{"gene":"DNAJC18","run_date":"2026-06-09T23:54:42","timeline":{"discoveries":[{"year":2017,"finding":"DNAJC18 (DnaJC18) is a type III DnaJ family protein expressed specifically in rat testis, with expression beginning at postnatal week 4 and localized to late pachytene spermatocytes, round, and elongated spermatids; confocal microscopy with GFP-tagged protein showed cytoplasmic localization, suggesting a role in germ cell maturation.","method":"Northern blot, in situ hybridization, Western blot, immunohistochemistry, confocal microscopy with GFP-tagged protein","journal":"Development & reproduction","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — multiple orthogonal localization and expression methods in a single study, but no functional rescue or loss-of-function experiment; no mechanistic pathway placement beyond correlation with spermatid maturation stages","pmids":["29082339"],"is_preprint":false},{"year":2022,"finding":"Loss-of-function of Dnajc18 in single-gene-null mouse lines causes developmental cardiac structural abnormalities; UK Biobank data further showed that human DNAJC18 loss-of-function variants are associated with altered left ventricular systolic function, establishing a role for DNAJC18 in cardiac homeostasis.","method":"In vivo electrocardiography, transthoracic echocardiography, microcomputed tomography imaging in single-gene-null mouse lines; human UK Biobank loss-of-function variant analysis","journal":"Nature cardiovascular research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean KO with defined cardiac structural phenotype plus human genetic validation, but no molecular mechanism or pathway placement established","pmids":["39195995"],"is_preprint":false}],"current_model":"DNAJC18 encodes a type III DnaJ/HSP40 family protein that localizes to the cytoplasm, is specifically expressed in male germ cells during spermatid maturation in rodents, and is required for normal cardiac structural development in mice, but its precise molecular mechanism, binding partners, and catalytic activities remain uncharacterized."},"narrative":{"mechanistic_narrative":"DNAJC18 is a type III DnaJ/HSP40 family protein implicated in germ cell maturation and cardiac development [PMID:29082339, PMID:39195995]. In rat testis it is expressed in a stage-restricted manner beginning at postnatal week 4, localizing to late pachytene spermatocytes and round and elongated spermatids, where GFP-tagged protein shows cytoplasmic distribution consistent with a role in spermatid maturation [PMID:29082339]. Loss-of-function of Dnajc18 in mice produces developmental cardiac structural abnormalities, and human DNAJC18 loss-of-function variants associate with altered left ventricular systolic function, establishing a requirement for the gene in cardiac homeostasis [PMID:39195995]. Beyond these expression and phenotypic findings, the molecular mechanism, binding partners (including any client proteins or HSP70 partner), and biochemical activity of DNAJC18 have not been characterized in the available corpus.","teleology":[{"year":2017,"claim":"Whether DNAJC18 has a tissue-restricted expression pattern pointing to a specialized function was unknown; establishing germ-cell-specific, stage-dependent expression placed it in spermatid maturation.","evidence":"Northern blot, in situ hybridization, immunohistochemistry, and confocal microscopy of GFP-tagged protein in rat testis","pmids":["29082339"],"confidence":"Medium","gaps":["No loss-of-function or rescue experiment to test functional requirement in spermatogenesis","No binding partner or client protein identified","Cytoplasmic localization does not define molecular activity or pathway"]},{"year":2022,"claim":"Whether DNAJC18 has a physiological role beyond the testis was unresolved; mouse knockout and human genetic data established a requirement in cardiac structural development and function.","evidence":"Electrocardiography, echocardiography, and microcomputed tomography in single-gene-null mouse lines plus UK Biobank loss-of-function variant analysis","pmids":["39195995"],"confidence":"Medium","gaps":["No molecular mechanism linking DNAJC18 to cardiac phenotype","No chaperone substrate or HSP70 partner demonstrated","Relationship between testicular and cardiac functions unexplained"]},{"year":null,"claim":"The biochemical activity of DNAJC18 as a putative HSP40 co-chaperone, its HSP70 partner, and its client proteins remain undefined.","evidence":"No direct mechanistic or interaction study present in the corpus","pmids":[],"confidence":"Low","gaps":["No reconstitution of J-domain/HSP70 stimulation","No interactome or substrate identification","No structural model"]}],"mechanism_profile":{"molecular_activity":[],"localization":[{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[0]}],"pathway":[],"complexes":[],"partners":[],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9H819","full_name":"DnaJ homolog subfamily C member 18","aliases":[],"length_aa":358,"mass_kda":41.6,"function":"(Microbial infection) In case of infection by polyomavirus, involved in the virus endoplasmic reticulum membrane penetration and infection (PubMed:25631089). Regulates the recruitment of DNAJB12:DNAJB14 into SV40-induced foci and all cooperate to guide SV40 across the endoplasmic reticulum membrane. The foci represent the site from which SV40 penetrates into the cytosol (PubMed:25631089)","subcellular_location":"","url":"https://www.uniprot.org/uniprotkb/Q9H819/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/DNAJC18","classification":"Not Classified","n_dependent_lines":0,"n_total_lines":1208,"dependency_fraction":0.0},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000170464","cell_line_id":"CID000027","localizations":[{"compartment":"er","grade":3},{"compartment":"big_aggregates","grade":1}],"interactors":[{"gene":"PAPSS2","stoichiometry":0.2},{"gene":"EIF2D","stoichiometry":0.2},{"gene":"CCNE1","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/target/CID000027","total_profiled":1310},"omim":[{"mim_id":"621108","title":"DNAJ/HSP40 HOMOLOG, SUBFAMILY C, MEMBER 18; DNAJC2","url":"https://www.omim.org/entry/621108"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Cell Junctions","reliability":"Approved"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Tissue enriched","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"testis","ntpm":73.9}],"url":"https://www.proteinatlas.org/search/DNAJC18"},"hgnc":{"alias_symbol":["MGC29463"],"prev_symbol":[]},"alphafold":{"accession":"Q9H819","domains":[{"cath_id":"1.10.287.110","chopping":"69-149_162-181","consensus_level":"high","plddt":79.8712,"start":69,"end":181},{"cath_id":"-","chopping":"255-358","consensus_level":"high","plddt":91.7448,"start":255,"end":358}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9H819","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9H819-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9H819-F1-predicted_aligned_error_v6.png","plddt_mean":71.44},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=DNAJC18","jax_strain_url":"https://www.jax.org/strain/search?query=DNAJC18"},"sequence":{"accession":"Q9H819","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9H819.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9H819/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9H819"}},"corpus_meta":[{"pmid":"39195995","id":"PMC_39195995","title":"Extensive identification of genes involved in congenital and structural heart disorders and cardiomyopathy.","date":"2022","source":"Nature cardiovascular research","url":"https://pubmed.ncbi.nlm.nih.gov/39195995","citation_count":44,"is_preprint":false},{"pmid":"33004001","id":"PMC_33004001","title":"Comparative analyses of copy number variations between Bos taurus and Bos indicus.","date":"2020","source":"BMC genomics","url":"https://pubmed.ncbi.nlm.nih.gov/33004001","citation_count":30,"is_preprint":false},{"pmid":"35715682","id":"PMC_35715682","title":"Genetic Analysis of HSP40/DNAJ Family Genes in Parkinson's Disease: a Large Case-Control Study.","date":"2022","source":"Molecular neurobiology","url":"https://pubmed.ncbi.nlm.nih.gov/35715682","citation_count":11,"is_preprint":false},{"pmid":"40513873","id":"PMC_40513873","title":"Selection signatures in Gir and Holstein cattle.","date":"2025","source":"Journal of dairy science","url":"https://pubmed.ncbi.nlm.nih.gov/40513873","citation_count":2,"is_preprint":false},{"pmid":"29082339","id":"PMC_29082339","title":"DnaJC18, a Novel Type III DnaJ Family Protein, is Expressed Specifically in Rat Male Germ Cells.","date":"2017","source":"Development & reproduction","url":"https://pubmed.ncbi.nlm.nih.gov/29082339","citation_count":0,"is_preprint":false},{"pmid":"41681977","id":"PMC_41681977","title":"Epigenome-Wide Association Studies of Proteasome Inhibitor-Related Cardiotoxicity in Patients with Multiple Myeloma.","date":"2026","source":"Cancers","url":"https://pubmed.ncbi.nlm.nih.gov/41681977","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5608,"output_tokens":591,"usd":0.012845,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6940,"output_tokens":1151,"usd":0.031738,"stage2_stop_reason":"end_turn"},"total_usd":0.044583,"stage1_batch_id":"msgbatch_01AsR7g8dGTEiEw9U83bJeWn","stage2_batch_id":"msgbatch_01YV5ZyxtFNUZEjxRcpd9jzb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2017,\n      \"finding\": \"DNAJC18 (DnaJC18) is a type III DnaJ family protein expressed specifically in rat testis, with expression beginning at postnatal week 4 and localized to late pachytene spermatocytes, round, and elongated spermatids; confocal microscopy with GFP-tagged protein showed cytoplasmic localization, suggesting a role in germ cell maturation.\",\n      \"method\": \"Northern blot, in situ hybridization, Western blot, immunohistochemistry, confocal microscopy with GFP-tagged protein\",\n      \"journal\": \"Development & reproduction\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — multiple orthogonal localization and expression methods in a single study, but no functional rescue or loss-of-function experiment; no mechanistic pathway placement beyond correlation with spermatid maturation stages\",\n      \"pmids\": [\"29082339\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Loss-of-function of Dnajc18 in single-gene-null mouse lines causes developmental cardiac structural abnormalities; UK Biobank data further showed that human DNAJC18 loss-of-function variants are associated with altered left ventricular systolic function, establishing a role for DNAJC18 in cardiac homeostasis.\",\n      \"method\": \"In vivo electrocardiography, transthoracic echocardiography, microcomputed tomography imaging in single-gene-null mouse lines; human UK Biobank loss-of-function variant analysis\",\n      \"journal\": \"Nature cardiovascular research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean KO with defined cardiac structural phenotype plus human genetic validation, but no molecular mechanism or pathway placement established\",\n      \"pmids\": [\"39195995\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"DNAJC18 encodes a type III DnaJ/HSP40 family protein that localizes to the cytoplasm, is specifically expressed in male germ cells during spermatid maturation in rodents, and is required for normal cardiac structural development in mice, but its precise molecular mechanism, binding partners, and catalytic activities remain uncharacterized.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"DNAJC18 is a type III DnaJ/HSP40 family protein implicated in germ cell maturation and cardiac development [#0, #1]. In rat testis it is expressed in a stage-restricted manner beginning at postnatal week 4, localizing to late pachytene spermatocytes and round and elongated spermatids, where GFP-tagged protein shows cytoplasmic distribution consistent with a role in spermatid maturation [#0]. Loss-of-function of Dnajc18 in mice produces developmental cardiac structural abnormalities, and human DNAJC18 loss-of-function variants associate with altered left ventricular systolic function, establishing a requirement for the gene in cardiac homeostasis [#1]. Beyond these expression and phenotypic findings, the molecular mechanism, binding partners (including any client proteins or HSP70 partner), and biochemical activity of DNAJC18 have not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2017,\n      \"claim\": \"Whether DNAJC18 has a tissue-restricted expression pattern pointing to a specialized function was unknown; establishing germ-cell-specific, stage-dependent expression placed it in spermatid maturation.\",\n      \"evidence\": \"Northern blot, in situ hybridization, immunohistochemistry, and confocal microscopy of GFP-tagged protein in rat testis\",\n      \"pmids\": [\"29082339\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No loss-of-function or rescue experiment to test functional requirement in spermatogenesis\",\n        \"No binding partner or client protein identified\",\n        \"Cytoplasmic localization does not define molecular activity or pathway\"\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Whether DNAJC18 has a physiological role beyond the testis was unresolved; mouse knockout and human genetic data established a requirement in cardiac structural development and function.\",\n      \"evidence\": \"Electrocardiography, echocardiography, and microcomputed tomography in single-gene-null mouse lines plus UK Biobank loss-of-function variant analysis\",\n      \"pmids\": [\"39195995\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No molecular mechanism linking DNAJC18 to cardiac phenotype\",\n        \"No chaperone substrate or HSP70 partner demonstrated\",\n        \"Relationship between testicular and cardiac functions unexplained\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The biochemical activity of DNAJC18 as a putative HSP40 co-chaperone, its HSP70 partner, and its client proteins remain undefined.\",\n      \"evidence\": \"No direct mechanistic or interaction study present in the corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No reconstitution of J-domain/HSP70 stimulation\",\n        \"No interactome or substrate identification\",\n        \"No structural model\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"tie","faith_supported":3,"faith_total":3,"faith_pct":100.0}}