{"gene":"MTMR10","run_date":"2026-06-10T02:59:51","timeline":{"discoveries":[{"year":2025,"finding":"A SNP in the MTMR10 promoter region (rs3743231 C allele) increases MTMR10 promoter activity, as demonstrated by luciferase reporter assay, indicating that this variant modulates MTMR10 transcription.","method":"Luciferase reporter assay (promoter activity assay)","journal":"Gene","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — single lab, single direct functional assay (luciferase) demonstrating promoter activity change; no replication or orthogonal method","pmids":["39875006"],"is_preprint":false}],"current_model":"MTMR10 (myotubularin-related protein 10) is a member of the myotubularin family encoded within the 15q13.3 locus; a promoter SNP (rs3743231) has been shown by luciferase assay to modulate its transcriptional activity, but no direct enzymatic activity, binding partners, or downstream signaling mechanism for MTMR10 protein has been experimentally established in the available literature."},"narrative":{"mechanistic_narrative":"MTMR10 is a member of the myotubularin-related protein family whose protein-level function remains uncharacterized in the available corpus. The only direct experimental evidence concerns its transcriptional regulation: a promoter SNP (rs3743231, C allele) increases MTMR10 promoter activity in a luciferase reporter assay, identifying this variant as a modulator of MTMR10 transcription [PMID:39875006]. Beyond this transcriptional finding, no enzymatic activity, binding partners, subcellular localization, or downstream signaling mechanism for MTMR10 has been experimentally established in the available corpus.","teleology":[{"year":2025,"claim":"It was unknown whether common variation at the MTMR10 locus affects its expression; a promoter reporter assay showed that the rs3743231 C allele raises promoter activity, establishing a cis-regulatory mechanism by which this variant tunes MTMR10 transcription.","evidence":"Luciferase reporter (promoter activity) assay comparing allelic constructs","pmids":["39875006"],"confidence":"Medium","gaps":["Single lab, single assay without replication or orthogonal validation (e.g. allele-specific expression, eQTL)","Does not establish the transcription factors or chromatin context mediating the allelic effect","Does not connect altered transcription to any downstream protein function or phenotype"]},{"year":null,"claim":"The molecular function of the MTMR10 protein — any catalytic activity, substrate, binding partners, localization, or pathway role — remains undefined in the available corpus.","evidence":"No direct experimental evidence in the timeline addresses protein-level function","pmids":[],"confidence":"Low","gaps":["No enzymatic activity demonstrated","No physical interaction partners identified","No subcellular localization or pathway placement established"]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":[],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9NXD2","full_name":"Myotubularin-related protein 10","aliases":["Inactive phosphatidylinositol 3-phosphatase 10"],"length_aa":777,"mass_kda":88.3,"function":"","subcellular_location":"","url":"https://www.uniprot.org/uniprotkb/Q9NXD2/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/MTMR10","classification":"Not Classified","n_dependent_lines":0,"n_total_lines":1208,"dependency_fraction":0.0},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"MTMR2","stoichiometry":4.0}],"url":"https://opencell.sf.czbiohub.org/search/MTMR10","total_profiled":1310},"omim":[{"mim_id":"208500","title":"SHORT-RIB THORACIC DYSPLASIA 1 WITH OR WITHOUT POLYDACTYLY; SRTD1","url":"https://www.omim.org/entry/208500"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nucleoplasm","reliability":"Approved"},{"location":"Nuclear bodies","reliability":"Approved"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in all","driving_tissues":[{"tissue":"brain","ntpm":77.6}],"url":"https://www.proteinatlas.org/search/MTMR10"},"hgnc":{"alias_symbol":["FLJ20313"],"prev_symbol":[]},"alphafold":{"accession":"Q9NXD2","domains":[{"cath_id":"2.30.29.30","chopping":"43-169","consensus_level":"high","plddt":89.1704,"start":43,"end":169},{"cath_id":"-","chopping":"223-337_373-551","consensus_level":"medium","plddt":95.8529,"start":223,"end":551},{"cath_id":"-","chopping":"658-768","consensus_level":"medium","plddt":71.7519,"start":658,"end":768}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9NXD2","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9NXD2-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9NXD2-F1-predicted_aligned_error_v6.png","plddt_mean":78.81},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=MTMR10","jax_strain_url":"https://www.jax.org/strain/search?query=MTMR10"},"sequence":{"accession":"Q9NXD2","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9NXD2.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9NXD2/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9NXD2"}},"corpus_meta":[{"pmid":"20425840","id":"PMC_20425840","title":"A 15q13.3 homozygous microdeletion associated with a severe neurodevelopmental disorder suggests putative functions of the TRPM1, CHRNA7, and other homozygously deleted genes.","date":"2010","source":"American journal of medical genetics. Part A","url":"https://pubmed.ncbi.nlm.nih.gov/20425840","citation_count":47,"is_preprint":false},{"pmid":"27459725","id":"PMC_27459725","title":"15q13.3 homozygous knockout mouse model display epilepsy-, autism- and schizophrenia-related phenotypes.","date":"2016","source":"Translational psychiatry","url":"https://pubmed.ncbi.nlm.nih.gov/27459725","citation_count":43,"is_preprint":false},{"pmid":"21596161","id":"PMC_21596161","title":"Homozygous deletion of chromosome 15q13.3 including CHRNA7 causes severe mental retardation, seizures, muscular hypotonia, and the loss of KLF13 and TRPM1 potentially cause macrocytosis and congenital retinal dysfunction in siblings.","date":"2011","source":"European journal of medical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/21596161","citation_count":43,"is_preprint":false},{"pmid":"25370694","id":"PMC_25370694","title":"Copy number variants in attention-deficit hyperactive disorder: identification of the 15q13 deletion and its functional role.","date":"2015","source":"Psychiatric genetics","url":"https://pubmed.ncbi.nlm.nih.gov/25370694","citation_count":22,"is_preprint":false},{"pmid":"32712126","id":"PMC_32712126","title":"Molecular, physiological and behavioral characterization of the heterozygous Df[h15q13]/+ mouse model associated with the human 15q13.3 microdeletion syndrome.","date":"2020","source":"Brain research","url":"https://pubmed.ncbi.nlm.nih.gov/32712126","citation_count":9,"is_preprint":false},{"pmid":"33785025","id":"PMC_33785025","title":"Mice with mutations in Trpm1, a gene in the locus of 15q13.3 microdeletion syndrome, display pronounced hyperactivity and decreased anxiety-like behavior.","date":"2021","source":"Molecular brain","url":"https://pubmed.ncbi.nlm.nih.gov/33785025","citation_count":9,"is_preprint":false},{"pmid":"31629107","id":"PMC_31629107","title":"Central and peripheral immune responses to low-dose lipopolysaccharide in a mouse model of the 15q13.3 microdeletion.","date":"2019","source":"Cytokine","url":"https://pubmed.ncbi.nlm.nih.gov/31629107","citation_count":6,"is_preprint":false},{"pmid":"39875006","id":"PMC_39875006","title":"Histone modification-based functional characterization and genetic association of polymorphisms in LRRC6 and MTMR10 within CRC susceptibility regions 8q24 and 15q13.3.","date":"2025","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/39875006","citation_count":2,"is_preprint":false},{"pmid":"36084604","id":"PMC_36084604","title":"Peripheral immune challenges elicit differential up-regulation of hippocampal cytokine and chemokine mRNA expression in a mouse model of the 15q13.3 microdeletion syndrome.","date":"2022","source":"Cytokine","url":"https://pubmed.ncbi.nlm.nih.gov/36084604","citation_count":2,"is_preprint":false},{"pmid":"40542392","id":"PMC_40542392","title":"Common and rare variant analyses implicate late-infancy cerebellar development and immune genes in ADHD.","date":"2025","source":"Journal of neurodevelopmental disorders","url":"https://pubmed.ncbi.nlm.nih.gov/40542392","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":8001,"output_tokens":320,"usd":0.014401,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6508,"output_tokens":779,"usd":0.026007,"stage2_stop_reason":"end_turn"},"total_usd":0.040408,"stage1_batch_id":"msgbatch_01BbTCMyrRPyhtEq6b1MdwCN","stage2_batch_id":"msgbatch_011dEed5bbxYvTAaQWKJevxu","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2025,\n      \"finding\": \"A SNP in the MTMR10 promoter region (rs3743231 C allele) increases MTMR10 promoter activity, as demonstrated by luciferase reporter assay, indicating that this variant modulates MTMR10 transcription.\",\n      \"method\": \"Luciferase reporter assay (promoter activity assay)\",\n      \"journal\": \"Gene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — single lab, single direct functional assay (luciferase) demonstrating promoter activity change; no replication or orthogonal method\",\n      \"pmids\": [\"39875006\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"MTMR10 (myotubularin-related protein 10) is a member of the myotubularin family encoded within the 15q13.3 locus; a promoter SNP (rs3743231) has been shown by luciferase assay to modulate its transcriptional activity, but no direct enzymatic activity, binding partners, or downstream signaling mechanism for MTMR10 protein has been experimentally established in the available literature.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"MTMR10 is a member of the myotubularin-related protein family whose protein-level function remains uncharacterized in the available corpus. The only direct experimental evidence concerns its transcriptional regulation: a promoter SNP (rs3743231, C allele) increases MTMR10 promoter activity in a luciferase reporter assay, identifying this variant as a modulator of MTMR10 transcription [#0]. Beyond this transcriptional finding, no enzymatic activity, binding partners, subcellular localization, or downstream signaling mechanism for MTMR10 has been experimentally established in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2025,\n      \"claim\": \"It was unknown whether common variation at the MTMR10 locus affects its expression; a promoter reporter assay showed that the rs3743231 C allele raises promoter activity, establishing a cis-regulatory mechanism by which this variant tunes MTMR10 transcription.\",\n      \"evidence\": \"Luciferase reporter (promoter activity) assay comparing allelic constructs\",\n      \"pmids\": [\n        \"39875006\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single lab, single assay without replication or orthogonal validation (e.g. allele-specific expression, eQTL)\",\n        \"Does not establish the transcription factors or chromatin context mediating the allelic effect\",\n        \"Does not connect altered transcription to any downstream protein function or phenotype\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The molecular function of the MTMR10 protein — any catalytic activity, substrate, binding partners, localization, or pathway role — remains undefined in the available corpus.\",\n      \"evidence\": \"No direct experimental evidence in the timeline addresses protein-level function\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No enzymatic activity demonstrated\",\n        \"No physical interaction partners identified\",\n        \"No subcellular localization or pathway placement established\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"faith_supported":1,"faith_total":1,"faith_pct":100.0}}