{"entity":{"id":"arhgef12","kind":"target","name":"ARHGEF12","aka":["Rho guanine nucleotide exchange factor 12","KIAA0382"],"tldr":"ARHGEF12 (Rho guanine nucleotide exchange factor 12) 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 Breast cancer, Renal cell carcinoma, Skin cancer and 5 more.","summary":"Acts as guanine nucleotide exchange factor (GEF) for RhoA GTPase and may act as GTPase-activating protein (GAP) for GNA12 and GNA13. May play a role in the regulation of RhoA GTPase by guanine nucleotide-binding alpha-12 (GNA12) and alpha-13 (GNA13). Promotes endothelial cell and actin stress fibre reorientation in response to mechanotransduction.\n\nOpen Targets scores its association with cancer at 0.65 (direct and indirect evidence; datatypes literature 0.92, genetic association 0.16, somatic mutation 0.83). IntOGen calls it a driver in 2 cohorts (1 activating, 1 loss-of-function), covering Invasive Breast Carcinoma, Renal Clear Cell Carcinoma.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:14193","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:14193"},{"label":"UniProt Q9NZN5","url":"https://www.uniprot.org/uniprotkb/Q9NZN5/entry"},{"label":"NCBI Gene 23365","url":"https://www.ncbi.nlm.nih.gov/gene/23365"},{"label":"Ensembl ENSG00000196914","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000196914"}],"tags":["cancer-genes-wave"],"related":["open-targets","intogen"],"cancers":["breast-cancer","rcc","skin-cancer","colorectal","lung-cancer","gastric","clear-cell-rcc","melanoma"],"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":"ARHGEF12","role":["oncogene-driver","tumour-suppressor","fusion-partner"],"evidenceTier":"cohort-driver","sources":[{"label":"HGNC HGNC:14193","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:14193","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt Q9NZN5","url":"https://www.uniprot.org/uniprotkb/Q9NZN5/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"Open Targets ENSG00000196914","url":"https://platform.opentargets.org/target/ENSG00000196914/associations","note":"association with cancer (MONDO_0004992) 0.65; per-cancer scores at or above 0.5: colorectal cancer 0.52, gastric cancer 0.51, melanoma 0.52, skin cancer 0.57, breast cancer 0.54, lung cancer 0.51 (GraphQL API, CC0)"},{"label":"IntOGen ARHGEF12","url":"https://www.intogen.org/search?gene=ARHGEF12","note":"driver in 2 cohorts (Act 1, LoF 1); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"specificitySources":[],"hgnc":"HGNC:14193","ensembl":"ENSG00000196914","uniprot":"Q9NZN5","entrez":"23365","firstDescribed":1997,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Nagase et al, DNA Res, 1997, \"Prediction of the coding sequences of unidentified human genes. VII. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/9205841/","biology":"Acts as guanine nucleotide exchange factor (GEF) for RhoA GTPase and may act as GTPase-activating protein (GAP) for GNA12 and GNA13. May play a role in the regulation of RhoA GTPase by guanine nucleotide-binding alpha-12 (GNA12) and alpha-13 (GNA13). Promotes endothelial cell and actin stress fibre reorientation in response to mechanotransduction. Location: Cytoplasm; Membrane (UniProt). Locus 11q23.3 (HGNC).","whereFound":["Breast cancer: Open Targets association 0.54 with breast cancer (MONDO_0007254); IntOGen driver in 1 cohort (BRCA)","Renal cell carcinoma: IntOGen driver in 1 cohort (CCRCC)","Skin cancer: Open Targets association 0.57 with skin cancer (MONDO_0002898)","Colorectal cancer: Open Targets association 0.52 with colorectal cancer (MONDO_0005575)","Lung cancer: Open Targets association 0.51 with lung cancer (MONDO_0008903)","Gastric & gastro-oesophageal junction cancer: Open Targets association 0.51 with gastric cancer (MONDO_0001056)"],"targetClass":"tumor-suppressor","prevalence":[]},"route":"/targets/arhgef12/","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":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"gastric","kind":"cancer","name":"Gastric & gastro-oesophageal junction cancer","route":"/cancers/gastric/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"},{"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/"}]}}