{"gene":"DYDC1","run_date":"2026-06-09T23:54:42","timeline":{"discoveries":[{"year":2009,"finding":"DYDC1 interacts with the BAR domain of SH3P13 (identified by yeast two-hybrid screen from human testis library), is exclusively expressed in brain and testis, accumulates in the acrosome area during late spermiogenesis, and is required for acrosome biogenesis: RNAi-mediated knockdown of Dydc1 in germ cells (via germ cell transplantation) disrupted acrosome formation and spermatid differentiation in mice.","method":"Yeast two-hybrid screen, RNA interference (knockdown), germ cell transplantation, expression analysis","journal":"European journal of cell biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — yeast two-hybrid plus in vivo RNAi/germ cell transplantation with defined acrosome phenotype, single lab, two orthogonal methods","pmids":["19545932"],"is_preprint":false},{"year":2025,"finding":"DYDC1 is a component of the radial spoke 1 (RS1) macromolecular complex in sperm flagella; it localizes to both the RS1 head and the head-neck complex. This was established through proteomic identification (protein mass spectrometry) in IQUB-deficient sperm where RS1 was disrupted, and bioinformatic structural modeling.","method":"Protein mass spectrometry, western blotting, bioinformatic structural modeling using Iqub-/- mouse and human IQUB mutant patient sperm","journal":"Cell communication and signaling : CCS","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — mass spectrometry-based interactome identification with genetic model (Iqub-/- mice and patient mutation), single lab, multiple orthogonal methods but no direct DYDC1 loss-of-function","pmids":["39849482"],"is_preprint":false}],"current_model":"DYDC1 is a testis-enriched protein that physically interacts with the BAR domain protein SH3P13 and is required for acrosome biogenesis during spermiogenesis (loss-of-function disrupts acrosome formation); it also localizes to the head and head-neck complex of radial spoke 1 (RS1) in sperm flagella, where it contributes to the macromolecular RS1 assembly that regulates flagellar beat."},"narrative":{"mechanistic_narrative":"DYDC1 is a brain- and testis-enriched protein that functions in sperm development, contributing to two distinct aspects of spermatogenesis: acrosome biogenesis and flagellar architecture [PMID:19545932, PMID:39849482]. During late spermiogenesis it accumulates in the acrosome region and physically interacts with the BAR domain of SH3P13; knockdown in germ cells disrupts acrosome formation and spermatid differentiation, establishing a requirement for DYDC1 in acrosome biogenesis [PMID:19545932]. DYDC1 is also a component of the radial spoke 1 (RS1) macromolecular complex of the sperm flagellum, localizing to both the RS1 head and the head-neck complex, consistent with a role in assembly of the RS1 structure that governs flagellar beat [PMID:39849482]. Beyond these two roles, the molecular activity of DYDC1 and the mechanism by which it bridges acrosome formation and radial spoke assembly have not been characterized in the available corpus.","teleology":[{"year":2009,"claim":"Established the first molecular function for DYDC1 by identifying a binding partner and an in vivo developmental role, answering whether this testis-expressed protein participates in sperm formation.","evidence":"Yeast two-hybrid screen of human testis library, plus RNAi knockdown via germ cell transplantation in mice with expression analysis","pmids":["19545932"],"confidence":"Medium","gaps":["Interaction with SH3P13 not validated by reciprocal endogenous co-IP or structural mapping","Molecular activity of DYDC1 in acrosome biogenesis undefined","RNAi knockdown rather than a clean genetic null"]},{"year":2025,"claim":"Placed DYDC1 within a defined flagellar substructure, answering where the protein acts beyond the acrosome and linking it to motility machinery.","evidence":"Mass spectrometry of RS1-disrupted sperm from Iqub-/- mice and IQUB-mutant patients, western blotting, and bioinformatic structural modeling","pmids":["39849482"],"confidence":"Medium","gaps":["No direct DYDC1 loss-of-function to test functional requirement in RS1 assembly or motility","Direct binding partners within RS1 not biochemically defined","Relationship between the acrosomal and flagellar roles unresolved"]},{"year":null,"claim":"The biochemical activity of DYDC1 and how a single protein contributes to both acrosome biogenesis and radial spoke assembly remain unknown.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No enzymatic or structural function assigned to DYDC1","No germline knockout phenotype reported in the corpus","Mechanism connecting the two cellular roles uncharacterized"]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["radial spoke 1 (RS1)"],"partners":["SH3P13","IQUB"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q8WWB3","full_name":"DPY30 domain-containing protein 1","aliases":[],"length_aa":177,"mass_kda":20.9,"function":"Functions as part of axonemal radial spoke complexes that play an important part in the motility of sperm and cilia (By similarity). Plays a crucial role during acrosome biogenesis (PubMed:19545932)","subcellular_location":"Cytoplasm, cytoskeleton, flagellum axoneme","url":"https://www.uniprot.org/uniprotkb/Q8WWB3/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/DYDC1","classification":"Not Classified","n_dependent_lines":12,"n_total_lines":1208,"dependency_fraction":0.009933774834437087},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/DYDC1","total_profiled":1310},"omim":[{"mim_id":"615154","title":"DPY30 DOMAIN-CONTAINING PROTEIN 1; DYDC1","url":"https://www.omim.org/entry/615154"},{"mim_id":"603362","title":"SH3 DOMAIN, GRB2-LIKE, 3; SH3GL3","url":"https://www.omim.org/entry/603362"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Mid piece","reliability":"Approved"},{"location":"Principal piece","reliability":"Approved"},{"location":"End piece","reliability":"Approved"}],"tissue_specificity":"Tissue enriched","tissue_distribution":"Detected in some","driving_tissues":[{"tissue":"testis","ntpm":114.4}],"url":"https://www.proteinatlas.org/search/DYDC1"},"hgnc":{"alias_symbol":["bA36D19.5","DPY30D1"],"prev_symbol":[]},"alphafold":{"accession":"Q8WWB3","domains":[{"cath_id":"1.20.890.10","chopping":"2-131","consensus_level":"medium","plddt":93.7031,"start":2,"end":131}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8WWB3","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q8WWB3-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q8WWB3-F1-predicted_aligned_error_v6.png","plddt_mean":83.25},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=DYDC1","jax_strain_url":"https://www.jax.org/strain/search?query=DYDC1"},"sequence":{"accession":"Q8WWB3","fasta_url":"https://rest.uniprot.org/uniprotkb/Q8WWB3.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q8WWB3/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8WWB3"}},"corpus_meta":[{"pmid":"19545932","id":"PMC_19545932","title":"Interaction of SH3P13 and DYDC1 protein: a germ cell component that regulates acrosome biogenesis during spermiogenesis.","date":"2009","source":"European journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/19545932","citation_count":23,"is_preprint":false},{"pmid":"18197198","id":"PMC_18197198","title":"Myofibrillar myopathy with arrhythmogenic right ventricular cardiomyopathy 7: corroboration and narrowing of the critical region on 10q22.3.","date":"2008","source":"European journal of human genetics : EJHG","url":"https://pubmed.ncbi.nlm.nih.gov/18197198","citation_count":14,"is_preprint":false},{"pmid":"30221015","id":"PMC_30221015","title":"Towards integrated oncogenic marker recognition through mutual information-based statistically significant feature extraction: an association rule mining based study on cancer expression and methylation profiles.","date":"2017","source":"Quantitative biology (Beijing, China)","url":"https://pubmed.ncbi.nlm.nih.gov/30221015","citation_count":11,"is_preprint":false},{"pmid":"39849482","id":"PMC_39849482","title":"IQUB mutation induces radial spoke 1 deficiency causing asthenozoospermia with normal sperm morphology in humans and mice.","date":"2025","source":"Cell communication and signaling : CCS","url":"https://pubmed.ncbi.nlm.nih.gov/39849482","citation_count":6,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4844,"output_tokens":663,"usd":0.012238,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6995,"output_tokens":1189,"usd":0.03235,"stage2_stop_reason":"end_turn"},"total_usd":0.044588,"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\": 2009,\n      \"finding\": \"DYDC1 interacts with the BAR domain of SH3P13 (identified by yeast two-hybrid screen from human testis library), is exclusively expressed in brain and testis, accumulates in the acrosome area during late spermiogenesis, and is required for acrosome biogenesis: RNAi-mediated knockdown of Dydc1 in germ cells (via germ cell transplantation) disrupted acrosome formation and spermatid differentiation in mice.\",\n      \"method\": \"Yeast two-hybrid screen, RNA interference (knockdown), germ cell transplantation, expression analysis\",\n      \"journal\": \"European journal of cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — yeast two-hybrid plus in vivo RNAi/germ cell transplantation with defined acrosome phenotype, single lab, two orthogonal methods\",\n      \"pmids\": [\"19545932\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"DYDC1 is a component of the radial spoke 1 (RS1) macromolecular complex in sperm flagella; it localizes to both the RS1 head and the head-neck complex. This was established through proteomic identification (protein mass spectrometry) in IQUB-deficient sperm where RS1 was disrupted, and bioinformatic structural modeling.\",\n      \"method\": \"Protein mass spectrometry, western blotting, bioinformatic structural modeling using Iqub-/- mouse and human IQUB mutant patient sperm\",\n      \"journal\": \"Cell communication and signaling : CCS\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — mass spectrometry-based interactome identification with genetic model (Iqub-/- mice and patient mutation), single lab, multiple orthogonal methods but no direct DYDC1 loss-of-function\",\n      \"pmids\": [\"39849482\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"DYDC1 is a testis-enriched protein that physically interacts with the BAR domain protein SH3P13 and is required for acrosome biogenesis during spermiogenesis (loss-of-function disrupts acrosome formation); it also localizes to the head and head-neck complex of radial spoke 1 (RS1) in sperm flagella, where it contributes to the macromolecular RS1 assembly that regulates flagellar beat.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"DYDC1 is a brain- and testis-enriched protein that functions in sperm development, contributing to two distinct aspects of spermatogenesis: acrosome biogenesis and flagellar architecture [#0, #1]. During late spermiogenesis it accumulates in the acrosome region and physically interacts with the BAR domain of SH3P13; knockdown in germ cells disrupts acrosome formation and spermatid differentiation, establishing a requirement for DYDC1 in acrosome biogenesis [#0]. DYDC1 is also a component of the radial spoke 1 (RS1) macromolecular complex of the sperm flagellum, localizing to both the RS1 head and the head-neck complex, consistent with a role in assembly of the RS1 structure that governs flagellar beat [#1]. Beyond these two roles, the molecular activity of DYDC1 and the mechanism by which it bridges acrosome formation and radial spoke assembly have not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2009,\n      \"claim\": \"Established the first molecular function for DYDC1 by identifying a binding partner and an in vivo developmental role, answering whether this testis-expressed protein participates in sperm formation.\",\n      \"evidence\": \"Yeast two-hybrid screen of human testis library, plus RNAi knockdown via germ cell transplantation in mice with expression analysis\",\n      \"pmids\": [\n        \"19545932\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Interaction with SH3P13 not validated by reciprocal endogenous co-IP or structural mapping\",\n        \"Molecular activity of DYDC1 in acrosome biogenesis undefined\",\n        \"RNAi knockdown rather than a clean genetic null\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Placed DYDC1 within a defined flagellar substructure, answering where the protein acts beyond the acrosome and linking it to motility machinery.\",\n      \"evidence\": \"Mass spectrometry of RS1-disrupted sperm from Iqub-/- mice and IQUB-mutant patients, western blotting, and bioinformatic structural modeling\",\n      \"pmids\": [\n        \"39849482\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No direct DYDC1 loss-of-function to test functional requirement in RS1 assembly or motility\",\n        \"Direct binding partners within RS1 not biochemically defined\",\n        \"Relationship between the acrosomal and flagellar roles unresolved\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The biochemical activity of DYDC1 and how a single protein contributes to both acrosome biogenesis and radial spoke assembly remain unknown.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No enzymatic or structural function assigned to DYDC1\",\n        \"No germline knockout phenotype reported in the corpus\",\n        \"Mechanism connecting the two cellular roles uncharacterized\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [],\n    \"pathway\": [],\n    \"complexes\": [\n      \"radial spoke 1 (RS1)\"\n    ],\n    \"partners\": [\n      \"SH3P13\",\n      \"IQUB\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":3,"faith_total":3,"faith_pct":100.0}}