{"gene":"MYH10","run_date":"2026-06-10T05:19:52","timeline":{"discoveries":[{"year":2014,"finding":"A motor-dead point mutation in NMII-B (MYH10) expressed at wild-type levels causes a dominant-negative effect by prolonging cross-linking of NMII-B to actin filaments, thereby interfering with actomyosin cytoskeletal dynamics. This gain-of-function (not loss-of-function) disrupts ventral body wall closure, midline fusion, and outflow tract myocardialization—phenotypes not seen in null or hypomorphic mice—demonstrating that NMII-B motor activity is required to disassemble actomyosin cross-links and drive myocyte cell-cell adhesion remodeling.","method":"Knock-in point mutant mice expressing motor-deficient NMII-B at wild-type levels; comparison with null and hypomorphic mouse phenotypes; histological and genetic analysis of cardiac outflow tract and body wall defects","journal":"Circulation. Cardiovascular genetics","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean genetic knock-in with rigorous comparison to null/hypomorphic models, multiple orthogonal phenotypic readouts establishing dominant-negative mechanism","pmids":["24825879"],"is_preprint":false},{"year":2015,"finding":"MYH10 is required for centriole migration to the apical plasma membrane at the onset of primary ciliogenesis. Knockdown of MYH10 in RPE1 cells reduces cortical filamentous actin (F-actin) and its binding protein EZRIN, impairs centriole migration, and blocks subsequent cilium assembly. MYH10 also influences centrosomal recruitment of IFT88 (required for intraflagellar transport), with IFT88 levels correlating with centriolar position along the apical-basal axis.","method":"siRNA knockdown of MYH10 in RPE1 cells; immunofluorescence of F-actin, EZRIN, centriole position, IFT88 recruitment; quantitative ciliogenesis assays","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean KD with defined cellular phenotype (centriole migration, ciliogenesis), two orthogonal readouts (actin, IFT88), single lab","pmids":["25881509"],"is_preprint":false},{"year":2018,"finding":"Loss of MYH10 in lung mesenchymal cells results in decreased Thrombospondin expression, increased matrix metalloproteinase (MMP) activity, and disrupted extracellular matrix (ECM) remodeling, causing ECM deposition defects and alveolar simplification. These effects were demonstrated both in Myh10 mutant lungs in vivo and in cultured mutant fibroblasts.","method":"Conditional knockout of Myh10 in mesenchymal cells (mouse genetics); omics analyses; cultured mutant fibroblast assays for Thrombospondin expression, MMP activity, and ECM deposition","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — conditional KO with defined cellular phenotype confirmed in both in vivo and in vitro systems, multiple molecular readouts","pmids":["30389913"],"is_preprint":false},{"year":2018,"finding":"MYH10 gene silencing in glioma cell lines reduces cell migration and invasion, accompanied by reduced expression of MTA-1, MMP-2, MMP-9, and vimentin, increased expression of TIMP-2, E-cadherin, and collagen 1, and inhibition of the Wnt/β-catenin pathway (reduced Wnt3a, β-catenin, cyclin D1 levels).","method":"siRNA/plasmid-mediated MYH10 silencing in U251, T98G, SHG44 glioma cell lines; scratch and transwell migration/invasion assays; Western blot and qRT-PCR for pathway components","journal":"Medical science monitor","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — KD with phenotype and pathway placement, multiple cell lines, but no direct biochemical interaction with Wnt pathway components shown","pmids":["30552850"],"is_preprint":false},{"year":2017,"finding":"NMHC IIB (MYH10) is required for epicardial cell function: a point mutation in the Myh10 splice donor site causes abnormal epicardial cell morphology, reduced capacity for epithelial-mesenchymal transition (EMT), and impaired migration of epicardial-derived cells (EPDCs) into the myocardium, thereby disrupting coronary vessel formation.","method":"ENU mutagenesis screen; positional cloning; complementation testing; histological and cell morphology analysis of epicardium; EMT and EPDC migration assays in EHC mutant mice","journal":"PLoS genetics","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic complementation confirmed causality, multiple orthogonal cellular phenotypic readouts (morphology, EMT, migration) in a well-controlled mutant mouse model","pmids":["29084269"],"is_preprint":false},{"year":2020,"finding":"Conditional knockout of both Myh9 and Myh10 in adult renal tubular epithelium causes intracellular accumulation of the GPI-anchored protein uromodulin (UMOD) and loss of Na+K+2Cl- cotransporter (NKCC2) from the apical membrane of thick ascending limb epithelia. UMOD accumulation coincides with expansion of ER tubules and activation of ER stress/unfolded protein response pathways, establishing that MYH9 and MYH10 are required for localization and intracellular transport of UMOD.","method":"Inducible conditional knockout of Myh9 and Myh10 in adult mouse renal tubules; immunofluorescence and fractionation for UMOD and NKCC2 localization; ER stress marker analysis","journal":"JCI insight","confidence":"High","confidence_rationale":"Tier 2 / Strong — inducible conditional KO with defined trafficking phenotype, multiple molecular readouts (UMOD, NKCC2, ER stress markers), replicated across nephron segment contexts","pmids":["33001861"],"is_preprint":false},{"year":2021,"finding":"Maternal-zygotic loss of Myh10 (NMHC II-B) alone causes only mild preimplantation phenotypes, whereas double maternal-zygotic loss of both Myh9 and Myh10 causes near-complete cytokinesis failure, demonstrating that MYH9 is the dominant non-muscle myosin II during mouse preimplantation development but that MYH10 provides redundant contractility for cytokinesis.","method":"Generation of single and double maternal-zygotic mutants of Myh9 and Myh10; multiscale live and fixed imaging; quantification of cytokinesis, compaction, differentiation, and lumen formation","journal":"eLife","confidence":"High","confidence_rationale":"Tier 2 / Strong — rigorous double-mutant genetic epistasis with multiscale imaging and quantitative phenotypic analysis establishing functional redundancy and hierarchy","pmids":["33871354"],"is_preprint":false},{"year":2021,"finding":"GATA1 directly represses MYH10 transcription during megakaryopoiesis via two binding sites in the MYH10 gene (one in the 3' UTR and one in intron 8), as shown by chromatin immunoprecipitation sequencing and luciferase reporter assays. GATA1 pathogenic variants impair intron 8-driven MYH10 transcriptional silencing, leading to elevated MYH10 levels that are associated with a polyploidization defect in megakaryocytes.","method":"Anti-GATA1 ChIP-seq revealing binding sites in MYH10 3' UTR and intron 8; luciferase reporter assays with wild-type and mutant GATA1 variants; patient platelet MYH10 protein measurements","journal":"Journal of thrombosis and haemostasis","confidence":"High","confidence_rationale":"Tier 1 / Moderate — direct ChIP-seq binding site identification plus functional luciferase validation, confirmed in patient samples, single lab","pmids":["34060193"],"is_preprint":false},{"year":2022,"finding":"MYH10 forms a complex with GLUT4 in adipocytes, an interaction regulated by insulin induction. MYH10 depletion in preadipocytes impairs adipogenesis and blocks GLUT4 translocation. PKCζ interacts with MYH10 to modify the localization and interaction of both GLUT4 and MYH10. Restoration of GLUT4 vesicle supply via co-culture rescues the adipogenic defect in MYH10 knockdown cells.","method":"siRNA knockdown of MYH10 in preadipocytes; co-immunoprecipitation of MYH10-GLUT4 complex; insulin stimulation assays; PKCζ interaction studies; co-culture rescue experiment","journal":"International journal of molecular sciences","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP and functional KD rescue experiment, insulin-regulated interaction, but single lab","pmids":["35216482"],"is_preprint":false},{"year":2022,"finding":"MYH10 knockout cells show defects in primary ciliogenesis (reduced ciliary length) and impaired Hedgehog signaling. Overexpression of MYH10 variants found in neurodevelopmental disorder patients exerts a dominant-negative effect on ciliary length, placing MYH10 in the pathway controlling primary cilia length and downstream Hedgehog signal transduction.","method":"CRISPR/Cas9 MYH10 knockout cell models; quantitative ciliogenesis assays (ciliary length measurement); Hedgehog signaling reporter assays; overexpression of patient-derived MYH10 variants in cells","journal":"Genetics in medicine","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — KO cells plus dominant-negative overexpression with two orthogonal readouts (cilia length and Hedgehog signaling), single lab","pmids":["35980381"],"is_preprint":false},{"year":2023,"finding":"MYH10 protein interacts directly with MYH9 (non-muscle myosin IIA) via its functional domain, and this complex recruits the deubiquitinating enzyme USP45, which deubiquitinates Snail to inhibit its proteasomal degradation. This MYH10-MYH9-USP45-Snail axis promotes EMT, migration, invasion, and cisplatin resistance in serous ovarian cancer cells.","method":"Co-immunoprecipitation; GST pull-down assays; confocal laser assays; knockdown and overexpression in vitro and in vivo; domain mapping of MYH10-MYH9 interaction","journal":"Advanced science","confidence":"High","confidence_rationale":"Tier 1 / Strong — reciprocal Co-IP, GST pull-down (in vitro binding), and in vivo functional validation with multiple orthogonal methods establishing the mechanistic axis","pmids":["36929633"],"is_preprint":false},{"year":2023,"finding":"MYH10 binds and recruits autophagy receptor proteins during autophagosome formation induced by mutant CHMP2B or nutrient starvation. MYH10 also interacts with ESCRT-III subunits to regulate phagophore closure by recruiting ESCRT-III to damaged mitochondria during PRKN/parkin-mediated mitophagy. Partial knockdown of MYH10 rescues neurodegeneration in Drosophila and human iPSC-derived cortical neurons expressing FTD-associated mutant CHMP2B.","method":"Co-immunoprecipitation of MYH10 with ESCRT-III and autophagy receptors; Drosophila genetic knockdown rescue assay; human iPSC-derived cortical neuron experiments; autophagy induction assays","journal":"Autophagy","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP plus genetic rescue in two model systems, but mechanistic details of ESCRT-III recruitment inferred from correlative data","pmids":["36849436"],"is_preprint":false},{"year":2023,"finding":"In arrhythmogenic cardiomyopathy caused by PKP2 C-terminal domain deletion mutations, PKP2 delocalization disrupts actomyosin network organization. Overexpression of MYH10 rescues actomyosin disorganization in mutant PKP2 cells, while expression of a dominant-negative MYH10 mutant mimics the pathogenic PKP2 CT-deletion phenotype (actin network abnormalities and right ventricle systolic dysfunction). The non-muscle myosin activator 4-hydroxyacetophenone (4-HAP) also restores normal contractility.","method":"Computational modeling of PKP2 variants; overexpression of MYH10 in mutant PKP2 cardiomyocytes; dominant-negative MYH10 mutant expression; pharmacological activation with 4-HAP; measurement of actomyosin organization and right ventricle systolic function","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — gain-of-function and dominant-negative genetic experiments with pharmacological corroboration, multiple orthogonal readouts including functional cardiac measurements","pmids":["37833253"],"is_preprint":false},{"year":2023,"finding":"LAMC2 forms protein complexes with both MYH9 and MYH10 to promote mitochondrial aggregation and increased ER-mitochondria interaction at the perinuclear region, attenuating ER stress and reducing reactive oxygen species and apoptosis in cancer cells.","method":"Co-immunoprecipitation identifying LAMC2-MYH9 and LAMC2-MYH10 complexes; LAMC2 overexpression/knockdown; measurement of mitochondrial membrane potential, ROS, ER-mitochondria contact sites; in vivo tumor growth assay","journal":"Cancer gene therapy","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — Co-IP establishes complex formation, functional consequences shown, but MYH10-specific contributions not separated from MYH9 in the same study; single lab","pmids":["37891404"],"is_preprint":false},{"year":2025,"finding":"CFAP57 interacts with MYH10 in sperm, as identified by immunoprecipitation-mass spectrometry. MYH10 localizes to the sperm flagella (confirmed by immunofluorescence and immunoelectron microscopy). In CFAP57 mutant sperm, MYH10 is mislocalized to the mid-piece region and absent from the principal and end pieces, causing downstream mislocalization of IFT88 and defective flagellar assembly (MMAF phenotype).","method":"Immunoprecipitation-mass spectrometry (IP-MS) identifying MYH10 as CFAP57 binding partner; immunofluorescence and immunoelectron microscopy of MYH10 and IFT88 localization in CFAP57 mutant sperm; CRISPR-Cas9 Cfap57 knockout mouse model","journal":"Human genomics","confidence":"High","confidence_rationale":"Tier 1 / Moderate — IP-MS binding, ultrastructural localization by immunoelectron microscopy, and CRISPR KO functional model with defined mislocalization phenotype; single lab but orthogonal methods","pmids":["41466333"],"is_preprint":false},{"year":2024,"finding":"LncRNA BlncAD1 binds MYH10 protein (identified by RNA pull-down) and protects MYH10 from ubiquitin-mediated degradation, thereby enhancing MYH10 protein stability and promoting bovine adipogenesis.","method":"RNA pull-down identifying MYH10 as BlncAD1 binding protein; BlncAD1 knockdown/overexpression with MYH10 ubiquitination measurement by Western blot","journal":"Journal of agricultural and food chemistry","confidence":"Low","confidence_rationale":"Tier 3 / Weak — RNA pull-down and ubiquitination assay, single lab, bovine model; mechanistic link between lncRNA binding and ubiquitination protection not fully established at molecular level","pmids":["38661523"],"is_preprint":false},{"year":2025,"finding":"In zebrafish, myh10 expression requires myh9b: myh9b null mutants show reduced myh10 expression, while myh10 null mutants show reduced myh9b expression, establishing reciprocal transcriptional or post-transcriptional regulatory interactions between myh9b and myh10 during development. Double myh9a/myh10 or myh9b/myh10 mutants display more severe phenotypes than single mutants at earlier time points, indicating tissue-specific genetic redundancy.","method":"CRISPR-Cas9 null mutants of myh9a, myh9b, and myh10 in zebrafish; qRT-PCR and protein analyses of expression levels in mutant backgrounds; double mutant epistasis analysis","journal":"G3 (Bethesda, Md.)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean null mutants with genetic epistasis and protein analyses, zebrafish ortholog study, single lab","pmids":["39503257"],"is_preprint":false},{"year":2025,"finding":"TAL-specific conditional knockout of Myh9 and Myh10 impairs NKCC2 expression and trafficking in thick ascending limb cells, causing progressive kidney disease. Loss of TAL NM2 function triggers a compensatory mechanism involving sex-specific upregulation of NCC in the distal nephron (males) and ENaC in medullary collecting ducts (both sexes), demonstrating a cell-autonomous role for MYH9/MYH10 in maintaining apical NKCC2 expression.","method":"TAL-specific conditional double knockout mouse model; histology; immunofluorescence for NKCC2, ENaC, NCC; ER stress markers; blood urea nitrogen and creatinine measurements; sex-stratified analysis","journal":"Function (Oxford, England)","confidence":"High","confidence_rationale":"Tier 2 / Strong — cell-type-specific conditional KO with defined molecular cargo (NKCC2), multiple nephron-segment readouts confirming cell-autonomous trafficking function; replicates and extends prior work (PMID:33001861)","pmids":["39500539"],"is_preprint":false},{"year":2025,"finding":"Tail-domain variants of MYH10 found in patients with ocular coloboma and ptosis cause mislocalization of the MYH10 protein and abnormal actin networks in patient fibroblasts, demonstrating that the tail domain is required for proper subcellular localization and maintenance of normal actin cytoskeletal architecture.","method":"Exome/genome sequencing identifying tail-domain variants; immunofluorescence of MYH10 localization and actin networks in patient vs. control fibroblasts; zebrafish morpholino/mutant model for eye and muscle phenotypes","journal":"European journal of human genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — direct localization experiment in patient fibroblasts with actin network readout and in vivo zebrafish validation; single lab, limited mechanistic depth","pmids":["40044823"],"is_preprint":false}],"current_model":"MYH10 (non-muscle myosin IIB heavy chain) functions as an actin-based motor that generates actomyosin contractility required for cytokinesis, cell migration, EMT, and cytoskeletal remodeling; its tail domain mediates filament assembly and subcellular localization, its motor activity is essential for disassembling actomyosin cross-links during morphogenetic events (with motor-dead mutants acting dominantly by prolonging actin cross-linking), and it participates in specific cargo trafficking pathways (UMOD/NKCC2 in renal epithelium; GLUT4 in adipocytes; IFT88 and centriole positioning during ciliogenesis), while also forming functional complexes with MYH9, LAMC2, ESCRT-III, and USP45 to regulate ER-mitochondria contacts, autophagosome closure, and Snail deubiquitination, with its transcription directly repressed by GATA1 during megakaryopoiesis via intronic regulatory elements."},"narrative":{"mechanistic_narrative":"MYH10 (non-muscle myosin IIB heavy chain) is an actin-based motor that generates and remodels actomyosin contractility to drive cell division, migration, epithelial-mesenchymal transition, and cytoskeletal architecture across developmental and disease contexts [PMID:24825879, PMID:29084269, PMID:33871354]. Its motor activity is required not merely to contract but to disassemble actomyosin cross-links: a motor-dead knock-in mutant expressed at wild-type levels acts dominantly by prolonging actin cross-linking, disrupting body wall closure, midline fusion, and outflow tract myocardialization—phenotypes absent in null or hypomorphic animals [PMID:24825879]. During mouse preimplantation development MYH10 provides contractility for cytokinesis that is redundant with the dominant paralog MYH9 [PMID:33871354], and the two heavy chains co-regulate one another's expression and act redundantly in tissue-specific contexts [PMID:39503257]. The tail domain controls subcellular localization and actin network maintenance; patient tail-domain variants mislocalize the protein and disorganize actin in fibroblasts [PMID:40044823]. MYH10 partners directly with MYH9 to recruit the deubiquitinase USP45, which stabilizes Snail to promote EMT, invasion, and chemoresistance [PMID:36929633], and both heavy chains complex with LAMC2 to regulate ER-mitochondria contacts and oxidative stress [PMID:37891404]. MYH10 mediates polarized intracellular trafficking and organelle positioning: it is required with MYH9 for apical localization and transport of UMOD and NKCC2 in renal thick ascending limb epithelium [PMID:33001861, PMID:39500539], for GLUT4 translocation and adipogenesis [PMID:35216482], for centriole migration and IFT88 recruitment during ciliogenesis with downstream Hedgehog signaling [PMID:25881509, PMID:35980381], and for sperm flagellar assembly via interaction with CFAP57 [PMID:41466333]. It also recruits ESCRT-III and autophagy receptors to drive autophagosome closure and mitophagy [PMID:36849436]. MYH10 transcription is directly repressed by GATA1 during megakaryopoiesis through binding sites in the 3' UTR and intron 8, and pathogenic GATA1 variants elevate MYH10 with associated megakaryocyte polyploidization defects [PMID:34060193]. Patient variants link MYH10 to neurodevelopmental disorders and to ocular coloboma with ptosis [PMID:35980381, PMID:40044823].","teleology":[{"year":2014,"claim":"Established that MYH10 motor activity functions to disassemble actomyosin cross-links rather than only to contract, resolving why a motor-dead allele is more damaging than gene loss.","evidence":"Knock-in motor-deficient point mutant mice expressed at wild-type levels, compared to null and hypomorphic models with cardiac/body wall readouts","pmids":["24825879"],"confidence":"High","gaps":["Does not define the molecular partners cross-linked at affected tissues","Mechanism of cross-link turnover at the filament level not resolved"]},{"year":2015,"claim":"Placed MYH10 upstream of centriole apical migration and ciliogenesis, linking it to cortical actin and IFT88 recruitment.","evidence":"siRNA knockdown in RPE1 cells with F-actin, EZRIN, centriole position, and IFT88 imaging","pmids":["25881509"],"confidence":"Medium","gaps":["Direct biochemical interaction with IFT88 not shown","Single cell line, single lab"]},{"year":2017,"claim":"Demonstrated a developmental requirement for MYH10 in epicardial EMT and EPDC migration during coronary vessel formation.","evidence":"ENU splice-donor mutant mice with complementation, EMT and migration assays","pmids":["29084269"],"confidence":"High","gaps":["Downstream signaling driving EMT not defined","Does not separate motor versus structural contributions"]},{"year":2018,"claim":"Extended MYH10 function to mesenchymal ECM remodeling, showing its loss alters Thrombospondin, MMP activity, and matrix deposition in the lung.","evidence":"Conditional mesenchymal KO mice plus cultured mutant fibroblasts with omics and ECM assays","pmids":["30389913"],"confidence":"High","gaps":["Mechanism linking myosin activity to Thrombospondin/MMP regulation unresolved"]},{"year":2018,"claim":"Linked MYH10 to glioma migration/invasion and placed it upstream of EMT markers and Wnt/β-catenin signaling.","evidence":"siRNA/plasmid silencing in three glioma lines with migration assays, Western blot, qRT-PCR","pmids":["30552850"],"confidence":"Medium","gaps":["No direct physical interaction with Wnt components shown","Pathway placement correlative"]},{"year":2020,"claim":"Identified a trafficking role for MYH9/MYH10 in renal epithelium, required for UMOD localization and apical NKCC2 placement.","evidence":"Inducible conditional Myh9/Myh10 KO mice with UMOD/NKCC2 localization and ER stress markers","pmids":["33001861"],"confidence":"High","gaps":["MYH10-specific contribution not separated from MYH9","Step in the secretory/trafficking pathway not pinpointed"]},{"year":2021,"claim":"Defined the genetic hierarchy of non-muscle myosin II in early embryogenesis, showing MYH10 provides cytokinetic contractility redundant with the dominant MYH9.","evidence":"Single and double maternal-zygotic Myh9/Myh10 mutants with multiscale imaging","pmids":["33871354"],"confidence":"High","gaps":["Molecular basis of the MYH9 dominance over MYH10 not defined"]},{"year":2021,"claim":"Showed MYH10 transcription is directly repressed by GATA1 during megakaryopoiesis via intron 8 and 3' UTR sites, connecting MYH10 dysregulation to polyploidization defects.","evidence":"Anti-GATA1 ChIP-seq, luciferase reporters with mutant GATA1, patient platelet measurements","pmids":["34060193"],"confidence":"High","gaps":["Causal contribution of elevated MYH10 to the polyploidization defect is associative"]},{"year":2022,"claim":"Established a MYH10-GLUT4 trafficking complex required for insulin-responsive GLUT4 translocation and adipogenesis.","evidence":"siRNA KD in preadipocytes, MYH10-GLUT4 Co-IP, PKCζ interaction, co-culture rescue","pmids":["35216482"],"confidence":"Medium","gaps":["Single lab","Direct versus indirect nature of MYH10-GLUT4 binding not fully resolved"]},{"year":2022,"claim":"Connected MYH10 to ciliary length control and Hedgehog signaling, and showed neurodevelopmental-disorder patient variants act dominant-negatively on cilia.","evidence":"CRISPR KO cells, ciliary length and Hedgehog reporter assays, patient-variant overexpression","pmids":["35980381"],"confidence":"Medium","gaps":["Mechanism linking MYH10 to ciliary length not defined","Single lab"]},{"year":2023,"claim":"Defined the MYH10-MYH9-USP45-Snail axis, mechanistically linking the myosin heavy-chain complex to Snail deubiquitination and EMT/chemoresistance.","evidence":"Reciprocal Co-IP, GST pull-down, domain mapping, in vitro and in vivo functional studies in ovarian cancer","pmids":["36929633"],"confidence":"High","gaps":["How the myosin complex recruits USP45 structurally not resolved"]},{"year":2023,"claim":"Implicated MYH10 in autophagosome closure and mitophagy via ESCRT-III and autophagy receptor recruitment, with knockdown rescuing FTD-associated neurodegeneration.","evidence":"Co-IP with ESCRT-III/autophagy receptors, Drosophila and iPSC-neuron rescue, autophagy induction assays","pmids":["36849436"],"confidence":"Medium","gaps":["ESCRT-III recruitment mechanism inferred from correlative data","Direct binding interface not mapped"]},{"year":2023,"claim":"Demonstrated MYH10 can rescue actomyosin disorganization in arrhythmogenic cardiomyopathy from PKP2 deletion, with a dominant-negative mutant phenocopying disease.","evidence":"MYH10 overexpression and dominant-negative expression in mutant cardiomyocytes, 4-HAP pharmacology, cardiac function measures","pmids":["37833253"],"confidence":"High","gaps":["Direct biochemical link between PKP2 and MYH10/actomyosin not established"]},{"year":2023,"claim":"Identified a LAMC2-MYH9/MYH10 complex regulating ER-mitochondria contacts, ROS, and apoptosis in cancer.","evidence":"Co-IP, LAMC2 overexpression/KD, mitochondrial/ER contact and ROS measures, in vivo tumor assay","pmids":["37891404"],"confidence":"Medium","gaps":["MYH10-specific contribution not separated from MYH9","Single lab"]},{"year":2024,"claim":"Identified an lncRNA (BlncAD1) that binds and stabilizes MYH10 protein against ubiquitin-mediated degradation to promote adipogenesis.","evidence":"RNA pull-down and ubiquitination Western blot in bovine model","pmids":["38661523"],"confidence":"Low","gaps":["Molecular link between lncRNA binding and ubiquitination protection not established","Single lab, bovine model only"]},{"year":2025,"claim":"Established a flagellar role: CFAP57 binds MYH10 and is required for its correct flagellar localization, with downstream IFT88 mislocalization and MMAF when lost.","evidence":"IP-MS, immunofluorescence/immunoEM, CRISPR Cfap57 KO mouse","pmids":["41466333"],"confidence":"High","gaps":["Whether MYH10 motor activity is required for flagellar assembly not tested","Single lab"]},{"year":2025,"claim":"Confirmed and extended the cell-autonomous renal trafficking role of MYH9/MYH10 in maintaining apical NKCC2 and revealed compensatory transporter upregulation.","evidence":"TAL-specific conditional double KO mouse with segment-specific transporter immunofluorescence and renal function measures","pmids":["39500539"],"confidence":"High","gaps":["MYH10-specific role not isolated from MYH9","Mechanism of compensatory NCC/ENaC induction not defined"]},{"year":2025,"claim":"Showed MYH9b and MYH10 reciprocally regulate one another's expression and act with tissue-specific redundancy in vertebrate development.","evidence":"CRISPR null mutants and double-mutant epistasis in zebrafish with expression analyses","pmids":["39503257"],"confidence":"Medium","gaps":["Whether regulation is transcriptional or post-transcriptional unresolved","Single lab, ortholog study"]},{"year":2025,"claim":"Demonstrated the tail domain is essential for MYH10 subcellular localization and actin network integrity, linking tail-domain variants to ocular coloboma and ptosis.","evidence":"Patient sequencing, fibroblast localization/actin imaging, zebrafish model","pmids":["40044823"],"confidence":"Medium","gaps":["Mechanism by which tail variants cause mislocalization not resolved","Single lab"]},{"year":null,"claim":"How MYH10 selectively engages distinct cargo and organelle systems (GLUT4, UMOD/NKCC2, IFT88, ESCRT-III) versus its bulk contractile role, and the structural basis of its many partner complexes, remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model of partner-binding interfaces","MYH10-specific versus MYH9-redundant contributions rarely separated","Regulation of cargo-specific recruitment unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003774","term_label":"cytoskeletal motor activity","supporting_discovery_ids":[0,6,12]},{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[0,18,12]},{"term_id":"GO:0140657","term_label":"ATP-dependent activity","supporting_discovery_ids":[0]}],"localization":[{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[0,18,12]},{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[1]},{"term_id":"GO:0005929","term_label":"cilium","supporting_discovery_ids":[1,9,14]},{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[5,17]}],"pathway":[{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[6]},{"term_id":"R-HSA-9612973","term_label":"Autophagy","supporting_discovery_ids":[11]},{"term_id":"R-HSA-9609507","term_label":"Protein localization","supporting_discovery_ids":[5,8,17]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[0,4,6]},{"term_id":"R-HSA-1474244","term_label":"Extracellular matrix organization","supporting_discovery_ids":[2]}],"complexes":["MYH9-MYH10 non-muscle myosin II complex","ESCRT-III (recruited)"],"partners":["MYH9","USP45","LAMC2","GLUT4","PKCΖ","CFAP57","IFT88"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"P35580","full_name":"Myosin-10","aliases":["Cellular myosin heavy chain, type B","Myosin heavy chain 10","Myosin heavy chain, non-muscle IIb","Non-muscle myosin heavy chain B","NMMHC-B","Non-muscle myosin heavy chain IIb","NMMHC II-b","NMMHC-IIB"],"length_aa":1976,"mass_kda":229.0,"function":"Cellular myosin that appears to play a role in cytokinesis, cell shape, and specialized functions such as secretion and capping. Involved with LARP6 in the stabilization of type I collagen mRNAs for CO1A1 and CO1A2. During cell spreading, plays an important role in cytoskeleton reorganization, focal contacts formation (in the central part but not the margins of spreading cells), and lamellipodial extension; this function is mechanically antagonized by MYH9 (Microbial infection) Acts as a receptor for herpes simplex virus 1/HHV-1 envelope glycoprotein B","subcellular_location":"Cell membrane","url":"https://www.uniprot.org/uniprotkb/P35580/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/MYH10","classification":"Not Classified","n_dependent_lines":2,"n_total_lines":1208,"dependency_fraction":0.0016556291390728477},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000133026","cell_line_id":"CID001435","localizations":[{"compartment":"cytoskeleton","grade":3}],"interactors":[{"gene":"MYL12A;MYL9","stoichiometry":10.0},{"gene":"MYL12A","stoichiometry":10.0},{"gene":"CAPZB","stoichiometry":0.2},{"gene":"MYL6B","stoichiometry":0.2},{"gene":"MYL6","stoichiometry":0.2},{"gene":"SPECC1","stoichiometry":0.2},{"gene":"PSMB10","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/target/CID001435","total_profiled":1310},"omim":[{"mim_id":"621374","title":"SERINE/THREONINE/TYROSINE-INTERACTING PROTEIN-LIKE 2; STYXL2","url":"https://www.omim.org/entry/621374"},{"mim_id":"617443","title":"BLEEDING DISORDER, PLATELET-TYPE, 21; BDPLT21","url":"https://www.omim.org/entry/617443"},{"mim_id":"616999","title":"RNA-BINDING FOX1 HOMOLOG 3; RBFOX3","url":"https://www.omim.org/entry/616999"},{"mim_id":"614026","title":"KINESIN FAMILY MEMBER 26B; KIF26B","url":"https://www.omim.org/entry/614026"},{"mim_id":"608568","title":"MYOSIN, HEAVY CHAIN 14, NONMUSCLE; MYH14","url":"https://www.omim.org/entry/608568"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Uncertain","locations":[{"location":"Actin filaments","reliability":"Uncertain"},{"location":"Mitochondria","reliability":"Additional"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Tissue enriched","tissue_distribution":"Detected in all","driving_tissues":[{"tissue":"blood vessel","ntpm":253.8}],"url":"https://www.proteinatlas.org/search/MYH10"},"hgnc":{"alias_symbol":["NMMHCB"],"prev_symbol":[]},"alphafold":{"accession":"P35580","domains":[{"cath_id":"1.20.5","chopping":"774-845","consensus_level":"medium","plddt":89.4919,"start":774,"end":845},{"cath_id":"1.20.5","chopping":"850-986","consensus_level":"medium","plddt":78.899,"start":850,"end":986}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P35580","model_url":"https://alphafold.ebi.ac.uk/files/AF-P35580-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P35580-F1-predicted_aligned_error_v6.png","plddt_mean":76.19},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=MYH10","jax_strain_url":"https://www.jax.org/strain/search?query=MYH10"},"sequence":{"accession":"P35580","fasta_url":"https://rest.uniprot.org/uniprotkb/P35580.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P35580/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P35580"}},"corpus_meta":[{"pmid":"30389913","id":"PMC_30389913","title":"Myh10 deficiency leads to defective extracellular matrix remodeling and pulmonary disease.","date":"2018","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/30389913","citation_count":43,"is_preprint":false},{"pmid":"24825879","id":"PMC_24825879","title":"A point mutation in Myh10 causes major defects in heart development and body wall closure.","date":"2014","source":"Circulation. Cardiovascular genetics","url":"https://pubmed.ncbi.nlm.nih.gov/24825879","citation_count":40,"is_preprint":false},{"pmid":"25003005","id":"PMC_25003005","title":"A human de novo mutation in MYH10 phenocopies the loss of function mutation in mice.","date":"2013","source":"Rare diseases (Austin, Tex.)","url":"https://pubmed.ncbi.nlm.nih.gov/25003005","citation_count":40,"is_preprint":false},{"pmid":"23665442","id":"PMC_23665442","title":"Nonmuscle myosin II-B (myh10) expression analysis during zebrafish embryonic development.","date":"2013","source":"Gene expression patterns : GEP","url":"https://pubmed.ncbi.nlm.nih.gov/23665442","citation_count":36,"is_preprint":false},{"pmid":"25881509","id":"PMC_25881509","title":"Myosin heavy chain 10 (MYH10) is required for centriole migration during the biogenesis of primary cilia.","date":"2015","source":"Biochemical and biophysical research 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for epicardial function and coronary vessel formation during mammalian development.","date":"2017","source":"PLoS genetics","url":"https://pubmed.ncbi.nlm.nih.gov/29084269","citation_count":27,"is_preprint":false},{"pmid":"33871354","id":"PMC_33871354","title":"Multiscale analysis of single and double maternal-zygotic Myh9 and Myh10 mutants during mouse preimplantation development.","date":"2021","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/33871354","citation_count":20,"is_preprint":false},{"pmid":"35216482","id":"PMC_35216482","title":"MYH10 Governs Adipocyte Function and Adipogenesis through Its Interaction with GLUT4.","date":"2022","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/35216482","citation_count":19,"is_preprint":false},{"pmid":"33001861","id":"PMC_33001861","title":"Conditional Myh9 and Myh10 inactivation in adult mouse renal epithelium results in progressive kidney disease.","date":"2020","source":"JCI 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activation of the EGFR pathway.","date":"2021","source":"Journal of cellular and molecular medicine","url":"https://pubmed.ncbi.nlm.nih.gov/34738311","citation_count":14,"is_preprint":false},{"pmid":"32226520","id":"PMC_32226520","title":"MiR-200a Regulates Nasopharyngeal Carcinoma Cell Migration and Invasion by Targeting MYH10.","date":"2020","source":"Journal of Cancer","url":"https://pubmed.ncbi.nlm.nih.gov/32226520","citation_count":11,"is_preprint":false},{"pmid":"37891404","id":"PMC_37891404","title":"LAMC2 mitigates ER stress by enhancing ER-mitochondria interaction via binding to MYH9 and MYH10.","date":"2023","source":"Cancer gene therapy","url":"https://pubmed.ncbi.nlm.nih.gov/37891404","citation_count":10,"is_preprint":false},{"pmid":"34060193","id":"PMC_34060193","title":"GATA1 pathogenic variants disrupt MYH10 silencing during megakaryopoiesis.","date":"2021","source":"Journal of thrombosis and haemostasis : JTH","url":"https://pubmed.ncbi.nlm.nih.gov/34060193","citation_count":7,"is_preprint":false},{"pmid":"36849436","id":"PMC_36849436","title":"Non-muscle MYH10/myosin IIB recruits ESCRT-III to participate in autophagosome closure to maintain neuronal homeostasis.","date":"2023","source":"Autophagy","url":"https://pubmed.ncbi.nlm.nih.gov/36849436","citation_count":7,"is_preprint":false},{"pmid":"37833253","id":"PMC_37833253","title":"MYH10 activation rescues contractile defects in arrhythmogenic cardiomyopathy (ACM).","date":"2023","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/37833253","citation_count":6,"is_preprint":false},{"pmid":"38661523","id":"PMC_38661523","title":"LncRNA BlncAD1 Modulates Bovine Adipogenesis by Binding to MYH10, PI3K/Akt Signaling Pathway, and miR-27a-5p/CDK6 Axis.","date":"2024","source":"Journal of agricultural and food chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/38661523","citation_count":4,"is_preprint":false},{"pmid":"40044823","id":"PMC_40044823","title":"Novel MYH10 heterozygous variants associated to a syndrome combining mainly ptosis and ocular coloboma expand the MYH10 related phenotypes.","date":"2025","source":"European journal of human genetics : EJHG","url":"https://pubmed.ncbi.nlm.nih.gov/40044823","citation_count":3,"is_preprint":false},{"pmid":"39503257","id":"PMC_39503257","title":"myh9b is a critical non-muscle myosin II encoding gene that interacts with myh9a and myh10 during zebrafish development in both compensatory and redundant pathways.","date":"2025","source":"G3 (Bethesda, Md.)","url":"https://pubmed.ncbi.nlm.nih.gov/39503257","citation_count":3,"is_preprint":false},{"pmid":"39500539","id":"PMC_39500539","title":"Thick Ascending Limb Specific Inactivation of Myh9 and Myh10 Myosin Motors Results in Progressive Kidney Disease and Drives Sex-specific Cellular Adaptation in the Distal Nephron and Collecting Duct.","date":"2025","source":"Function (Oxford, England)","url":"https://pubmed.ncbi.nlm.nih.gov/39500539","citation_count":2,"is_preprint":false},{"pmid":"40694286","id":"PMC_40694286","title":"Disulfidptosis-related LncRNA signatures in gastric cancer: regulation of MYH10-driven cytoskeletal remodeling and therapeutic implications.","date":"2025","source":"Discover oncology","url":"https://pubmed.ncbi.nlm.nih.gov/40694286","citation_count":1,"is_preprint":false},{"pmid":"40873555","id":"PMC_40873555","title":"Case Report: CD34-Negative, S100-Positive Spindle Cell Tumor With a MYH10-RET Fusion.","date":"2025","source":"Case reports in pathology","url":"https://pubmed.ncbi.nlm.nih.gov/40873555","citation_count":1,"is_preprint":false},{"pmid":"41466333","id":"PMC_41466333","title":"Mutations in CFAP57 disrupt the localization of MYH10 and IFT88, leading to flagellogenesis failure in humans and mice.","date":"2025","source":"Human genomics","url":"https://pubmed.ncbi.nlm.nih.gov/41466333","citation_count":0,"is_preprint":false},{"pmid":"42007117","id":"PMC_42007117","title":"ECE1c promotes glioblastoma invasion via the ROCK2-MYH10 axis and interaction with ACTB.","date":"2026","source":"American journal of translational research","url":"https://pubmed.ncbi.nlm.nih.gov/42007117","citation_count":0,"is_preprint":false},{"pmid":"41491534","id":"PMC_41491534","title":"CORT silencing impairs migration and invasion: validation of a glycosylation-based risk model (CORT/LPAR5/CEBPA/MYH10/MAGEA11) in osteosarcoma.","date":"2026","source":"European journal of medical research","url":"https://pubmed.ncbi.nlm.nih.gov/41491534","citation_count":0,"is_preprint":false},{"pmid":"34864222","id":"PMC_34864222","title":"Generation of heterozygous (MRli003-A-1) and homozygous (MRli003-A-2) MYH10 knockout human iPSC lines.","date":"2021","source":"Stem cell research","url":"https://pubmed.ncbi.nlm.nih.gov/34864222","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.09.16.676497","title":"MAP7-driven microtubule remodeling builds the Sertoli apical domain that supports timely meiotic progression","date":"2025-09-17","source":"bioRxiv","url":"https://doi.org/10.1101/2025.09.16.676497","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.04.14.648628","title":"Transcriptomic profiling of a novel gastric implantation model identifies mechanisms and pathways that drive implantation into explanted human 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This gain-of-function (not loss-of-function) disrupts ventral body wall closure, midline fusion, and outflow tract myocardialization—phenotypes not seen in null or hypomorphic mice—demonstrating that NMII-B motor activity is required to disassemble actomyosin cross-links and drive myocyte cell-cell adhesion remodeling.\",\n      \"method\": \"Knock-in point mutant mice expressing motor-deficient NMII-B at wild-type levels; comparison with null and hypomorphic mouse phenotypes; histological and genetic analysis of cardiac outflow tract and body wall defects\",\n      \"journal\": \"Circulation. Cardiovascular genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean genetic knock-in with rigorous comparison to null/hypomorphic models, multiple orthogonal phenotypic readouts establishing dominant-negative mechanism\",\n      \"pmids\": [\"24825879\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"MYH10 is required for centriole migration to the apical plasma membrane at the onset of primary ciliogenesis. Knockdown of MYH10 in RPE1 cells reduces cortical filamentous actin (F-actin) and its binding protein EZRIN, impairs centriole migration, and blocks subsequent cilium assembly. MYH10 also influences centrosomal recruitment of IFT88 (required for intraflagellar transport), with IFT88 levels correlating with centriolar position along the apical-basal axis.\",\n      \"method\": \"siRNA knockdown of MYH10 in RPE1 cells; immunofluorescence of F-actin, EZRIN, centriole position, IFT88 recruitment; quantitative ciliogenesis assays\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean KD with defined cellular phenotype (centriole migration, ciliogenesis), two orthogonal readouts (actin, IFT88), single lab\",\n      \"pmids\": [\"25881509\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Loss of MYH10 in lung mesenchymal cells results in decreased Thrombospondin expression, increased matrix metalloproteinase (MMP) activity, and disrupted extracellular matrix (ECM) remodeling, causing ECM deposition defects and alveolar simplification. These effects were demonstrated both in Myh10 mutant lungs in vivo and in cultured mutant fibroblasts.\",\n      \"method\": \"Conditional knockout of Myh10 in mesenchymal cells (mouse genetics); omics analyses; cultured mutant fibroblast assays for Thrombospondin expression, MMP activity, and ECM deposition\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — conditional KO with defined cellular phenotype confirmed in both in vivo and in vitro systems, multiple molecular readouts\",\n      \"pmids\": [\"30389913\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"MYH10 gene silencing in glioma cell lines reduces cell migration and invasion, accompanied by reduced expression of MTA-1, MMP-2, MMP-9, and vimentin, increased expression of TIMP-2, E-cadherin, and collagen 1, and inhibition of the Wnt/β-catenin pathway (reduced Wnt3a, β-catenin, cyclin D1 levels).\",\n      \"method\": \"siRNA/plasmid-mediated MYH10 silencing in U251, T98G, SHG44 glioma cell lines; scratch and transwell migration/invasion assays; Western blot and qRT-PCR for pathway components\",\n      \"journal\": \"Medical science monitor\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — KD with phenotype and pathway placement, multiple cell lines, but no direct biochemical interaction with Wnt pathway components shown\",\n      \"pmids\": [\"30552850\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"NMHC IIB (MYH10) is required for epicardial cell function: a point mutation in the Myh10 splice donor site causes abnormal epicardial cell morphology, reduced capacity for epithelial-mesenchymal transition (EMT), and impaired migration of epicardial-derived cells (EPDCs) into the myocardium, thereby disrupting coronary vessel formation.\",\n      \"method\": \"ENU mutagenesis screen; positional cloning; complementation testing; histological and cell morphology analysis of epicardium; EMT and EPDC migration assays in EHC mutant mice\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic complementation confirmed causality, multiple orthogonal cellular phenotypic readouts (morphology, EMT, migration) in a well-controlled mutant mouse model\",\n      \"pmids\": [\"29084269\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Conditional knockout of both Myh9 and Myh10 in adult renal tubular epithelium causes intracellular accumulation of the GPI-anchored protein uromodulin (UMOD) and loss of Na+K+2Cl- cotransporter (NKCC2) from the apical membrane of thick ascending limb epithelia. UMOD accumulation coincides with expansion of ER tubules and activation of ER stress/unfolded protein response pathways, establishing that MYH9 and MYH10 are required for localization and intracellular transport of UMOD.\",\n      \"method\": \"Inducible conditional knockout of Myh9 and Myh10 in adult mouse renal tubules; immunofluorescence and fractionation for UMOD and NKCC2 localization; ER stress marker analysis\",\n      \"journal\": \"JCI insight\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — inducible conditional KO with defined trafficking phenotype, multiple molecular readouts (UMOD, NKCC2, ER stress markers), replicated across nephron segment contexts\",\n      \"pmids\": [\"33001861\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Maternal-zygotic loss of Myh10 (NMHC II-B) alone causes only mild preimplantation phenotypes, whereas double maternal-zygotic loss of both Myh9 and Myh10 causes near-complete cytokinesis failure, demonstrating that MYH9 is the dominant non-muscle myosin II during mouse preimplantation development but that MYH10 provides redundant contractility for cytokinesis.\",\n      \"method\": \"Generation of single and double maternal-zygotic mutants of Myh9 and Myh10; multiscale live and fixed imaging; quantification of cytokinesis, compaction, differentiation, and lumen formation\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — rigorous double-mutant genetic epistasis with multiscale imaging and quantitative phenotypic analysis establishing functional redundancy and hierarchy\",\n      \"pmids\": [\"33871354\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"GATA1 directly represses MYH10 transcription during megakaryopoiesis via two binding sites in the MYH10 gene (one in the 3' UTR and one in intron 8), as shown by chromatin immunoprecipitation sequencing and luciferase reporter assays. GATA1 pathogenic variants impair intron 8-driven MYH10 transcriptional silencing, leading to elevated MYH10 levels that are associated with a polyploidization defect in megakaryocytes.\",\n      \"method\": \"Anti-GATA1 ChIP-seq revealing binding sites in MYH10 3' UTR and intron 8; luciferase reporter assays with wild-type and mutant GATA1 variants; patient platelet MYH10 protein measurements\",\n      \"journal\": \"Journal of thrombosis and haemostasis\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — direct ChIP-seq binding site identification plus functional luciferase validation, confirmed in patient samples, single lab\",\n      \"pmids\": [\"34060193\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"MYH10 forms a complex with GLUT4 in adipocytes, an interaction regulated by insulin induction. MYH10 depletion in preadipocytes impairs adipogenesis and blocks GLUT4 translocation. PKCζ interacts with MYH10 to modify the localization and interaction of both GLUT4 and MYH10. Restoration of GLUT4 vesicle supply via co-culture rescues the adipogenic defect in MYH10 knockdown cells.\",\n      \"method\": \"siRNA knockdown of MYH10 in preadipocytes; co-immunoprecipitation of MYH10-GLUT4 complex; insulin stimulation assays; PKCζ interaction studies; co-culture rescue experiment\",\n      \"journal\": \"International journal of molecular sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP and functional KD rescue experiment, insulin-regulated interaction, but single lab\",\n      \"pmids\": [\"35216482\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"MYH10 knockout cells show defects in primary ciliogenesis (reduced ciliary length) and impaired Hedgehog signaling. Overexpression of MYH10 variants found in neurodevelopmental disorder patients exerts a dominant-negative effect on ciliary length, placing MYH10 in the pathway controlling primary cilia length and downstream Hedgehog signal transduction.\",\n      \"method\": \"CRISPR/Cas9 MYH10 knockout cell models; quantitative ciliogenesis assays (ciliary length measurement); Hedgehog signaling reporter assays; overexpression of patient-derived MYH10 variants in cells\",\n      \"journal\": \"Genetics in medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — KO cells plus dominant-negative overexpression with two orthogonal readouts (cilia length and Hedgehog signaling), single lab\",\n      \"pmids\": [\"35980381\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"MYH10 protein interacts directly with MYH9 (non-muscle myosin IIA) via its functional domain, and this complex recruits the deubiquitinating enzyme USP45, which deubiquitinates Snail to inhibit its proteasomal degradation. This MYH10-MYH9-USP45-Snail axis promotes EMT, migration, invasion, and cisplatin resistance in serous ovarian cancer cells.\",\n      \"method\": \"Co-immunoprecipitation; GST pull-down assays; confocal laser assays; knockdown and overexpression in vitro and in vivo; domain mapping of MYH10-MYH9 interaction\",\n      \"journal\": \"Advanced science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — reciprocal Co-IP, GST pull-down (in vitro binding), and in vivo functional validation with multiple orthogonal methods establishing the mechanistic axis\",\n      \"pmids\": [\"36929633\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"MYH10 binds and recruits autophagy receptor proteins during autophagosome formation induced by mutant CHMP2B or nutrient starvation. MYH10 also interacts with ESCRT-III subunits to regulate phagophore closure by recruiting ESCRT-III to damaged mitochondria during PRKN/parkin-mediated mitophagy. Partial knockdown of MYH10 rescues neurodegeneration in Drosophila and human iPSC-derived cortical neurons expressing FTD-associated mutant CHMP2B.\",\n      \"method\": \"Co-immunoprecipitation of MYH10 with ESCRT-III and autophagy receptors; Drosophila genetic knockdown rescue assay; human iPSC-derived cortical neuron experiments; autophagy induction assays\",\n      \"journal\": \"Autophagy\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP plus genetic rescue in two model systems, but mechanistic details of ESCRT-III recruitment inferred from correlative data\",\n      \"pmids\": [\"36849436\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"In arrhythmogenic cardiomyopathy caused by PKP2 C-terminal domain deletion mutations, PKP2 delocalization disrupts actomyosin network organization. Overexpression of MYH10 rescues actomyosin disorganization in mutant PKP2 cells, while expression of a dominant-negative MYH10 mutant mimics the pathogenic PKP2 CT-deletion phenotype (actin network abnormalities and right ventricle systolic dysfunction). The non-muscle myosin activator 4-hydroxyacetophenone (4-HAP) also restores normal contractility.\",\n      \"method\": \"Computational modeling of PKP2 variants; overexpression of MYH10 in mutant PKP2 cardiomyocytes; dominant-negative MYH10 mutant expression; pharmacological activation with 4-HAP; measurement of actomyosin organization and right ventricle systolic function\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — gain-of-function and dominant-negative genetic experiments with pharmacological corroboration, multiple orthogonal readouts including functional cardiac measurements\",\n      \"pmids\": [\"37833253\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"LAMC2 forms protein complexes with both MYH9 and MYH10 to promote mitochondrial aggregation and increased ER-mitochondria interaction at the perinuclear region, attenuating ER stress and reducing reactive oxygen species and apoptosis in cancer cells.\",\n      \"method\": \"Co-immunoprecipitation identifying LAMC2-MYH9 and LAMC2-MYH10 complexes; LAMC2 overexpression/knockdown; measurement of mitochondrial membrane potential, ROS, ER-mitochondria contact sites; in vivo tumor growth assay\",\n      \"journal\": \"Cancer gene therapy\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — Co-IP establishes complex formation, functional consequences shown, but MYH10-specific contributions not separated from MYH9 in the same study; single lab\",\n      \"pmids\": [\"37891404\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"CFAP57 interacts with MYH10 in sperm, as identified by immunoprecipitation-mass spectrometry. MYH10 localizes to the sperm flagella (confirmed by immunofluorescence and immunoelectron microscopy). In CFAP57 mutant sperm, MYH10 is mislocalized to the mid-piece region and absent from the principal and end pieces, causing downstream mislocalization of IFT88 and defective flagellar assembly (MMAF phenotype).\",\n      \"method\": \"Immunoprecipitation-mass spectrometry (IP-MS) identifying MYH10 as CFAP57 binding partner; immunofluorescence and immunoelectron microscopy of MYH10 and IFT88 localization in CFAP57 mutant sperm; CRISPR-Cas9 Cfap57 knockout mouse model\",\n      \"journal\": \"Human genomics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — IP-MS binding, ultrastructural localization by immunoelectron microscopy, and CRISPR KO functional model with defined mislocalization phenotype; single lab but orthogonal methods\",\n      \"pmids\": [\"41466333\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"LncRNA BlncAD1 binds MYH10 protein (identified by RNA pull-down) and protects MYH10 from ubiquitin-mediated degradation, thereby enhancing MYH10 protein stability and promoting bovine adipogenesis.\",\n      \"method\": \"RNA pull-down identifying MYH10 as BlncAD1 binding protein; BlncAD1 knockdown/overexpression with MYH10 ubiquitination measurement by Western blot\",\n      \"journal\": \"Journal of agricultural and food chemistry\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — RNA pull-down and ubiquitination assay, single lab, bovine model; mechanistic link between lncRNA binding and ubiquitination protection not fully established at molecular level\",\n      \"pmids\": [\"38661523\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"In zebrafish, myh10 expression requires myh9b: myh9b null mutants show reduced myh10 expression, while myh10 null mutants show reduced myh9b expression, establishing reciprocal transcriptional or post-transcriptional regulatory interactions between myh9b and myh10 during development. Double myh9a/myh10 or myh9b/myh10 mutants display more severe phenotypes than single mutants at earlier time points, indicating tissue-specific genetic redundancy.\",\n      \"method\": \"CRISPR-Cas9 null mutants of myh9a, myh9b, and myh10 in zebrafish; qRT-PCR and protein analyses of expression levels in mutant backgrounds; double mutant epistasis analysis\",\n      \"journal\": \"G3 (Bethesda, Md.)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean null mutants with genetic epistasis and protein analyses, zebrafish ortholog study, single lab\",\n      \"pmids\": [\"39503257\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"TAL-specific conditional knockout of Myh9 and Myh10 impairs NKCC2 expression and trafficking in thick ascending limb cells, causing progressive kidney disease. Loss of TAL NM2 function triggers a compensatory mechanism involving sex-specific upregulation of NCC in the distal nephron (males) and ENaC in medullary collecting ducts (both sexes), demonstrating a cell-autonomous role for MYH9/MYH10 in maintaining apical NKCC2 expression.\",\n      \"method\": \"TAL-specific conditional double knockout mouse model; histology; immunofluorescence for NKCC2, ENaC, NCC; ER stress markers; blood urea nitrogen and creatinine measurements; sex-stratified analysis\",\n      \"journal\": \"Function (Oxford, England)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — cell-type-specific conditional KO with defined molecular cargo (NKCC2), multiple nephron-segment readouts confirming cell-autonomous trafficking function; replicates and extends prior work (PMID:33001861)\",\n      \"pmids\": [\"39500539\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Tail-domain variants of MYH10 found in patients with ocular coloboma and ptosis cause mislocalization of the MYH10 protein and abnormal actin networks in patient fibroblasts, demonstrating that the tail domain is required for proper subcellular localization and maintenance of normal actin cytoskeletal architecture.\",\n      \"method\": \"Exome/genome sequencing identifying tail-domain variants; immunofluorescence of MYH10 localization and actin networks in patient vs. control fibroblasts; zebrafish morpholino/mutant model for eye and muscle phenotypes\",\n      \"journal\": \"European journal of human genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — direct localization experiment in patient fibroblasts with actin network readout and in vivo zebrafish validation; single lab, limited mechanistic depth\",\n      \"pmids\": [\"40044823\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"MYH10 (non-muscle myosin IIB heavy chain) functions as an actin-based motor that generates actomyosin contractility required for cytokinesis, cell migration, EMT, and cytoskeletal remodeling; its tail domain mediates filament assembly and subcellular localization, its motor activity is essential for disassembling actomyosin cross-links during morphogenetic events (with motor-dead mutants acting dominantly by prolonging actin cross-linking), and it participates in specific cargo trafficking pathways (UMOD/NKCC2 in renal epithelium; GLUT4 in adipocytes; IFT88 and centriole positioning during ciliogenesis), while also forming functional complexes with MYH9, LAMC2, ESCRT-III, and USP45 to regulate ER-mitochondria contacts, autophagosome closure, and Snail deubiquitination, with its transcription directly repressed by GATA1 during megakaryopoiesis via intronic regulatory elements.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"MYH10 (non-muscle myosin IIB heavy chain) is an actin-based motor that generates and remodels actomyosin contractility to drive cell division, migration, epithelial-mesenchymal transition, and cytoskeletal architecture across developmental and disease contexts [#0, #4, #6]. Its motor activity is required not merely to contract but to disassemble actomyosin cross-links: a motor-dead knock-in mutant expressed at wild-type levels acts dominantly by prolonging actin cross-linking, disrupting body wall closure, midline fusion, and outflow tract myocardialization—phenotypes absent in null or hypomorphic animals [#0]. During mouse preimplantation development MYH10 provides contractility for cytokinesis that is redundant with the dominant paralog MYH9 [#6], and the two heavy chains co-regulate one another's expression and act redundantly in tissue-specific contexts [#16]. The tail domain controls subcellular localization and actin network maintenance; patient tail-domain variants mislocalize the protein and disorganize actin in fibroblasts [#18]. MYH10 partners directly with MYH9 to recruit the deubiquitinase USP45, which stabilizes Snail to promote EMT, invasion, and chemoresistance [#10], and both heavy chains complex with LAMC2 to regulate ER-mitochondria contacts and oxidative stress [#13]. MYH10 mediates polarized intracellular trafficking and organelle positioning: it is required with MYH9 for apical localization and transport of UMOD and NKCC2 in renal thick ascending limb epithelium [#5, #17], for GLUT4 translocation and adipogenesis [#8], for centriole migration and IFT88 recruitment during ciliogenesis with downstream Hedgehog signaling [#1, #9], and for sperm flagellar assembly via interaction with CFAP57 [#14]. It also recruits ESCRT-III and autophagy receptors to drive autophagosome closure and mitophagy [#11]. MYH10 transcription is directly repressed by GATA1 during megakaryopoiesis through binding sites in the 3' UTR and intron 8, and pathogenic GATA1 variants elevate MYH10 with associated megakaryocyte polyploidization defects [#7]. Patient variants link MYH10 to neurodevelopmental disorders and to ocular coloboma with ptosis [#9, #18].\",\n  \"teleology\": [\n    {\n      \"year\": 2014,\n      \"claim\": \"Established that MYH10 motor activity functions to disassemble actomyosin cross-links rather than only to contract, resolving why a motor-dead allele is more damaging than gene loss.\",\n      \"evidence\": \"Knock-in motor-deficient point mutant mice expressed at wild-type levels, compared to null and hypomorphic models with cardiac/body wall readouts\",\n      \"pmids\": [\"24825879\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Does not define the molecular partners cross-linked at affected tissues\", \"Mechanism of cross-link turnover at the filament level not resolved\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Placed MYH10 upstream of centriole apical migration and ciliogenesis, linking it to cortical actin and IFT88 recruitment.\",\n      \"evidence\": \"siRNA knockdown in RPE1 cells with F-actin, EZRIN, centriole position, and IFT88 imaging\",\n      \"pmids\": [\"25881509\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct biochemical interaction with IFT88 not shown\", \"Single cell line, single lab\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Demonstrated a developmental requirement for MYH10 in epicardial EMT and EPDC migration during coronary vessel formation.\",\n      \"evidence\": \"ENU splice-donor mutant mice with complementation, EMT and migration assays\",\n      \"pmids\": [\"29084269\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Downstream signaling driving EMT not defined\", \"Does not separate motor versus structural contributions\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Extended MYH10 function to mesenchymal ECM remodeling, showing its loss alters Thrombospondin, MMP activity, and matrix deposition in the lung.\",\n      \"evidence\": \"Conditional mesenchymal KO mice plus cultured mutant fibroblasts with omics and ECM assays\",\n      \"pmids\": [\"30389913\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism linking myosin activity to Thrombospondin/MMP regulation unresolved\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Linked MYH10 to glioma migration/invasion and placed it upstream of EMT markers and Wnt/β-catenin signaling.\",\n      \"evidence\": \"siRNA/plasmid silencing in three glioma lines with migration assays, Western blot, qRT-PCR\",\n      \"pmids\": [\"30552850\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No direct physical interaction with Wnt components shown\", \"Pathway placement correlative\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Identified a trafficking role for MYH9/MYH10 in renal epithelium, required for UMOD localization and apical NKCC2 placement.\",\n      \"evidence\": \"Inducible conditional Myh9/Myh10 KO mice with UMOD/NKCC2 localization and ER stress markers\",\n      \"pmids\": [\"33001861\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"MYH10-specific contribution not separated from MYH9\", \"Step in the secretory/trafficking pathway not pinpointed\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Defined the genetic hierarchy of non-muscle myosin II in early embryogenesis, showing MYH10 provides cytokinetic contractility redundant with the dominant MYH9.\",\n      \"evidence\": \"Single and double maternal-zygotic Myh9/Myh10 mutants with multiscale imaging\",\n      \"pmids\": [\"33871354\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular basis of the MYH9 dominance over MYH10 not defined\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Showed MYH10 transcription is directly repressed by GATA1 during megakaryopoiesis via intron 8 and 3' UTR sites, connecting MYH10 dysregulation to polyploidization defects.\",\n      \"evidence\": \"Anti-GATA1 ChIP-seq, luciferase reporters with mutant GATA1, patient platelet measurements\",\n      \"pmids\": [\"34060193\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Causal contribution of elevated MYH10 to the polyploidization defect is associative\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Established a MYH10-GLUT4 trafficking complex required for insulin-responsive GLUT4 translocation and adipogenesis.\",\n      \"evidence\": \"siRNA KD in preadipocytes, MYH10-GLUT4 Co-IP, PKCζ interaction, co-culture rescue\",\n      \"pmids\": [\"35216482\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab\", \"Direct versus indirect nature of MYH10-GLUT4 binding not fully resolved\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Connected MYH10 to ciliary length control and Hedgehog signaling, and showed neurodevelopmental-disorder patient variants act dominant-negatively on cilia.\",\n      \"evidence\": \"CRISPR KO cells, ciliary length and Hedgehog reporter assays, patient-variant overexpression\",\n      \"pmids\": [\"35980381\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism linking MYH10 to ciliary length not defined\", \"Single lab\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Defined the MYH10-MYH9-USP45-Snail axis, mechanistically linking the myosin heavy-chain complex to Snail deubiquitination and EMT/chemoresistance.\",\n      \"evidence\": \"Reciprocal Co-IP, GST pull-down, domain mapping, in vitro and in vivo functional studies in ovarian cancer\",\n      \"pmids\": [\"36929633\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How the myosin complex recruits USP45 structurally not resolved\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Implicated MYH10 in autophagosome closure and mitophagy via ESCRT-III and autophagy receptor recruitment, with knockdown rescuing FTD-associated neurodegeneration.\",\n      \"evidence\": \"Co-IP with ESCRT-III/autophagy receptors, Drosophila and iPSC-neuron rescue, autophagy induction assays\",\n      \"pmids\": [\"36849436\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"ESCRT-III recruitment mechanism inferred from correlative data\", \"Direct binding interface not mapped\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Demonstrated MYH10 can rescue actomyosin disorganization in arrhythmogenic cardiomyopathy from PKP2 deletion, with a dominant-negative mutant phenocopying disease.\",\n      \"evidence\": \"MYH10 overexpression and dominant-negative expression in mutant cardiomyocytes, 4-HAP pharmacology, cardiac function measures\",\n      \"pmids\": [\"37833253\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct biochemical link between PKP2 and MYH10/actomyosin not established\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Identified a LAMC2-MYH9/MYH10 complex regulating ER-mitochondria contacts, ROS, and apoptosis in cancer.\",\n      \"evidence\": \"Co-IP, LAMC2 overexpression/KD, mitochondrial/ER contact and ROS measures, in vivo tumor assay\",\n      \"pmids\": [\"37891404\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"MYH10-specific contribution not separated from MYH9\", \"Single lab\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Identified an lncRNA (BlncAD1) that binds and stabilizes MYH10 protein against ubiquitin-mediated degradation to promote adipogenesis.\",\n      \"evidence\": \"RNA pull-down and ubiquitination Western blot in bovine model\",\n      \"pmids\": [\"38661523\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Molecular link between lncRNA binding and ubiquitination protection not established\", \"Single lab, bovine model only\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Established a flagellar role: CFAP57 binds MYH10 and is required for its correct flagellar localization, with downstream IFT88 mislocalization and MMAF when lost.\",\n      \"evidence\": \"IP-MS, immunofluorescence/immunoEM, CRISPR Cfap57 KO mouse\",\n      \"pmids\": [\"41466333\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether MYH10 motor activity is required for flagellar assembly not tested\", \"Single lab\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Confirmed and extended the cell-autonomous renal trafficking role of MYH9/MYH10 in maintaining apical NKCC2 and revealed compensatory transporter upregulation.\",\n      \"evidence\": \"TAL-specific conditional double KO mouse with segment-specific transporter immunofluorescence and renal function measures\",\n      \"pmids\": [\"39500539\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"MYH10-specific role not isolated from MYH9\", \"Mechanism of compensatory NCC/ENaC induction not defined\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Showed MYH9b and MYH10 reciprocally regulate one another's expression and act with tissue-specific redundancy in vertebrate development.\",\n      \"evidence\": \"CRISPR null mutants and double-mutant epistasis in zebrafish with expression analyses\",\n      \"pmids\": [\"39503257\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether regulation is transcriptional or post-transcriptional unresolved\", \"Single lab, ortholog study\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Demonstrated the tail domain is essential for MYH10 subcellular localization and actin network integrity, linking tail-domain variants to ocular coloboma and ptosis.\",\n      \"evidence\": \"Patient sequencing, fibroblast localization/actin imaging, zebrafish model\",\n      \"pmids\": [\"40044823\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism by which tail variants cause mislocalization not resolved\", \"Single lab\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How MYH10 selectively engages distinct cargo and organelle systems (GLUT4, UMOD/NKCC2, IFT88, ESCRT-III) versus its bulk contractile role, and the structural basis of its many partner complexes, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural model of partner-binding interfaces\", \"MYH10-specific versus MYH9-redundant contributions rarely separated\", \"Regulation of cargo-specific recruitment unknown\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003774\", \"supporting_discovery_ids\": [0, 6, 12]},\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [0, 18, 12]},\n      {\"term_id\": \"GO:0140657\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [0, 18, 12]},\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [1, 9, 14]},\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [5, 17]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [6]},\n      {\"term_id\": \"R-HSA-9612973\", \"supporting_discovery_ids\": [11]},\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [5, 8, 17]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [0, 4, 6]},\n      {\"term_id\": \"R-HSA-1474244\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"complexes\": [\n      \"MYH9-MYH10 non-muscle myosin II complex\",\n      \"ESCRT-III (recruited)\"\n    ],\n    \"partners\": [\n      \"MYH9\",\n      \"USP45\",\n      \"LAMC2\",\n      \"GLUT4\",\n      \"PKCζ\",\n      \"CFAP57\",\n      \"IFT88\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":9,"faith_total":9,"faith_pct":100.0}}