{"gene":"YLPM1","run_date":"2026-06-11T09:02:06","timeline":{"discoveries":[{"year":2024,"finding":"YLPM1 inactivation promotes GIST (gastrointestinal stromal tumor) cell proliferation, growth, and oxidative phosphorylation, as demonstrated by functional studies of recurrent inactivating YLPM1 mutations identified in high-risk/metastatic GIST.","method":"Functional study of inactivating mutations in GIST cells (loss-of-function with specific phenotypic readouts: proliferation, growth, oxidative phosphorylation)","journal":"Nature communications","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — single lab, functional loss-of-function study with defined cellular phenotypes, but abstract provides limited methodological detail","pmids":["39489749"],"is_preprint":false},{"year":2019,"finding":"Nuclear Ago2 physically associates with YLP motif-containing protein 1 (YLPM1) and single-stranded DNA binding protein 1 (SSBP1) in cardiomyocytes, as revealed by liquid chromatography-mass spectrometry analysis of nuclear Ago2 complexes.","method":"Liquid chromatography-mass spectrometry (LC-MS) analysis of nuclear Ago2-associated proteins","journal":"Molecular therapy. Nucleic acids","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single Co-IP/MS experiment, single lab, no functional validation of the YLPM1-Ago2 interaction itself","pmids":["31837603"],"is_preprint":false},{"year":2024,"finding":"A novel YLPM1::PRKD1 gene fusion was identified in a cribriform subtype of polymorphous adenocarcinoma of the salivary gland, representing a previously unreported chromosomal rearrangement involving YLPM1.","method":"Molecular pathology / fusion gene identification in tumor sample","journal":"Head and neck pathology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single case report, descriptive identification of fusion, no functional characterization of the fusion protein","pmids":["38735907"],"is_preprint":false}],"current_model":"YLPM1 functions as a tumor suppressor whose inactivation promotes cell proliferation, growth, and oxidative phosphorylation in gastrointestinal stromal tumors; it also physically associates with nuclear Ago2 in cardiomyocytes and can undergo chromosomal rearrangement (YLPM1::PRKD1 fusion) in salivary gland tumors, but its precise molecular mechanism of action remains largely uncharacterized."},"narrative":{"mechanistic_narrative":"YLPM1 acts as a tumor suppressor in gastrointestinal stromal tumors (GIST), where recurrent inactivating mutations in high-risk and metastatic disease drive cell proliferation, growth, and oxidative phosphorylation upon loss of function [PMID:39489749]. Beyond this loss-of-function phenotype, the molecular mechanism of YLPM1 is largely uncharacterized in the available corpus: it has been detected in nuclear Ago2-associated complexes alongside SSBP1 in cardiomyocytes [PMID:31837603], and a YLPM1::PRKD1 gene fusion has been identified in a cribriform polymorphous adenocarcinoma of the salivary gland [PMID:38735907], but neither the consequences of the nuclear interaction nor the function of the fusion protein has been defined.","teleology":[{"year":2019,"claim":"To begin placing YLPM1 in a molecular context, it was unknown what protein complexes it participates in; mass spectrometry of nuclear Ago2 complexes established YLPM1 as a physical associate of nuclear Ago2 and SSBP1.","evidence":"LC-MS analysis of nuclear Ago2-associated proteins in cardiomyocytes","pmids":["31837603"],"confidence":"Low","gaps":["Single Co-IP/MS experiment with no reciprocal validation of the YLPM1-Ago2 interaction","No functional consequence of the YLPM1-Ago2-SSBP1 association established","Direct versus indirect nature of the interaction unresolved"]},{"year":2024,"claim":"Whether YLPM1 has a causal role in cancer was unknown; functional study of recurrent inactivating mutations in GIST established YLPM1 as a tumor suppressor whose loss promotes proliferation, growth, and oxidative phosphorylation.","evidence":"Functional loss-of-function study of inactivating YLPM1 mutations in GIST cells with proliferation, growth, and OXPHOS readouts","pmids":["39489749"],"confidence":"Medium","gaps":["Molecular mechanism linking YLPM1 loss to increased oxidative phosphorylation not defined","Single-lab study with limited methodological detail","Direct molecular substrates or targets of YLPM1 not identified"]},{"year":2024,"claim":"Genomic involvement of YLPM1 in other tumors was unexplored; a case of salivary gland adenocarcinoma revealed a previously unreported YLPM1::PRKD1 fusion, expanding the genomic contexts in which YLPM1 is altered.","evidence":"Molecular pathology / fusion gene identification in a single salivary gland tumor","pmids":["38735907"],"confidence":"Low","gaps":["Single case report with no functional characterization of the fusion protein","Oncogenic contribution of the fusion not tested","Relationship of this rearrangement to YLPM1 loss-of-function in GIST unknown"]},{"year":null,"claim":"The core biochemical activity of YLPM1 and the mechanism by which its inactivation reprograms cell metabolism and proliferation remain undefined.","evidence":"No timeline discovery assigns a molecular activity, substrate, or mechanistic pathway to YLPM1","pmids":[],"confidence":"Low","gaps":["No molecular activity or catalytic function defined","No mechanism connecting YLPM1 loss to oxidative phosphorylation","Functional significance of nuclear Ago2/SSBP1 association untested"]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["AGO2","SSBP1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"P49750","full_name":"YLP motif-containing protein 1","aliases":["Nuclear protein ZAP3","ZAP113"],"length_aa":2146,"mass_kda":241.6,"function":"Plays a role in the reduction of telomerase activity during differentiation of embryonic stem cells by binding to the core promoter of TERT and controlling its down-regulation","subcellular_location":"Nucleus; Nucleus speckle","url":"https://www.uniprot.org/uniprotkb/P49750/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/YLPM1","classification":"Not Classified","n_dependent_lines":26,"n_total_lines":1208,"dependency_fraction":0.02152317880794702},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"CPSF6","stoichiometry":0.2},{"gene":"DDX21","stoichiometry":0.2},{"gene":"HNRNPD","stoichiometry":0.2},{"gene":"HNRNPH1","stoichiometry":0.2},{"gene":"ILF3","stoichiometry":0.2},{"gene":"PSPC1","stoichiometry":0.2},{"gene":"RBM14","stoichiometry":0.2},{"gene":"RBM3","stoichiometry":0.2},{"gene":"RBM39","stoichiometry":0.2},{"gene":"RBM42","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/YLPM1","total_profiled":1310},"omim":[{"mim_id":"619766","title":"YLP MOTIF-CONTAINING PROTEIN 1; YLPM1","url":"https://www.omim.org/entry/619766"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nuclear speckles","reliability":"Supported"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/YLPM1"},"hgnc":{"alias_symbol":["ZAP","PPP1R169"],"prev_symbol":["C14orf170"]},"alphafold":{"accession":"P49750","domains":[{"cath_id":"3.40.50.300","chopping":"1817-2007","consensus_level":"high","plddt":82.4062,"start":1817,"end":2007},{"cath_id":"-","chopping":"2114-2146","consensus_level":"medium","plddt":55.7342,"start":2114,"end":2146},{"cath_id":"1.20.58","chopping":"393-501","consensus_level":"medium","plddt":79.8453,"start":393,"end":501}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P49750","model_url":"https://alphafold.ebi.ac.uk/files/AF-P49750-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P49750-F1-predicted_aligned_error_v6.png","plddt_mean":43.25},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=YLPM1","jax_strain_url":"https://www.jax.org/strain/search?query=YLPM1"},"sequence":{"accession":"P49750","fasta_url":"https://rest.uniprot.org/uniprotkb/P49750.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P49750/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P49750"}},"corpus_meta":[{"pmid":"38744975","id":"PMC_38744975","title":"Analysis of somatic mutations in whole blood from 200,618 individuals identifies pervasive positive selection and novel drivers of clonal hematopoiesis.","date":"2024","source":"Nature genetics","url":"https://pubmed.ncbi.nlm.nih.gov/38744975","citation_count":68,"is_preprint":false},{"pmid":"26830357","id":"PMC_26830357","title":"Revealing new candidate genes for reproductive traits in pigs: combining Bayesian GWAS and functional pathways.","date":"2016","source":"Genetics, selection, evolution : GSE","url":"https://pubmed.ncbi.nlm.nih.gov/26830357","citation_count":56,"is_preprint":false},{"pmid":"39210047","id":"PMC_39210047","title":"Rare coding variant analysis for human diseases across biobanks and ancestries.","date":"2024","source":"Nature genetics","url":"https://pubmed.ncbi.nlm.nih.gov/39210047","citation_count":42,"is_preprint":false},{"pmid":"34568833","id":"PMC_34568833","title":"ZBTB33 is mutated in clonal hematopoiesis and myelodysplastic syndromes and impacts RNA splicing.","date":"2021","source":"Blood cancer discovery","url":"https://pubmed.ncbi.nlm.nih.gov/34568833","citation_count":34,"is_preprint":false},{"pmid":"31837603","id":"PMC_31837603","title":"Identification of ncRNA-Mediated Functions of Nucleus-Localized miR-320 in Cardiomyocytes.","date":"2019","source":"Molecular therapy. Nucleic acids","url":"https://pubmed.ncbi.nlm.nih.gov/31837603","citation_count":24,"is_preprint":false},{"pmid":"39489749","id":"PMC_39489749","title":"Genomic and transcriptomic landscape of human gastrointestinal stromal tumors.","date":"2024","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/39489749","citation_count":20,"is_preprint":false},{"pmid":"27648443","id":"PMC_27648443","title":"Transcriptome Analysis of HepG2 Cells Expressing ORF3 from Swine Hepatitis E Virus to Determine the Effects of ORF3 on Host Cells.","date":"2016","source":"BioMed research international","url":"https://pubmed.ncbi.nlm.nih.gov/27648443","citation_count":10,"is_preprint":false},{"pmid":"39484254","id":"PMC_39484254","title":"Discovery of novel obesity genes through cross-ancestry analysis.","date":"2025","source":"medRxiv : the preprint server for health sciences","url":"https://pubmed.ncbi.nlm.nih.gov/39484254","citation_count":4,"is_preprint":false},{"pmid":"41168175","id":"PMC_41168175","title":"Discovery of obesity genes through cross-ancestry analysis.","date":"2025","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/41168175","citation_count":3,"is_preprint":false},{"pmid":"35953823","id":"PMC_35953823","title":"Integration of protein context improves protein-based COVID-19 patient stratification.","date":"2022","source":"Clinical proteomics","url":"https://pubmed.ncbi.nlm.nih.gov/35953823","citation_count":3,"is_preprint":false},{"pmid":"29805546","id":"PMC_29805546","title":"Sub-pathway analysis for severe burns injury patients: Identification of potential key lncRNAs by analyzing lncRNA-mRNA profile.","date":"2018","source":"Experimental and therapeutic medicine","url":"https://pubmed.ncbi.nlm.nih.gov/29805546","citation_count":2,"is_preprint":false},{"pmid":"30936989","id":"PMC_30936989","title":"Sub-pathway based approach to systematically track candidate sub-pathway biomarkers for heart failure.","date":"2019","source":"Experimental and therapeutic medicine","url":"https://pubmed.ncbi.nlm.nih.gov/30936989","citation_count":1,"is_preprint":false},{"pmid":"38735907","id":"PMC_38735907","title":"A Novel Gene Fusion YLPM1::PRKD1 Identified in a Cribriform Subtype of Polymorphous Adenocarcinoma.","date":"2024","source":"Head and neck pathology","url":"https://pubmed.ncbi.nlm.nih.gov/38735907","citation_count":0,"is_preprint":false},{"pmid":"41463911","id":"PMC_41463911","title":"Integrative Multi-Omics Analysis Unveils Candidate Genes and Functional Variants for Growth and Reproductive Traits in Duroc Pigs.","date":"2025","source":"Animals : an open access journal from MDPI","url":"https://pubmed.ncbi.nlm.nih.gov/41463911","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.08.27.25334581","title":"Clonal Hematopoiesis Dynamics and Evolutionary Fitness During Cancer Treatment Impact Clinical Outcomes","date":"2025-09-02","source":"bioRxiv","url":"https://doi.org/10.1101/2025.08.27.25334581","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":9099,"output_tokens":731,"usd":0.019131,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7154,"output_tokens":1436,"usd":0.035835,"stage2_stop_reason":"end_turn"},"total_usd":0.054966,"stage1_batch_id":"msgbatch_01UT1AahFPCAyn2uVweS7A9z","stage2_batch_id":"msgbatch_01HuKWtKNT4Pqj1bc8eEP5RV","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2024,\n      \"finding\": \"YLPM1 inactivation promotes GIST (gastrointestinal stromal tumor) cell proliferation, growth, and oxidative phosphorylation, as demonstrated by functional studies of recurrent inactivating YLPM1 mutations identified in high-risk/metastatic GIST.\",\n      \"method\": \"Functional study of inactivating mutations in GIST cells (loss-of-function with specific phenotypic readouts: proliferation, growth, oxidative phosphorylation)\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — single lab, functional loss-of-function study with defined cellular phenotypes, but abstract provides limited methodological detail\",\n      \"pmids\": [\"39489749\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Nuclear Ago2 physically associates with YLP motif-containing protein 1 (YLPM1) and single-stranded DNA binding protein 1 (SSBP1) in cardiomyocytes, as revealed by liquid chromatography-mass spectrometry analysis of nuclear Ago2 complexes.\",\n      \"method\": \"Liquid chromatography-mass spectrometry (LC-MS) analysis of nuclear Ago2-associated proteins\",\n      \"journal\": \"Molecular therapy. Nucleic acids\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single Co-IP/MS experiment, single lab, no functional validation of the YLPM1-Ago2 interaction itself\",\n      \"pmids\": [\"31837603\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"A novel YLPM1::PRKD1 gene fusion was identified in a cribriform subtype of polymorphous adenocarcinoma of the salivary gland, representing a previously unreported chromosomal rearrangement involving YLPM1.\",\n      \"method\": \"Molecular pathology / fusion gene identification in tumor sample\",\n      \"journal\": \"Head and neck pathology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single case report, descriptive identification of fusion, no functional characterization of the fusion protein\",\n      \"pmids\": [\"38735907\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"YLPM1 functions as a tumor suppressor whose inactivation promotes cell proliferation, growth, and oxidative phosphorylation in gastrointestinal stromal tumors; it also physically associates with nuclear Ago2 in cardiomyocytes and can undergo chromosomal rearrangement (YLPM1::PRKD1 fusion) in salivary gland tumors, but its precise molecular mechanism of action remains largely uncharacterized.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"YLPM1 acts as a tumor suppressor in gastrointestinal stromal tumors (GIST), where recurrent inactivating mutations in high-risk and metastatic disease drive cell proliferation, growth, and oxidative phosphorylation upon loss of function [#0]. Beyond this loss-of-function phenotype, the molecular mechanism of YLPM1 is largely uncharacterized in the available corpus: it has been detected in nuclear Ago2-associated complexes alongside SSBP1 in cardiomyocytes [#1], and a YLPM1::PRKD1 gene fusion has been identified in a cribriform polymorphous adenocarcinoma of the salivary gland [#2], but neither the consequences of the nuclear interaction nor the function of the fusion protein has been defined.\",\n  \"teleology\": [\n    {\n      \"year\": 2019,\n      \"claim\": \"To begin placing YLPM1 in a molecular context, it was unknown what protein complexes it participates in; mass spectrometry of nuclear Ago2 complexes established YLPM1 as a physical associate of nuclear Ago2 and SSBP1.\",\n      \"evidence\": \"LC-MS analysis of nuclear Ago2-associated proteins in cardiomyocytes\",\n      \"pmids\": [\"31837603\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single Co-IP/MS experiment with no reciprocal validation of the YLPM1-Ago2 interaction\",\n        \"No functional consequence of the YLPM1-Ago2-SSBP1 association established\",\n        \"Direct versus indirect nature of the interaction unresolved\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Whether YLPM1 has a causal role in cancer was unknown; functional study of recurrent inactivating mutations in GIST established YLPM1 as a tumor suppressor whose loss promotes proliferation, growth, and oxidative phosphorylation.\",\n      \"evidence\": \"Functional loss-of-function study of inactivating YLPM1 mutations in GIST cells with proliferation, growth, and OXPHOS readouts\",\n      \"pmids\": [\"39489749\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Molecular mechanism linking YLPM1 loss to increased oxidative phosphorylation not defined\",\n        \"Single-lab study with limited methodological detail\",\n        \"Direct molecular substrates or targets of YLPM1 not identified\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Genomic involvement of YLPM1 in other tumors was unexplored; a case of salivary gland adenocarcinoma revealed a previously unreported YLPM1::PRKD1 fusion, expanding the genomic contexts in which YLPM1 is altered.\",\n      \"evidence\": \"Molecular pathology / fusion gene identification in a single salivary gland tumor\",\n      \"pmids\": [\"38735907\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single case report with no functional characterization of the fusion protein\",\n        \"Oncogenic contribution of the fusion not tested\",\n        \"Relationship of this rearrangement to YLPM1 loss-of-function in GIST unknown\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The core biochemical activity of YLPM1 and the mechanism by which its inactivation reprograms cell metabolism and proliferation remain undefined.\",\n      \"evidence\": \"No timeline discovery assigns a molecular activity, substrate, or mechanistic pathway to YLPM1\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No molecular activity or catalytic function defined\",\n        \"No mechanism connecting YLPM1 loss to oxidative phosphorylation\",\n        \"Functional significance of nuclear Ago2/SSBP1 association untested\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [\"AGO2\", \"SSBP1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"tie","faith_supported":1,"faith_total":1,"faith_pct":100.0}}