{"gene":"MPHOSPH6","run_date":"2026-06-10T02:59:51","timeline":{"discoveries":[{"year":2017,"finding":"MPHOSPH6 plays an important role in the recruitment of the exosome to the pre-rRNA, implicating it in ribosome biogenesis.","method":"Literature-based functional annotation cited within a genetic association study context","journal":"Oncotarget","confidence":"Low","confidence_rationale":"Tier 4 / Weak — functional claim stated as background knowledge in a GWAS paper, no direct experiment performed in this study","pmids":["29069794"],"is_preprint":false},{"year":2026,"finding":"Two variants at the novel locus 16q23.3 regulate MPHOSPH6 expression and protein function, influencing telomere length and lung cancer risk, as demonstrated by functional assays.","method":"Functional assays validating variants at 16q23.3 locus (described as regulating MPHOSPH6 expression and protein function), combined with eQTL colocalization and genome-wide meta-analysis","journal":"Genome medicine","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional assays plus colocalization in a single study; abstract does not detail specific assay methodology, limiting full tier assignment","pmids":["42152146"],"is_preprint":false},{"year":2018,"finding":"MPHOSPH6 mRNA is a novel target of miR-146b-5p (and miR-146a-5p), as validated in hepatocytes overexpressing miR-146b-5p followed by RNA-Seq and further validation experiments.","method":"Inducible miRNA overexpression in PH5CH8 cells followed by RNA-Seq and validation experiments","journal":"Journal of leukocyte biology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, miRNA target validation by expression change after overexpression; no direct binding/reporter assay described in abstract","pmids":["30145833"],"is_preprint":false}],"current_model":"MPHOSPH6 is implicated in recruiting the RNA exosome to pre-rRNA (ribosome biogenesis), and functional genetic variants at the 16q23.3 locus regulate MPHOSPH6 expression and protein function to influence telomere length; its mRNA is also a target of miR-146b-5p, but direct biochemical characterization of its enzymatic or structural mechanism remains limited."},"narrative":{"mechanistic_narrative":"MPHOSPH6 functions in ribosome biogenesis, where it contributes to recruitment of the RNA exosome to pre-rRNA [PMID:29069794]. Functional genetic variants at the 16q23.3 locus regulate MPHOSPH6 expression and protein function, linking it to telomere length and lung cancer risk [PMID:42152146]. Its mRNA is a target of miR-146b-5p, placing it under post-transcriptional control [PMID:30145833]. Beyond these associations, direct biochemical characterization of its enzymatic or structural mechanism has not been established in the available corpus.","teleology":[{"year":2017,"claim":"Established a functional role for MPHOSPH6 in ribosome biogenesis by linking it to recruitment of the RNA exosome to pre-rRNA.","evidence":"Functional annotation cited as background within a genetic association study","pmids":["29069794"],"confidence":"Low","gaps":["Claim is stated as background, not experimentally demonstrated in this study","No direct biochemical assay of exosome recruitment shown","No structural or domain-level mechanism defined"]},{"year":2018,"claim":"Identified MPHOSPH6 mRNA as a target of miR-146b-5p, indicating post-transcriptional regulation of its expression.","evidence":"Inducible miR-146b-5p overexpression in PH5CH8 hepatocytes followed by RNA-Seq and validation","pmids":["30145833"],"confidence":"Low","gaps":["No direct binding or reporter assay establishing a physical miRNA-mRNA interaction described","Single cell-type context","Functional consequence of repression on ribosome biogenesis not tested"]},{"year":2026,"claim":"Demonstrated that variants at 16q23.3 regulate MPHOSPH6 expression and protein function, connecting the gene to telomere length and lung cancer risk.","evidence":"Functional assays plus eQTL colocalization and genome-wide meta-analysis","pmids":["42152146"],"confidence":"Medium","gaps":["Specific functional assay methodology not detailed","Mechanism linking MPHOSPH6 to telomere length not resolved","Causal protein-level effect on ribosome biogenesis pathway not connected"]},{"year":null,"claim":"The direct molecular and structural mechanism by which MPHOSPH6 acts on the exosome and pre-rRNA, and how this relates to telomere maintenance, remains unresolved.","evidence":"No direct biochemical or structural study present in the corpus","pmids":[],"confidence":"Low","gaps":["No reconstitution of MPHOSPH6-exosome interaction","No structural model","Mechanistic link between expression and telomere length undefined"]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":[],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q99547","full_name":"M-phase phosphoprotein 6","aliases":[],"length_aa":160,"mass_kda":19.0,"function":"RNA-binding protein that associates with the RNA exosome complex. Involved in the 3'-processing of the 7S pre-RNA to the mature 5.8S rRNA and play a role in recruiting the RNA exosome complex to pre-rRNA; this function may include C1D","subcellular_location":"Nucleus, nucleolus; Cytoplasm","url":"https://www.uniprot.org/uniprotkb/Q99547/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/MPHOSPH6","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":"NUMA1","stoichiometry":0.2},{"gene":"SRP9","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/MPHOSPH6","total_profiled":1310},"omim":[{"mim_id":"605500","title":"M-PHASE PHOSPHOPROTEIN 6; MPHOSPH6","url":"https://www.omim.org/entry/605500"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"},{"location":"Nucleoli","reliability":"Supported"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/MPHOSPH6"},"hgnc":{"alias_symbol":["MPP6"],"prev_symbol":[]},"alphafold":{"accession":"Q99547","domains":[{"cath_id":"-","chopping":"16-40","consensus_level":"medium","plddt":82.5676,"start":16,"end":40}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q99547","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q99547-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q99547-F1-predicted_aligned_error_v6.png","plddt_mean":76.38},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=MPHOSPH6","jax_strain_url":"https://www.jax.org/strain/search?query=MPHOSPH6"},"sequence":{"accession":"Q99547","fasta_url":"https://rest.uniprot.org/uniprotkb/Q99547.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q99547/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q99547"}},"corpus_meta":[{"pmid":"31171785","id":"PMC_31171785","title":"Loci for human leukocyte telomere length in the Singaporean Chinese population and trans-ethnic genetic studies.","date":"2019","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/31171785","citation_count":73,"is_preprint":false},{"pmid":"28117656","id":"PMC_28117656","title":"Epigenetic profiling of human brain differential DNA methylation networks in schizophrenia.","date":"2016","source":"BMC medical genomics","url":"https://pubmed.ncbi.nlm.nih.gov/28117656","citation_count":30,"is_preprint":false},{"pmid":"30145833","id":"PMC_30145833","title":"Cytokine-mediated modulation of the hepatic miRNome: miR-146b-5p is an IL-6-inducible miRNA with multiple targets.","date":"2018","source":"Journal of leukocyte biology","url":"https://pubmed.ncbi.nlm.nih.gov/30145833","citation_count":20,"is_preprint":false},{"pmid":"37079368","id":"PMC_37079368","title":"Common genetic variations in telomere length genes and lung cancer: a Mendelian randomisation study and its novel application in lung tumour transcriptome.","date":"2023","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/37079368","citation_count":16,"is_preprint":false},{"pmid":"34745207","id":"PMC_34745207","title":"Genome-Wide Association Study of Growth Performance and Immune Response to Newcastle Disease Virus of Indigenous Chicken in Rwanda.","date":"2021","source":"Frontiers in genetics","url":"https://pubmed.ncbi.nlm.nih.gov/34745207","citation_count":14,"is_preprint":false},{"pmid":"29156773","id":"PMC_29156773","title":"Association of ACYP2 and MPHOSPH6 genetic polymorphisms with the risk of hepatocellular carcinoma in chronic hepatitis B virus carriers.","date":"2017","source":"Oncotarget","url":"https://pubmed.ncbi.nlm.nih.gov/29156773","citation_count":7,"is_preprint":false},{"pmid":"35082523","id":"PMC_35082523","title":"FOXO4 May Be a Biomarker of Postmenopausal Osteoporosis.","date":"2022","source":"International journal of general medicine","url":"https://pubmed.ncbi.nlm.nih.gov/35082523","citation_count":4,"is_preprint":false},{"pmid":"29209388","id":"PMC_29209388","title":"A Genome-Wide Association Study Identifies UTRN Gene Polymorphism for Restless Legs Syndrome in a Korean Population.","date":"2017","source":"Psychiatry investigation","url":"https://pubmed.ncbi.nlm.nih.gov/29209388","citation_count":4,"is_preprint":false},{"pmid":"29069794","id":"PMC_29069794","title":"Association between MPHOSPH6 gene polymorphisms and IgA nephropathy risk in a Chinese Han population.","date":"2017","source":"Oncotarget","url":"https://pubmed.ncbi.nlm.nih.gov/29069794","citation_count":2,"is_preprint":false},{"pmid":"40425712","id":"PMC_40425712","title":"Novel ribosome biogenesis-related biomarkers and therapeutic targets identified in psoriasis.","date":"2025","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/40425712","citation_count":1,"is_preprint":false},{"pmid":"40354008","id":"PMC_40354008","title":"Multi-omics identify ribosome related causal genes methylation, splicing, and expression in prostate cancer.","date":"2025","source":"Discover oncology","url":"https://pubmed.ncbi.nlm.nih.gov/40354008","citation_count":1,"is_preprint":false},{"pmid":"31966846","id":"PMC_31966846","title":"Polymorphisms of telomere-length related genes in three China ethnic groups.","date":"2017","source":"International journal of clinical and experimental pathology","url":"https://pubmed.ncbi.nlm.nih.gov/31966846","citation_count":1,"is_preprint":false},{"pmid":"40336248","id":"PMC_40336248","title":"Whole-genome resequencing reveals genetic differentiation and selection signatures among wild, local and commercial duck populations.","date":"2024","source":"Animal bioscience","url":"https://pubmed.ncbi.nlm.nih.gov/40336248","citation_count":1,"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},{"pmid":"42152146","id":"PMC_42152146","title":"Genome-wide meta-analysis across East Asian and European populations provides insights into the molecular basis of lung cancer.","date":"2026","source":"Genome medicine","url":"https://pubmed.ncbi.nlm.nih.gov/42152146","citation_count":0,"is_preprint":false},{"pmid":"41909697","id":"PMC_41909697","title":"Machine learning meets psoriasis: identifying key lactylation biomarkers as potential targets for diagnosis and therapies.","date":"2026","source":"Frontiers in immunology","url":"https://pubmed.ncbi.nlm.nih.gov/41909697","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.01.02.25319933","title":"Identifying Potential Drug Targets for Prostate Cancer from a Genetic Perspective: A Mendelian Randomization Study","date":"2025-01-03","source":"bioRxiv","url":"https://doi.org/10.1101/2025.01.02.25319933","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":12049,"output_tokens":688,"usd":0.023234,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7053,"output_tokens":1153,"usd":0.032045,"stage2_stop_reason":"end_turn"},"total_usd":0.055279,"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\": 2017,\n      \"finding\": \"MPHOSPH6 plays an important role in the recruitment of the exosome to the pre-rRNA, implicating it in ribosome biogenesis.\",\n      \"method\": \"Literature-based functional annotation cited within a genetic association study context\",\n      \"journal\": \"Oncotarget\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — functional claim stated as background knowledge in a GWAS paper, no direct experiment performed in this study\",\n      \"pmids\": [\"29069794\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"Two variants at the novel locus 16q23.3 regulate MPHOSPH6 expression and protein function, influencing telomere length and lung cancer risk, as demonstrated by functional assays.\",\n      \"method\": \"Functional assays validating variants at 16q23.3 locus (described as regulating MPHOSPH6 expression and protein function), combined with eQTL colocalization and genome-wide meta-analysis\",\n      \"journal\": \"Genome medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional assays plus colocalization in a single study; abstract does not detail specific assay methodology, limiting full tier assignment\",\n      \"pmids\": [\"42152146\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"MPHOSPH6 mRNA is a novel target of miR-146b-5p (and miR-146a-5p), as validated in hepatocytes overexpressing miR-146b-5p followed by RNA-Seq and further validation experiments.\",\n      \"method\": \"Inducible miRNA overexpression in PH5CH8 cells followed by RNA-Seq and validation experiments\",\n      \"journal\": \"Journal of leukocyte biology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, miRNA target validation by expression change after overexpression; no direct binding/reporter assay described in abstract\",\n      \"pmids\": [\"30145833\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"MPHOSPH6 is implicated in recruiting the RNA exosome to pre-rRNA (ribosome biogenesis), and functional genetic variants at the 16q23.3 locus regulate MPHOSPH6 expression and protein function to influence telomere length; its mRNA is also a target of miR-146b-5p, but direct biochemical characterization of its enzymatic or structural mechanism remains limited.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"MPHOSPH6 functions in ribosome biogenesis, where it contributes to recruitment of the RNA exosome to pre-rRNA [#0]. Functional genetic variants at the 16q23.3 locus regulate MPHOSPH6 expression and protein function, linking it to telomere length and lung cancer risk [#1]. Its mRNA is a target of miR-146b-5p, placing it under post-transcriptional control [#2]. Beyond these associations, direct biochemical characterization of its enzymatic or structural mechanism has not been established in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2017,\n      \"claim\": \"Established a functional role for MPHOSPH6 in ribosome biogenesis by linking it to recruitment of the RNA exosome to pre-rRNA.\",\n      \"evidence\": \"Functional annotation cited as background within a genetic association study\",\n      \"pmids\": [\"29069794\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Claim is stated as background, not experimentally demonstrated in this study\",\n        \"No direct biochemical assay of exosome recruitment shown\",\n        \"No structural or domain-level mechanism defined\"\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Identified MPHOSPH6 mRNA as a target of miR-146b-5p, indicating post-transcriptional regulation of its expression.\",\n      \"evidence\": \"Inducible miR-146b-5p overexpression in PH5CH8 hepatocytes followed by RNA-Seq and validation\",\n      \"pmids\": [\"30145833\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No direct binding or reporter assay establishing a physical miRNA-mRNA interaction described\",\n        \"Single cell-type context\",\n        \"Functional consequence of repression on ribosome biogenesis not tested\"\n      ]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Demonstrated that variants at 16q23.3 regulate MPHOSPH6 expression and protein function, connecting the gene to telomere length and lung cancer risk.\",\n      \"evidence\": \"Functional assays plus eQTL colocalization and genome-wide meta-analysis\",\n      \"pmids\": [\"42152146\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Specific functional assay methodology not detailed\",\n        \"Mechanism linking MPHOSPH6 to telomere length not resolved\",\n        \"Causal protein-level effect on ribosome biogenesis pathway not connected\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The direct molecular and structural mechanism by which MPHOSPH6 acts on the exosome and pre-rRNA, and how this relates to telomere maintenance, remains unresolved.\",\n      \"evidence\": \"No direct biochemical or structural study present in the corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No reconstitution of MPHOSPH6-exosome interaction\",\n        \"No structural model\",\n        \"Mechanistic link between expression and telomere length undefined\"\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":{"pairwise":"win","faith_supported":3,"faith_total":3,"faith_pct":100.0}}