{"entity":{"id":"arhgap35","kind":"target","name":"ARHGAP35","aka":["Rho GTPase activating protein 35","Rho GTPase-activating protein 35","GRF-1","p190ARhoGAP","P190A","KIAA1722","p190RhoGAP","GRLF1"],"tldr":"ARHGAP35 (Rho GTPase-activating protein 35) is a protein that switches other genes on and off. The public catalogues list it as 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, Bladder & urothelial cancer, Breast cancer and 5 more.","summary":"Rho GTPase-activating protein (GAP). Binds several acidic phospholipids which inhibits the Rho GAP activity to promote the Rac GAP activity. This binding is inhibited by phosphorylation by PRKCA.\n\nCIViC holds 4 clinical evidence items and 0 assertions across 4 variants. Open Targets scores its association with cancer at 0.75 (direct and indirect evidence; datatypes literature 0.93, animal model 0.46, genetic association 0.00, somatic mutation 0.90). IntOGen calls it a driver in 15 cohorts (1 activating, 14 loss-of-function), covering Acute Myeloid Leukaemia, Basal Cell Carcinoma, Bladder Urothelial Carcinoma, Invasive Breast Carcinoma, Renal Clear Cell Carcinoma, Lung Squamous Cell Carcinoma and others.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:4591","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:4591"},{"label":"UniProt Q9NRY4","url":"https://www.uniprot.org/uniprotkb/Q9NRY4/entry"},{"label":"NCBI Gene 2909","url":"https://www.ncbi.nlm.nih.gov/gene/2909"},{"label":"Ensembl ENSG00000160007","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000160007"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets","intogen"],"cancers":["endometrial","urothelial","breast-cancer","rcc","ovarian","skin-cancer","lung-cancer","basal-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 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."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"ARHGAP35","role":["oncogene-driver","tumour-suppressor","biomarker"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:4591","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:4591","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt Q9NRY4","url":"https://www.uniprot.org/uniprotkb/Q9NRY4/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene ARHGAP35","url":"https://civicdb.org/features/2438","note":"4 evidence items, 0 assertions, 4 variants; diseases:  (GraphQL API, CC0)"},{"label":"Open Targets ENSG00000160007","url":"https://platform.opentargets.org/target/ENSG00000160007/associations","note":"association with cancer (MONDO_0004992) 0.75; per-cancer scores at or above 0.5: endometrial cancer 0.61, melanoma 0.56, skin cancer 0.56, breast cancer 0.57, lung cancer 0.51 (GraphQL API, CC0)"},{"label":"IntOGen ARHGAP35","url":"https://www.intogen.org/search?gene=ARHGAP35","note":"driver in 15 cohorts (Act 1, LoF 14); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"specificity":"tumour-specific","distribution":"many-types","specificityNote":"Tumour-specific alteration: the catalogues call it an oncogene driver (IntOGen cohort analysis finds it activated more often than chance) and a tumour suppressor (IntOGen finds it knocked out more often than chance), so the direction differs between cohorts but the alteration is somatic either way; what a medicine would aim at or exploit is the altered form or its loss, absent from normal cells; no corpus medicine is aimed at it yet. HPA ARHGAP35: RNA low tissue specificity; high antibody staining in 14 normal tissues; highest cancer staining breast cancer (5 of 12 high). Distribution: 7 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Endometrial cancer, Bladder & urothelial cancer, Breast cancer (all types), Renal cell carcinoma, Ovarian cancer, Skin cancer (all types), Lung cancer (all types)); Open Targets associates it with 1 specific cancer type at or above 0.5 (endometrial cancer). (Rule 6 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"UniProt Q9NRY4","url":"https://www.uniprot.org/uniprotkb/Q9NRY4/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene ARHGAP35","url":"https://civicdb.org/features/2438","note":"4 evidence items, 0 assertions, 4 variants; diseases:  (GraphQL API, CC0)"},{"label":"IntOGen ARHGAP35","url":"https://www.intogen.org/search?gene=ARHGAP35","note":"driver in 15 cohorts (Act 1, LoF 14); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"},{"label":"Human Protein Atlas ARHGAP35 tissue","url":"https://www.proteinatlas.org/ENSG00000160007-ARHGAP35/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000160007 associations","url":"https://platform.opentargets.org/target/ENSG00000160007/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:4591","ensembl":"ENSG00000160007","uniprot":"Q9NRY4","entrez":"2909","firstDescribed":1991,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: LeClerc et al, J. Biol. Chem, 1991, \"Molecular cloning and characterization of a factor that binds the human glucocorticoid receptor gene and represses its expression\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/1894621/","biology":"Rho GTPase-activating protein (GAP). Binds several acidic phospholipids which inhibits the Rho GAP activity to promote the Rac GAP activity. This binding is inhibited by phosphorylation by PRKCA. Involved in cell differentiation as well as cell adhesion and migration, plays an important role in retinal tissue morphogenesis, neural tube fusion, midline fusion of the cerebral hemispheres and mammary gland branching morphogenesis. Transduces signals from p21-ras to the nucleus, acting via the ras GTPase-activating protein (GAP). Transduces SRC-dependent signals from cell-surface adhesion molecules, such as laminin, to promote neurite outgrowth. Location: Cytoplasm, cytoskeleton, cilium basal body; Cytoplasm; Nucleus; Cell membrane (UniProt). Locus 19q13.32 (HGNC).","whereFound":["Endometrial cancer: Open Targets association 0.61 with endometrial cancer (MONDO_0011962); IntOGen driver in 4 cohorts (UCEC)","Bladder & urothelial cancer: IntOGen driver in 3 cohorts (BLCA, UTUC)","Breast cancer: Open Targets association 0.57 with breast cancer (MONDO_0007254); IntOGen driver in 2 cohorts (BRCA)","Renal cell carcinoma: IntOGen driver in 1 cohort (CCRCC)","Ovarian cancer: IntOGen driver in 1 cohort (OVT)","Skin cancer: Open Targets association 0.56 with skin cancer (MONDO_0002898)"],"targetClass":"transcription","prevalence":[]},"route":"/targets/arhgap35/","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":"basal-cell-carcinoma","kind":"cancer","name":"Basal cell carcinoma","route":"/cancers/basal-cell-carcinoma/"},{"id":"urothelial","kind":"cancer","name":"Bladder & urothelial cancer","route":"/cancers/urothelial/"},{"id":"breast-cancer","kind":"cancer","name":"Breast cancer (all types)","route":"/cancers/breast-cancer/"},{"id":"endometrial","kind":"cancer","name":"Endometrial cancer","route":"/cancers/endometrial/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"ovarian","kind":"cancer","name":"Ovarian cancer","route":"/cancers/ovarian/"},{"id":"rcc","kind":"cancer","name":"Renal cell carcinoma","route":"/cancers/rcc/"},{"id":"skin-cancer","kind":"cancer","name":"Skin cancer (all types)","route":"/cancers/skin-cancer/"}]}}