{"gene":"FAM161B","run_date":"2026-04-28T17:46:03","timeline":{"discoveries":[{"year":2012,"finding":"FAM161B interacts with FAM161A through the evolutionarily conserved UPF0564 domain, which also mediates microtubule binding; this heterotypic interaction was demonstrated by pull-down and co-immunoprecipitation experiments in cultured cells.","method":"Pull-down / co-immunoprecipitation; domain deletion/mutagenesis in cultured cells","journal":"Human molecular genetics","confidence":"Medium","confidence_rationale":"Tier 2 — direct binding assay with domain-level mapping, single lab, two orthogonal methods","pmids":["22791751"],"is_preprint":false},{"year":2010,"finding":"FAM161B was identified as a physical interactor of TACC3 by interactome mapping (co-purification/pull-down), placing FAM161B in a centrosome-associated protein complex involved in cell division.","method":"Interactome mapping / co-purification (TACC3 pull-down)","journal":"Cell cycle (Georgetown, Tex.)","confidence":"Low","confidence_rationale":"Tier 3 — single identification in an interactome screen, no further mechanistic follow-up on FAM161B itself","pmids":["20237422"],"is_preprint":false},{"year":2024,"finding":"The Drosophila orthologue of FAM161A/FAM161B (Fam161) localizes to centrioles and the cilium transition zone in a cell-type-specific manner; loss-of-function mutants display reduced male reproduction and abnormal geotaxis, establishing it as an essential centriole and transition zone protein.","method":"Genetic knockout (loss-of-function mutant), immunofluorescence localization, behavioral assay","journal":"Open biology","confidence":"Medium","confidence_rationale":"Tier 2 — clean KO with defined cellular and organismal phenotypes, direct localization imaging; Drosophila orthologue study","pmids":["39255847"],"is_preprint":false}],"current_model":"FAM161B is a microtubule-associated protein that localizes to centrosomes/centrioles and interacts with FAM161A via the conserved UPF0564 domain; it is part of the TACC3 interactome at the centrosome and, based on its Drosophila orthologue, functions as an essential component of the centriole and cilium transition zone required for ciliary integrity and cell division."},"narrative":{"teleology":[{"year":2010,"claim":"Placing FAM161B within a centrosome-associated complex: an interactome screen identified FAM161B as a physical interactor of TACC3, linking FAM161B for the first time to centrosome biology and cell division.","evidence":"Co-purification/pull-down from a TACC3-centered interactome mapping in human cells","pmids":["20237422"],"confidence":"Low","gaps":["Single interactome hit without reciprocal validation or mechanistic follow-up on FAM161B","No functional characterization of FAM161B's role at the centrosome","Interaction stoichiometry and directness not established"]},{"year":2012,"claim":"Defining the molecular basis of the FAM161A–FAM161B interaction and connecting both proteins to microtubules: the conserved UPF0564 domain was shown to mediate heterotypic binding between FAM161A and FAM161B as well as direct microtubule association, establishing a shared structural platform for cytoskeletal engagement.","evidence":"Pull-down and co-immunoprecipitation with domain deletion/mutagenesis in cultured mammalian cells","pmids":["22791751"],"confidence":"Medium","gaps":["Functional consequence of the FAM161A–FAM161B interaction in cells was not tested (e.g., by co-depletion)","No structural data on the UPF0564 domain or the interaction interface","Endogenous complex stoichiometry and tissue-specific relevance remain undefined"]},{"year":2024,"claim":"Establishing in vivo essentiality for centriole and cilium transition zone function: loss-of-function of the Drosophila FAM161A/B orthologue demonstrated that this protein family is required for ciliary integrity, male fertility, and geotaxis behavior, grounding the biochemical observations in an organismal context.","evidence":"Genetic knockout, immunofluorescence localization to centrioles and transition zone, and behavioral/reproductive phenotyping in Drosophila","pmids":["39255847"],"confidence":"Medium","gaps":["Drosophila has a single orthologue for both FAM161A and FAM161B, so individual contributions of mammalian paralogues remain unresolved","No mammalian loss-of-function data for FAM161B specifically","Mechanism by which FAM161B contributes to transition zone assembly or ciliary gating is unknown"]},{"year":null,"claim":"The specific, non-redundant functions of FAM161B versus FAM161A in mammalian cells — including whether FAM161B is required for ciliogenesis, centrosome integrity, or cell division — remain uncharacterized by direct mammalian genetic or functional studies.","evidence":"","pmids":[],"confidence":"Low","gaps":["No mammalian knockout or knockdown phenotype reported for FAM161B","No disease association established for FAM161B mutations (unlike FAM161A in retinitis pigmentosa)","Structural basis for UPF0564-mediated microtubule binding and partner selectivity is unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[0]}],"localization":[{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[1,2]},{"term_id":"GO:0005929","term_label":"cilium","supporting_discovery_ids":[2]}],"pathway":[{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[2]}],"complexes":[],"partners":["FAM161A","TACC3"],"other_free_text":[]},"mechanistic_narrative":"FAM161B is a microtubule-associated protein that interacts with FAM161A through the conserved UPF0564 domain, which also mediates direct microtubule binding [PMID:22791751]. FAM161B is part of a centrosome-associated protein network, physically interacting with the mitotic spindle regulator TACC3 [PMID:20237422]. Studies of the Drosophila orthologue (Fam161, orthologous to both FAM161A and FAM161B) demonstrate that this protein family localizes to centrioles and the cilium transition zone and is essential for male reproduction and sensory-dependent behavior, establishing a conserved role in centriole and ciliary function [PMID:39255847]."},"prefetch_data":{"uniprot":{"accession":"Q96MY7","full_name":"Protein FAM161B","aliases":[],"length_aa":647,"mass_kda":73.6,"function":"","subcellular_location":"","url":"https://www.uniprot.org/uniprotkb/Q96MY7/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/FAM161B","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/FAM161B","total_profiled":1310},"omim":[],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nucleoplasm","reliability":"Approved"},{"location":"Plasma membrane","reliability":"Approved"},{"location":"Vesicles","reliability":"Additional"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/FAM161B"},"hgnc":{"alias_symbol":["FLJ31697"],"prev_symbol":["C14orf44"]},"alphafold":{"accession":"Q96MY7","domains":[{"cath_id":"-","chopping":"549-585","consensus_level":"medium","plddt":89.9841,"start":549,"end":585},{"cath_id":"1.20.5","chopping":"508-546","consensus_level":"medium","plddt":92.5131,"start":508,"end":546}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96MY7","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q96MY7-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q96MY7-F1-predicted_aligned_error_v6.png","plddt_mean":67.38},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=FAM161B","jax_strain_url":"https://www.jax.org/strain/search?query=FAM161B"},"sequence":{"accession":"Q96MY7","fasta_url":"https://rest.uniprot.org/uniprotkb/Q96MY7.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q96MY7/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96MY7"}},"corpus_meta":[{"pmid":"22940612","id":"PMC_22940612","title":"FAM161A, associated with retinitis pigmentosa, is a component of the cilia-basal body complex and interacts with proteins involved in ciliopathies.","date":"2012","source":"Human molecular genetics","url":"https://pubmed.ncbi.nlm.nih.gov/22940612","citation_count":52,"is_preprint":false},{"pmid":"22791751","id":"PMC_22791751","title":"The retinitis pigmentosa 28 protein FAM161A is a novel ciliary protein involved in intermolecular protein interaction and microtubule association.","date":"2012","source":"Human molecular genetics","url":"https://pubmed.ncbi.nlm.nih.gov/22791751","citation_count":49,"is_preprint":false},{"pmid":"28356075","id":"PMC_28356075","title":"Genome-wide association study and accuracy of genomic prediction for teat number in Duroc pigs using genotyping-by-sequencing.","date":"2017","source":"Genetics, selection, evolution : GSE","url":"https://pubmed.ncbi.nlm.nih.gov/28356075","citation_count":43,"is_preprint":false},{"pmid":"23049694","id":"PMC_23049694","title":"Genome-wide screening of genes regulated by DNA methylation in colon cancer development.","date":"2012","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/23049694","citation_count":40,"is_preprint":false},{"pmid":"20237422","id":"PMC_20237422","title":"TACC3-TSC2 maintains nuclear envelope structure and controls cell division.","date":"2010","source":"Cell cycle (Georgetown, Tex.)","url":"https://pubmed.ncbi.nlm.nih.gov/20237422","citation_count":34,"is_preprint":false},{"pmid":"41056823","id":"PMC_41056823","title":"Genome-wide association study implicates possible causal genes for growth, fatness, and reproductive traits in pig.","date":"2025","source":"Animal : an international journal of animal bioscience","url":"https://pubmed.ncbi.nlm.nih.gov/41056823","citation_count":2,"is_preprint":false},{"pmid":"39255847","id":"PMC_39255847","title":"Fly Fam161 is an essential centriole and cilium transition zone protein with unique and diverse cell type-specific localizations.","date":"2024","source":"Open biology","url":"https://pubmed.ncbi.nlm.nih.gov/39255847","citation_count":1,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5173,"output_tokens":698,"usd":0.012995},"stage2":{"model":"claude-opus-4-6","input_tokens":3879,"output_tokens":1254,"usd":0.076118},"total_usd":0.089113,"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\": 2012,\n      \"finding\": \"FAM161B interacts with FAM161A through the evolutionarily conserved UPF0564 domain, which also mediates microtubule binding; this heterotypic interaction was demonstrated by pull-down and co-immunoprecipitation experiments in cultured cells.\",\n      \"method\": \"Pull-down / co-immunoprecipitation; domain deletion/mutagenesis in cultured cells\",\n      \"journal\": \"Human molecular genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — direct binding assay with domain-level mapping, single lab, two orthogonal methods\",\n      \"pmids\": [\"22791751\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"FAM161B was identified as a physical interactor of TACC3 by interactome mapping (co-purification/pull-down), placing FAM161B in a centrosome-associated protein complex involved in cell division.\",\n      \"method\": \"Interactome mapping / co-purification (TACC3 pull-down)\",\n      \"journal\": \"Cell cycle (Georgetown, Tex.)\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — single identification in an interactome screen, no further mechanistic follow-up on FAM161B itself\",\n      \"pmids\": [\"20237422\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"The Drosophila orthologue of FAM161A/FAM161B (Fam161) localizes to centrioles and the cilium transition zone in a cell-type-specific manner; loss-of-function mutants display reduced male reproduction and abnormal geotaxis, establishing it as an essential centriole and transition zone protein.\",\n      \"method\": \"Genetic knockout (loss-of-function mutant), immunofluorescence localization, behavioral assay\",\n      \"journal\": \"Open biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — clean KO with defined cellular and organismal phenotypes, direct localization imaging; Drosophila orthologue study\",\n      \"pmids\": [\"39255847\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"FAM161B is a microtubule-associated protein that localizes to centrosomes/centrioles and interacts with FAM161A via the conserved UPF0564 domain; it is part of the TACC3 interactome at the centrosome and, based on its Drosophila orthologue, functions as an essential component of the centriole and cilium transition zone required for ciliary integrity and cell division.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"FAM161B is a microtubule-associated protein that interacts with FAM161A through the conserved UPF0564 domain, which also mediates direct microtubule binding [PMID:22791751]. FAM161B is part of a centrosome-associated protein network, physically interacting with the mitotic spindle regulator TACC3 [PMID:20237422]. Studies of the Drosophila orthologue (Fam161, orthologous to both FAM161A and FAM161B) demonstrate that this protein family localizes to centrioles and the cilium transition zone and is essential for male reproduction and sensory-dependent behavior, establishing a conserved role in centriole and ciliary function [PMID:39255847].\",\n  \"teleology\": [\n    {\n      \"year\": 2010,\n      \"claim\": \"Placing FAM161B within a centrosome-associated complex: an interactome screen identified FAM161B as a physical interactor of TACC3, linking FAM161B for the first time to centrosome biology and cell division.\",\n      \"evidence\": \"Co-purification/pull-down from a TACC3-centered interactome mapping in human cells\",\n      \"pmids\": [\"20237422\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single interactome hit without reciprocal validation or mechanistic follow-up on FAM161B\",\n        \"No functional characterization of FAM161B's role at the centrosome\",\n        \"Interaction stoichiometry and directness not established\"\n      ]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Defining the molecular basis of the FAM161A–FAM161B interaction and connecting both proteins to microtubules: the conserved UPF0564 domain was shown to mediate heterotypic binding between FAM161A and FAM161B as well as direct microtubule association, establishing a shared structural platform for cytoskeletal engagement.\",\n      \"evidence\": \"Pull-down and co-immunoprecipitation with domain deletion/mutagenesis in cultured mammalian cells\",\n      \"pmids\": [\"22791751\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Functional consequence of the FAM161A–FAM161B interaction in cells was not tested (e.g., by co-depletion)\",\n        \"No structural data on the UPF0564 domain or the interaction interface\",\n        \"Endogenous complex stoichiometry and tissue-specific relevance remain undefined\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Establishing in vivo essentiality for centriole and cilium transition zone function: loss-of-function of the Drosophila FAM161A/B orthologue demonstrated that this protein family is required for ciliary integrity, male fertility, and geotaxis behavior, grounding the biochemical observations in an organismal context.\",\n      \"evidence\": \"Genetic knockout, immunofluorescence localization to centrioles and transition zone, and behavioral/reproductive phenotyping in Drosophila\",\n      \"pmids\": [\"39255847\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Drosophila has a single orthologue for both FAM161A and FAM161B, so individual contributions of mammalian paralogues remain unresolved\",\n        \"No mammalian loss-of-function data for FAM161B specifically\",\n        \"Mechanism by which FAM161B contributes to transition zone assembly or ciliary gating is unknown\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The specific, non-redundant functions of FAM161B versus FAM161A in mammalian cells — including whether FAM161B is required for ciliogenesis, centrosome integrity, or cell division — remain uncharacterized by direct mammalian genetic or functional studies.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No mammalian knockout or knockdown phenotype reported for FAM161B\",\n        \"No disease association established for FAM161B mutations (unlike FAM161A in retinitis pigmentosa)\",\n        \"Structural basis for UPF0564-mediated microtubule binding and partner selectivity is unknown\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [1, 2]},\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"FAM161A\",\n      \"TACC3\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}