{"gene":"FAM161B","run_date":"2026-06-09T23:54:43","timeline":{"discoveries":[{"year":2012,"finding":"The evolutionarily conserved UPF0564 domain of FAM161A mediates homo- and heterotypic interaction between FAM161A and FAM161B, as demonstrated by in vitro binding studies.","method":"Pull-down experiments, yeast two-hybrid, co-immunoprecipitation in cultured cells","journal":"Human molecular genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal binding assays in cultured cells and retinal extracts, single lab, two orthogonal methods; finding is specifically about FAM161B as an interacting partner of FAM161A via UPF0564 domain","pmids":["22791751"],"is_preprint":false},{"year":2010,"finding":"FAM161B was identified as a physical interactor of TACC3 in an interactome mapping study; this interaction is described as evolutionarily conserved.","method":"TACC3 interactome mapping (protein interaction screen)","journal":"Cell cycle (Georgetown, Tex.)","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single interactome mapping study, no direct functional follow-up specific to FAM161B, single method","pmids":["20237422"],"is_preprint":false},{"year":2024,"finding":"The sole Drosophila orthologue of FAM161A/FAM161B (Fam161) localizes to centrioles and the cilium transition zone in a cell type-specific manner; loss-of-function mutants show reduced male reproduction and abnormal geotaxis, establishing it as an essential centriole and transition zone protein.","method":"Drosophila mutant analysis (loss-of-function), immunofluorescence localization","journal":"Open biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean loss-of-function with defined phenotypic readouts and direct localization in multiple cell types; single lab but orthogonal methods (genetics + imaging); note this is the fly orthologue covering both FAM161A and FAM161B","pmids":["39255847"],"is_preprint":false}],"current_model":"FAM161B is a conserved microtubule-associated ciliary protein whose UPF0564 domain mediates heterotypic interaction with its paralog FAM161A, and which physically associates with the centrosomal/spindle regulator TACC3; fly orthologue studies establish that Fam161 family members are essential centriole and transition zone proteins required for cilium integrity and cell type-specific ciliary functions."},"narrative":{"mechanistic_narrative":"FAM161B is a conserved component of the centriole and ciliary apparatus, inferred from its paralog relationship and orthologue function within the FAM161 family [PMID:22791751, PMID:39255847]. It engages its paralog FAM161A through the evolutionarily conserved UPF0564 domain, which mediates both homo- and heterotypic binding among FAM161 family members [PMID:22791751]. The sole Drosophila orthologue of the FAM161A/FAM161B pair localizes to centrioles and the cilium transition zone in a cell type-specific manner, and its loss impairs male reproduction and geotaxis, establishing the family as essential centriole and transition zone proteins required for cilium integrity [PMID:39255847]. Beyond these interaction and orthologue-based findings, no FAM161B-specific molecular activity, substrate, or direct ciliary mechanism has been characterized in the available corpus.","teleology":[{"year":2010,"claim":"Before any function was assigned, it was unknown what proteins FAM161B associates with; an interactome screen placed it in the orbit of the centrosomal/spindle regulator TACC3, providing the first hint of a centriole-associated role.","evidence":"TACC3 interactome mapping protein interaction screen","pmids":["20237422"],"confidence":"Low","gaps":["Single interactome screen with no reciprocal or functional validation specific to FAM161B","Biological consequence of the TACC3 association untested","Does not establish direct binding versus complex co-membership"]},{"year":2012,"claim":"The basis for FAM161 family self-association was unknown; binding assays showed the conserved UPF0564 domain mediates homo- and heterotypic interaction between FAM161A and FAM161B, defining FAM161B as a paralog-interacting partner.","evidence":"Pull-down, yeast two-hybrid, and co-immunoprecipitation in cultured cells and retinal extracts","pmids":["22791751"],"confidence":"Medium","gaps":["Functional consequence of the FAM161A–FAM161B interaction not defined","FAM161B-specific subcellular localization in mammalian cells not resolved","Stoichiometry and structural detail of the UPF0564 interface unknown"]},{"year":2024,"claim":"Whether the FAM161 family is functionally essential at cilia was unresolved; loss-of-function in the single Drosophila orthologue localized the protein to centrioles and the transition zone and produced reproductive and behavioral defects, establishing the family as essential for cilium integrity.","evidence":"Drosophila loss-of-function mutant analysis with immunofluorescence localization across cell types","pmids":["39255847"],"confidence":"Medium","gaps":["Fly orthologue covers both FAM161A and FAM161B, so FAM161B-specific contribution cannot be separated","Mammalian FAM161B loss-of-function phenotype not established","Molecular activity at the transition zone not defined"]},{"year":null,"claim":"The FAM161B-specific molecular function, its mammalian ciliary localization, and the functional role of its interactions with FAM161A and TACC3 remain undetermined.","evidence":"No further direct evidence in the available corpus","pmids":[],"confidence":"Low","gaps":["No FAM161B-specific catalytic or structural activity identified","No mammalian knockout or disease association established in the corpus","Distinct roles of FAM161B versus FAM161A not disentangled"]}],"mechanism_profile":{"molecular_activity":[],"localization":[{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[2]},{"term_id":"GO:0005929","term_label":"cilium","supporting_discovery_ids":[2]}],"pathway":[],"complexes":[],"partners":["FAM161A","TACC3"],"other_free_text":[]}},"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":4,"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":5938,"output_tokens":727,"usd":0.01436,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7113,"output_tokens":1472,"usd":0.036182,"stage2_stop_reason":"end_turn"},"total_usd":0.050542,"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\": 2012,\n      \"finding\": \"The evolutionarily conserved UPF0564 domain of FAM161A mediates homo- and heterotypic interaction between FAM161A and FAM161B, as demonstrated by in vitro binding studies.\",\n      \"method\": \"Pull-down experiments, yeast two-hybrid, co-immunoprecipitation in cultured cells\",\n      \"journal\": \"Human molecular genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal binding assays in cultured cells and retinal extracts, single lab, two orthogonal methods; finding is specifically about FAM161B as an interacting partner of FAM161A via UPF0564 domain\",\n      \"pmids\": [\"22791751\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"FAM161B was identified as a physical interactor of TACC3 in an interactome mapping study; this interaction is described as evolutionarily conserved.\",\n      \"method\": \"TACC3 interactome mapping (protein interaction screen)\",\n      \"journal\": \"Cell cycle (Georgetown, Tex.)\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single interactome mapping study, no direct functional follow-up specific to FAM161B, single method\",\n      \"pmids\": [\"20237422\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"The sole Drosophila orthologue of FAM161A/FAM161B (Fam161) localizes to centrioles and the cilium transition zone in a cell type-specific manner; loss-of-function mutants show reduced male reproduction and abnormal geotaxis, establishing it as an essential centriole and transition zone protein.\",\n      \"method\": \"Drosophila mutant analysis (loss-of-function), immunofluorescence localization\",\n      \"journal\": \"Open biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean loss-of-function with defined phenotypic readouts and direct localization in multiple cell types; single lab but orthogonal methods (genetics + imaging); note this is the fly orthologue covering both FAM161A and FAM161B\",\n      \"pmids\": [\"39255847\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"FAM161B is a conserved microtubule-associated ciliary protein whose UPF0564 domain mediates heterotypic interaction with its paralog FAM161A, and which physically associates with the centrosomal/spindle regulator TACC3; fly orthologue studies establish that Fam161 family members are essential centriole and transition zone proteins required for cilium integrity and cell type-specific ciliary functions.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"FAM161B is a conserved component of the centriole and ciliary apparatus, inferred from its paralog relationship and orthologue function within the FAM161 family [#0, #2]. It engages its paralog FAM161A through the evolutionarily conserved UPF0564 domain, which mediates both homo- and heterotypic binding among FAM161 family members [#0]. The sole Drosophila orthologue of the FAM161A/FAM161B pair localizes to centrioles and the cilium transition zone in a cell type-specific manner, and its loss impairs male reproduction and geotaxis, establishing the family as essential centriole and transition zone proteins required for cilium integrity [#2]. Beyond these interaction and orthologue-based findings, no FAM161B-specific molecular activity, substrate, or direct ciliary mechanism has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2010,\n      \"claim\": \"Before any function was assigned, it was unknown what proteins FAM161B associates with; an interactome screen placed it in the orbit of the centrosomal/spindle regulator TACC3, providing the first hint of a centriole-associated role.\",\n      \"evidence\": \"TACC3 interactome mapping protein interaction screen\",\n      \"pmids\": [\"20237422\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single interactome screen with no reciprocal or functional validation specific to FAM161B\",\n        \"Biological consequence of the TACC3 association untested\",\n        \"Does not establish direct binding versus complex co-membership\"\n      ]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"The basis for FAM161 family self-association was unknown; binding assays showed the conserved UPF0564 domain mediates homo- and heterotypic interaction between FAM161A and FAM161B, defining FAM161B as a paralog-interacting partner.\",\n      \"evidence\": \"Pull-down, yeast two-hybrid, and co-immunoprecipitation in cultured cells and retinal extracts\",\n      \"pmids\": [\"22791751\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Functional consequence of the FAM161A\\u2013FAM161B interaction not defined\",\n        \"FAM161B-specific subcellular localization in mammalian cells not resolved\",\n        \"Stoichiometry and structural detail of the UPF0564 interface unknown\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Whether the FAM161 family is functionally essential at cilia was unresolved; loss-of-function in the single Drosophila orthologue localized the protein to centrioles and the transition zone and produced reproductive and behavioral defects, establishing the family as essential for cilium integrity.\",\n      \"evidence\": \"Drosophila loss-of-function mutant analysis with immunofluorescence localization across cell types\",\n      \"pmids\": [\"39255847\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Fly orthologue covers both FAM161A and FAM161B, so FAM161B-specific contribution cannot be separated\",\n        \"Mammalian FAM161B loss-of-function phenotype not established\",\n        \"Molecular activity at the transition zone not defined\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The FAM161B-specific molecular function, its mammalian ciliary localization, and the functional role of its interactions with FAM161A and TACC3 remain undetermined.\",\n      \"evidence\": \"No further direct evidence in the available corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No FAM161B-specific catalytic or structural activity identified\",\n        \"No mammalian knockout or disease association established in the corpus\",\n        \"Distinct roles of FAM161B versus FAM161A not disentangled\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [2]},\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [\"FAM161A\", \"TACC3\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"faith_supported":2,"faith_total":3,"faith_pct":66.66666666666667}}