{"gene":"DYDC1","run_date":"2026-04-28T17:46:03","timeline":{"discoveries":[{"year":2009,"finding":"DYDC1 interacts with the BAR domain of SH3P13 (identified by yeast two-hybrid screen from a human testis library), is exclusively expressed in brain and testis, accumulates in the acrosome area during late spermiogenesis, and its knockdown via RNA interference and germ cell transplantation disrupts acrosome formation and spermatid differentiation in mice, establishing a role in acrosome biogenesis.","method":"Yeast two-hybrid screen, immunolocalization, RNA interference knockdown with germ cell transplantation in vivo","journal":"European journal of cell biology","confidence":"Medium","confidence_rationale":"Tier 2 — clean KD with defined cellular phenotype (acrosome disruption) + protein interaction identification, single lab","pmids":["19545932"],"is_preprint":false},{"year":2025,"finding":"DYDC1 was identified as a critical component of radial spoke 1 (RS1) in sperm flagella; specifically, DYDC1 contributes to both the RS1 head and the head-neck complex, as determined by protein mass spectrometry and structural modeling in IQUB-deficient human and mouse sperm where RS1 is specifically absent.","method":"Protein mass spectrometry, western blotting, bioinformatic structural modeling, electron microscopy of Iqub-/- mice and IQUB mutant patient sperm","journal":"Cell communication and signaling : CCS","confidence":"Medium","confidence_rationale":"Tier 2 — MS-based identification of RS1 components with functional validation in KO model, single lab","pmids":["39849482"],"is_preprint":false}],"current_model":"DYDC1 is a testis-enriched protein that physically interacts with the BAR-domain protein SH3P13 to regulate acrosome biogenesis during spermiogenesis, and additionally localizes as a structural component of the radial spoke 1 (RS1) head and head-neck complex in sperm flagella, where it contributes to flagellar beat regulation."},"narrative":{"teleology":[{"year":2009,"claim":"The first functional characterization of DYDC1 established that it interacts with SH3P13, localizes to the acrosome during spermiogenesis, and is required for normal acrosome biogenesis — answering what role this uncharacterized testis-enriched gene plays in male germ cell development.","evidence":"Yeast two-hybrid screen from human testis library, immunolocalization in spermatids, and RNAi knockdown with germ cell transplantation in mice","pmids":["19545932"],"confidence":"Medium","gaps":["Knockdown phenotype from a single lab has not been independently replicated","Molecular mechanism by which DYDC1–SH3P13 interaction drives acrosome formation is undefined","Whether DYDC1 loss causes male infertility in a full knockout model was not tested"]},{"year":2025,"claim":"Proteomic dissection of radial spoke composition revealed that DYDC1 is a structural subunit of the RS1 head and head-neck complex in sperm flagella — extending its function beyond acrosome biogenesis to axonemal architecture and motility regulation.","evidence":"Mass spectrometry of IQUB-deficient human and mouse sperm lacking RS1, combined with western blotting and structural modeling","pmids":["39849482"],"confidence":"Medium","gaps":["Identification is based on loss of DYDC1 in RS1-depleted sperm; direct structural placement within the RS1 complex awaits cryo-EM validation","Whether DYDC1 loss alone is sufficient to disrupt RS1 assembly or flagellar motility is untested","Relationship between DYDC1's acrosomal and flagellar roles is unexplored"]},{"year":null,"claim":"It remains unknown whether DYDC1 mutations cause human infertility, how its dual localization to the acrosome and radial spoke is regulated, and what its precise molecular activity is within either structure.","evidence":"","pmids":[],"confidence":"Low","gaps":["No human disease-causing mutations in DYDC1 have been reported","No enzymatic or scaffolding activity has been biochemically assigned","No structural model of DYDC1 at atomic resolution exists"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[1]}],"localization":[{"term_id":"GO:0005929","term_label":"cilium","supporting_discovery_ids":[0,1]}],"pathway":[{"term_id":"R-HSA-1474165","term_label":"Reproduction","supporting_discovery_ids":[0,1]}],"complexes":[],"partners":["SH3P13","IQUB"],"other_free_text":[]},"mechanistic_narrative":"DYDC1 is a testis-enriched protein that functions in both acrosome biogenesis and flagellar structure during spermiogenesis. It physically interacts with the BAR-domain protein SH3P13, accumulates in the acrosome area during late spermiogenesis, and its knockdown disrupts acrosome formation and spermatid differentiation in mice [PMID:19545932]. DYDC1 is also a structural component of the radial spoke 1 (RS1) head and head-neck complex in sperm flagella, where loss of RS1 (in IQUB-deficient sperm) correlates with flagellar beat defects [PMID:39849482]."},"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":5,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4076,"output_tokens":580,"usd":0.010464},"stage2":{"model":"claude-opus-4-6","input_tokens":3743,"output_tokens":980,"usd":0.064823},"total_usd":0.075287,"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\": 2009,\n      \"finding\": \"DYDC1 interacts with the BAR domain of SH3P13 (identified by yeast two-hybrid screen from a human testis library), is exclusively expressed in brain and testis, accumulates in the acrosome area during late spermiogenesis, and its knockdown via RNA interference and germ cell transplantation disrupts acrosome formation and spermatid differentiation in mice, establishing a role in acrosome biogenesis.\",\n      \"method\": \"Yeast two-hybrid screen, immunolocalization, RNA interference knockdown with germ cell transplantation in vivo\",\n      \"journal\": \"European journal of cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — clean KD with defined cellular phenotype (acrosome disruption) + protein interaction identification, single lab\",\n      \"pmids\": [\"19545932\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"DYDC1 was identified as a critical component of radial spoke 1 (RS1) in sperm flagella; specifically, DYDC1 contributes to both the RS1 head and the head-neck complex, as determined by protein mass spectrometry and structural modeling in IQUB-deficient human and mouse sperm where RS1 is specifically absent.\",\n      \"method\": \"Protein mass spectrometry, western blotting, bioinformatic structural modeling, electron microscopy of Iqub-/- mice and IQUB mutant patient sperm\",\n      \"journal\": \"Cell communication and signaling : CCS\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — MS-based identification of RS1 components with functional validation in KO model, single lab\",\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 to regulate acrosome biogenesis during spermiogenesis, and additionally localizes as a structural component of the radial spoke 1 (RS1) head and head-neck complex in sperm flagella, where it contributes to flagellar beat regulation.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"DYDC1 is a testis-enriched protein that functions in both acrosome biogenesis and flagellar structure during spermiogenesis. It physically interacts with the BAR-domain protein SH3P13, accumulates in the acrosome area during late spermiogenesis, and its knockdown disrupts acrosome formation and spermatid differentiation in mice [PMID:19545932]. DYDC1 is also a structural component of the radial spoke 1 (RS1) head and head-neck complex in sperm flagella, where loss of RS1 (in IQUB-deficient sperm) correlates with flagellar beat defects [PMID:39849482].\",\n  \"teleology\": [\n    {\n      \"year\": 2009,\n      \"claim\": \"The first functional characterization of DYDC1 established that it interacts with SH3P13, localizes to the acrosome during spermiogenesis, and is required for normal acrosome biogenesis — answering what role this uncharacterized testis-enriched gene plays in male germ cell development.\",\n      \"evidence\": \"Yeast two-hybrid screen from human testis library, immunolocalization in spermatids, and RNAi knockdown with germ cell transplantation in mice\",\n      \"pmids\": [\"19545932\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Knockdown phenotype from a single lab has not been independently replicated\",\n        \"Molecular mechanism by which DYDC1–SH3P13 interaction drives acrosome formation is undefined\",\n        \"Whether DYDC1 loss causes male infertility in a full knockout model was not tested\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Proteomic dissection of radial spoke composition revealed that DYDC1 is a structural subunit of the RS1 head and head-neck complex in sperm flagella — extending its function beyond acrosome biogenesis to axonemal architecture and motility regulation.\",\n      \"evidence\": \"Mass spectrometry of IQUB-deficient human and mouse sperm lacking RS1, combined with western blotting and structural modeling\",\n      \"pmids\": [\"39849482\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Identification is based on loss of DYDC1 in RS1-depleted sperm; direct structural placement within the RS1 complex awaits cryo-EM validation\",\n        \"Whether DYDC1 loss alone is sufficient to disrupt RS1 assembly or flagellar motility is untested\",\n        \"Relationship between DYDC1's acrosomal and flagellar roles is unexplored\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown whether DYDC1 mutations cause human infertility, how its dual localization to the acrosome and radial spoke is regulated, and what its precise molecular activity is within either structure.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No human disease-causing mutations in DYDC1 have been reported\",\n        \"No enzymatic or scaffolding activity has been biochemically assigned\",\n        \"No structural model of DYDC1 at atomic resolution exists\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1474165\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"SH3P13\", \"IQUB\"],\n    \"other_free_text\": []\n  }\n}\n```"}