{"gene":"RIBC1","run_date":"2026-06-10T06:43:36","timeline":{"discoveries":[{"year":2025,"finding":"RIBC1 and RIBC2 are microtubule inner proteins (MIPs) localized in the inner lumen of the doublet microtubules (DMTs) in mouse sperm flagella, as shown by cryo-electron microscopy and AI-based structural studies. Knockout of RIBC1 alone reduces sperm velocity, while knockout of both RIBC1 and RIBC2 causes significantly greater reduction in sperm motility and decreased litter size, without detectable axonemal structural abnormalities at the TEM level, indicating RIBC1 and RIBC2 function cooperatively in sperm motility and that RIBC2's function in this context depends on RIBC1.","method":"CRISPR/Cas9 knockout mice (single and double KO), sperm motility analysis, transmission electron microscopy, cryo-electron microscopy, AI structural analysis","journal":"Andrology","confidence":"High","confidence_rationale":"Tier 2 / Moderate — genetic loss-of-function with defined cellular phenotype, multiple orthogonal methods (cryo-EM localization, TEM, motility analysis, fertility assay) in a single rigorous study","pmids":["40265983"],"is_preprint":false}],"current_model":"RIBC1 is a microtubule inner protein (MIP) that localizes to the inner lumen of doublet microtubules in sperm flagella and cooperates with its paralog RIBC2 to support sperm motility; loss of RIBC1 alone reduces sperm velocity, and combined loss of both RIBC1 and RIBC2 further impairs motility and fertility without gross axonemal structural defects detectable by TEM."},"narrative":{"mechanistic_narrative":"RIBC1 is a microtubule inner protein (MIP) that localizes to the inner lumen of the doublet microtubules in mouse sperm flagella, where it acts together with its paralog RIBC2 to support sperm motility [PMID:40265983]. Knockout of RIBC1 alone reduces sperm velocity, while combined loss of both RIBC1 and RIBC2 produces a markedly greater motility defect and reduced litter size, with RIBC2's contribution depending on RIBC1 and without axonemal structural abnormalities detectable by TEM [PMID:40265983]. Beyond this localization and genetic role in flagellar motility [PMID:40265983], no further mechanistic detail—including binding partners, the structural basis of its association with the microtubule lumen, or molecular activity—has been characterized in the available corpus.","teleology":[{"year":2025,"claim":"Whether RIBC1 has a defined location and function within the sperm flagellar axoneme was unknown; this work established it as a microtubule inner protein essential for normal sperm motility and fertility.","evidence":"CRISPR/Cas9 single and double knockout mice with sperm motility analysis, fertility assays, TEM, and cryo-EM/AI structural localization","pmids":["40265983"],"confidence":"High","gaps":["The molecular activity of RIBC1 and how it binds the doublet microtubule lumen are not defined","Direct physical partners, including the nature of the RIBC1–RIBC2 interaction, are not established","How loss of RIBC1 reduces motility without detectable axonemal structural defects is unexplained"]},{"year":null,"claim":"The biochemical mechanism by which RIBC1 stabilizes or organizes the doublet microtubule lumen to support flagellar beating remains unresolved.","evidence":"","pmids":[],"confidence":"High","gaps":["No structural model of RIBC1 bound within the microtubule lumen","No identified molecular activity or direct interaction interface with tubulin or RIBC2"]}],"mechanism_profile":{"molecular_activity":[],"localization":[{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[0]},{"term_id":"GO:0005929","term_label":"cilium","supporting_discovery_ids":[0]}],"pathway":[],"complexes":[],"partners":["RIBC2"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q8N443","full_name":"RIB43A-like with coiled-coils protein 1","aliases":[],"length_aa":379,"mass_kda":44.0,"function":"","subcellular_location":"Cytoplasm, cytoskeleton, flagellum axoneme","url":"https://www.uniprot.org/uniprotkb/Q8N443/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/RIBC1","classification":"Not Classified","n_dependent_lines":2,"n_total_lines":1208,"dependency_fraction":0.0016556291390728477},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/RIBC1","total_profiled":1310},"omim":[],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nuclear bodies","reliability":"Approved"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"choroid plexus","ntpm":26.6},{"tissue":"fallopian tube","ntpm":25.8},{"tissue":"testis","ntpm":35.4}],"url":"https://www.proteinatlas.org/search/RIBC1"},"hgnc":{"alias_symbol":["FLJ32783"],"prev_symbol":[]},"alphafold":{"accession":"Q8N443","domains":[],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8N443","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q8N443-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q8N443-F1-predicted_aligned_error_v6.png","plddt_mean":83.81},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=RIBC1","jax_strain_url":"https://www.jax.org/strain/search?query=RIBC1"},"sequence":{"accession":"Q8N443","fasta_url":"https://rest.uniprot.org/uniprotkb/Q8N443.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q8N443/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8N443"}},"corpus_meta":[{"pmid":"18252223","id":"PMC_18252223","title":"Submicroscopic duplications of the hydroxysteroid dehydrogenase HSD17B10 and the E3 ubiquitin ligase HUWE1 are associated with mental retardation.","date":"2008","source":"American journal of human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/18252223","citation_count":178,"is_preprint":false},{"pmid":"29982135","id":"PMC_29982135","title":"Identification of biomarker candidates for fertility in spermatozoa of crossbred bulls through comparative proteomics.","date":"2018","source":"Theriogenology","url":"https://pubmed.ncbi.nlm.nih.gov/29982135","citation_count":46,"is_preprint":false},{"pmid":"40265983","id":"PMC_40265983","title":"The absence of both RIBC1 and RIBC2 induces decreased sperm motility and litter size in male mice.","date":"2025","source":"Andrology","url":"https://pubmed.ncbi.nlm.nih.gov/40265983","citation_count":3,"is_preprint":false},{"pmid":"22931212","id":"PMC_22931212","title":"Elucidation of the mechanism of ribose conjugation in a pyrazole-containing compound in rodent liver.","date":"2012","source":"Xenobiotica; the fate of foreign compounds in biological systems","url":"https://pubmed.ncbi.nlm.nih.gov/22931212","citation_count":3,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4532,"output_tokens":464,"usd":0.010278,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6729,"output_tokens":904,"usd":0.028123,"stage2_stop_reason":"end_turn"},"total_usd":0.038401,"stage1_batch_id":"msgbatch_01CNoDbkChHEkgrJnL7BwtGJ","stage2_batch_id":"msgbatch_016Y4x9E9Wg5VQDANj9quSQD","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2025,\n      \"finding\": \"RIBC1 and RIBC2 are microtubule inner proteins (MIPs) localized in the inner lumen of the doublet microtubules (DMTs) in mouse sperm flagella, as shown by cryo-electron microscopy and AI-based structural studies. Knockout of RIBC1 alone reduces sperm velocity, while knockout of both RIBC1 and RIBC2 causes significantly greater reduction in sperm motility and decreased litter size, without detectable axonemal structural abnormalities at the TEM level, indicating RIBC1 and RIBC2 function cooperatively in sperm motility and that RIBC2's function in this context depends on RIBC1.\",\n      \"method\": \"CRISPR/Cas9 knockout mice (single and double KO), sperm motility analysis, transmission electron microscopy, cryo-electron microscopy, AI structural analysis\",\n      \"journal\": \"Andrology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic loss-of-function with defined cellular phenotype, multiple orthogonal methods (cryo-EM localization, TEM, motility analysis, fertility assay) in a single rigorous study\",\n      \"pmids\": [\"40265983\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"RIBC1 is a microtubule inner protein (MIP) that localizes to the inner lumen of doublet microtubules in sperm flagella and cooperates with its paralog RIBC2 to support sperm motility; loss of RIBC1 alone reduces sperm velocity, and combined loss of both RIBC1 and RIBC2 further impairs motility and fertility without gross axonemal structural defects detectable by TEM.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"RIBC1 is a microtubule inner protein (MIP) that localizes to the inner lumen of the doublet microtubules in mouse sperm flagella, where it acts together with its paralog RIBC2 to support sperm motility [#0]. Knockout of RIBC1 alone reduces sperm velocity, while combined loss of both RIBC1 and RIBC2 produces a markedly greater motility defect and reduced litter size, with RIBC2's contribution depending on RIBC1 and without axonemal structural abnormalities detectable by TEM [#0]. Beyond this localization and genetic role in flagellar motility [#0], no further mechanistic detail—including binding partners, the structural basis of its association with the microtubule lumen, or molecular activity—has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2025,\n      \"claim\": \"Whether RIBC1 has a defined location and function within the sperm flagellar axoneme was unknown; this work established it as a microtubule inner protein essential for normal sperm motility and fertility.\",\n      \"evidence\": \"CRISPR/Cas9 single and double knockout mice with sperm motility analysis, fertility assays, TEM, and cryo-EM/AI structural localization\",\n      \"pmids\": [\"40265983\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The molecular activity of RIBC1 and how it binds the doublet microtubule lumen are not defined\",\n        \"Direct physical partners, including the nature of the RIBC1–RIBC2 interaction, are not established\",\n        \"How loss of RIBC1 reduces motility without detectable axonemal structural defects is unexplained\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The biochemical mechanism by which RIBC1 stabilizes or organizes the doublet microtubule lumen to support flagellar beating remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No structural model of RIBC1 bound within the microtubule lumen\",\n        \"No identified molecular activity or direct interaction interface with tubulin or RIBC2\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [\"RIBC2\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"faith_supported":3,"faith_total":3,"faith_pct":100.0}}