RAP1GDS1
RAP1GDS1 (Rap1 GTPase-GDP dissociation stimulator 1) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as an oncogene driver, a tumour suppressor and a fusion partner, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Renal cell carcinoma, Oesophageal cancer, Breast cancer and 2 more.
Overview
Acts as a GEF (guanine nucleotide exchange factor) for the Rho family of small GTP-binding proteins (G proteins) that stimulates the dissociation of GDP to enable subsequent binding of GTP. Additionally, appears to chaperone the processing and/or trafficking of small GTPases containing a C-terminal polybasic region independently of GEF activity. Targets include RAP1A/RAP1B, RHOA, RHOB, RHOC, RAC1 and KRAS.
Open Targets scores its association with cancer at 0.68 (direct and indirect evidence; datatypes literature 0.43, animal model 0.36, genetic association 0.34, somatic mutation 0.83). IntOGen calls it a driver in 2 cohorts (1 activating, 1 loss-of-function), covering Renal Clear Cell Carcinoma, Oesophageal Squamous Cell Carcinoma.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · RAP1GDS1 (Rap1 GTPase-GDP dissociation stimulator 1) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as an oncogene driver, a tumour suppressor and a fusion partner, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Renal cell carcinoma, Oesophageal cancer, Breast cancer and 2 more.
- 1 · What it is
RAP1GDS1 (Rap1 GTPase-GDP dissociation stimulator 1) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as an oncogene driver, a tumour suppressor and a fusion partner, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Renal cell carcinoma, Oesophageal cancer, Breast cancer and 2 more.
- 2 · What goes wrong in cancer
Acts as a GEF (guanine nucleotide exchange factor) for the Rho family of small GTP-binding proteins (G proteins) that stimulates the dissociation of GDP to enable subsequent binding of GTP.
- 3 · How drugs use it
No product in this corpus aims at RAP1GDS1 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:9859 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt P52306 (protein name, function text, keywords and locations (REST API)); Open Targets ENSG00000138698 (association with cancer (MONDO_0004992) 0.68; per-cancer scores at or above 0.5: breast cancer 0.53 (GraphQL API, CC0)); IntOGen RAP1GDS1 (driver in 2 cohorts (Act 1, LoF 1); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Biology
Acts as a GEF (guanine nucleotide exchange factor) for the Rho family of small GTP-binding proteins (G proteins) that stimulates the dissociation of GDP to enable subsequent binding of GTP. Additionally, appears to chaperone the processing and/or trafficking of small GTPases containing a C-terminal polybasic region independently of GEF activity. Targets include RAP1A/RAP1B, RHOA, RHOB, RHOC, RAC1 and KRAS. Regulates mitochondrial dynamics by controlling RHOT function to promote mitochondrial fission during high calcium conditions. Able to promote the Ca(2+) release from the endoplasmic reticulum via both inositol trisphosphate (Ins3P) and ryanodine sensitive receptors leading to a enhanced mitochondrial Ca(2+) uptake. Acts as a GEF (guanine nucleotide exchange factor) for unprenylated RHOA. Location: Cytoplasm, cytosol; Endoplasmic reticulum; Mitochondrion; Nucleus (UniProt). Locus 4q23 (HGNC).
- Renal cell carcinoma: IntOGen driver in 1 cohort (CCRCC)
- Oesophageal cancer: IntOGen driver in 1 cohort (ESCC)
- Breast cancer: Open Targets association 0.53 with breast cancer (MONDO_0007254)
- Clear cell renal cell carcinoma: IntOGen driver in 1 cohort (CCRCC)
- Oesophageal squamous cell carcinoma: IntOGen driver in 1 cohort (ESCC)
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 an activating (Act) driver in 1 cohort; IntOGen calls it a loss-of-function (LoF) driver in 1 cohort; UniProt disease notes describe a translocation or gene fusion involving the gene. Evidence tier "cohort-driver" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.
Latest papers
topQuery for this target: (TITLE:"RAP1GDS1" OR ABSTRACT:"RAP1GDS1" OR TITLE:"Rap1 GTPase-GDP dissociation stimulator 1" OR ABSTRACT:"Rap1 GTPase-GDP dissociation stimulator 1" OR TITLE:"SmgGDS" OR ABSTRACT:"SmgGDS") 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 RAP1GDS1, not a curated reading list.
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