{"gene":"CFAP263","run_date":"2026-06-09T22:57:18","timeline":{"discoveries":[{"year":2014,"finding":"CCDC113 (CFAP263) localizes to centriolar satellites in cultured cells, forms a complex with satellite proteins HAP1 and PCM1, and is required for primary cilium formation, as determined by mass spectrometry of sperm centrioles followed by localization and functional studies in cultured cells.","method":"Mass spectrometry of sperm centrioles; immunofluorescence localization; co-immunoprecipitation with HAP1 and PCM1; loss-of-function assay for primary cilium formation","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP establishing complex, direct localization with functional consequence (cilium formation), single lab with multiple orthogonal methods","pmids":["25074808"],"is_preprint":false},{"year":2021,"finding":"Ccdc113 (CFAP263) forms an evolutionarily conserved complex with Ccdc96 in cilia, positioned parallel to the nexin-dynein regulatory complex (N-DRC), connecting radial spoke 3 (RS3) to dynein g and N-DRC. Deletion of CCDC113 alters ciliary beating frequency, amplitude, and waveform. Stable docking and function of Ccdc113 requires co-presence of Ccdc96, although each protein can be transported to cilia independently.","method":"Genetic deletion; structural analysis of axoneme; ciliary beat frequency and waveform measurements; epistasis between Ccdc113 and Ccdc96 knockouts","journal":"PLoS genetics","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic deletion in Tetrahymena/Chlamydomonas model with defined structural and functional readouts, multiple orthogonal methods (structural, motility, genetic epistasis), independently corroborated by sperm studies","pmids":["33661892"],"is_preprint":false},{"year":2024,"finding":"CCDC113 (CFAP263) in mouse sperm acts as an adaptor protein connecting radial spokes, the nexin-dynein regulatory complex (N-DRC), and doublet microtubules (DMTs) in the sperm axoneme by binding to CFAP57 and CFAP91. Additionally, CCDC113 is a structural component of the head-tail coupling apparatus (HTCA), collaborating with SUN5 and CENTLEIN to connect sperm head to tail during spermiogenesis. Disruption of CCDC113 produces spermatozoa with disorganized flagella and HTCA, causing male infertility in mice.","method":"Co-immunoprecipitation (binding to CFAP57 and CFAP91, SUN5, CENTLEIN); knockout mouse model; ultrastructural analysis (TEM); fertility assays","journal":"eLife","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP identifying multiple binding partners, KO mouse with defined structural and fertility phenotypes, multiple orthogonal methods in single study","pmids":["39671309"],"is_preprint":false},{"year":2024,"finding":"CCDC113 (CFAP263) promotes colorectal cancer cell proliferation and migration via the TGF-β signaling pathway; the TGF-β pathway inhibitor galunisertib reverses the increased proliferation and migration caused by CCDC113 overexpression both in vitro and in vivo.","method":"RNA-seq; TCGA database analysis; overexpression and knockdown in CRC cell lines; in vitro proliferation/migration assays; in vivo tumor models; pharmacological inhibition with galunisertib","journal":"Cell death & disease","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional assays with OE/KD, pharmacological rescue, in vivo validation, single lab but multiple orthogonal methods","pmids":["39261464"],"is_preprint":false},{"year":2026,"finding":"Biallelic loss-of-function mutations in CCDC113 (p.K301Q and p.E135A) in humans cause oligoasthenoteratozoospermia with defective sperm flagella and less stable CCDC113 protein. Ccdc113 knockout mice recapitulate the human infertility phenotypes, including abnormal sperm morphology, impaired motility, and defective spermatogenesis.","method":"Whole-exome sequencing; functional protein stability analysis; Ccdc113 knockout mouse model; sperm morphology and motility assays; ultrastructural analysis","journal":"Asian journal of andrology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — human genetics with cosegregation, KO mouse recapitulation, protein stability assays, single lab","pmids":["41645397"],"is_preprint":false}],"current_model":"CFAP263/CCDC113 is an evolutionarily conserved coiled-coil domain-containing protein that functions as a structural adaptor in cilia and sperm flagella, forming a complex with CCDC96 to connect radial spoke 3, dynein g, and the nexin-dynein regulatory complex (N-DRC) to regulate ciliary beat pattern; in sperm, it additionally binds CFAP57, CFAP91, SUN5, and CENTLEIN to stabilize the axoneme and the head-tail coupling apparatus, with loss-of-function causing male infertility; in somatic cells it localizes to centriolar satellites in a complex with HAP1 and PCM1 to support primary ciliogenesis; and it has also been found to promote colorectal cancer cell proliferation and metastasis via TGF-β signaling."},"narrative":{"mechanistic_narrative":"CFAP263/CCDC113 is an evolutionarily conserved coiled-coil adaptor protein that organizes the axonemal machinery governing ciliary and flagellar motility [PMID:33661892, PMID:39671309]. In cilia it forms an evolutionarily conserved complex with CCDC96 positioned parallel to the nexin-dynein regulatory complex (N-DRC), physically linking radial spoke 3 to dynein g and the N-DRC; its stable docking requires co-presence of CCDC96, and its loss alters ciliary beat frequency, amplitude, and waveform [PMID:33661892]. In mouse sperm it serves the analogous adaptor role, binding CFAP57 and CFAP91 to connect radial spokes, the N-DRC, and doublet microtubules, and additionally acts as a structural component of the head-tail coupling apparatus together with SUN5 and CENTLEIN to join the sperm head to the flagellum during spermiogenesis [PMID:39671309]. Loss of CCDC113 produces disorganized flagella and head-tail coupling defects, and biallelic loss-of-function mutations cause oligoasthenoteratozoospermia and male infertility in humans, recapitulated in knockout mice [PMID:39671309, PMID:41645397]. In cultured somatic cells CCDC113 localizes to centriolar satellites in a complex with HAP1 and PCM1 and is required for primary cilium formation [PMID:25074808]. A distinct role in promoting colorectal cancer cell proliferation and migration via TGF-β signaling has also been reported [PMID:39261464].","teleology":[{"year":2014,"claim":"Identifying CCDC113 at centriolar satellites and in complex with established satellite proteins placed it within the ciliogenesis machinery of somatic cells before its axonemal role was known.","evidence":"Mass spectrometry of sperm centrioles, immunofluorescence, reciprocal Co-IP with HAP1 and PCM1, and loss-of-function assay for cilium formation in cultured cells","pmids":["25074808"],"confidence":"Medium","gaps":["Did not define the molecular function of the protein within the satellite complex","Mechanism by which it supports cilium assembly not resolved","No axonemal structural role established at this stage"]},{"year":2021,"claim":"Genetic and structural dissection in ciliate/algal models established CCDC113 as a structural adaptor wiring radial spoke 3 to dynein g and the N-DRC, defining how it regulates beat pattern.","evidence":"Genetic deletion, axonemal structural analysis, ciliary beat frequency/waveform measurements, and CCDC113/CCDC96 epistasis","pmids":["33661892"],"confidence":"High","gaps":["Atomic-resolution structure of the CCDC113-CCDC96 complex not determined","Mechanism linking the structural connection to specific waveform changes not detailed","Conservation of the role in mammalian sperm not yet tested at this point"]},{"year":2024,"claim":"A knockout mouse and binding studies extended the adaptor role to sperm and revealed a second function in the head-tail coupling apparatus, connecting axonemal organization to whole-flagellum and head-tail integrity.","evidence":"Co-IP mapping binding to CFAP57, CFAP91, SUN5, and CENTLEIN; knockout mouse; TEM ultrastructure; fertility assays","pmids":["39671309"],"confidence":"High","gaps":["Whether CCDC96 partnership is conserved in mammalian sperm not addressed","Stoichiometry and direct vs indirect nature of HTCA interactions not resolved","How the two roles (axoneme vs HTCA) are temporally coordinated unclear"]},{"year":2024,"claim":"A reported cancer phenotype linked CCDC113 to TGF-β signaling in a context distinct from its ciliary structural role.","evidence":"RNA-seq, TCGA analysis, overexpression/knockdown in CRC lines, in vitro and in vivo tumor assays, and galunisertib rescue","pmids":["39261464"],"confidence":"Medium","gaps":["Direct molecular link between CCDC113 and TGF-β pathway components not defined","Relationship to its ciliary/centriolar function unexplained","Single-lab finding without orthogonal mechanistic validation"]},{"year":2026,"claim":"Human genetics confirmed CCDC113 as a disease gene, tying loss-of-function and reduced protein stability to oligoasthenoteratozoospermia.","evidence":"Whole-exome sequencing of patients, protein stability analysis of variants, and knockout mouse recapitulation with sperm morphology/motility and ultrastructural assays","pmids":["41645397"],"confidence":"Medium","gaps":["Genotype-phenotype correlation across additional patients limited","Mechanism by which point mutations destabilize the protein not detailed","Single-lab cohort"]},{"year":null,"claim":"How CCDC113's conserved axonemal adaptor function relates mechanistically to its reported somatic and oncogenic roles remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No high-resolution structure of CCDC113 in any complex","Unclear whether the centriolar-satellite and axonemal roles share a common molecular activity","Mechanistic basis of the TGF-β connection unestablished"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[1,2]},{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[1,2]}],"localization":[{"term_id":"GO:0005929","term_label":"cilium","supporting_discovery_ids":[0,1,2]},{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[0]},{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[1,2]}],"pathway":[{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[0]},{"term_id":"R-HSA-1474165","term_label":"Reproduction","supporting_discovery_ids":[2,4]}],"complexes":["CCDC113-CCDC96 complex","centriolar satellite (HAP1-PCM1) complex","head-tail coupling apparatus"],"partners":["CCDC96","CFAP57","CFAP91","SUN5","CENTLEIN","HAP1","PCM1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9H0I3","full_name":"Cilia- and flagella-associated protein 263","aliases":[],"length_aa":377,"mass_kda":44.2,"function":"Component of centriolar satellites contributing to primary cilium formation (PubMed:25074808). In complex with CFAP263, acts as a regulator of ciliary beating that connects radial spoke 3 (RS3) to the inner dynein arm (IDA) and the nexin-dynein regulatory complex (N-DRC). The complex is positioned parallel to N-DRC and forms a connection between the arch at the base of RS3, the IDA tail and N-DRC (By similarity)","subcellular_location":"Cytoplasm, cytoskeleton, microtubule organizing center, centrosome, centriolar satellite; Cell projection, cilium","url":"https://www.uniprot.org/uniprotkb/Q9H0I3/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/CFAP263","classification":"Not Classified","n_dependent_lines":6,"n_total_lines":1208,"dependency_fraction":0.004966887417218543},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/CFAP263","total_profiled":1310},"omim":[],"hpa":{"profiled":true,"resolved_as":"CCDC113","reliability":"","locations":[],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"fallopian tube","ntpm":29.4}],"url":"https://www.proteinatlas.org/search/CCDC113"},"hgnc":{"alias_symbol":["HSPC065","DKFZp434N1418"],"prev_symbol":["CCDC113"]},"alphafold":{"accession":"Q9H0I3","domains":[{"cath_id":"-","chopping":"26-54_99-217","consensus_level":"medium","plddt":90.0161,"start":26,"end":217},{"cath_id":"1.20.5","chopping":"219-291","consensus_level":"medium","plddt":96.9918,"start":219,"end":291},{"cath_id":"1.10.287","chopping":"322-374","consensus_level":"medium","plddt":80.6449,"start":322,"end":374}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9H0I3","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9H0I3-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9H0I3-F1-predicted_aligned_error_v6.png","plddt_mean":83.19},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=CFAP263","jax_strain_url":"https://www.jax.org/strain/search?query=CFAP263"},"sequence":{"accession":"Q9H0I3","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9H0I3.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9H0I3/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9H0I3"}},"corpus_meta":[{"pmid":"25074808","id":"PMC_25074808","title":"Proteomic analysis of mammalian sperm cells identifies new components of the centrosome.","date":"2014","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/25074808","citation_count":93,"is_preprint":false},{"pmid":"33661892","id":"PMC_33661892","title":"Ccdc113/Ccdc96 complex, a novel regulator of ciliary beating that connects radial spoke 3 to dynein g and the nexin link.","date":"2021","source":"PLoS genetics","url":"https://pubmed.ncbi.nlm.nih.gov/33661892","citation_count":38,"is_preprint":false},{"pmid":"34280480","id":"PMC_34280480","title":"Different combinations of high-frequency rTMS and cognitive training improve the cognitive function of cerebral ischemic rats.","date":"2021","source":"Brain research bulletin","url":"https://pubmed.ncbi.nlm.nih.gov/34280480","citation_count":13,"is_preprint":false},{"pmid":"39261464","id":"PMC_39261464","title":"CCDC113 promotes colorectal cancer tumorigenesis and metastasis via TGF-β signaling pathway.","date":"2024","source":"Cell death & disease","url":"https://pubmed.ncbi.nlm.nih.gov/39261464","citation_count":11,"is_preprint":false},{"pmid":"39671309","id":"PMC_39671309","title":"CCDC113 stabilizes sperm axoneme and head-tail coupling apparatus to ensure male fertility.","date":"2024","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/39671309","citation_count":9,"is_preprint":false},{"pmid":"35923697","id":"PMC_35923697","title":"Looking for the Genes Related to Lung Cancer From Nasal Epithelial Cells by Network and Pathway Analysis.","date":"2022","source":"Frontiers in genetics","url":"https://pubmed.ncbi.nlm.nih.gov/35923697","citation_count":7,"is_preprint":false},{"pmid":"38006387","id":"PMC_38006387","title":"A robust mRNA signature obtained via recursive ensemble feature selection predicts the responsiveness of omalizumab in moderate-to-severe asthma.","date":"2023","source":"Clinical and translational allergy","url":"https://pubmed.ncbi.nlm.nih.gov/38006387","citation_count":5,"is_preprint":false},{"pmid":"40356234","id":"PMC_40356234","title":"Genetics of Childhood-Onset Systemic Lupus Erythematosus.","date":"2025","source":"Arthritis & rheumatology (Hoboken, N.J.)","url":"https://pubmed.ncbi.nlm.nih.gov/40356234","citation_count":4,"is_preprint":false},{"pmid":"39676709","id":"PMC_39676709","title":"Cross-Phenotype Genome-Wide Association Study on the Shared Genetic Susceptibility to Systemic Sclerosis and Primary Biliary Cholangitis.","date":"2025","source":"Arthritis & rheumatology (Hoboken, N.J.)","url":"https://pubmed.ncbi.nlm.nih.gov/39676709","citation_count":3,"is_preprint":false},{"pmid":"39006426","id":"PMC_39006426","title":"Cross-Phenotype GWAS Supports Shared Genetic Susceptibility to Systemic Sclerosis and Primary Biliary Cholangitis.","date":"2024","source":"medRxiv : the preprint server for health sciences","url":"https://pubmed.ncbi.nlm.nih.gov/39006426","citation_count":1,"is_preprint":false},{"pmid":"41645397","id":"PMC_41645397","title":"Loss-of-function mutations in Ccdc113 cause male infertility in both humans and mice.","date":"2026","source":"Asian journal of andrology","url":"https://pubmed.ncbi.nlm.nih.gov/41645397","citation_count":0,"is_preprint":false},{"pmid":"42117808","id":"PMC_42117808","title":"A Novel Circular RNA circSPEF2 Regulates Testis Development in Crucian Carp.","date":"2026","source":"Biology","url":"https://pubmed.ncbi.nlm.nih.gov/42117808","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":8060,"output_tokens":1549,"usd":0.023707,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":8322,"output_tokens":2479,"usd":0.051792,"stage2_stop_reason":"end_turn"},"total_usd":0.075499,"stage1_batch_id":"msgbatch_01ACAxJQabDsht39JXeWG22d","stage2_batch_id":"msgbatch_01QEU22A9U5sbPTgsMzTmvSf","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2014,\n      \"finding\": \"CCDC113 (CFAP263) localizes to centriolar satellites in cultured cells, forms a complex with satellite proteins HAP1 and PCM1, and is required for primary cilium formation, as determined by mass spectrometry of sperm centrioles followed by localization and functional studies in cultured cells.\",\n      \"method\": \"Mass spectrometry of sperm centrioles; immunofluorescence localization; co-immunoprecipitation with HAP1 and PCM1; loss-of-function assay for primary cilium formation\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP establishing complex, direct localization with functional consequence (cilium formation), single lab with multiple orthogonal methods\",\n      \"pmids\": [\"25074808\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Ccdc113 (CFAP263) forms an evolutionarily conserved complex with Ccdc96 in cilia, positioned parallel to the nexin-dynein regulatory complex (N-DRC), connecting radial spoke 3 (RS3) to dynein g and N-DRC. Deletion of CCDC113 alters ciliary beating frequency, amplitude, and waveform. Stable docking and function of Ccdc113 requires co-presence of Ccdc96, although each protein can be transported to cilia independently.\",\n      \"method\": \"Genetic deletion; structural analysis of axoneme; ciliary beat frequency and waveform measurements; epistasis between Ccdc113 and Ccdc96 knockouts\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic deletion in Tetrahymena/Chlamydomonas model with defined structural and functional readouts, multiple orthogonal methods (structural, motility, genetic epistasis), independently corroborated by sperm studies\",\n      \"pmids\": [\"33661892\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"CCDC113 (CFAP263) in mouse sperm acts as an adaptor protein connecting radial spokes, the nexin-dynein regulatory complex (N-DRC), and doublet microtubules (DMTs) in the sperm axoneme by binding to CFAP57 and CFAP91. Additionally, CCDC113 is a structural component of the head-tail coupling apparatus (HTCA), collaborating with SUN5 and CENTLEIN to connect sperm head to tail during spermiogenesis. Disruption of CCDC113 produces spermatozoa with disorganized flagella and HTCA, causing male infertility in mice.\",\n      \"method\": \"Co-immunoprecipitation (binding to CFAP57 and CFAP91, SUN5, CENTLEIN); knockout mouse model; ultrastructural analysis (TEM); fertility assays\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP identifying multiple binding partners, KO mouse with defined structural and fertility phenotypes, multiple orthogonal methods in single study\",\n      \"pmids\": [\"39671309\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"CCDC113 (CFAP263) promotes colorectal cancer cell proliferation and migration via the TGF-β signaling pathway; the TGF-β pathway inhibitor galunisertib reverses the increased proliferation and migration caused by CCDC113 overexpression both in vitro and in vivo.\",\n      \"method\": \"RNA-seq; TCGA database analysis; overexpression and knockdown in CRC cell lines; in vitro proliferation/migration assays; in vivo tumor models; pharmacological inhibition with galunisertib\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional assays with OE/KD, pharmacological rescue, in vivo validation, single lab but multiple orthogonal methods\",\n      \"pmids\": [\"39261464\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"Biallelic loss-of-function mutations in CCDC113 (p.K301Q and p.E135A) in humans cause oligoasthenoteratozoospermia with defective sperm flagella and less stable CCDC113 protein. Ccdc113 knockout mice recapitulate the human infertility phenotypes, including abnormal sperm morphology, impaired motility, and defective spermatogenesis.\",\n      \"method\": \"Whole-exome sequencing; functional protein stability analysis; Ccdc113 knockout mouse model; sperm morphology and motility assays; ultrastructural analysis\",\n      \"journal\": \"Asian journal of andrology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — human genetics with cosegregation, KO mouse recapitulation, protein stability assays, single lab\",\n      \"pmids\": [\"41645397\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"CFAP263/CCDC113 is an evolutionarily conserved coiled-coil domain-containing protein that functions as a structural adaptor in cilia and sperm flagella, forming a complex with CCDC96 to connect radial spoke 3, dynein g, and the nexin-dynein regulatory complex (N-DRC) to regulate ciliary beat pattern; in sperm, it additionally binds CFAP57, CFAP91, SUN5, and CENTLEIN to stabilize the axoneme and the head-tail coupling apparatus, with loss-of-function causing male infertility; in somatic cells it localizes to centriolar satellites in a complex with HAP1 and PCM1 to support primary ciliogenesis; and it has also been found to promote colorectal cancer cell proliferation and metastasis via TGF-β signaling.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CFAP263/CCDC113 is an evolutionarily conserved coiled-coil adaptor protein that organizes the axonemal machinery governing ciliary and flagellar motility [#1, #2]. In cilia it forms an evolutionarily conserved complex with CCDC96 positioned parallel to the nexin-dynein regulatory complex (N-DRC), physically linking radial spoke 3 to dynein g and the N-DRC; its stable docking requires co-presence of CCDC96, and its loss alters ciliary beat frequency, amplitude, and waveform [#1]. In mouse sperm it serves the analogous adaptor role, binding CFAP57 and CFAP91 to connect radial spokes, the N-DRC, and doublet microtubules, and additionally acts as a structural component of the head-tail coupling apparatus together with SUN5 and CENTLEIN to join the sperm head to the flagellum during spermiogenesis [#2]. Loss of CCDC113 produces disorganized flagella and head-tail coupling defects, and biallelic loss-of-function mutations cause oligoasthenoteratozoospermia and male infertility in humans, recapitulated in knockout mice [#2, #4]. In cultured somatic cells CCDC113 localizes to centriolar satellites in a complex with HAP1 and PCM1 and is required for primary cilium formation [#0]. A distinct role in promoting colorectal cancer cell proliferation and migration via TGF-\\u03b2 signaling has also been reported [#3].\",\n  \"teleology\": [\n    {\n      \"year\": 2014,\n      \"claim\": \"Identifying CCDC113 at centriolar satellites and in complex with established satellite proteins placed it within the ciliogenesis machinery of somatic cells before its axonemal role was known.\",\n      \"evidence\": \"Mass spectrometry of sperm centrioles, immunofluorescence, reciprocal Co-IP with HAP1 and PCM1, and loss-of-function assay for cilium formation in cultured cells\",\n      \"pmids\": [\"25074808\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Did not define the molecular function of the protein within the satellite complex\", \"Mechanism by which it supports cilium assembly not resolved\", \"No axonemal structural role established at this stage\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Genetic and structural dissection in ciliate/algal models established CCDC113 as a structural adaptor wiring radial spoke 3 to dynein g and the N-DRC, defining how it regulates beat pattern.\",\n      \"evidence\": \"Genetic deletion, axonemal structural analysis, ciliary beat frequency/waveform measurements, and CCDC113/CCDC96 epistasis\",\n      \"pmids\": [\"33661892\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Atomic-resolution structure of the CCDC113-CCDC96 complex not determined\", \"Mechanism linking the structural connection to specific waveform changes not detailed\", \"Conservation of the role in mammalian sperm not yet tested at this point\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"A knockout mouse and binding studies extended the adaptor role to sperm and revealed a second function in the head-tail coupling apparatus, connecting axonemal organization to whole-flagellum and head-tail integrity.\",\n      \"evidence\": \"Co-IP mapping binding to CFAP57, CFAP91, SUN5, and CENTLEIN; knockout mouse; TEM ultrastructure; fertility assays\",\n      \"pmids\": [\"39671309\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether CCDC96 partnership is conserved in mammalian sperm not addressed\", \"Stoichiometry and direct vs indirect nature of HTCA interactions not resolved\", \"How the two roles (axoneme vs HTCA) are temporally coordinated unclear\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"A reported cancer phenotype linked CCDC113 to TGF-\\u03b2 signaling in a context distinct from its ciliary structural role.\",\n      \"evidence\": \"RNA-seq, TCGA analysis, overexpression/knockdown in CRC lines, in vitro and in vivo tumor assays, and galunisertib rescue\",\n      \"pmids\": [\"39261464\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct molecular link between CCDC113 and TGF-\\u03b2 pathway components not defined\", \"Relationship to its ciliary/centriolar function unexplained\", \"Single-lab finding without orthogonal mechanistic validation\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Human genetics confirmed CCDC113 as a disease gene, tying loss-of-function and reduced protein stability to oligoasthenoteratozoospermia.\",\n      \"evidence\": \"Whole-exome sequencing of patients, protein stability analysis of variants, and knockout mouse recapitulation with sperm morphology/motility and ultrastructural assays\",\n      \"pmids\": [\"41645397\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Genotype-phenotype correlation across additional patients limited\", \"Mechanism by which point mutations destabilize the protein not detailed\", \"Single-lab cohort\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How CCDC113's conserved axonemal adaptor function relates mechanistically to its reported somatic and oncogenic roles remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No high-resolution structure of CCDC113 in any complex\", \"Unclear whether the centriolar-satellite and axonemal roles share a common molecular activity\", \"Mechanistic basis of the TGF-\\u03b2 connection unestablished\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [1, 2]},\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [1, 2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [0, 1, 2]},\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [1, 2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"R-HSA-1474165\", \"supporting_discovery_ids\": [2, 4]}\n    ],\n    \"complexes\": [\n      \"CCDC113-CCDC96 complex\",\n      \"centriolar satellite (HAP1-PCM1) complex\",\n      \"head-tail coupling apparatus\"\n    ],\n    \"partners\": [\n      \"CCDC96\",\n      \"CFAP57\",\n      \"CFAP91\",\n      \"SUN5\",\n      \"CENTLEIN\",\n      \"HAP1\",\n      \"PCM1\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":6,"faith_pct":100.0}}