{"gene":"SOWAHC","run_date":"2026-04-28T20:42:08","timeline":{"discoveries":[{"year":2007,"finding":"The mouse ortholog of SOWAHC (TSC77, homologous to human C2orf26/SOWAHC at 76% amino acid identity) localizes to the nucleus, as demonstrated by GFP-TSC77 fusion protein imaging in Cos-7 cells. The protein (681 aa, ~77 kDa) contains predicted NAD(P)-nitrite reductase (NirB), HcaD, and NADH dehydrogenase (Ndh) domains and is preferentially expressed in mouse testis, with expression increasing from postnatal day 9 to day 21, implicating it in spermatogenesis.","method":"GFP fusion protein subcellular localization (live imaging), RT-PCR tissue distribution, DNA microarray developmental expression profiling, bioinformatics domain analysis","journal":"Croatian medical journal","confidence":"Low","confidence_rationale":"Tier 3 — single lab, single localization method (GFP fusion), no functional follow-up beyond expression correlation; mouse ortholog only","pmids":["17309138"],"is_preprint":false},{"year":2012,"finding":"The SOWAHC locus (Sowah genes) is syntenic with Iroquois homeobox genes across nearly all studied bilaterians despite ~600 million years of independent evolution. Iroquois-specific cis-regulatory modules (CRMs) populate the Sowah locus, indicating that regulatory constraints imposed by these embedded CRMs underlie the conservation of the Iroquois-Sowah genomic regulatory block. In tetrapods, Sowah orthologs became intronless (via retroposition), allowing the physical decoupling of Sowah exons from the Iroquois regulatory landscape while retaining associated CRMs in gene deserts.","method":"Comparative genomics across 39 metazoan species, identification of conserved non-coding elements and CRMs within Sowah introns, analysis of retrogene replacement events in tetrapods","journal":"Genome research","confidence":"Medium","confidence_rationale":"Tier 2 — multi-species comparative genomics with functional genomic inference, single study but broad phylogenetic sampling providing strong evidence for regulatory role of locus","pmids":["22234889"],"is_preprint":false}],"current_model":"SOWAHC (C2orf26) encodes a nuclear-localizing ankyrin repeat domain protein whose locus ancestrally harbored cis-regulatory modules for neighboring Iroquois homeobox genes, imposing genomic architectural constraints conserved across bilaterians; the mouse ortholog (TSC77) is preferentially expressed in testis during spermatogenesis, but direct biochemical mechanism and molecular function of the SOWAHC protein remain largely uncharacterized."},"narrative":{"teleology":[{"year":2007,"claim":"Determining where SOWAHC protein resides and when it is expressed established that the mouse ortholog is a nuclear protein with testis-enriched expression during spermatogenesis, providing the first cellular context for its function.","evidence":"GFP-TSC77 fusion imaging in Cos-7 cells and RT-PCR/microarray developmental profiling in mouse tissues","pmids":["17309138"],"confidence":"Low","gaps":["Nuclear localization demonstrated by a single method (GFP fusion) in a heterologous cell line without endogenous antibody confirmation","No loss-of-function or gain-of-function experiments to test a role in spermatogenesis","No binding partners or enzymatic activity identified"]},{"year":2012,"claim":"Resolving why the SOWAHC locus is conserved in synteny with Iroquois genes revealed that Iroquois-specific cis-regulatory modules embedded within the Sowah locus impose deep genomic regulatory constraints, explaining locus architecture rather than SOWAHC protein function per se.","evidence":"Comparative genomics across 39 metazoan species identifying conserved non-coding elements and CRMs within Sowah introns","pmids":["22234889"],"confidence":"Medium","gaps":["Does not address the molecular function of SOWAHC protein itself","Functional validation of the identified CRMs (e.g., reporter assays) was not performed in this study","Whether SOWAHC protein has any regulatory interplay with Iroquois genes is unknown"]},{"year":null,"claim":"The direct molecular activity, binding partners, and physiological role of SOWAHC protein remain entirely undefined; no loss-of-function model, interactome data, or enzymatic characterization exists.","evidence":"","pmids":[],"confidence":"Low","gaps":["No substrate, binding partner, or enzymatic activity has been identified","No knockout or knockdown phenotype reported in any organism","Role of the ankyrin repeat domain in protein–protein interactions is unexplored"]}],"mechanism_profile":{"molecular_activity":[],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[0]}],"pathway":[],"complexes":[],"partners":[],"other_free_text":[]},"mechanistic_narrative":"SOWAHC encodes a nuclear-localizing ankyrin repeat domain-containing protein whose direct biochemical function remains uncharacterized. The mouse ortholog (TSC77, 76% amino acid identity) localizes to the nucleus in heterologous cells and is preferentially expressed in testis with developmental upregulation during spermatogenesis [PMID:17309138]. The SOWAHC locus is embedded within a deeply conserved genomic regulatory block shared with Iroquois homeobox genes across bilaterians, where cis-regulatory modules for Iroquois transcription reside within or adjacent to the Sowah gene, imposing strong syntenic constraints over ~600 million years of evolution [PMID:22234889]."},"prefetch_data":{"uniprot":{"accession":"Q53LP3","full_name":"Ankyrin repeat domain-containing protein SOWAHC","aliases":["Ankyrin repeat domain-containing protein 57","Protein sosondowah homolog C"],"length_aa":525,"mass_kda":55.7,"function":"","subcellular_location":"","url":"https://www.uniprot.org/uniprotkb/Q53LP3/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/SOWAHC","classification":"Not Classified","n_dependent_lines":126,"n_total_lines":1208,"dependency_fraction":0.10430463576158941},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"CAPZB","stoichiometry":0.2},{"gene":"DIAPH1","stoichiometry":0.2},{"gene":"PFN1","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/SOWAHC","total_profiled":1310},"omim":[],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Cytosol","reliability":"Approved"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in many","driving_tissues":[],"url":"https://www.proteinatlas.org/search/SOWAHC"},"hgnc":{"alias_symbol":["FLJ21870"],"prev_symbol":["C2orf26","ANKRD57"]},"alphafold":{"accession":"Q53LP3","domains":[{"cath_id":"1.10.10","chopping":"16-84","consensus_level":"high","plddt":87.6081,"start":16,"end":84},{"cath_id":"1.25.40.20","chopping":"267-395","consensus_level":"high","plddt":90.9774,"start":267,"end":395}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q53LP3","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q53LP3-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q53LP3-F1-predicted_aligned_error_v6.png","plddt_mean":60.25},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=SOWAHC","jax_strain_url":"https://www.jax.org/strain/search?query=SOWAHC"},"sequence":{"accession":"Q53LP3","fasta_url":"https://rest.uniprot.org/uniprotkb/Q53LP3.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q53LP3/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q53LP3"}},"corpus_meta":[{"pmid":"20224928","id":"PMC_20224928","title":"Identification 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This describes localization (nucleus) and expression pattern but limited mechanism — KEEP (potential ortholog/alias, nuclear localization finding)\n- Paper [3] (GWAS chicken ALV): GWAS/expression study, no mechanistic finding — EXCLUDE (GWAS/expression)\n- Papers from gene2pubmed [1-12, 14-22, 24, 26-30]: Large-scale proteomics/interactome studies, cDNA sequencing, chromosome sequencing — no SOWAHC-specific mechanistic findings, just catalog entries — EXCLUDE\n- Paper [23] (Iroquois-Sowah syntenic block): describes genomic regulatory block, Sowah locus contains Iroquois CRMs, synteny conservation — KEEP (describes SOWAHC locus biology with functional genomic context)\n- Paper [25] (methylation-driven genes LUSC): expression/methylation biomarker study — EXCLUDE (prognostic biomarker, no mechanism)\n\n**Kept papers with mechanistic content:**\n- PMID:17309138 — TSC77 (mouse ortholog of SOWAHC/C2orf26): nuclear localization shown by GFP fusion\n- PMID:22234889 — Iroquois-Sowah syntenic block: Sowah locus harbors Iroquois CRMs, regulatory constraints maintain synteny\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2007,\n      \"finding\": \"The mouse ortholog of SOWAHC (TSC77, homologous to human C2orf26/SOWAHC at 76% amino acid identity) localizes to the nucleus, as demonstrated by GFP-TSC77 fusion protein imaging in Cos-7 cells. The protein (681 aa, ~77 kDa) contains predicted NAD(P)-nitrite reductase (NirB), HcaD, and NADH dehydrogenase (Ndh) domains and is preferentially expressed in mouse testis, with expression increasing from postnatal day 9 to day 21, implicating it in spermatogenesis.\",\n      \"method\": \"GFP fusion protein subcellular localization (live imaging), RT-PCR tissue distribution, DNA microarray developmental expression profiling, bioinformatics domain analysis\",\n      \"journal\": \"Croatian medical journal\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — single lab, single localization method (GFP fusion), no functional follow-up beyond expression correlation; mouse ortholog only\",\n      \"pmids\": [\"17309138\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"The SOWAHC locus (Sowah genes) is syntenic with Iroquois homeobox genes across nearly all studied bilaterians despite ~600 million years of independent evolution. Iroquois-specific cis-regulatory modules (CRMs) populate the Sowah locus, indicating that regulatory constraints imposed by these embedded CRMs underlie the conservation of the Iroquois-Sowah genomic regulatory block. In tetrapods, Sowah orthologs became intronless (via retroposition), allowing the physical decoupling of Sowah exons from the Iroquois regulatory landscape while retaining associated CRMs in gene deserts.\",\n      \"method\": \"Comparative genomics across 39 metazoan species, identification of conserved non-coding elements and CRMs within Sowah introns, analysis of retrogene replacement events in tetrapods\",\n      \"journal\": \"Genome research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — multi-species comparative genomics with functional genomic inference, single study but broad phylogenetic sampling providing strong evidence for regulatory role of locus\",\n      \"pmids\": [\"22234889\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"SOWAHC (C2orf26) encodes a nuclear-localizing ankyrin repeat domain protein whose locus ancestrally harbored cis-regulatory modules for neighboring Iroquois homeobox genes, imposing genomic architectural constraints conserved across bilaterians; the mouse ortholog (TSC77) is preferentially expressed in testis during spermatogenesis, but direct biochemical mechanism and molecular function of the SOWAHC protein remain largely uncharacterized.\"\n}\n```","stage2_raw":"\n\n--- ROUND 2 (R2/R3, augmented corpus) ---\n\n```json\n{\n  \"mechanistic_narrative\": \"SOWAHC encodes a nuclear-localizing ankyrin repeat domain-containing protein whose direct biochemical function remains uncharacterized. The mouse ortholog (TSC77, 76% amino acid identity) localizes to the nucleus in heterologous cells and is preferentially expressed in testis with developmental upregulation during spermatogenesis [PMID:17309138]. The SOWAHC locus is embedded within a deeply conserved genomic regulatory block shared with Iroquois homeobox genes across bilaterians, where cis-regulatory modules for Iroquois transcription reside within or adjacent to the Sowah gene, imposing strong syntenic constraints over ~600 million years of evolution [PMID:22234889].\",\n  \"teleology\": [\n    {\n      \"year\": 2007,\n      \"claim\": \"Determining where SOWAHC protein resides and when it is expressed established that the mouse ortholog is a nuclear protein with testis-enriched expression during spermatogenesis, providing the first cellular context for its function.\",\n      \"evidence\": \"GFP-TSC77 fusion imaging in Cos-7 cells and RT-PCR/microarray developmental profiling in mouse tissues\",\n      \"pmids\": [\"17309138\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Nuclear localization demonstrated by a single method (GFP fusion) in a heterologous cell line without endogenous antibody confirmation\",\n        \"No loss-of-function or gain-of-function experiments to test a role in spermatogenesis\",\n        \"No binding partners or enzymatic activity identified\"\n      ]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Resolving why the SOWAHC locus is conserved in synteny with Iroquois genes revealed that Iroquois-specific cis-regulatory modules embedded within the Sowah locus impose deep genomic regulatory constraints, explaining locus architecture rather than SOWAHC protein function per se.\",\n      \"evidence\": \"Comparative genomics across 39 metazoan species identifying conserved non-coding elements and CRMs within Sowah introns\",\n      \"pmids\": [\"22234889\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Does not address the molecular function of SOWAHC protein itself\",\n        \"Functional validation of the identified CRMs (e.g., reporter assays) was not performed in this study\",\n        \"Whether SOWAHC protein has any regulatory interplay with Iroquois genes is unknown\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The direct molecular activity, binding partners, and physiological role of SOWAHC protein remain entirely undefined; no loss-of-function model, interactome data, or enzymatic characterization exists.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No substrate, binding partner, or enzymatic activity has been identified\",\n        \"No knockout or knockdown phenotype reported in any organism\",\n        \"Role of the ankyrin repeat domain in protein–protein interactions is unexplored\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": []\n  }\n}\n```"}