PIK3R1
PIK3R1 (Phosphatidylinositol 3-kinase regulatory subunit alpha) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Endometrial cancer, Colorectal cancer, Breast cancer and 5 more.
Overview
Binds to activated (phosphorylated) protein-Tyr kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane. Necessary for the insulin-stimulated increase in glucose uptake and glycogen synthesis in insulin-sensitive tissues. Plays an important role in signalling in response to FGFR1, FGFR2, FGFR3, FGFR4, KITLG/SCF, KIT, PDGFRA and PDGFRB.
CIViC holds 4 clinical evidence items and 0 assertions across 2 variants, naming Doxorubicin, Buparlisib, MTOR Kinase Inhibitor PP242 and Aspirin. Open Targets scores its association with cancer at 0.87 (direct and indirect evidence; datatypes clinical 0.67, affected pathway 0.85, literature 0.98, genetic association 0.71, somatic mutation 0.91). IntOGen calls it a driver in 24 cohorts (9 activating, 14 loss-of-function), covering Adenoid Cystic Carcinoma, Invasive Breast Carcinoma, Cholangiocarcinoma, Colon Adenocarcinoma, Colorectal Adenocarcinoma, Glioblastoma and others.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · PIK3R1 (Phosphatidylinositol 3-kinase regulatory subunit alpha) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Endometrial cancer, Colorectal cancer, Breast cancer and 5 more.
- 1 · What it is
PIK3R1 (Phosphatidylinositol 3-kinase regulatory subunit alpha) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Endometrial cancer, Colorectal cancer, Breast cancer and 5 more.
- 2 · What goes wrong in cancer
Binds to activated (phosphorylated) protein-Tyr kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane.
- 3 · How drugs use it
No product in this corpus aims at PIK3R1 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:8979 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt P27986 (protein name, function text, keywords and locations (REST API)); CIViC gene PIK3R1 (4 evidence items, 0 assertions, 2 variants; diseases: Colorectal Cancer, Glioblastoma, Breast Cancer, Sarcoma (GraphQL API, CC0)); Open Targets ENSG00000145675 (association with cancer (MONDO_0004992) 0.87; per-cancer scores at or above 0.5: colorectal cancer 0.68, ovarian cancer 0.56, endometrial cancer 0.71, melanoma 0.57, glioblastoma 0.59, skin cancer 0.63 (GraphQL API, CC0)); IntOGen PIK3R1 (driver in 24 cohorts (Act 9, LoF 14); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Biology
Binds to activated (phosphorylated) protein-Tyr kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane. Necessary for the insulin-stimulated increase in glucose uptake and glycogen synthesis in insulin-sensitive tissues. Plays an important role in signalling in response to FGFR1, FGFR2, FGFR3, FGFR4, KITLG/SCF, KIT, PDGFRA and PDGFRB. Likewise, plays a role in ITGB2 signalling. Modulates the cellular response to ER stress by promoting nuclear translocation of XBP1 isoform 2 in a ER stress- and/or insulin-dependent manner during metabolic overloading in the liver and hence plays a role in glucose tolerance improvement. Location: Cytoplasm (UniProt). Locus 5q13.1 (HGNC).
- Endometrial cancer: Open Targets association 0.71 with endometrial cancer (MONDO_0011962); IntOGen driver in 4 cohorts (UCEC)
- Colorectal cancer: Open Targets association 0.68 with colorectal cancer (MONDO_0005575); CIViC evidence names this disease
- Breast cancer: Open Targets association 0.60 with breast cancer (MONDO_0007254); CIViC evidence names this disease
- Skin cancer: Open Targets association 0.63 with skin cancer (MONDO_0002898)
- Sarcomas: CIViC evidence names this disease
- Gastric & gastro-oesophageal junction cancer: IntOGen driver in 2 cohorts (STAD)
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: Open Targets known-drug datatype score 0.67; IntOGen calls it an activating (Act) driver in 9 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 14 cohorts; CIViC holds 4 clinical evidence items on its variants. Evidence tier "clinical-evidence" 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: Low-Grade Glioma, NOS.
Latest papers
topQuery for this target: (TITLE:"PIK3R1" OR ABSTRACT:"PIK3R1" OR TITLE:"phosphoinositide-3-kinase regulatory subunit 1" OR ABSTRACT:"phosphoinositide-3-kinase regulatory subunit 1" OR TITLE:"Phosphatidylinositol 3-kinase regulatory subunit alpha" OR ABSTRACT:"Phosphatidylinositol 3-kinase regulatory subunit alpha" OR TITLE:"GRB1" OR ABSTRACT:"GRB1" OR TITLE:"p85-ALPHA" OR ABSTRACT:"p85-ALPHA" OR TITLE:"p85" OR ABSTRACT:"p85") 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 PIK3R1, not a curated reading list.
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