PPM1D
PPM1D (Protein phosphatase 1D) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Breast cancer, Ovarian cancer, Myeloproliferative neoplasms and 5 more.
Overview
Involved in the negative regulation of p53 expression. Required for the relief of p53-dependent checkpoint mediated cell cycle arrest. Binds to and dephosphorylates 'Ser-15' of TP53 and 'Ser-345' of CHEK1 which contributes to the functional inactivation of these proteins.
Open Targets scores its association with cancer at 0.81 (direct and indirect evidence; datatypes genetic literature 0.38, affected pathway 0.34, literature 0.99, genetic association 0.72, somatic mutation 0.93, animal model 0.29). IntOGen calls it a driver in 6 cohorts (0 activating, 6 loss-of-function), covering Basal Cell Carcinoma, Invasive Breast Carcinoma, High-Grade Glioma, NOS, Lung Adenocarcinoma, Pilocytic Astrocytoma.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · PPM1D (Protein phosphatase 1D) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Breast cancer, Ovarian cancer, Myeloproliferative neoplasms and 5 more.
- 1 · What it is
PPM1D (Protein phosphatase 1D) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Breast cancer, Ovarian cancer, Myeloproliferative neoplasms and 5 more.
- 2 · What goes wrong in cancer
Involved in the negative regulation of p53 expression. Required for the relief of p53-dependent checkpoint mediated cell cycle arrest.
- 3 · How drugs use it
No product in this corpus aims at PPM1D yet. Because the protein is lost rather than overactive, drugs either restore its function or exploit the weakness its loss leaves (synthetic lethality).
External identifiers
Sources: HGNC HGNC:9277 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt O15297 (protein name, function text, keywords and locations (REST API)); Open Targets ENSG00000170836 (association with cancer (MONDO_0004992) 0.81; per-cancer scores at or above 0.5: colorectal cancer 0.51, ovarian cancer 0.58, skin cancer 0.52, myeloproliferative neoplasm 0.56, breast cancer 0.71 (GraphQL API, CC0)); IntOGen PPM1D (driver in 6 cohorts (Act 0, LoF 6); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Biology
Involved in the negative regulation of p53 expression. Required for the relief of p53-dependent checkpoint mediated cell cycle arrest. Binds to and dephosphorylates 'Ser-15' of TP53 and 'Ser-345' of CHEK1 which contributes to the functional inactivation of these proteins. Mediates MAPK14 dephosphorylation and inactivation. Is also an important regulator of global heterochromatin silencing and critical in maintaining genome integrity. Location: Nucleus; Cytoplasm, cytosol (UniProt). Locus 17q23.3 (HGNC).
- Breast cancer: Open Targets association 0.71 with breast cancer (MONDO_0007254); IntOGen driver in 1 cohort (BRCA)
- Ovarian cancer: Open Targets association 0.58 with ovarian cancer (MONDO_0008170)
- Myeloproliferative neoplasms: Open Targets association 0.56 with myeloproliferative neoplasm (MONDO_0020076)
- Skin cancer: Open Targets association 0.52 with skin cancer (MONDO_0002898)
- Colorectal cancer: Open Targets association 0.51 with colorectal cancer (MONDO_0005575)
- Non-small-cell lung cancer: IntOGen driver in 2 cohorts (LUAD)
Notes
top- 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: IntOGen calls it a loss-of-function (LoF) driver in 6 cohorts. Evidence tier "cohort-driver" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.
- Diseases the sources name that have no OnCo cancer page yet, so they are not linked: High-Grade Glioma, NOS.
Latest papers
topQuery for this target: (TITLE:"PPM1D" OR ABSTRACT:"PPM1D" OR TITLE:"protein phosphatase, Mg2+/Mn2+ dependent 1D" OR ABSTRACT:"protein phosphatase, Mg2+/Mn2+ dependent 1D" OR TITLE:"Protein phosphatase 1D" OR ABSTRACT:"Protein phosphatase 1D" OR TITLE:"Wip1" OR ABSTRACT:"Wip1" OR TITLE:"PP2C-DELTA" OR ABSTRACT:"PP2C-DELTA") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about PPM1D, not a curated reading list.
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