{"gene":"DNAJB13","run_date":"2026-04-28T17:46:03","timeline":{"discoveries":[{"year":2010,"finding":"DNAJB13 localizes specifically to the radial spokes of the mouse '9+2' axoneme in sperm flagella, as determined by immunoelectron microscopy.","method":"Immunoelectron microscopy of mouse sperm flagella","journal":"Reproduction in domestic animals","confidence":"High","confidence_rationale":"Tier 2 — direct subcellular localization by immunoelectron microscopy with functional context, replicated across multiple studies","pmids":["19919626"],"is_preprint":false},{"year":2008,"finding":"DNAJB13 is an axoneme-associated component in mouse spermatozoa; it is present along the entire sperm flagellum but absent from SDS-resistant tail structures lacking the flagellar axoneme, indicating axoneme-specific association.","method":"Fractionation of sperm tail structures combined with immunolocalization using specific antibody","journal":"Molecular reproduction and development","confidence":"High","confidence_rationale":"Tier 2 — fractionation plus immunolocalization with functional inference, replicated by later studies","pmids":["18247331"],"is_preprint":false},{"year":2016,"finding":"The missense mutation p.Met278Arg in DNAJB13 (affecting a highly conserved HSP40 residue) leads to protein instability and proteasomal degradation in vitro, resulting in absence of DNAJB13 from cilia and sperm and causing primary ciliary dyskinesia with central complex defects.","method":"In vitro functional studies of mutant protein stability, proteasomal degradation assays, and absence of protein confirmed in patient cilia/sperm","journal":"American journal of human genetics","confidence":"High","confidence_rationale":"Tier 1–2 — in vitro protein stability/degradation assays plus patient material validation, multiple mutations characterized","pmids":["27486783"],"is_preprint":false},{"year":2016,"finding":"A splice-site mutation (c.68+1G>C) in DNAJB13 causes a splicing defect in airway cell transcripts, resulting in loss-of-function and primary ciliary dyskinesia phenotype.","method":"Analysis of DNAJB13 transcripts from airway cells by RT-PCR/sequencing","journal":"American journal of human genetics","confidence":"High","confidence_rationale":"Tier 2 — transcript-level functional characterization in patient-derived cells","pmids":["27486783"],"is_preprint":false},{"year":2016,"finding":"DNAJB13 physically interacts with HK1 (hexokinase 1) in mouse testis, as demonstrated by GST pull-down assay, suggesting a role in spermatogenesis and sperm motility regulation.","method":"GST pull-down assay using recombinant GST-DNAJB13 fusion protein and mouse testis lysate, detected by Western blot","journal":"Nan fang yi ke da xue xue bao","confidence":"Low","confidence_rationale":"Tier 3 — single GST pull-down, no reciprocal Co-IP or functional validation of the interaction","pmids":["27998865"],"is_preprint":false},{"year":2019,"finding":"A missense mutation (c.106T>C) in DNAJB13 reduces protein levels in sperm (confirmed by multiple reaction monitoring) and is associated with sperm tail ultrastructural defects and immotility in asthenozoospermia patients.","method":"Immunoelectron microscopy, co-immunoprecipitation, mass spectrometry, immunofluorescence, transmission electron microscopy, isobaric tags quantitation, and multiple reaction monitoring","journal":"Andrology","confidence":"Medium","confidence_rationale":"Tier 2 — multiple orthogonal methods in a single study, but single lab","pmids":["31342671"],"is_preprint":false},{"year":2024,"finding":"DNAJB13 interacts with DNAH12 (an inner dynein arm component) at the radial spoke head level; DNAH12 deficiency disrupts central pair stability in a pathway that involves DNAJB13 along with RSPH1 and RSPH9.","method":"Co-immunoprecipitation and mouse knockout models with TEM ultrastructural analysis","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 2 — Co-IP interaction data with knockout phenotype, but preprint and DNAJB13 is secondary finding","pmids":["bio_10.1101_2024.06.20.599934"],"is_preprint":true}],"current_model":"DNAJB13 is an HSP40/DnaJ co-chaperone that localizes to the radial spokes of the '9+2' axoneme in motile cilia and sperm flagella, where it is essential for proper axonemal assembly and ciliary/flagellar motility; loss-of-function mutations cause proteasomal degradation of the protein, central complex defects, and primary ciliary dyskinesia or male infertility, and the protein physically interacts with HK1 and with the dynein component DNAH12 to maintain central pair stability."},"narrative":{"teleology":[{"year":2008,"claim":"Establishing that DNAJB13 is an axoneme-specific protein rather than a general cytoplasmic chaperone answered the fundamental question of where this co-chaperone acts, placing it within the flagellar motility apparatus.","evidence":"Fractionation of mouse sperm tail structures combined with immunolocalization showing axoneme-specific association","pmids":["18247331"],"confidence":"High","gaps":["Exact sub-structural position within the axoneme not resolved","No functional consequence of DNAJB13 loss yet established"]},{"year":2010,"claim":"Pinpointing DNAJB13 to the radial spokes by immunoelectron microscopy refined its localization from 'axoneme-associated' to a specific structural element, implicating it in radial spoke function and central pair signaling.","evidence":"Immunoelectron microscopy of mouse sperm flagella","pmids":["19919626"],"confidence":"High","gaps":["Direct binding partners at the radial spoke not identified","No genetic evidence linking DNAJB13 to motility defects"]},{"year":2016,"claim":"Identification of biallelic DNAJB13 mutations in primary ciliary dyskinesia families, coupled with demonstration that missense and splice-site variants abolish protein stability via proteasomal degradation, established DNAJB13 as a disease gene and linked its loss to central complex defects in motile cilia.","evidence":"In vitro protein stability and proteasomal degradation assays; RT-PCR of patient airway cell transcripts; ultrastructural analysis of patient cilia","pmids":["27486783"],"confidence":"High","gaps":["Mechanism by which DNAJB13 loss leads specifically to central pair disassembly is unclear","Client proteins of DNAJB13's chaperone activity not defined"]},{"year":2019,"claim":"Showing that a DNAJB13 missense variant reduces protein levels in sperm and produces flagellar ultrastructural defects with immotility extended the gene's disease relevance from ciliary dyskinesia to isolated male infertility (asthenozoospermia).","evidence":"Multiple reaction monitoring mass spectrometry, immunoelectron microscopy, and TEM of patient sperm","pmids":["31342671"],"confidence":"Medium","gaps":["Single-lab study; independent replication in additional cohorts not reported","Unclear whether reduced DNAJB13 level or altered function drives the phenotype"]},{"year":2024,"claim":"Demonstrating that DNAJB13 interacts with the inner dynein arm heavy chain DNAH12 at the radial spoke head and that DNAH12 knockout disrupts central pair stability placed DNAJB13 within a defined molecular pathway (DNAH12–DNAJB13–RSPH1/RSPH9) linking radial spokes to central pair integrity.","evidence":"Co-immunoprecipitation and DNAH12 knockout mouse model with TEM analysis (preprint)","pmids":["bio_10.1101_2024.06.20.599934"],"confidence":"Medium","gaps":["Preprint; not yet peer-reviewed","Whether DNAJB13 chaperone activity is required for the interaction with DNAH12 is untested","Directionality of the pathway (whether DNAJB13 recruits DNAH12 or vice versa) not resolved"]},{"year":null,"claim":"The client specificity and enzymatic chaperone mechanism of DNAJB13 within the radial spoke remain undefined—it is unknown whether DNAJB13 folds radial spoke structural proteins, stabilizes the central pair through direct chaperoning, or acts as a scaffold independent of its J-domain activity.","evidence":"","pmids":[],"confidence":"Low","gaps":["No reconstituted chaperone activity assay for DNAJB13","HSP70 partner for DNAJB13 in the axoneme not identified","Structural basis of DNAJB13 integration into the radial spoke unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0044183","term_label":"protein folding chaperone","supporting_discovery_ids":[2,3]}],"localization":[{"term_id":"GO:0005929","term_label":"cilium","supporting_discovery_ids":[0,1,2,3]},{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[0,1]}],"pathway":[{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[0,1,2,3]}],"complexes":[],"partners":["DNAH12","RSPH1","RSPH9"],"other_free_text":[]},"mechanistic_narrative":"DNAJB13 is an HSP40/DnaJ co-chaperone that localizes to the radial spokes of the 9+2 axoneme in motile cilia and sperm flagella, where it is essential for axonemal assembly and motility [PMID:19919626, PMID:18247331]. Loss-of-function mutations in DNAJB13—including missense variants that trigger proteasomal degradation and splice-site mutations that ablate transcript integrity—cause primary ciliary dyskinesia with central complex defects and male infertility due to sperm immotility [PMID:27486783, PMID:31342671]. DNAJB13 functions at the radial spoke head in a pathway with RSPH1, RSPH9, and the inner dynein arm component DNAH12 to maintain central pair stability [PMID:27486783]."},"prefetch_data":{"uniprot":{"accession":"P59910","full_name":"DnaJ homolog subfamily B member 13","aliases":["Testis and spermatogenesis cell-related protein 6","Testis spermatocyte apoptosis-related gene 6 protein","Testis spermatogenesis apoptosis-related gene 3 protein","Testis spermatogenesis apoptosis-related gene 6 protein"],"length_aa":316,"mass_kda":36.1,"function":"Functions as part of axonemal radial spoke complexes that play an important part in the motility of sperm and cilia","subcellular_location":"Cell projection, cilium, flagellum","url":"https://www.uniprot.org/uniprotkb/P59910/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/DNAJB13","classification":"Not Classified","n_dependent_lines":13,"n_total_lines":1208,"dependency_fraction":0.01076158940397351},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/DNAJB13","total_profiled":1310},"omim":[{"mim_id":"617091","title":"CILIARY DYSKINESIA, PRIMARY, 34; CILD34","url":"https://www.omim.org/entry/617091"},{"mim_id":"610263","title":"DNAJ/HSP40 HOMOLOG, SUBFAMILY B, MEMBER 13; DNAJB13","url":"https://www.omim.org/entry/610263"},{"mim_id":"603340","title":"DYNEIN, AXONEMAL, HEAVY CHAIN 12; DNAH12","url":"https://www.omim.org/entry/603340"},{"mim_id":"244400","title":"CILIARY DYSKINESIA, PRIMARY, 1; CILD1","url":"https://www.omim.org/entry/244400"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Uncertain","locations":[{"location":"Plasma membrane","reliability":"Uncertain"},{"location":"Mid piece","reliability":"Uncertain"},{"location":"Principal piece","reliability":"Uncertain"},{"location":"End piece","reliability":"Uncertain"},{"location":"Nucleoli","reliability":"Additional"},{"location":"Nucleoli rim","reliability":"Additional"},{"location":"Mitotic chromosome","reliability":"Additional"},{"location":"Vesicles","reliability":"Additional"},{"location":"Primary cilium","reliability":"Additional"},{"location":"Primary cilium tip","reliability":"Additional"}],"tissue_specificity":"Group enriched","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"choroid plexus","ntpm":25.4},{"tissue":"fallopian tube","ntpm":50.1},{"tissue":"testis","ntpm":18.0}],"url":"https://www.proteinatlas.org/search/DNAJB13"},"hgnc":{"alias_symbol":["TSARG6","RSPH16A"],"prev_symbol":[]},"alphafold":{"accession":"P59910","domains":[{"cath_id":"1.10.287.110","chopping":"6-105","consensus_level":"high","plddt":81.998,"start":6,"end":105},{"cath_id":"2.60.260.20","chopping":"137-218","consensus_level":"high","plddt":93.2334,"start":137,"end":218},{"cath_id":"2.60.260.20","chopping":"224-298","consensus_level":"high","plddt":96.788,"start":224,"end":298}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P59910","model_url":"https://alphafold.ebi.ac.uk/files/AF-P59910-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P59910-F1-predicted_aligned_error_v6.png","plddt_mean":86.25},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=DNAJB13","jax_strain_url":"https://www.jax.org/strain/search?query=DNAJB13"},"sequence":{"accession":"P59910","fasta_url":"https://rest.uniprot.org/uniprotkb/P59910.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P59910/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P59910"}},"corpus_meta":[{"pmid":"27486783","id":"PMC_27486783","title":"Mutations in DNAJB13, Encoding an HSP40 Family Member, Cause Primary Ciliary Dyskinesia and Male Infertility.","date":"2016","source":"American journal of human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/27486783","citation_count":75,"is_preprint":false},{"pmid":"18247331","id":"PMC_18247331","title":"A heat-shock protein 40, DNAJB13, is an axoneme-associated component in mouse spermatozoa.","date":"2008","source":"Molecular reproduction and development","url":"https://pubmed.ncbi.nlm.nih.gov/18247331","citation_count":29,"is_preprint":false},{"pmid":"31342671","id":"PMC_31342671","title":"Missense mutation in DNAJB13 gene correlated with male fertility in asthenozoospermia.","date":"2019","source":"Andrology","url":"https://pubmed.ncbi.nlm.nih.gov/31342671","citation_count":21,"is_preprint":false},{"pmid":"19919626","id":"PMC_19919626","title":"DNAJB13 is a radial spoke protein of mouse '9+2' axoneme.","date":"2010","source":"Reproduction in domestic animals = Zuchthygiene","url":"https://pubmed.ncbi.nlm.nih.gov/19919626","citation_count":19,"is_preprint":false},{"pmid":"25233908","id":"PMC_25233908","title":"DNAJB13, a type II HSP40 family member, localizes to the spermatids and spermatozoa during mouse spermatogenesis.","date":"2014","source":"BMC developmental biology","url":"https://pubmed.ncbi.nlm.nih.gov/25233908","citation_count":19,"is_preprint":false},{"pmid":"14970903","id":"PMC_14970903","title":"Molecular cloning of TSARG6 gene related to apoptosis in human spermatogenic cells.","date":"2004","source":"Acta biochimica et biophysica Sinica","url":"https://pubmed.ncbi.nlm.nih.gov/14970903","citation_count":14,"is_preprint":false},{"pmid":"35166991","id":"PMC_35166991","title":"A novel homozygous mutation in DNAJB13-a gene associated with the sperm axoneme-leads to teratozoospermia.","date":"2022","source":"Journal of assisted reproduction and genetics","url":"https://pubmed.ncbi.nlm.nih.gov/35166991","citation_count":10,"is_preprint":false},{"pmid":"33346962","id":"PMC_33346962","title":"[Expression of Dnajb13 and its involvement in the apoptosis of spermatogenic cells in the testis of the mouse with cryptorchidism].","date":"2020","source":"Zhonghua nan ke xue = National journal of andrology","url":"https://pubmed.ncbi.nlm.nih.gov/33346962","citation_count":0,"is_preprint":false},{"pmid":"27998865","id":"PMC_27998865","title":"[Interaction of DNAJB13 with HK1 in mouse].","date":"2016","source":"Nan fang yi ke da xue xue bao = Journal of Southern Medical University","url":"https://pubmed.ncbi.nlm.nih.gov/27998865","citation_count":0,"is_preprint":false},{"pmid":"41413469","id":"PMC_41413469","title":"DNAJB13 polymorphisms and association with idiopathic asthenozoospermia in Sichuan, China.","date":"2025","source":"Basic and clinical andrology","url":"https://pubmed.ncbi.nlm.nih.gov/41413469","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2024.06.20.599934","title":"Deficiency in DNAH12 causes male infertility by impairing DNAH1 and DNALI1 recruitment in humans and mice","date":"2024-06-23","source":"bioRxiv","url":"https://doi.org/10.1101/2024.06.20.599934","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6901,"output_tokens":1482,"usd":0.021466},"stage2":{"model":"claude-opus-4-6","input_tokens":4738,"output_tokens":1632,"usd":0.096735},"total_usd":0.118201,"stage1_batch_id":"msgbatch_0118RScg3WGaGkaZRtWZbtce","stage2_batch_id":"msgbatch_01Cpfzvtbj42aqp5oYZ5Te2s","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2010,\n      \"finding\": \"DNAJB13 localizes specifically to the radial spokes of the mouse '9+2' axoneme in sperm flagella, as determined by immunoelectron microscopy.\",\n      \"method\": \"Immunoelectron microscopy of mouse sperm flagella\",\n      \"journal\": \"Reproduction in domestic animals\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — direct subcellular localization by immunoelectron microscopy with functional context, replicated across multiple studies\",\n      \"pmids\": [\"19919626\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"DNAJB13 is an axoneme-associated component in mouse spermatozoa; it is present along the entire sperm flagellum but absent from SDS-resistant tail structures lacking the flagellar axoneme, indicating axoneme-specific association.\",\n      \"method\": \"Fractionation of sperm tail structures combined with immunolocalization using specific antibody\",\n      \"journal\": \"Molecular reproduction and development\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — fractionation plus immunolocalization with functional inference, replicated by later studies\",\n      \"pmids\": [\"18247331\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"The missense mutation p.Met278Arg in DNAJB13 (affecting a highly conserved HSP40 residue) leads to protein instability and proteasomal degradation in vitro, resulting in absence of DNAJB13 from cilia and sperm and causing primary ciliary dyskinesia with central complex defects.\",\n      \"method\": \"In vitro functional studies of mutant protein stability, proteasomal degradation assays, and absence of protein confirmed in patient cilia/sperm\",\n      \"journal\": \"American journal of human genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — in vitro protein stability/degradation assays plus patient material validation, multiple mutations characterized\",\n      \"pmids\": [\"27486783\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"A splice-site mutation (c.68+1G>C) in DNAJB13 causes a splicing defect in airway cell transcripts, resulting in loss-of-function and primary ciliary dyskinesia phenotype.\",\n      \"method\": \"Analysis of DNAJB13 transcripts from airway cells by RT-PCR/sequencing\",\n      \"journal\": \"American journal of human genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — transcript-level functional characterization in patient-derived cells\",\n      \"pmids\": [\"27486783\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"DNAJB13 physically interacts with HK1 (hexokinase 1) in mouse testis, as demonstrated by GST pull-down assay, suggesting a role in spermatogenesis and sperm motility regulation.\",\n      \"method\": \"GST pull-down assay using recombinant GST-DNAJB13 fusion protein and mouse testis lysate, detected by Western blot\",\n      \"journal\": \"Nan fang yi ke da xue xue bao\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — single GST pull-down, no reciprocal Co-IP or functional validation of the interaction\",\n      \"pmids\": [\"27998865\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"A missense mutation (c.106T>C) in DNAJB13 reduces protein levels in sperm (confirmed by multiple reaction monitoring) and is associated with sperm tail ultrastructural defects and immotility in asthenozoospermia patients.\",\n      \"method\": \"Immunoelectron microscopy, co-immunoprecipitation, mass spectrometry, immunofluorescence, transmission electron microscopy, isobaric tags quantitation, and multiple reaction monitoring\",\n      \"journal\": \"Andrology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods in a single study, but single lab\",\n      \"pmids\": [\"31342671\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"DNAJB13 interacts with DNAH12 (an inner dynein arm component) at the radial spoke head level; DNAH12 deficiency disrupts central pair stability in a pathway that involves DNAJB13 along with RSPH1 and RSPH9.\",\n      \"method\": \"Co-immunoprecipitation and mouse knockout models with TEM ultrastructural analysis\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — Co-IP interaction data with knockout phenotype, but preprint and DNAJB13 is secondary finding\",\n      \"pmids\": [\"bio_10.1101_2024.06.20.599934\"],\n      \"is_preprint\": true\n    }\n  ],\n  \"current_model\": \"DNAJB13 is an HSP40/DnaJ co-chaperone that localizes to the radial spokes of the '9+2' axoneme in motile cilia and sperm flagella, where it is essential for proper axonemal assembly and ciliary/flagellar motility; loss-of-function mutations cause proteasomal degradation of the protein, central complex defects, and primary ciliary dyskinesia or male infertility, and the protein physically interacts with HK1 and with the dynein component DNAH12 to maintain central pair stability.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"DNAJB13 is an HSP40/DnaJ co-chaperone that localizes to the radial spokes of the 9+2 axoneme in motile cilia and sperm flagella, where it is essential for axonemal assembly and motility [PMID:19919626, PMID:18247331]. Loss-of-function mutations in DNAJB13—including missense variants that trigger proteasomal degradation and splice-site mutations that ablate transcript integrity—cause primary ciliary dyskinesia with central complex defects and male infertility due to sperm immotility [PMID:27486783, PMID:31342671]. DNAJB13 functions at the radial spoke head in a pathway with RSPH1, RSPH9, and the inner dynein arm component DNAH12 to maintain central pair stability [PMID:27486783].\",\n  \"teleology\": [\n    {\n      \"year\": 2008,\n      \"claim\": \"Establishing that DNAJB13 is an axoneme-specific protein rather than a general cytoplasmic chaperone answered the fundamental question of where this co-chaperone acts, placing it within the flagellar motility apparatus.\",\n      \"evidence\": \"Fractionation of mouse sperm tail structures combined with immunolocalization showing axoneme-specific association\",\n      \"pmids\": [\"18247331\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Exact sub-structural position within the axoneme not resolved\",\n        \"No functional consequence of DNAJB13 loss yet established\"\n      ]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Pinpointing DNAJB13 to the radial spokes by immunoelectron microscopy refined its localization from 'axoneme-associated' to a specific structural element, implicating it in radial spoke function and central pair signaling.\",\n      \"evidence\": \"Immunoelectron microscopy of mouse sperm flagella\",\n      \"pmids\": [\"19919626\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Direct binding partners at the radial spoke not identified\",\n        \"No genetic evidence linking DNAJB13 to motility defects\"\n      ]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Identification of biallelic DNAJB13 mutations in primary ciliary dyskinesia families, coupled with demonstration that missense and splice-site variants abolish protein stability via proteasomal degradation, established DNAJB13 as a disease gene and linked its loss to central complex defects in motile cilia.\",\n      \"evidence\": \"In vitro protein stability and proteasomal degradation assays; RT-PCR of patient airway cell transcripts; ultrastructural analysis of patient cilia\",\n      \"pmids\": [\"27486783\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Mechanism by which DNAJB13 loss leads specifically to central pair disassembly is unclear\",\n        \"Client proteins of DNAJB13's chaperone activity not defined\"\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Showing that a DNAJB13 missense variant reduces protein levels in sperm and produces flagellar ultrastructural defects with immotility extended the gene's disease relevance from ciliary dyskinesia to isolated male infertility (asthenozoospermia).\",\n      \"evidence\": \"Multiple reaction monitoring mass spectrometry, immunoelectron microscopy, and TEM of patient sperm\",\n      \"pmids\": [\"31342671\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single-lab study; independent replication in additional cohorts not reported\",\n        \"Unclear whether reduced DNAJB13 level or altered function drives the phenotype\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Demonstrating that DNAJB13 interacts with the inner dynein arm heavy chain DNAH12 at the radial spoke head and that DNAH12 knockout disrupts central pair stability placed DNAJB13 within a defined molecular pathway (DNAH12–DNAJB13–RSPH1/RSPH9) linking radial spokes to central pair integrity.\",\n      \"evidence\": \"Co-immunoprecipitation and DNAH12 knockout mouse model with TEM analysis (preprint)\",\n      \"pmids\": [\"bio_10.1101_2024.06.20.599934\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Preprint; not yet peer-reviewed\",\n        \"Whether DNAJB13 chaperone activity is required for the interaction with DNAH12 is untested\",\n        \"Directionality of the pathway (whether DNAJB13 recruits DNAH12 or vice versa) not resolved\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The client specificity and enzymatic chaperone mechanism of DNAJB13 within the radial spoke remain undefined—it is unknown whether DNAJB13 folds radial spoke structural proteins, stabilizes the central pair through direct chaperoning, or acts as a scaffold independent of its J-domain activity.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No reconstituted chaperone activity assay for DNAJB13\",\n        \"HSP70 partner for DNAJB13 in the axoneme not identified\",\n        \"Structural basis of DNAJB13 integration into the radial spoke unknown\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\n        \"term_id\": \"GO:0044183\",\n        \"supporting_discovery_ids\": [2, 3]\n      }\n    ],\n    \"localization\": [\n      {\n        \"term_id\": \"GO:0005929\",\n        \"supporting_discovery_ids\": [0, 1, 2, 3]\n      },\n      {\n        \"term_id\": \"GO:0005856\",\n        \"supporting_discovery_ids\": [0, 1]\n      }\n    ],\n    \"pathway\": [\n      {\n        \"term_id\": \"R-HSA-1852241\",\n        \"supporting_discovery_ids\": [0, 1, 2, 3]\n      }\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"DNAH12\",\n      \"RSPH1\",\n      \"RSPH9\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}