{"gene":"FAM241A","run_date":"2026-06-09T23:54:43","timeline":{"discoveries":[{"year":2024,"finding":"FAM241A and FAM241B proteins contain a conserved domain of unknown function (DUF4605; pfam15378) and appear to co-localize with proteins of the endoplasmic reticulum, suggesting ER association.","method":"Subcellular co-localization (previously reported experiments cited in this paper)","journal":"Mammalian genome : official journal of the International Mammalian Genome Society","confidence":"Low","confidence_rationale":"Tier 3 / Weak — co-localization data cited from prior studies without detailed experimental description in this abstract; single indirect reference","pmids":["39715844"],"is_preprint":false},{"year":2024,"finding":"Experimental knockout of mouse Fam241a, Fam241b, and the double knockout did not generate a visible phenotype, and double knockout did not exacerbate the phenotype of FIG4 null mice, indicating FAM241A is not required for FIG4-dependent lysosomal pathways in vivo.","method":"Genetic knockout mouse models (single and double KO), phenotypic assessment and epistasis with FIG4 null mice","journal":"Mammalian genome : official journal of the International Mammalian Genome Society","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean KO with defined phenotypic readout and genetic epistasis test, single lab but multiple genotypes tested","pmids":["39715844"],"is_preprint":false},{"year":2024,"finding":"RNAseq of brain RNA from Fam241a/Fam241b double knockout mice detected reduced expression of several genes including Arke1e1 and RnaseL, suggesting FAM241A participates in transcriptional or post-transcriptional regulation of a subset of genes.","method":"RNAseq of double knockout mouse brain tissue","journal":"Mammalian genome : official journal of the International Mammalian Genome Society","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single method (RNAseq from DKO), no mechanistic follow-up; confounded by double KO making FAM241A-specific contribution unclear","pmids":["39715844"],"is_preprint":false}],"current_model":"FAM241A is a small, ancient protein (132 aa) containing the conserved DUF4605 domain that appears to localize to the endoplasmic reticulum; knockout of Fam241a alone or together with its paralog Fam241b in mice causes no overt phenotype and does not worsen FIG4-null lysosomal disease, though the double knockout alters brain expression of a subset of genes, leaving the molecular function of FAM241A undetermined."},"narrative":{"mechanistic_narrative":"FAM241A is a small, ancient protein containing the conserved DUF4605 domain that associates with the endoplasmic reticulum, though its molecular function remains undefined [PMID:39715844]. Genetic knockout of mouse Fam241a, its paralog Fam241b, or both together produces no overt phenotype, and the double knockout does not exacerbate the lysosomal disease of FIG4-null mice, indicating that FAM241A is dispensable for FIG4-dependent lysosomal pathways in vivo [PMID:39715844]. Brain transcriptomics of double-knockout mice show reduced expression of a small subset of genes, the only functional readout linking FAM241A loss to a downstream consequence [PMID:39715844]. Beyond these observations, no biochemical activity, direct partner, or mechanism has been characterized in the available corpus.","teleology":[{"year":2024,"claim":"Establishing where an uncharacterized DUF4605 protein acts narrows its candidate function; co-localization placed FAM241A and its paralog at the endoplasmic reticulum.","evidence":"Subcellular co-localization with ER proteins (cited from prior work)","pmids":["39715844"],"confidence":"Low","gaps":["Co-localization cited without detailed experimental description; not independently confirmed here","ER association does not define a molecular activity","No direct ER-resident partner identified"]},{"year":2024,"claim":"To test whether FAM241A is required in vivo, single and double knockouts were generated and crossed into a FIG4-null background, showing FAM241A is not essential and not needed for FIG4-dependent lysosomal function.","evidence":"Single and double knockout mice with phenotypic assessment and genetic epistasis against FIG4-null mice","pmids":["39715844"],"confidence":"Medium","gaps":["Absence of overt phenotype may reflect redundancy beyond the paralog or context-specific roles not assayed","No molecular activity established by the genetic test","Epistasis tested only against FIG4, leaving other pathways unexplored"]},{"year":2024,"claim":"To find a molecular consequence of FAM241A loss, brain RNAseq of double knockouts revealed reduced expression of a subset of genes including Rnasel, hinting at a role in gene expression regulation.","evidence":"RNAseq of double knockout mouse brain tissue","pmids":["39715844"],"confidence":"Low","gaps":["Double-knockout design cannot separate FAM241A-specific from FAM241B contributions","No mechanistic link between an ER protein and transcriptional/post-transcriptional changes established","Single tissue, single method, no follow-up validation"]},{"year":null,"claim":"The molecular activity of FAM241A, its direct partners, and how an ER-associated DUF4605 protein influences gene expression all remain unknown.","evidence":"","pmids":[],"confidence":"Low","gaps":["No biochemical activity assigned to the DUF4605 domain","No direct physical partner identified","Causal link between ER localization and the observed transcriptomic changes unestablished"]}],"mechanism_profile":{"molecular_activity":[],"localization":[{"term_id":"GO:0005783","term_label":"endoplasmic reticulum","supporting_discovery_ids":[0]}],"pathway":[],"complexes":[],"partners":[],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q8N8J7","full_name":"Uncharacterized protein FAM241A","aliases":[],"length_aa":132,"mass_kda":14.7,"function":"","subcellular_location":"Membrane","url":"https://www.uniprot.org/uniprotkb/Q8N8J7/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/FAM241A","classification":"Not Classified","n_dependent_lines":0,"n_total_lines":1208,"dependency_fraction":0.0},"opencell":{"profiled":true,"resolved_as":"C4ORF32","ensg_id":"ENSG00000174749","cell_line_id":"CID002014","localizations":[{"compartment":"er","grade":3}],"interactors":[{"gene":"DAD1","stoichiometry":10.0},{"gene":"STT3A","stoichiometry":10.0},{"gene":"RPN2","stoichiometry":4.0},{"gene":"DDOST","stoichiometry":0.2},{"gene":"OST4","stoichiometry":0.2},{"gene":"RPN1","stoichiometry":0.2},{"gene":"MMGT1","stoichiometry":0.2},{"gene":"SLC4A2","stoichiometry":0.2},{"gene":"ATP1A1","stoichiometry":0.2},{"gene":"RER1","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/target/CID002014","total_profiled":1310},"omim":[],"hpa":{"profiled":true,"resolved_as":"","reliability":"Enhanced","locations":[{"location":"Golgi apparatus","reliability":"Enhanced"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in many","driving_tissues":[],"url":"https://www.proteinatlas.org/search/FAM241A"},"hgnc":{"alias_symbol":["FLJ39370"],"prev_symbol":["C4orf32"]},"alphafold":{"accession":"Q8N8J7","domains":[{"cath_id":"-","chopping":"69-132","consensus_level":"medium","plddt":73.5489,"start":69,"end":132}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8N8J7","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q8N8J7-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q8N8J7-F1-predicted_aligned_error_v6.png","plddt_mean":58.09},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=FAM241A","jax_strain_url":"https://www.jax.org/strain/search?query=FAM241A"},"sequence":{"accession":"Q8N8J7","fasta_url":"https://rest.uniprot.org/uniprotkb/Q8N8J7.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q8N8J7/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8N8J7"}},"corpus_meta":[{"pmid":"36289596","id":"PMC_36289596","title":"The Oncogenic and Tumor Suppressive Long Non-Coding RNA-microRNA-Messenger RNA Regulatory Axes Identified by Analyzing Multiple Platform Omics Data from Cr(VI)-Transformed Cells and Their Implications in Lung Cancer.","date":"2022","source":"Biomedicines","url":"https://pubmed.ncbi.nlm.nih.gov/36289596","citation_count":15,"is_preprint":false},{"pmid":"39715844","id":"PMC_39715844","title":"Protein family FAM241 in human and mouse.","date":"2024","source":"Mammalian genome : official journal of the International Mammalian Genome Society","url":"https://pubmed.ncbi.nlm.nih.gov/39715844","citation_count":2,"is_preprint":false},{"pmid":"41436647","id":"PMC_41436647","title":"Unveiling novel potential drug targets for lung cancer through Mendelian randomization analysis.","date":"2025","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/41436647","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4125,"output_tokens":766,"usd":0.011933,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7152,"output_tokens":1299,"usd":0.034118,"stage2_stop_reason":"end_turn"},"total_usd":0.046051,"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\": 2024,\n      \"finding\": \"FAM241A and FAM241B proteins contain a conserved domain of unknown function (DUF4605; pfam15378) and appear to co-localize with proteins of the endoplasmic reticulum, suggesting ER association.\",\n      \"method\": \"Subcellular co-localization (previously reported experiments cited in this paper)\",\n      \"journal\": \"Mammalian genome : official journal of the International Mammalian Genome Society\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — co-localization data cited from prior studies without detailed experimental description in this abstract; single indirect reference\",\n      \"pmids\": [\"39715844\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Experimental knockout of mouse Fam241a, Fam241b, and the double knockout did not generate a visible phenotype, and double knockout did not exacerbate the phenotype of FIG4 null mice, indicating FAM241A is not required for FIG4-dependent lysosomal pathways in vivo.\",\n      \"method\": \"Genetic knockout mouse models (single and double KO), phenotypic assessment and epistasis with FIG4 null mice\",\n      \"journal\": \"Mammalian genome : official journal of the International Mammalian Genome Society\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean KO with defined phenotypic readout and genetic epistasis test, single lab but multiple genotypes tested\",\n      \"pmids\": [\"39715844\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"RNAseq of brain RNA from Fam241a/Fam241b double knockout mice detected reduced expression of several genes including Arke1e1 and RnaseL, suggesting FAM241A participates in transcriptional or post-transcriptional regulation of a subset of genes.\",\n      \"method\": \"RNAseq of double knockout mouse brain tissue\",\n      \"journal\": \"Mammalian genome : official journal of the International Mammalian Genome Society\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single method (RNAseq from DKO), no mechanistic follow-up; confounded by double KO making FAM241A-specific contribution unclear\",\n      \"pmids\": [\"39715844\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"FAM241A is a small, ancient protein (132 aa) containing the conserved DUF4605 domain that appears to localize to the endoplasmic reticulum; knockout of Fam241a alone or together with its paralog Fam241b in mice causes no overt phenotype and does not worsen FIG4-null lysosomal disease, though the double knockout alters brain expression of a subset of genes, leaving the molecular function of FAM241A undetermined.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"FAM241A is a small, ancient protein containing the conserved DUF4605 domain that associates with the endoplasmic reticulum, though its molecular function remains undefined [#0]. Genetic knockout of mouse Fam241a, its paralog Fam241b, or both together produces no overt phenotype, and the double knockout does not exacerbate the lysosomal disease of FIG4-null mice, indicating that FAM241A is dispensable for FIG4-dependent lysosomal pathways in vivo [#1]. Brain transcriptomics of double-knockout mice show reduced expression of a small subset of genes, the only functional readout linking FAM241A loss to a downstream consequence [#2]. Beyond these observations, no biochemical activity, direct partner, or mechanism has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2024,\n      \"claim\": \"Establishing where an uncharacterized DUF4605 protein acts narrows its candidate function; co-localization placed FAM241A and its paralog at the endoplasmic reticulum.\",\n      \"evidence\": \"Subcellular co-localization with ER proteins (cited from prior work)\",\n      \"pmids\": [\"39715844\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Co-localization cited without detailed experimental description; not independently confirmed here\",\n        \"ER association does not define a molecular activity\",\n        \"No direct ER-resident partner identified\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"To test whether FAM241A is required in vivo, single and double knockouts were generated and crossed into a FIG4-null background, showing FAM241A is not essential and not needed for FIG4-dependent lysosomal function.\",\n      \"evidence\": \"Single and double knockout mice with phenotypic assessment and genetic epistasis against FIG4-null mice\",\n      \"pmids\": [\"39715844\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Absence of overt phenotype may reflect redundancy beyond the paralog or context-specific roles not assayed\",\n        \"No molecular activity established by the genetic test\",\n        \"Epistasis tested only against FIG4, leaving other pathways unexplored\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"To find a molecular consequence of FAM241A loss, brain RNAseq of double knockouts revealed reduced expression of a subset of genes including Rnasel, hinting at a role in gene expression regulation.\",\n      \"evidence\": \"RNAseq of double knockout mouse brain tissue\",\n      \"pmids\": [\"39715844\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Double-knockout design cannot separate FAM241A-specific from FAM241B contributions\",\n        \"No mechanistic link between an ER protein and transcriptional/post-transcriptional changes established\",\n        \"Single tissue, single method, no follow-up validation\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The molecular activity of FAM241A, its direct partners, and how an ER-associated DUF4605 protein influences gene expression all remain unknown.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No biochemical activity assigned to the DUF4605 domain\",\n        \"No direct physical partner identified\",\n        \"Causal link between ER localization and the observed transcriptomic changes unestablished\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0005783\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"faith_supported":1,"faith_total":2,"faith_pct":50.0}}