{"entity":{"id":"rhoa","kind":"target","name":"RHOA","aka":["ras homolog family member A","Transforming protein RhoA","Rho12","RHOH12","ARH12"],"tldr":"RHOA (Transforming protein RhoA) is an enzyme. 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 Non-Hodgkin lymphoma, Gastric & gastro-oesophageal junction cancer, Bladder & urothelial cancer and 5 more.","summary":"Small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state. Mainly associated with cytoskeleton organisation, in active state binds to a variety of effector proteins to regulate cellular responses such as cytoskeletal dynamics, cell migration and cell cycle. Regulates a signal transduction pathway linking plasma membrane receptors to the assembly of focal adhesions and actin stress fibres.\n\nCIViC holds 3 clinical evidence items and 0 assertions across 1 variant. Open Targets scores its association with cancer at 0.75 (direct and indirect evidence; datatypes literature 0.99, affected pathway 0.34, genetic association 0.03, somatic mutation 0.95). IntOGen calls it a driver in 14 cohorts (13 activating, 1 loss-of-function), covering Burkitt Lymphoma, Bladder Urothelial Carcinoma, Diffuse Large B-Cell Lymphoma, NOS, Head and Neck Squamous Cell Carcinoma, Malignant Lymphoma, Non-Hodgkin Lymphoma and others.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:667","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:667"},{"label":"UniProt P61586","url":"https://www.uniprot.org/uniprotkb/P61586/entry"},{"label":"NCBI Gene 387","url":"https://www.ncbi.nlm.nih.gov/gene/387"},{"label":"Ensembl ENSG00000067560","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000067560"},{"label":"Sakata-Yanagimoto et al., Nat Genet 2014: somatic RHOA G17V in angioimmunoblastic T-cell lymphoma","url":"https://doi.org/10.1038/ng.2872"},{"label":"Palomero et al., Nat Genet 2014: recurrent mutations in epigenetic regulators, RHOA and FYN in peripheral T-cell lymphoma","url":"https://doi.org/10.1038/ng.2873"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets","intogen"],"cancers":["non-hodgkin-lymphoma","gastric","urothelial","head-and-neck","mesothelioma","prostate","leukaemia","burkitt-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["epigenetic-reprogramming","clonal-haematopoiesis"],"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 13 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 1 cohort; CIViC holds 3 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.","Lymphoma, RHOA G17V and the epigenetic mutations of T-follicular-helper lymphoma: A single substitution, G17V, in the small GTPase RHOA produces a protein that does not bind GTP and that blocks the wild-type protein as well. It is specific to the tumour cell, whereas the TET2 mutations that accompany it are found in non-tumour haematopoietic cells too, which places the TET2 lesion earlier, in the stem cell, and makes this lymphoma a disease that grows out of clonal haematopoiesis. Frequency: RHOA G17V in 68% of angioimmunoblastic T-cell lymphoma samples, with every G17V case also carrying a TET2 mutation (Sakata-Yanagimoto 2014); independently, in 22 of 35 angioimmunoblastic cases, 67%, and 8 of 44 peripheral T-cell lymphoma not otherwise specified, 18%, alongside recurrent TET2, DNMT3A and IDH2 mutations and less frequent FYN, ATM, B2M and CD58 lesions (Palomero 2014). What it changes about treatment: Not through an approved test. The hypomethylating agents are used in this disease on the strength of the TET2 and DNMT3A biology rather than on a mutation result, and azacitidine-containing regimens have shown activity in T-follicular-helper histology specifically."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"RHOA","role":["oncogene-driver","tumour-suppressor","biomarker"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:667","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:667","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt P61586","url":"https://www.uniprot.org/uniprotkb/P61586/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene RHOA","url":"https://civicdb.org/features/399","note":"3 evidence items, 0 assertions, 1 variants; diseases: Diffuse Large B-cell Lymphoma, Burkitt Lymphoma, Stomach Carcinoma (GraphQL API, CC0)"},{"label":"Open Targets ENSG00000067560","url":"https://platform.opentargets.org/target/ENSG00000067560/associations","note":"association with cancer (MONDO_0004992) 0.75; per-cancer scores at or above 0.5: gastric cancer 0.65, urinary bladder cancer 0.56, non-Hodgkin lymphoma 0.72, Burkitt lymphoma 0.53, leukaemia 0.56 (GraphQL API, CC0)"},{"label":"IntOGen RHOA","url":"https://www.intogen.org/search?gene=RHOA","note":"driver in 14 cohorts (Act 13, LoF 1); 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 RHOA: RNA low tissue specificity; no normal tissue stained high. Distribution: 7 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Lymphoma, Gastric & gastro-oesophageal junction cancer, Bladder & urothelial cancer, Head and neck squamous cell carcinoma, Mesothelioma, Prostate cancer, Leukaemia); Open Targets associates it with 2 specific cancer types at or above 0.5 (Burkitt lymphoma, gastric adenocarcinoma). (Rule 6 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"UniProt P61586","url":"https://www.uniprot.org/uniprotkb/P61586/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene RHOA","url":"https://civicdb.org/features/399","note":"3 evidence items, 0 assertions, 1 variants; diseases: Diffuse Large B-cell Lymphoma, Burkitt Lymphoma, Stomach Carcinoma (GraphQL API, CC0)"},{"label":"IntOGen RHOA","url":"https://www.intogen.org/search?gene=RHOA","note":"driver in 14 cohorts (Act 13, LoF 1); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"},{"label":"Human Protein Atlas RHOA tissue","url":"https://www.proteinatlas.org/ENSG00000067560-RHOA/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000067560 associations","url":"https://platform.opentargets.org/target/ENSG00000067560/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:667","ensembl":"ENSG00000067560","uniprot":"P61586","entrez":"387","firstDescribed":1987,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Yeramian et al, Nucleic Acids Res, 1987, \"Nucleotide sequence of human rho cDNA clone 12\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/3822842/","biology":"Small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state. Mainly associated with cytoskeleton organisation, in active state binds to a variety of effector proteins to regulate cellular responses such as cytoskeletal dynamics, cell migration and cell cycle. Regulates a signal transduction pathway linking plasma membrane receptors to the assembly of focal adhesions and actin stress fibres. Involved in a microtubule-dependent signal that is required for the myosin contractile ring formation during cell cycle cytokinesis. Plays an essential role in cleavage furrow formation. Required for the apical junction formation of keratinocyte cell-cell adhesion. Location: Cell membrane; Cytoplasm, cytoskeleton; Cleavage furrow; Cytoplasm, cell cortex (UniProt). Locus 3p21.31 (HGNC).","whereFound":["Non-Hodgkin lymphoma: Open Targets association 0.72 with non-Hodgkin lymphoma (MONDO_0018908); IntOGen driver in 2 cohorts (MLYM, NHL)","Gastric & gastro-oesophageal junction cancer: Open Targets association 0.65 with gastric cancer (MONDO_0001056); CIViC evidence names this disease","Bladder & urothelial cancer: Open Targets association 0.56 with urinary bladder cancer (MONDO_0001187); IntOGen driver in 2 cohorts (BLCA)","Head and neck squamous cell carcinoma: IntOGen driver in 1 cohort (HNSC)","Mesothelioma: IntOGen driver in 1 cohort (PLMESO)","Prostate cancer: IntOGen driver in 1 cohort (PRAD)"],"targetClass":"enzyme","prevalence":[]},"route":"/targets/rhoa/","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":"urothelial","kind":"cancer","name":"Bladder & urothelial cancer","route":"/cancers/urothelial/"},{"id":"burkitt-lymphoma","kind":"cancer","name":"Burkitt lymphoma","route":"/cancers/burkitt-lymphoma/"},{"id":"gastric","kind":"cancer","name":"Gastric & gastro-oesophageal junction cancer","route":"/cancers/gastric/"},{"id":"head-and-neck","kind":"cancer","name":"Head and neck squamous cell carcinoma","route":"/cancers/head-and-neck/"},{"id":"leukaemia","kind":"cancer","name":"Leukaemia (all types)","route":"/cancers/leukaemia/"},{"id":"mesothelioma","kind":"cancer","name":"Mesothelioma","route":"/cancers/mesothelioma/"},{"id":"angioimmunoblastic-t-cell-lymphoma","kind":"cancer","name":"Nodal T-follicular helper cell lymphoma, angioimmunoblastic type (angioimmunoblastic T-cell lymphoma)","route":"/cancers/angioimmunoblastic-t-cell-lymphoma/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"},{"id":"peripheral-t-cell-lymphoma","kind":"cancer","name":"Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma)","route":"/cancers/peripheral-t-cell-lymphoma/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"}],"pathway":[{"id":"clonal-haematopoiesis","kind":"pathway","name":"Clonal haematopoiesis (CHIP)","route":"/pathways/clonal-haematopoiesis/"},{"id":"epigenetic-reprogramming","kind":"pathway","name":"Epigenetic reprogramming","route":"/pathways/epigenetic-reprogramming/"}],"biomarker":[{"id":"rhoa-g17v","kind":"biomarker","name":"RHOA G17V","route":"/biomarkers/rhoa-g17v/"}]}}