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During ciliogenesis regulates the ciliary transition zone localization of some MKS complex proteins (PubMed:26518474)","subcellular_location":"Membrane; Cell projection, cilium","url":"https://www.uniprot.org/uniprotkb/Q6UX40/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/TMEM107","classification":"Not Classified","n_dependent_lines":4,"n_total_lines":1208,"dependency_fraction":0.0033112582781456954},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/TMEM107","total_profiled":1310},"omim":[{"mim_id":"620107","title":"OROFACIODIGITAL SYNDROME XIX; OFD19","url":"https://www.omim.org/entry/620107"},{"mim_id":"617563","title":"OROFACIODIGITAL SYNDROME XVI; OFD16","url":"https://www.omim.org/entry/617563"},{"mim_id":"617562","title":"MECKEL SYNDROME 13; 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the ciliary transition zone (TZ) and occupies an intermediate layer of the TZ-localized MKS module, where it organizes recruitment of the ciliopathy proteins MKS-1, TMEM-231 (JBTS20), and JBTS-14 (TMEM237). In C. elegans, TMEM-107 controls ciliary composition, functions redundantly with NPHP-4 to regulate cilium integrity, TZ docking, and assembly of membrane-to-microtubule Y-link connectors.\",\n      \"method\": \"Genetic epistasis in C. elegans, super-resolution microscopy in worms and mammalian cells, bioinformatics (coexpression and co-evolution)\",\n      \"journal\": \"Nature cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal genetic epistasis, super-resolution imaging, and multiple orthogonal methods in both C. elegans and mammalian cells; replicated across organisms\",\n      \"pmids\": [\"26595381\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Tmem107 is required for ciliogenesis and normal Sonic hedgehog (Shh) signaling in the mouse neural tube. Loss-of-function (schlei allele) disrupts cilia formation in a tissue-specific manner and acts in combination with Gli2 and Gli3 to pattern ventral and intermediate neuronal cell types, while retaining partial Gli activator and repressor function.\",\n      \"method\": \"Forward genetics (ENU mutagenesis), mouse knockout/hypomorphic allele, in situ hybridization, phenotypic analysis of neural tube and digit patterning\",\n      \"journal\": \"Developmental biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — clean genetic loss-of-function with defined cellular and pathway phenotypes, epistasis with Gli2/Gli3\",\n      \"pmids\": [\"22698544\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"TMEM107 regulates ciliary protein composition; key ciliary proteins fail to localize normally in cilia from Tmem107 mouse mutants and a human OFD patient. TMEM107 functions within cilia to control the protein content of the ciliary compartment.\",\n      \"method\": \"Immunofluorescence localization of ciliary proteins in Tmem107 mutant mouse cells and patient fibroblasts; ciliogenesis assays\",\n      \"journal\": \"Human mutation\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — direct localization experiments in mouse mutant and human patient cells; single lab but multiple cell types\",\n      \"pmids\": [\"26518474\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"TMEM107 mutation causes a ciliogenesis defect in patient fibroblasts accompanied by perturbation of Sonic hedgehog signaling, consistent with its assignment as an MKS module transition zone protein (MKS13 locus).\",\n      \"method\": \"Patient fibroblast ciliogenesis assay, Shh signaling readout in cells from TMEM107 splice-\n\n--- ROUND 2 (R2/R3, augmented corpus) ---\n\nI'll systematically classify each paper before extracting discoveries.\n\n**CLASSIFICATION:**\n\nKEEP:\n- [1] PMID:26595381 — Direct mechanistic study of TMEM107 at TZ\n- [2] PMID:28289185 — TMEM107 identified as TZ/OFD gene (functional studies mentioned)\n- [3] PMID:22698544 — Mouse Tmem107 forward genetics, ciliogenesis/Shh\n- [4] PMID:26123494 — TMEM107 mutations in MKS, patient fibroblast functional studies\n- [6] PMID:32163404 — TMEM107 role in ciliary shedding (Paramecium model)\n- [8] PMID:28954202 — Tmem107 KO mouse craniofacial/ciliary roles\n- [10] PMID:26518474 — TMEM107 regulates ciliary protein composition\n- [12] PMID:36084634 — SCNM1→TMEM107 splicing link (mechanistic context for TMEM107)\n- [13] PMID:32853754 — Tissue-specific protein complex analysis using TMEM107 as bait\n- [14] PMID:31887266 — TMEM107 in L-R patterning, null vs hypomorph\n- [15] PMID:37863656 — TMEM107 in eye development, retinal organoids, SHH pathway\n\nEXCLUDE:\n- [5] PMID:34294125 — EGR1/HSC aging paper; TMEM107 mentioned only as trajectory correlate (expression correlation)\n- [7] PMID:25213383 — MMR/microsatellite instability paper; TMEM107 is incidental target\n- [9] PMID:17437276 — MKS1 paper, not about TMEM107\n- [11] PMID:33124203 — RETRACTED (see [19]); exclude\n- [16] PMID:38158857 — ZRSR2/OFD paper; TMEM107 mentioned as downstream splicing target only\n- [17] PMID:37341229 — GWAS/association study; no mechanistic data\n- [18] PMID:41152979 — \"TMEM107+ NK cells\" is a cell cluster label, not about TMEM107 protein function\n- [19] PMID:40","stage2_raw":"\n\n--- ROUND 2 (refusal — no on-target evidence) ---\n"}