{"entity":{"id":"rap1gds1","kind":"target","name":"RAP1GDS1","aka":["Rap1 GTPase-GDP dissociation stimulator 1","SmgGDS"],"tldr":"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.","summary":"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.\n\nOpen 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.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:9859","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:9859"},{"label":"UniProt P52306","url":"https://www.uniprot.org/uniprotkb/P52306/entry"},{"label":"NCBI Gene 5910","url":"https://www.ncbi.nlm.nih.gov/gene/5910"},{"label":"Ensembl ENSG00000138698","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000138698"}],"tags":["cancer-genes-wave"],"related":["open-targets","intogen"],"cancers":["rcc","esophageal","breast-cancer","clear-cell-rcc","oesophageal-squamous-cell-carcinoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"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: 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."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"RAP1GDS1","role":["oncogene-driver","tumour-suppressor","fusion-partner"],"evidenceTier":"cohort-driver","sources":[{"label":"HGNC HGNC:9859","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:9859","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt P52306","url":"https://www.uniprot.org/uniprotkb/P52306/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"Open Targets ENSG00000138698","url":"https://platform.opentargets.org/target/ENSG00000138698/associations","note":"association with cancer (MONDO_0004992) 0.68; per-cancer scores at or above 0.5: breast cancer 0.53 (GraphQL API, CC0)"},{"label":"IntOGen RAP1GDS1","url":"https://www.intogen.org/search?gene=RAP1GDS1","note":"driver in 2 cohorts (Act 1, LoF 1); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"hgnc":"HGNC:9859","ensembl":"ENSG00000138698","uniprot":"P52306","entrez":"5910","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).","whereFound":["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)"],"targetClass":"tumor-suppressor","prevalence":[]},"route":"/targets/rap1gds1/","neighbours":{"collection":[{"id":"intogen","kind":"collection","name":"IntOGen","route":"/collections/intogen/"},{"id":"open-targets","kind":"collection","name":"Open Targets Platform","route":"/collections/open-targets/"}],"cancer":[{"id":"breast-cancer","kind":"cancer","name":"Breast cancer (all types)","route":"/cancers/breast-cancer/"},{"id":"clear-cell-rcc","kind":"cancer","name":"Clear cell renal cell carcinoma","route":"/cancers/clear-cell-rcc/"},{"id":"esophageal","kind":"cancer","name":"Oesophageal cancer","route":"/cancers/esophageal/"},{"id":"oesophageal-squamous-cell-carcinoma","kind":"cancer","name":"Oesophageal squamous cell carcinoma","route":"/cancers/oesophageal-squamous-cell-carcinoma/"},{"id":"rcc","kind":"cancer","name":"Renal cell carcinoma","route":"/cancers/rcc/"}]}}