{"entity":{"id":"pml","kind":"target","name":"PML","aka":["PML nuclear body scaffold","TRIM19","RNF71"],"tldr":"PML (PML nuclear body scaffold) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a drug target, a tumour suppressor, a biomarker and a fusion partner, and an approved or late-stage drug is recorded against it. Tied to Leukaemia, Thyroid cancer, Lung cancer and 3 more.","summary":"Functions via its association with PML-nuclear bodies (PML-NBs) in a wide range of important cellular processes, including tumour suppression, transcriptional regulation, apoptosis, senescence, DNA damage response, and viral defense mechanisms. Acts as the scaffold of PML-NBs allowing other proteins to shuttle in and out, a process which is regulated by SUMO-mediated modifications and interactions. Inhibits EIF4E-mediated mRNA nuclear export by reducing EIF4E affinity for the 5' 7-methylguanosine (m7G) cap of target mRNAs.\n\nCIViC holds 7 clinical evidence items and 0 assertions across 6 variants, naming Tretinoin, Arsenic Trioxide and Tamibarotene. Open Targets scores its association with cancer at 0.75 (direct and indirect evidence; datatypes literature 0.99, affected pathway 0.87, genetic association 0.63, somatic mutation 0.80). IntOGen calls it a driver in 1 cohort (0 activating, 1 loss-of-function), covering Lung. In OnCo, 2 product records name it (Arsenic trioxide and Tretinoin (all-trans retinoic acid, ATRA)).","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:9113","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:9113"},{"label":"UniProt P29590","url":"https://www.uniprot.org/uniprotkb/P29590/entry"},{"label":"NCBI Gene 5371","url":"https://www.ncbi.nlm.nih.gov/gene/5371"},{"label":"Ensembl ENSG00000140464","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000140464"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets","intogen"],"cancers":["leukaemia","thyroid","lung-cancer","skin-cancer","myeloproliferative-neoplasms","apl"],"sections":[],"technologies":[],"targets":[],"drugs":["arsenic-trioxide","tretinoin-atra"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: CIViC lists 3 therapies; IntOGen calls it a loss-of-function (LoF) driver in 1 cohort; CIViC holds 7 clinical evidence items on its variants; UniProt disease notes describe a translocation or gene fusion involving the gene. Evidence tier \"approved-drug\" is the strongest of those signals.","Prevalence not recorded: none of the sources gives a positivity rate."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"PML","role":["drug-target","tumour-suppressor","biomarker","fusion-partner"],"evidenceTier":"approved-drug","sources":[{"label":"HGNC HGNC:9113","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:9113","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt P29590","url":"https://www.uniprot.org/uniprotkb/P29590/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene PML","url":"https://civicdb.org/features/39","note":"7 evidence items, 0 assertions, 6 variants; diseases: Acute Promyelocytic Leukaemia (GraphQL API, CC0)"},{"label":"Open Targets ENSG00000140464","url":"https://platform.opentargets.org/target/ENSG00000140464/associations","note":"association with cancer (MONDO_0004992) 0.75; per-cancer scores at or above 0.5: thyroid cancer 0.57, skin cancer 0.53, myeloproliferative neoplasm 0.52, leukaemia 0.58 (GraphQL API, CC0)"},{"label":"IntOGen PML","url":"https://www.intogen.org/search?gene=PML","note":"driver in 1 cohort (Act 0, LoF 1); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"hgnc":"HGNC:9113","ensembl":"ENSG00000140464","uniprot":"P29590","entrez":"5371","biology":"Functions via its association with PML-nuclear bodies (PML-NBs) in a wide range of important cellular processes, including tumour suppression, transcriptional regulation, apoptosis, senescence, DNA damage response, and viral defense mechanisms. Acts as the scaffold of PML-NBs allowing other proteins to shuttle in and out, a process which is regulated by SUMO-mediated modifications and interactions. Inhibits EIF4E-mediated mRNA nuclear export by reducing EIF4E affinity for the 5' 7-methylguanosine (m7G) cap of target mRNAs. Isoform PML-4 has a multifaceted role in the regulation of apoptosis and growth suppression: activates RB1 and inhibits AKT1 via interactions with PP1 and PP2A phosphatases respectively, negatively affects the PI3K pathway by inhibiting MTOR and activating PTEN, and positively regulates p53/TP53 by acting at different levels (by promoting its acetylation and phosphorylation and by inhibiting its MDM2-dependent degradation). Isoform PML-4 also: acts as a transcriptional repressor of TBX2 during cellular senescence and the repression is dependent on a functional RBL2/E2F4 repressor complex, regulates double-strand break repair in gamma-irradiation-induced DNA damage responses via its interaction with WRN, acts as a negative regulator of telomerase by interacting with TERT, and regulates PER2 nuclear localisation and circadian function. Isoform PML-6 inhibits specifically the activity of the tetrameric form of PKM. Location: Nucleus; Nucleus, nucleoplasm; Cytoplasm; Nucleus, PML body (UniProt). Locus 15q24.1 (HGNC).","whereFound":["Leukaemia: Open Targets association 0.58 with leukaemia (MONDO_0005059)","Thyroid cancer: Open Targets association 0.57 with thyroid cancer (MONDO_0002108)","Lung cancer: IntOGen driver in 1 cohort (LUNG)","Skin cancer: Open Targets association 0.53 with skin cancer (MONDO_0002898)","Myeloproliferative neoplasms: Open Targets association 0.52 with myeloproliferative neoplasm (MONDO_0020076)","Acute promyelocytic leukaemia: CIViC evidence names this disease"],"targetClass":"tumor-suppressor","prevalence":[]},"route":"/targets/pml/","neighbours":{"collection":[{"id":"civic","kind":"collection","name":"CIViC","route":"/collections/civic/"},{"id":"intogen","kind":"collection","name":"IntOGen","route":"/collections/intogen/"},{"id":"open-targets","kind":"collection","name":"Open Targets Platform","route":"/collections/open-targets/"}],"cancer":[{"id":"apl","kind":"cancer","name":"Acute promyelocytic leukaemia","route":"/cancers/apl/"},{"id":"leukaemia","kind":"cancer","name":"Leukaemia (all types)","route":"/cancers/leukaemia/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"myeloproliferative-neoplasms","kind":"cancer","name":"Myeloproliferative neoplasms (PV, ET, myelofibrosis)","route":"/cancers/myeloproliferative-neoplasms/"},{"id":"skin-cancer","kind":"cancer","name":"Skin cancer (all types)","route":"/cancers/skin-cancer/"},{"id":"thyroid","kind":"cancer","name":"Thyroid cancer","route":"/cancers/thyroid/"}],"drug":[{"id":"arsenic-trioxide","kind":"drug","name":"Arsenic trioxide","route":"/drugs/arsenic-trioxide/"},{"id":"tretinoin-atra","kind":"drug","name":"Tretinoin (all-trans retinoic acid, ATRA)","route":"/drugs/tretinoin-atra/"}]}}