Nucleic acids 118 27802265
2010 Ablation of whirlin long isoform disrupts the USH2 protein complex and causes vision and hearing loss. PLoS genetics 118 20502675
2015 A detailed clinical and molecular survey of subjects with nonsyndromic USH2A retinopathy reveals an allelic hierarchy of disease-causing variants. European journal of human genetics : EJHG 107 25649381
2004 Comprehensive screening of the USH2A gene in Usher syndrome type II and non-syndromic recessive retinitis pigmentosa. Experimental eye research 100 15325563
2011 Usher syndrome type 2 caused by activation of an USH2A pseudoexon: implications for diagnosis and therapy. Human mutation 96 22009552
2008 Usher syndromes due to MYO7A, PCDH15, USH2A or GPR98 mutations share retinal disease mechanism. Human molecular genetics 95 18463160
2008 Spectrum of USH2A mutations in Scandinavian patients with Usher syndrome type II. Human mutation 91 18273898
2008 Disease course in patients with autosomal recessive retinitis pigmentosa due to the USH2A gene. Investigative ophthalmology & visual science 88 18641288
2020 USH2A-retinopathy: From genetics to therapeutics. Experimental eye research 84 33121974
2015 Whole USH2A Gene Sequencing Identifies Several New Deep Intronic Mutations. Human mutation 74 26629787
2000 Identification of novel USH2A mutations: implications for the structure of USH2A protein. European journal of human genetics : EJHG 74 10909849
2019 Modeling Retinitis Pigmentosa: Retinal Organoids Generated From the iPSCs of a Patient With the USH2A Mutation Show Early Developmental Abnormalities. Frontiers in cellular neuroscience 69 31481876
2001 A common ancestral origin of the frequent and widespread 2299delG USH2A mutation. American journal of human genetics 69 11402400
2006 Identification of 14 novel mutations in the long isoform of USH2A in Spanish patients with Usher syndrome type II. Journal of medical genetics 68 17085681
2014 Enrichment of LOVD-USHbases with 152 USH2A genotypes defines an extensive mutational spectrum and highlights missense hotspots. Human mutation 62 24944099
2015 Clinical aspects of Usher syndrome and the USH2A gene in a cohort of 433 patients. JAMA ophthalmology 57 25375654
2011 Whirlin replacement restores the formation of the USH2 protein complex in whirlin knockout photoreceptors. Investigative ophthalmology & visual science 57 21212183
2017 USH2A Gene Editing Using the CRISPR System. Molecular therapy. Nucleic acids 55 28918053
2013 Targeted exome sequencing identified novel USH2A mutations in Usher syndrome families. PloS one 55 23737954
2002 Paternal uniparental heterodisomy with partial isodisomy of chromosome 1 in a patient with retinitis pigmentosa without hearing loss and a missense mutation in the Usher syndrome type II gene USH2A. Archives of ophthalmology (Chicago, Ill. : 1960) 55 12427073
2012 Non-USH2A mutations in USH2 patients. Human mutation 54 22147658
2011 Mutational screening of the USH2A gene in Spanish USH patients reveals 23 novel pathogenic mutations. Orphanet journal of rare diseases 52 22004887
2020 USH2A is a Meissner's corpuscle protein necessary for normal vibration sensing in mice and humans. Nature neuroscience 51 33288907
2005 Disease expression in Usher syndrome caused by VLGR1 gene mutation (USH2C) and comparison with USH2A phenotype. Investigative ophthalmology & visual science 51 15671307
2004 Genetic analysis of 2299delG and C759F mutations (USH2A) in patients with visual and/or auditory impairments. European journal of human genetics : EJHG 51 14970843
2010 The USH2A c.2299delG mutation: dating its common origin in a Southern European population. European journal of human genetics : EJHG 48 20145675
2017 Characterization of the ternary Usher syndrome SANS/ush2a/whirlin protein complex. Human molecular genetics 47 28137943
2013 Screening for duplications, deletions and a common intronic mutation detects 35% of second mutations in patients with USH2A monoallelic mutations on Sanger sequencing. Orphanet journal of rare diseases 47 23924366
2002 Mutations in myosin VIIA (MYO7A) and usherin (USH2A) in Spanish patients with Usher syndrome types I and II, respectively. Human mutation 47 12112664
2016 A combination of two truncating mutations in USH2A causes more severe and progressive hearing impairment in Usher syndrome type IIa. Hearing research 46 27318125
2018 Knockout of ush2a gene in zebrafish causes hearing impairment and late onset rod-cone dystrophy. Human genetics 43 30242501
2004 USH2A mutation analysis in 70 Dutch families with Usher syndrome type II. Human mutation 43 15241801
2001 Spectrum of mutations in USH2A in British patients with Usher syndrome type II. Experimental eye research 43 11311042
2017 The roles of USH1 proteins and PDZ domain-containing USH proteins in USH2 complex integrity in cochlear hair cells. Human molecular genetics 38 28031293
2015 Individual USH2 proteins make distinct contributions to the ankle link complex during development of the mouse cochlear stereociliary bundle. Human molecular genetics 38 26401052
2019 Severe or Profound Sensorineural Hearing Loss Caused by Novel USH2A Variants in Korea: Potential Genotype-Phenotype Correlation. Clinical and experimental otorhinolaryngology 37 31674169
2011 Seven novel mutations in the long isoform of the USH2A gene in Chinese families with nonsyndromic retinitis pigmentosa and Usher syndrome Type II. Molecular vision 37 21686329
2009 Identification of 11 novel mutations in USH2A among Japanese patients with Usher syndrome type 2. Clinical genetics 37 19737284
2020 USH2A variants in Chinese patients with Usher syndrome type II and non-syndromic retinitis pigmentosa. The British journal of ophthalmology 32 32675063
2011 Audiological findings in 100 USH2 patients. Clinical genetics 32 21895633
2009 Mutation analysis in the long isoform of USH2A in American patients with Usher Syndrome type II. Journal of human genetics 32 19881469
2020 Prevalence and genetic-phenotypic characteristics of patients with USH2A mutations in a large cohort of Chinese patients with inherited retinal disease. The British journal of ophthalmology 31 32188678
2008 Identification of five novel mutations in the long isoform of the USH2A gene in Chinese families with Usher syndrome type II. Molecular vision 31 19023448
2000 Three novel mutations and twelve polymorphisms identified in the USH2A gene in Israeli USH2 families. Human mutation 31 10738000
2007 Novel USH2A mutations in Israeli patients with retinitis pigmentosa and Usher syndrome type 2. Archives of ophthalmology (Chicago, Ill. : 1960) 29 17296898
2017 Electroretinography Reveals Difference in Cone Function between Syndromic and Nonsyndromic USH2A Patients. Scientific reports 28 28894305
2014 Targeted next-generation sequencing reveals novel USH2A mutations associated with diverse disease phenotypes: implications for clinical and molecular diagnosis. PloS one 28 25133613
2003 Pure tone hearing thresholds and speech recognition scores in Dutch patients carrying mutations in the USH2A gene. Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 28 12544030
2019 In Vivo Assessment of Potential Therapeutic Approaches for USH2A-Associated Diseases. Advances in experimental medicine and biology 27 31884594
2009 Cell transplantation to arrest early changes in an ush2a animal model. Investigative ophthalmology & visual science 27 19959642
2008 Four USH2A founder mutations underlie the majority of Usher syndrome type 2 cases among non-Ashkenazi Jews. Genetic testing 27 18452394
2008 An USH2A founder mutation is the major cause of Usher syndrome type 2 in Canadians of French origin and confirms common roots of Quebecois and Acadians. European journal of human genetics : EJHG 27 18665195
2018 Poor Splice-Site Recognition in a Humanized Zebrafish Knockin Model for the Recurrent Deep-Intronic c.7595-2144A>G Mutation in USH2A. Zebrafish 25 30281416
2021 Generation and Genetic Correction of USH2A c.2299delG Mutation in Patient-Derived Induced Pluripotent Stem Cells. Genes 24 34070435
2018 Searching the second hit in patients with inherited retinal dystrophies and monoallelic variants in ABCA4, USH2A and CEP290 by whole-gene targeted sequencing. Scientific reports 24 30190494
1996 The construction of a yeast artificial chromosome (YAC) contig in the vicinity of the Usher syndrome type IIa (USH2A) gene in 1q41. Genomics 24 8661107
2022 Retinal organoids and microfluidic chip-based approaches to explore the retinitis pigmentosa with USH2A mutations. Frontiers in bioengineering and biotechnology 23 36185441
2014 The effect of the common c.2299delG mutation in USH2A on RNA splicing. Experimental eye research 23 24607488
2014 MYO7A and USH2A gene sequence variants in Italian patients with Usher syndrome. Molecular vision 23 25558175
2000 [Molecular genetics of pigmentary retinopathies: identification of mutations in CHM, RDS, RHO, RPE65, USH2A and XLRS1 genes]. Journal francais d'ophtalmologie 22 11139690
2018 Efficacy Outcome Measures for Clinical Trials of USH2A Caused by the Common c.2299delG Mutation. American journal of ophthalmology 21 29953849
2011 Novel USH2A mutations in Japanese Usher syndrome type 2 patients: marked differences in the mutation spectrum between the Japanese and other populations. Journal of human genetics 20 21593743
2023 USH2A variants causing retinitis pigmentosa or Usher syndrome provoke differential retinal phenotypes in disease-specific organoids. HGG advances 19 37654703
2015 Re-evaluation casts doubt on the pathogenicity of homozygous USH2A p.C759F. American journal of medical genetics. Part A 18 25823529
2013 Whole-exome sequencing identifies novel compound heterozygous mutations in USH2A in Spanish patients with autosomal recessive retinitis pigmentosa. Molecular vision 18 24227914
2009 Audiometric characteristics of USH2a patients. Audiology & neuro-otology 18 19129697
2022 The RUSH2A Study: Dark-Adapted Visual Fields in Patients With Retinal Degeneration Associated With Biallelic Variants in the USH2A Gene. Investigative ophthalmology & visual science 17 35293952
2022 Global spectrum of USH2A mutation in inherited retinal dystrophies: Prompt message for development of base editing therapy. Frontiers in aging neuroscience 17 36034145
2020 Truncating Variants Contribute to Hearing Loss and Severe Retinopathy in USH2A-Associated Retinitis Pigmentosa in Japanese Patients. International journal of molecular sciences 17 33105608
2019 Whole exome sequencing identifies novel USH2A mutations and confirms Usher syndrome 2 diagnosis in Chinese retinitis pigmentosa patients. Scientific reports 17 30948794
2016 Immunogenicity and protective efficacy of Brucella abortus recombinant protein cocktail (rOmp19+rP39) against B. abortus 544 and B. melitensis 16M infection in murine model. Molecular immunology 17 26826463
2002 Identification of the mouse and rat orthologs of the gene mutated in Usher syndrome type IIA and the cellular source of USH2A mRNA in retina, a target tissue of the disease. Genomics 17 12160733
2023 A protein domain-oriented approach to expand the opportunities of therapeutic exon skipping for USH2A-associated retinitis pigmentosa. Molecular therapy. Nucleic acids 16 37313440
2023 Successful large gene augmentation of USH2A with non-viral episomal vectors. Molecular therapy : the journal of the American Society of Gene Therapy 16 37337429
2021 USH2A Mutation is Associated With Tumor Mutation Burden and Antitumor Immunity in Patients With Colon Adenocarcinoma. Frontiers in genetics 16 34795697
2020 Correlation between Genotype and Phenotype in 69 Chinese Patients with USH2A Mutations: A comparative study of the patients with Usher Syndrome and Nonsyndromic Retinitis Pigmentosa. Acta ophthalmologica 16 33124170
2018 Unravelling the pathogenic role and genotype-phenotype correlation of the USH2A p.(Cys759Phe) variant among Spanish families. PloS one 16 29912909
2020 Establishing Genotype-phenotype Correlation in USH2A-related Disorders to Personalize Audiological Surveillance and Rehabilitation. Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 15 32176120
2019 Clinical and Haplotypic Variability of Slovenian USH2A Patients Homozygous for the c. 11864G>A Nonsense Mutation. Genes 15 31817543
2014 Novel deletions involving the USH2A gene in patients with Usher syndrome and retinitis pigmentosa. Molecular vision 15 25352746
2020 A case of Usher syndrome type IIA caused by a rare USH2A homozygous frameshift variant with maternal uniparental disomy (UPD) in a Chinese family. Journal of cellular and molecular medicine 14 32449591
2018 Mutation screening of the USH2A gene in retinitis pigmentosa and USHER patients in a Han Chinese population. Eye (London, England) 14 29899460
1998 The Usher syndrome in the Lebanese population and further refinement of the USH2A candidate region. Human genetics 14 9760205
2023 Deafness-Associated ADGRV1 Mutation Impairs USH2A Stability through Improper Phosphorylation of WHRN and WDSUB1 Recruitment. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 13 37066759
2021 The Study of a 231 French Patient Cohort Significantly Extends the Mutational Spectrum of the Two Major Usher Genes MYO7A and USH2A. International journal of molecular sciences 13 34948090
2014 The first USH2A mutation analysis of Japanese autosomal recessive retinitis pigmentosa patients: a totally different mutation profile with the lack of frequent mutations found in Caucasian patients. Journal of human genetics 13 25078356
2011 Functional analysis of splicing mutations in MYO7A and USH2A genes. Clinical genetics 13 20497194
2023 USH2A Gene Mutations in Rabbits Lead to Progressive Retinal Degeneration and Hearing Loss. Translational vision science & technology 12 36795064
2022 Genetic Characteristics and Variation Spectrum of USH2A-Related Retinitis Pigmentosa and Usher Syndrome. Frontiers in genetics 12 36110214
2021 Spectral-Domain Optical Coherence Tomography Analysis in Syndromic and Nonsyndromic Forms of Retinitis Pigmentosa due to USH2A Genetic Variants. Ophthalmic research 12 34781295
2019 Double Hyperautofluorescent Rings in Patients with USH2A-Retinopathy. Genes 12 31766479
2010 Novel USH2A compound heterozygous mutations cause RP/USH2 in a Chinese family. Molecular vision 12 20309401
2000 Prevalence of 2314delG mutation in Spanish patients with Usher syndrome type II (USH2). Ophthalmic genetics 12 10916187
2021 USH2A-Related Retinitis Pigmentosa: Staging of Disease Severity and Morpho-Functional Studies. Diagnostics (Basel, Switzerland) 10 33535592
2019 Novel USH1G homozygous variant underlying USH2-like phenotype of Usher syndrome. European journal of ophthalmology 10 31566003