{"gene":"MYO18B","run_date":"2026-06-10T05:19:52","timeline":{"discoveries":[{"year":2002,"finding":"Restoration of MYO18B expression in lung carcinoma cells suppressed anchorage-independent growth, establishing a functional tumor-suppressive role for MYO18B.","method":"Re-expression (restoration) of MYO18B in lung cancer cell lines followed by anchorage-independent growth assay","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean gain-of-function with defined cellular phenotype, replicated across ovarian, colorectal, and mesothelioma studies","pmids":["12209013"],"is_preprint":false},{"year":2003,"finding":"MYO18B protein is located in the cytoplasm of undifferentiated myoblasts; upon differentiation into myotubes, a fraction accumulates in a subset of myonuclei. In cardiomyocytes and adult muscle sections, nuclear localization was confirmed. In the cytoplasm it shows a punctate staining and a partial sarcomeric pattern alternating with alpha-actinin-2 in cardiomyocytes.","method":"Immunolocalization by immunofluorescence in skeletal muscle cells, primary cardiomyocytes, and adult muscle sections","journal":"Journal of molecular biology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — immunofluorescence localization replicated in multiple cell types and confirmed by independent studies, but no direct functional consequence of nuclear localization established","pmids":["12547197"],"is_preprint":false},{"year":2004,"finding":"Histone H3 and H4 deacetylation at the MYO18B promoter region correlates with reduced MYO18B expression in lung cancer cells; TSA-mediated restoration of histone acetylation restores MYO18B expression, demonstrating that histone deacetylation is a mechanism for MYO18B epigenetic silencing.","method":"Chromatin immunoprecipitation (ChIP) assay for histone H3/H4 acetylation at MYO18B promoter; TSA treatment with quantitative expression analysis in 8 lung cancer cell lines","journal":"Genes, chromosomes & cancer","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP with functional restoration, single lab but two orthogonal methods (ChIP + expression rescue)","pmids":["15101048"],"is_preprint":false},{"year":2005,"finding":"Restoration of MYO18B expression in colorectal cancer cell lines HT29 and DLD-1 suppressed anchorage-independent growth but did not affect in vitro growth rate, indicating a specific role in anchorage-independent proliferation.","method":"Re-expression of MYO18B in colorectal cancer cell lines with anchorage-independent growth assay","journal":"Genes, chromosomes & cancer","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — gain-of-function with defined cellular phenotype, replicates lung cancer findings in independent cancer type","pmids":["15751041"],"is_preprint":false},{"year":2006,"finding":"MYO18B interacts with the 19S proteasomal regulatory subunit Sug1 via its C-terminal tail region, and MYO18B is polyubiquitinated in vivo and degraded via the ubiquitin-proteasome pathway; knockdown of Sug1 or proteasome inhibition causes MYO18B upregulation.","method":"Yeast two-hybrid screen, GST pull-down, co-immunoprecipitation, immunocytochemistry, proteasome inhibitor treatment, siRNA-mediated Sug1 knockdown, in vivo polyubiquitination assay","journal":"Biochemical and biophysical research communications","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — multiple orthogonal methods (Y2H, GST pulldown, Co-IP, ubiquitination assay, siRNA rescue) in a single study establishing mechanism","pmids":["16499872"],"is_preprint":false},{"year":2006,"finding":"Restored MYO18B expression in malignant pleural mesothelioma cells inhibited anchorage-independent growth, cell motility in vitro, and ectopic/orthotopic tumor growth in SCID mice, associated with increased apoptosis.","method":"MYO18B transfection into EHMES-10 MPM cells; anchorage-independent growth assay, motility assay, subcutaneous and orthotopic xenograft in SCID mice","journal":"Oncology research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — gain-of-function with in vitro and in vivo phenotypic readouts, single lab","pmids":["17294804"],"is_preprint":false},{"year":2007,"finding":"MYO18B interacts with HOMER2 (a Homer/Vesl family protein); the two proteins co-localize at membrane protrusions and stress fibers (F-actin-rich structures), and HOMER2 enhances MYO18B-dependent suppression of anchorage-independent growth.","method":"Yeast two-hybrid screen for MYO18B-interacting proteins; co-localization by immunofluorescence; functional anchorage-independent growth assay with co-expression","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Y2H plus co-localization plus functional assay in single lab","pmids":["17386922"],"is_preprint":false},{"year":2008,"finding":"Myo18B is localized to Z-lines of myofibrils in striated muscle (not A-bands as for conventional myosins). The N-terminal unique domain (not the motor domain or coiled-coil tail) is critical for localization to F-actin in myocytes. Myo18B expression is induced by myogenic differentiation via binding of MEF2 to its promoter. Myo18B knockout in mice is embryonic lethal with disruption of myofibrillar structures in cardiac myocytes at E10.5.","method":"Immunofluorescence/localization studies in myocytes; domain deletion/mutation analysis for F-actin localization; promoter binding assay (MEF2); Myo18B knockout mouse generation with cardiac histology at E10.5","journal":"Genes to cells : devoted to molecular & cellular mechanisms","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — KO mouse with defined lethal cardiac phenotype, domain mutagenesis establishing N-terminal domain requirement, promoter binding assay, multiple orthogonal methods","pmids":["18761673"],"is_preprint":false},{"year":2015,"finding":"Homozygous truncating mutation in MYO18B (nonsense mutation in last exon) causes loss of full-length protein (confirmed by Western blot and immunostaining) and results in severe nemaline myopathy with cardiomyopathy in humans.","method":"Exome sequencing, Western blot, immunostaining in patient muscle biopsy","journal":"Journal of neuromuscular diseases","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function with defined cellular/histological phenotype, protein absence confirmed by two methods, single case","pmids":["27858739"],"is_preprint":false},{"year":2015,"finding":"Truncating mutation in MYO18B leads to near-complete loss of transcript (nonsense-mediated decay) and is associated with a syndrome of Klippel-Feil anomaly, myopathy, and abnormal myosin filaments on electron microscopy, establishing MYO18B as required for normal myosin filament structure in humans.","method":"Autozygome/exome analysis; RT-PCR for transcript levels; electron microscopy of muscle biopsy","journal":"Journal of medical genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function with ultrastructural phenotype (EM), two independent families, single lab","pmids":["25748484"],"is_preprint":false},{"year":2016,"finding":"In zebrafish, loss of myo18b (frozen/fro mutant) causes sarcomeric assembly failure specifically in fast-twitch myocytes, with disorganized accumulation of actin, myosin, and α-actinin and complete loss of myofibrillar organization; myo18b transcription is restricted to fast-twitch myocytes.","method":"Meiotic mapping and positional cloning of zebrafish frozen mutant; loss-of-birefringency assay; immunofluorescence for sarcomeric proteins; in situ hybridization for expression pattern","journal":"Genetics","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic loss-of-function in zebrafish with defined structural phenotype, confirmed by multiple labs studying Myo18B in muscle","pmids":["27879346"],"is_preprint":false},{"year":2017,"finding":"In zebrafish myo18b null mutants, sarcomeres completely fail to assemble despite scattered thin and thick filaments being present; partial loss-of-function results in sarcomeres with misaligned filaments. This establishes Myo18b as essential for coordinating integration of preformed thick and thin filaments into sarcomere structure.","method":"Zebrafish myo18b null and hypomorphic mutant analysis; electron microscopy and immunofluorescence for sarcomeric organization","journal":"Human molecular genetics","confidence":"High","confidence_rationale":"Tier 2 / Strong — allelic series (null vs partial loss-of-function) with ultrastructural readout, replicates and extends findings from independent zebrafish study","pmids":["28104788"],"is_preprint":false},{"year":2018,"finding":"MYO18B knockdown in HepG2 hepatocellular carcinoma cells inhibits proliferation, migration, and invasion, and suppresses phosphorylation of PI3K, AKT, mTOR, and P70S6K, placing MYO18B upstream of the PI3K/AKT/mTOR pathway in HCC cells.","method":"siRNA knockdown of MYO18B; CCK-8 and colony formation assays; wound healing and transwell invasion assays; Western blot for PI3K/AKT/mTOR pathway phosphorylation","journal":"Diagnostic pathology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, knockdown phenotype with pathway readout but no direct binding or epistasis experiment establishing mechanism","pmids":["30390677"],"is_preprint":false},{"year":2025,"finding":"MYO18B, functioning as an actin crosslinker, is required for focal adhesion maturation, which in turn facilitates lysosomal exocytosis and release of paucimannosidic proteins to the extracellular milieu. PIEZO1 at focal adhesions imports Ca2+ for lysosome-plasma membrane fusion.","method":"Genome-wide knockout screen; focal adhesion maturation assays; lysosomal exocytosis assays; glycoproteomic analysis of paucimannosidic proteins","journal":"The Journal of cell biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genome-wide KO screen plus mechanistic follow-up establishing pathway position, single lab","pmids":["39751400"],"is_preprint":false}],"current_model":"MYO18B is an unconventional class XVIII myosin expressed predominantly in striated muscle that localizes to Z-lines/sarcomeres via its N-terminal domain (not motor domain), is essential for sarcomere assembly by coordinating integration of thick and thin filaments, is regulated transcriptionally by MEF2 and epigenetically by histone deacetylation, is degraded via the ubiquitin-proteasome pathway through interaction with the Sug1/19S subunit, and in non-muscle contexts acts as an actin crosslinker required for focal adhesion maturation and lysosomal exocytosis; in cancer cells its re-expression suppresses anchorage-independent growth, an activity enhanced by its binding partner HOMER2."},"narrative":{"mechanistic_narrative":"MYO18B is an unconventional class XVIII myosin expressed predominantly in striated muscle, where it is essential for the assembly and integrity of the sarcomere [PMID:18761673, PMID:28104788]. It localizes to Z-lines of myofibrils rather than the A-bands occupied by conventional myosins, and its targeting to F-actin in myocytes depends on its N-terminal unique domain rather than the motor domain or coiled-coil tail [PMID:18761673]. Functionally, MYO18B coordinates the integration of preformed thick and thin filaments into ordered sarcomeres: in its complete absence sarcomeres fail to assemble despite the presence of scattered actin and myosin filaments, and partial loss yields misaligned filaments [PMID:28104788, PMID:27879346]. Loss of MYO18B is embryonic lethal in mice with disrupted cardiac myofibrils [PMID:18761673], and in humans truncating mutations cause nemaline myopathy with cardiomyopathy and a Klippel-Feil/myopathy syndrome with abnormal myosin filaments [PMID:27858739, PMID:25748484]. Its muscle expression is driven transcriptionally by MEF2 binding to its promoter during myogenic differentiation [PMID:18761673], while protein levels are controlled by polyubiquitination and proteasomal degradation through interaction of its C-terminal tail with the 19S subunit Sug1 [PMID:16499872]. Beyond muscle, MYO18B acts as an actin crosslinker required for focal adhesion maturation, which enables PIEZO1-dependent lysosomal exocytosis [PMID:39751400], and its re-expression suppresses anchorage-independent growth across multiple cancer cell types, an activity enhanced by its binding partner HOMER2 [PMID:12209013, PMID:17386922].","teleology":[{"year":2002,"claim":"Whether MYO18B had a cell-autonomous role in malignancy was unknown; restoring its expression directly tested a tumor-suppressive function.","evidence":"Re-expression in lung carcinoma cells with anchorage-independent growth assay","pmids":["12209013"],"confidence":"Medium","gaps":["Molecular basis of growth suppression not defined","No link to a specific signaling pathway in this study"]},{"year":2003,"claim":"Establishing where the protein resides addressed which cellular compartment its function operates in, revealing both nuclear and partial sarcomeric distributions.","evidence":"Immunofluorescence in myoblasts, myotubes, cardiomyocytes, and adult muscle sections","pmids":["12547197"],"confidence":"Medium","gaps":["Functional consequence of nuclear accumulation not established","Sarcomeric sub-localization not mapped to a band"]},{"year":2004,"claim":"The mechanism of MYO18B silencing in cancer was unknown; promoter chromatin analysis showed epigenetic repression underlies its loss.","evidence":"ChIP for H3/H4 acetylation at the MYO18B promoter and TSA-mediated expression rescue in lung cancer lines","pmids":["15101048"],"confidence":"Medium","gaps":["Does not identify the responsible HDAC or recruiting factor","Relationship to promoter methylation not addressed"]},{"year":2005,"claim":"Whether the tumor-suppressive activity generalized beyond lung cancer was tested by re-expression in colorectal lines, refining the phenotype to anchorage-independent proliferation specifically.","evidence":"Re-expression in HT29 and DLD-1 with anchorage-independent versus in vitro growth assays","pmids":["15751041"],"confidence":"Medium","gaps":["Effector mechanism of anchorage-dependent suppression unknown"]},{"year":2006,"claim":"How MYO18B protein levels are controlled was unresolved; identifying Sug1 binding established proteasomal turnover as the regulatory mechanism.","evidence":"Yeast two-hybrid, GST pull-down, Co-IP, in vivo polyubiquitination, proteasome inhibition, and Sug1 siRNA rescue","pmids":["16499872"],"confidence":"High","gaps":["E3 ligase responsible for ubiquitination not identified","Physiological trigger for degradation unknown"]},{"year":2006,"claim":"The in vivo relevance of growth suppression was tested in mesothelioma, extending the phenotype to motility and tumor formation in animals.","evidence":"MYO18B transfection in EHMES-10 cells with motility assays and SCID mouse xenografts","pmids":["17294804"],"confidence":"Medium","gaps":["Mechanism of apoptosis induction not defined","No molecular partner implicated in this context"]},{"year":2007,"claim":"To find effectors of the suppressive activity, an interaction screen identified HOMER2 and placed MYO18B at F-actin structures where the partner enhances its function.","evidence":"Yeast two-hybrid screen, co-localization at protrusions/stress fibers, co-expression growth assay","pmids":["17386922"],"confidence":"Medium","gaps":["Structural basis of the HOMER2 interaction unknown","How HOMER2 potentiates suppression mechanistically unclear"]},{"year":2008,"claim":"The physiological function and localization determinants in muscle were unresolved; combined localization, domain mutagenesis, promoter, and knockout work established a Z-line role driven by MEF2 and an N-terminal targeting domain.","evidence":"Immunofluorescence, domain deletion analysis, MEF2 promoter binding, and embryonic-lethal knockout mouse with cardiac histology","pmids":["18761673"],"confidence":"High","gaps":["Direct binding partners at the Z-line not identified","Motor/ATPase activity not characterized"]},{"year":2015,"claim":"Whether MYO18B loss causes human disease was answered by truncating mutations linking it causatively to myopathy and abnormal myosin filaments.","evidence":"Exome/autozygome analysis, Western blot, immunostaining, RT-PCR for NMD, and electron microscopy of patient biopsies","pmids":["27858739","25748484"],"confidence":"Medium","gaps":["Single case / two families limit genotype-phenotype breadth","Molecular step disrupted in filament assembly not resolved in patient tissue"]},{"year":2017,"claim":"The precise step in sarcomerogenesis that MYO18B controls was unknown; zebrafish allelic series showed it coordinates integration of preformed thick and thin filaments rather than their initial synthesis.","evidence":"Zebrafish frozen/null and hypomorphic mutants with birefringence, immunofluorescence, and electron microscopy of sarcomeres","pmids":["27879346","28104788"],"confidence":"High","gaps":["Direct molecular interactions enabling filament alignment not identified","Fiber-type specificity (fast-twitch) mechanism unexplained"]},{"year":2018,"claim":"A signaling context for MYO18B in cancer was probed, linking knockdown to reduced PI3K/AKT/mTOR phosphorylation in hepatocellular carcinoma.","evidence":"siRNA knockdown with proliferation, migration, invasion assays and pathway Western blots in HepG2","pmids":["30390677"],"confidence":"Low","gaps":["No direct binding or epistasis establishing the pathway link","Oncogenic direction conflicts with tumor-suppressor findings and is not reconciled"]},{"year":2025,"claim":"A non-muscle molecular role was defined, showing MYO18B acts as an actin crosslinker required for focal adhesion maturation that enables PIEZO1-driven lysosomal exocytosis.","evidence":"Genome-wide knockout screen with focal adhesion, lysosomal exocytosis, and glycoproteomic assays","pmids":["39751400"],"confidence":"Medium","gaps":["Direct biochemical demonstration of actin crosslinking by MYO18B not shown","Relationship between this role and its muscle function unclear"]},{"year":null,"claim":"How a single N-terminally targeted myosin mechanically coordinates filament integration, and whether its muscle, adhesion, and tumor-suppressive activities share a common biochemical activity, remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["Motor/ATPase activity and structural basis of F-actin engagement uncharacterized","Z-line binding partners that mediate sarcomere assembly unidentified","Reconciliation of tumor-suppressor versus pro-oncogenic reports lacking"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[7,13]}],"localization":[{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[1,7,10]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[1]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[1]}],"pathway":[{"term_id":"R-HSA-397014","term_label":"Muscle contraction","supporting_discovery_ids":[7,11]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[7,10]}],"complexes":[],"partners":["SUG1","HOMER2"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q8IUG5","full_name":"Unconventional myosin-XVIIIb","aliases":[],"length_aa":2567,"mass_kda":285.2,"function":"May be involved in intracellular trafficking of the muscle cell when in the cytoplasm, whereas entering the nucleus, may be involved in the regulation of muscle specific genes. May play a role in the control of tumor development and progression; restored MYO18B expression in lung cancer cells suppresses anchorage-independent growth","subcellular_location":"Cytoplasm; Nucleus; Cytoplasm, myofibril, sarcomere","url":"https://www.uniprot.org/uniprotkb/Q8IUG5/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/MYO18B","classification":"Not Classified","n_dependent_lines":2,"n_total_lines":1208,"dependency_fraction":0.0016556291390728477},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/MYO18B","total_profiled":1310},"omim":[{"mim_id":"620310","title":"CONGENITAL MYOPATHY 20; CMYO20","url":"https://www.omim.org/entry/620310"},{"mim_id":"616549","title":"KLIPPEL-FEIL SYNDROME 4, AUTOSOMAL RECESSIVE, WITH NEMALINE MYOPATHY AND FACIAL DYSMORPHISM; KFS4","url":"https://www.omim.org/entry/616549"},{"mim_id":"607295","title":"MYOSIN XVIIIB; MYO18B","url":"https://www.omim.org/entry/607295"},{"mim_id":"180903","title":"RYANODINE RECEPTOR 3; RYR3","url":"https://www.omim.org/entry/180903"},{"mim_id":"118100","title":"KLIPPEL-FEIL SYNDROME 1, AUTOSOMAL DOMINANT; KFS1","url":"https://www.omim.org/entry/118100"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"},{"location":"Centrosome","reliability":"Supported"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in some","driving_tissues":[{"tissue":"heart muscle","ntpm":114.3},{"tissue":"skeletal muscle","ntpm":251.6},{"tissue":"tongue","ntpm":51.9}],"url":"https://www.proteinatlas.org/search/MYO18B"},"hgnc":{"alias_symbol":["BK125H2.1"],"prev_symbol":[]},"alphafold":{"accession":"Q8IUG5","domains":[{"cath_id":"3.40.850.10","chopping":"567-618_626-883_902-999_1006-1020_1033-1062_1073-1208_1234-1260","consensus_level":"medium","plddt":85.5787,"start":567,"end":1260},{"cath_id":"3.30.70","chopping":"1283-1356","consensus_level":"high","plddt":85.7872,"start":1283,"end":1356},{"cath_id":"1.10.287.1490","chopping":"1884-2047","consensus_level":"medium","plddt":79.8476,"start":1884,"end":2047},{"cath_id":"1.20.5","chopping":"1522-1583","consensus_level":"medium","plddt":74.9418,"start":1522,"end":1583}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8IUG5","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q8IUG5-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q8IUG5-F1-predicted_aligned_error_v6.png","plddt_mean":59.75},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=MYO18B","jax_strain_url":"https://www.jax.org/strain/search?query=MYO18B"},"sequence":{"accession":"Q8IUG5","fasta_url":"https://rest.uniprot.org/uniprotkb/Q8IUG5.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q8IUG5/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8IUG5"}},"corpus_meta":[{"pmid":"12209013","id":"PMC_12209013","title":"MYO18B, a candidate tumor suppressor gene at chromosome 22q12.1, deleted, mutated, and methylated in human lung cancer.","date":"2002","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/12209013","citation_count":85,"is_preprint":false},{"pmid":"27858739","id":"PMC_27858739","title":"A Premature Stop Codon in MYO18B is Associated with Severe Nemaline Myopathy with Cardiomyopathy.","date":"2015","source":"Journal of neuromuscular diseases","url":"https://pubmed.ncbi.nlm.nih.gov/27858739","citation_count":75,"is_preprint":false},{"pmid":"25748484","id":"PMC_25748484","title":"A novel syndrome of Klippel-Feil anomaly, myopathy, and characteristic facies is linked to a null mutation in MYO18B.","date":"2015","source":"Journal of medical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/25748484","citation_count":63,"is_preprint":false},{"pmid":"12547197","id":"PMC_12547197","title":"Human MYO18B, a novel unconventional myosin heavy chain expressed in striated muscles moves into the myonuclei upon differentiation.","date":"2003","source":"Journal of molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/12547197","citation_count":61,"is_preprint":false},{"pmid":"18761673","id":"PMC_18761673","title":"Deficiency of Myo18B in mice results in embryonic lethality with cardiac myofibrillar aberrations.","date":"2008","source":"Genes to cells : devoted to molecular & cellular mechanisms","url":"https://pubmed.ncbi.nlm.nih.gov/18761673","citation_count":52,"is_preprint":false},{"pmid":"15305387","id":"PMC_15305387","title":"Reduced expression of MYO18B, a candidate tumor-suppressor gene on chromosome arm 22q, in ovarian cancer.","date":"2004","source":"International journal of cancer","url":"https://pubmed.ncbi.nlm.nih.gov/15305387","citation_count":45,"is_preprint":false},{"pmid":"15751041","id":"PMC_15751041","title":"Genetic and epigenetic alterations of the candidate tumor-suppressor gene MYO18B, on chromosome arm 22q, in colorectal cancer.","date":"2005","source":"Genes, chromosomes & cancer","url":"https://pubmed.ncbi.nlm.nih.gov/15751041","citation_count":35,"is_preprint":false},{"pmid":"28104788","id":"PMC_28104788","title":"Myo18b is essential for sarcomere assembly in fast skeletal muscle.","date":"2017","source":"Human molecular genetics","url":"https://pubmed.ncbi.nlm.nih.gov/28104788","citation_count":32,"is_preprint":false},{"pmid":"17386922","id":"PMC_17386922","title":"HOMER2 binds MYO18B and enhances its activity to suppress anchorage independent growth.","date":"2007","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/17386922","citation_count":26,"is_preprint":false},{"pmid":"15101048","id":"PMC_15101048","title":"Correlation between histone acetylation and expression of the MYO18B gene in human lung cancer cells.","date":"2004","source":"Genes, chromosomes & cancer","url":"https://pubmed.ncbi.nlm.nih.gov/15101048","citation_count":25,"is_preprint":false},{"pmid":"27879346","id":"PMC_27879346","title":"A Zebrafish Model for a Human Myopathy Associated with Mutation of the Unconventional Myosin MYO18B.","date":"2016","source":"Genetics","url":"https://pubmed.ncbi.nlm.nih.gov/27879346","citation_count":23,"is_preprint":false},{"pmid":"30390677","id":"PMC_30390677","title":"MYO18B promotes hepatocellular carcinoma progression by activating PI3K/AKT/mTOR signaling pathway.","date":"2018","source":"Diagnostic pathology","url":"https://pubmed.ncbi.nlm.nih.gov/30390677","citation_count":22,"is_preprint":false},{"pmid":"32704163","id":"PMC_32704163","title":"Regulation of MYO18B mRNA by a network of C19MC miRNA-520G, IFN-γ, CEBPB, p53 and bFGF in hepatocellular carcinoma.","date":"2020","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/32704163","citation_count":15,"is_preprint":false},{"pmid":"31661144","id":"PMC_31661144","title":"miR‑760 regulates skeletal muscle proliferation in rheumatoid arthritis by targeting Myo18b.","date":"2019","source":"Molecular medicine reports","url":"https://pubmed.ncbi.nlm.nih.gov/31661144","citation_count":15,"is_preprint":false},{"pmid":"17294804","id":"PMC_17294804","title":"Restored expression of the MYO18B gene suppresses orthotopic growth and the production of bloody pleural effusion by human malignant pleural mesothelioma cells in SCID mice.","date":"2006","source":"Oncology research","url":"https://pubmed.ncbi.nlm.nih.gov/17294804","citation_count":12,"is_preprint":false},{"pmid":"16499872","id":"PMC_16499872","title":"MYO18B interacts with the proteasomal subunit Sug1 and is degraded by the ubiquitin-proteasome pathway.","date":"2006","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/16499872","citation_count":11,"is_preprint":false},{"pmid":"39751400","id":"PMC_39751400","title":"MYO18B promotes lysosomal exocytosis by facilitating focal adhesion maturation.","date":"2025","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/39751400","citation_count":9,"is_preprint":false},{"pmid":"38784114","id":"PMC_38784114","title":"Are the class 18 myosins Myo18A and Myo18B specialist sarcomeric proteins?","date":"2024","source":"Frontiers in physiology","url":"https://pubmed.ncbi.nlm.nih.gov/38784114","citation_count":4,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2024.08.02.24310874","title":"Genetics of Cardiac Aging Implicate Organ-Specific Variation","date":"2024-08-06","source":"bioRxiv","url":"https://doi.org/10.1101/2024.08.02.24310874","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":11059,"output_tokens":3423,"usd":0.042261,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10993,"output_tokens":3581,"usd":0.072245,"stage2_stop_reason":"end_turn"},"total_usd":0.114506,"stage1_batch_id":"msgbatch_013a8chtv3AWyTqv4z4sEF4C","stage2_batch_id":"msgbatch_01AHsuW63vinsvuTgzmQ3n62","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2002,\n      \"finding\": \"Restoration of MYO18B expression in lung carcinoma cells suppressed anchorage-independent growth, establishing a functional tumor-suppressive role for MYO18B.\",\n      \"method\": \"Re-expression (restoration) of MYO18B in lung cancer cell lines followed by anchorage-independent growth assay\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean gain-of-function with defined cellular phenotype, replicated across ovarian, colorectal, and mesothelioma studies\",\n      \"pmids\": [\"12209013\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"MYO18B protein is located in the cytoplasm of undifferentiated myoblasts; upon differentiation into myotubes, a fraction accumulates in a subset of myonuclei. In cardiomyocytes and adult muscle sections, nuclear localization was confirmed. In the cytoplasm it shows a punctate staining and a partial sarcomeric pattern alternating with alpha-actinin-2 in cardiomyocytes.\",\n      \"method\": \"Immunolocalization by immunofluorescence in skeletal muscle cells, primary cardiomyocytes, and adult muscle sections\",\n      \"journal\": \"Journal of molecular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — immunofluorescence localization replicated in multiple cell types and confirmed by independent studies, but no direct functional consequence of nuclear localization established\",\n      \"pmids\": [\"12547197\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"Histone H3 and H4 deacetylation at the MYO18B promoter region correlates with reduced MYO18B expression in lung cancer cells; TSA-mediated restoration of histone acetylation restores MYO18B expression, demonstrating that histone deacetylation is a mechanism for MYO18B epigenetic silencing.\",\n      \"method\": \"Chromatin immunoprecipitation (ChIP) assay for histone H3/H4 acetylation at MYO18B promoter; TSA treatment with quantitative expression analysis in 8 lung cancer cell lines\",\n      \"journal\": \"Genes, chromosomes & cancer\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP with functional restoration, single lab but two orthogonal methods (ChIP + expression rescue)\",\n      \"pmids\": [\"15101048\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"Restoration of MYO18B expression in colorectal cancer cell lines HT29 and DLD-1 suppressed anchorage-independent growth but did not affect in vitro growth rate, indicating a specific role in anchorage-independent proliferation.\",\n      \"method\": \"Re-expression of MYO18B in colorectal cancer cell lines with anchorage-independent growth assay\",\n      \"journal\": \"Genes, chromosomes & cancer\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — gain-of-function with defined cellular phenotype, replicates lung cancer findings in independent cancer type\",\n      \"pmids\": [\"15751041\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"MYO18B interacts with the 19S proteasomal regulatory subunit Sug1 via its C-terminal tail region, and MYO18B is polyubiquitinated in vivo and degraded via the ubiquitin-proteasome pathway; knockdown of Sug1 or proteasome inhibition causes MYO18B upregulation.\",\n      \"method\": \"Yeast two-hybrid screen, GST pull-down, co-immunoprecipitation, immunocytochemistry, proteasome inhibitor treatment, siRNA-mediated Sug1 knockdown, in vivo polyubiquitination assay\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — multiple orthogonal methods (Y2H, GST pulldown, Co-IP, ubiquitination assay, siRNA rescue) in a single study establishing mechanism\",\n      \"pmids\": [\"16499872\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"Restored MYO18B expression in malignant pleural mesothelioma cells inhibited anchorage-independent growth, cell motility in vitro, and ectopic/orthotopic tumor growth in SCID mice, associated with increased apoptosis.\",\n      \"method\": \"MYO18B transfection into EHMES-10 MPM cells; anchorage-independent growth assay, motility assay, subcutaneous and orthotopic xenograft in SCID mice\",\n      \"journal\": \"Oncology research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — gain-of-function with in vitro and in vivo phenotypic readouts, single lab\",\n      \"pmids\": [\"17294804\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"MYO18B interacts with HOMER2 (a Homer/Vesl family protein); the two proteins co-localize at membrane protrusions and stress fibers (F-actin-rich structures), and HOMER2 enhances MYO18B-dependent suppression of anchorage-independent growth.\",\n      \"method\": \"Yeast two-hybrid screen for MYO18B-interacting proteins; co-localization by immunofluorescence; functional anchorage-independent growth assay with co-expression\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Y2H plus co-localization plus functional assay in single lab\",\n      \"pmids\": [\"17386922\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"Myo18B is localized to Z-lines of myofibrils in striated muscle (not A-bands as for conventional myosins). The N-terminal unique domain (not the motor domain or coiled-coil tail) is critical for localization to F-actin in myocytes. Myo18B expression is induced by myogenic differentiation via binding of MEF2 to its promoter. Myo18B knockout in mice is embryonic lethal with disruption of myofibrillar structures in cardiac myocytes at E10.5.\",\n      \"method\": \"Immunofluorescence/localization studies in myocytes; domain deletion/mutation analysis for F-actin localization; promoter binding assay (MEF2); Myo18B knockout mouse generation with cardiac histology at E10.5\",\n      \"journal\": \"Genes to cells : devoted to molecular & cellular mechanisms\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — KO mouse with defined lethal cardiac phenotype, domain mutagenesis establishing N-terminal domain requirement, promoter binding assay, multiple orthogonal methods\",\n      \"pmids\": [\"18761673\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Homozygous truncating mutation in MYO18B (nonsense mutation in last exon) causes loss of full-length protein (confirmed by Western blot and immunostaining) and results in severe nemaline myopathy with cardiomyopathy in humans.\",\n      \"method\": \"Exome sequencing, Western blot, immunostaining in patient muscle biopsy\",\n      \"journal\": \"Journal of neuromuscular diseases\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function with defined cellular/histological phenotype, protein absence confirmed by two methods, single case\",\n      \"pmids\": [\"27858739\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Truncating mutation in MYO18B leads to near-complete loss of transcript (nonsense-mediated decay) and is associated with a syndrome of Klippel-Feil anomaly, myopathy, and abnormal myosin filaments on electron microscopy, establishing MYO18B as required for normal myosin filament structure in humans.\",\n      \"method\": \"Autozygome/exome analysis; RT-PCR for transcript levels; electron microscopy of muscle biopsy\",\n      \"journal\": \"Journal of medical genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function with ultrastructural phenotype (EM), two independent families, single lab\",\n      \"pmids\": [\"25748484\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"In zebrafish, loss of myo18b (frozen/fro mutant) causes sarcomeric assembly failure specifically in fast-twitch myocytes, with disorganized accumulation of actin, myosin, and α-actinin and complete loss of myofibrillar organization; myo18b transcription is restricted to fast-twitch myocytes.\",\n      \"method\": \"Meiotic mapping and positional cloning of zebrafish frozen mutant; loss-of-birefringency assay; immunofluorescence for sarcomeric proteins; in situ hybridization for expression pattern\",\n      \"journal\": \"Genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic loss-of-function in zebrafish with defined structural phenotype, confirmed by multiple labs studying Myo18B in muscle\",\n      \"pmids\": [\"27879346\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"In zebrafish myo18b null mutants, sarcomeres completely fail to assemble despite scattered thin and thick filaments being present; partial loss-of-function results in sarcomeres with misaligned filaments. This establishes Myo18b as essential for coordinating integration of preformed thick and thin filaments into sarcomere structure.\",\n      \"method\": \"Zebrafish myo18b null and hypomorphic mutant analysis; electron microscopy and immunofluorescence for sarcomeric organization\",\n      \"journal\": \"Human molecular genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — allelic series (null vs partial loss-of-function) with ultrastructural readout, replicates and extends findings from independent zebrafish study\",\n      \"pmids\": [\"28104788\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"MYO18B knockdown in HepG2 hepatocellular carcinoma cells inhibits proliferation, migration, and invasion, and suppresses phosphorylation of PI3K, AKT, mTOR, and P70S6K, placing MYO18B upstream of the PI3K/AKT/mTOR pathway in HCC cells.\",\n      \"method\": \"siRNA knockdown of MYO18B; CCK-8 and colony formation assays; wound healing and transwell invasion assays; Western blot for PI3K/AKT/mTOR pathway phosphorylation\",\n      \"journal\": \"Diagnostic pathology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, knockdown phenotype with pathway readout but no direct binding or epistasis experiment establishing mechanism\",\n      \"pmids\": [\"30390677\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"MYO18B, functioning as an actin crosslinker, is required for focal adhesion maturation, which in turn facilitates lysosomal exocytosis and release of paucimannosidic proteins to the extracellular milieu. PIEZO1 at focal adhesions imports Ca2+ for lysosome-plasma membrane fusion.\",\n      \"method\": \"Genome-wide knockout screen; focal adhesion maturation assays; lysosomal exocytosis assays; glycoproteomic analysis of paucimannosidic proteins\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genome-wide KO screen plus mechanistic follow-up establishing pathway position, single lab\",\n      \"pmids\": [\"39751400\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"MYO18B is an unconventional class XVIII myosin expressed predominantly in striated muscle that localizes to Z-lines/sarcomeres via its N-terminal domain (not motor domain), is essential for sarcomere assembly by coordinating integration of thick and thin filaments, is regulated transcriptionally by MEF2 and epigenetically by histone deacetylation, is degraded via the ubiquitin-proteasome pathway through interaction with the Sug1/19S subunit, and in non-muscle contexts acts as an actin crosslinker required for focal adhesion maturation and lysosomal exocytosis; in cancer cells its re-expression suppresses anchorage-independent growth, an activity enhanced by its binding partner HOMER2.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"MYO18B is an unconventional class XVIII myosin expressed predominantly in striated muscle, where it is essential for the assembly and integrity of the sarcomere [#7, #11]. It localizes to Z-lines of myofibrils rather than the A-bands occupied by conventional myosins, and its targeting to F-actin in myocytes depends on its N-terminal unique domain rather than the motor domain or coiled-coil tail [#7]. Functionally, MYO18B coordinates the integration of preformed thick and thin filaments into ordered sarcomeres: in its complete absence sarcomeres fail to assemble despite the presence of scattered actin and myosin filaments, and partial loss yields misaligned filaments [#11, #10]. Loss of MYO18B is embryonic lethal in mice with disrupted cardiac myofibrils [#7], and in humans truncating mutations cause nemaline myopathy with cardiomyopathy and a Klippel-Feil/myopathy syndrome with abnormal myosin filaments [#8, #9]. Its muscle expression is driven transcriptionally by MEF2 binding to its promoter during myogenic differentiation [#7], while protein levels are controlled by polyubiquitination and proteasomal degradation through interaction of its C-terminal tail with the 19S subunit Sug1 [#4]. Beyond muscle, MYO18B acts as an actin crosslinker required for focal adhesion maturation, which enables PIEZO1-dependent lysosomal exocytosis [#13], and its re-expression suppresses anchorage-independent growth across multiple cancer cell types, an activity enhanced by its binding partner HOMER2 [#0, #6].\",\n  \"teleology\": [\n    {\n      \"year\": 2002,\n      \"claim\": \"Whether MYO18B had a cell-autonomous role in malignancy was unknown; restoring its expression directly tested a tumor-suppressive function.\",\n      \"evidence\": \"Re-expression in lung carcinoma cells with anchorage-independent growth assay\",\n      \"pmids\": [\"12209013\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular basis of growth suppression not defined\", \"No link to a specific signaling pathway in this study\"]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"Establishing where the protein resides addressed which cellular compartment its function operates in, revealing both nuclear and partial sarcomeric distributions.\",\n      \"evidence\": \"Immunofluorescence in myoblasts, myotubes, cardiomyocytes, and adult muscle sections\",\n      \"pmids\": [\"12547197\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional consequence of nuclear accumulation not established\", \"Sarcomeric sub-localization not mapped to a band\"]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"The mechanism of MYO18B silencing in cancer was unknown; promoter chromatin analysis showed epigenetic repression underlies its loss.\",\n      \"evidence\": \"ChIP for H3/H4 acetylation at the MYO18B promoter and TSA-mediated expression rescue in lung cancer lines\",\n      \"pmids\": [\"15101048\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Does not identify the responsible HDAC or recruiting factor\", \"Relationship to promoter methylation not addressed\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Whether the tumor-suppressive activity generalized beyond lung cancer was tested by re-expression in colorectal lines, refining the phenotype to anchorage-independent proliferation specifically.\",\n      \"evidence\": \"Re-expression in HT29 and DLD-1 with anchorage-independent versus in vitro growth assays\",\n      \"pmids\": [\"15751041\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Effector mechanism of anchorage-dependent suppression unknown\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"How MYO18B protein levels are controlled was unresolved; identifying Sug1 binding established proteasomal turnover as the regulatory mechanism.\",\n      \"evidence\": \"Yeast two-hybrid, GST pull-down, Co-IP, in vivo polyubiquitination, proteasome inhibition, and Sug1 siRNA rescue\",\n      \"pmids\": [\"16499872\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"E3 ligase responsible for ubiquitination not identified\", \"Physiological trigger for degradation unknown\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"The in vivo relevance of growth suppression was tested in mesothelioma, extending the phenotype to motility and tumor formation in animals.\",\n      \"evidence\": \"MYO18B transfection in EHMES-10 cells with motility assays and SCID mouse xenografts\",\n      \"pmids\": [\"17294804\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism of apoptosis induction not defined\", \"No molecular partner implicated in this context\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"To find effectors of the suppressive activity, an interaction screen identified HOMER2 and placed MYO18B at F-actin structures where the partner enhances its function.\",\n      \"evidence\": \"Yeast two-hybrid screen, co-localization at protrusions/stress fibers, co-expression growth assay\",\n      \"pmids\": [\"17386922\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Structural basis of the HOMER2 interaction unknown\", \"How HOMER2 potentiates suppression mechanistically unclear\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"The physiological function and localization determinants in muscle were unresolved; combined localization, domain mutagenesis, promoter, and knockout work established a Z-line role driven by MEF2 and an N-terminal targeting domain.\",\n      \"evidence\": \"Immunofluorescence, domain deletion analysis, MEF2 promoter binding, and embryonic-lethal knockout mouse with cardiac histology\",\n      \"pmids\": [\"18761673\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct binding partners at the Z-line not identified\", \"Motor/ATPase activity not characterized\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Whether MYO18B loss causes human disease was answered by truncating mutations linking it causatively to myopathy and abnormal myosin filaments.\",\n      \"evidence\": \"Exome/autozygome analysis, Western blot, immunostaining, RT-PCR for NMD, and electron microscopy of patient biopsies\",\n      \"pmids\": [\"27858739\", \"25748484\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single case / two families limit genotype-phenotype breadth\", \"Molecular step disrupted in filament assembly not resolved in patient tissue\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"The precise step in sarcomerogenesis that MYO18B controls was unknown; zebrafish allelic series showed it coordinates integration of preformed thick and thin filaments rather than their initial synthesis.\",\n      \"evidence\": \"Zebrafish frozen/null and hypomorphic mutants with birefringence, immunofluorescence, and electron microscopy of sarcomeres\",\n      \"pmids\": [\"27879346\", \"28104788\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct molecular interactions enabling filament alignment not identified\", \"Fiber-type specificity (fast-twitch) mechanism unexplained\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"A signaling context for MYO18B in cancer was probed, linking knockdown to reduced PI3K/AKT/mTOR phosphorylation in hepatocellular carcinoma.\",\n      \"evidence\": \"siRNA knockdown with proliferation, migration, invasion assays and pathway Western blots in HepG2\",\n      \"pmids\": [\"30390677\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No direct binding or epistasis establishing the pathway link\", \"Oncogenic direction conflicts with tumor-suppressor findings and is not reconciled\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"A non-muscle molecular role was defined, showing MYO18B acts as an actin crosslinker required for focal adhesion maturation that enables PIEZO1-driven lysosomal exocytosis.\",\n      \"evidence\": \"Genome-wide knockout screen with focal adhesion, lysosomal exocytosis, and glycoproteomic assays\",\n      \"pmids\": [\"39751400\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct biochemical demonstration of actin crosslinking by MYO18B not shown\", \"Relationship between this role and its muscle function unclear\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How a single N-terminally targeted myosin mechanically coordinates filament integration, and whether its muscle, adhesion, and tumor-suppressive activities share a common biochemical activity, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Motor/ATPase activity and structural basis of F-actin engagement uncharacterized\", \"Z-line binding partners that mediate sarcomere assembly unidentified\", \"Reconciliation of tumor-suppressor versus pro-oncogenic reports lacking\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [7, 13]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [1, 7, 10]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-397014\", \"supporting_discovery_ids\": [7, 11]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [7, 10]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"SUG1\", \"HOMER2\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":6,"faith_pct":100.0}}