{"entity":{"id":"rps6ka3","kind":"target","name":"RPS6KA3","aka":["ribosomal protein S6 kinase A3","Ribosomal protein S6 kinase alpha-3","RSK2","HU-3","MRX19"],"tldr":"RPS6KA3 (Ribosomal protein S6 kinase alpha-3) is a protein kinase, an enzyme that switches other proteins on by adding phosphate groups. The public catalogues list it as a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Hepatocellular carcinoma.","summary":"Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signalling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 and EIF4B phosphorylation, and mediates cellular proliferation, survival, and differentiation by modulating mTOR signalling and repressing pro-apoptotic function of BAD and DAPK1. In fibroblast, is required for EGF-stimulated phosphorylation of CREB1 and histone H3 at 'Ser-10', which results in the subsequent transcriptional activation of several immediate-early genes. In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP.\n\nOpen Targets scores its association with cancer at 0.54 (direct and indirect evidence; datatypes literature 0.96, genetic association 0.00, somatic mutation 0.84). IntOGen calls it a driver in 4 cohorts (0 activating, 4 loss-of-function), covering Hepatocellular Carcinoma.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:10432","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:10432"},{"label":"UniProt P51812","url":"https://www.uniprot.org/uniprotkb/P51812/entry"},{"label":"NCBI Gene 6197","url":"https://www.ncbi.nlm.nih.gov/gene/6197"},{"label":"Ensembl ENSG00000177189","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000177189"}],"tags":["cancer-genes-wave"],"related":["open-targets","intogen"],"cancers":["hcc"],"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 a loss-of-function (LoF) driver in 4 cohorts. 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":"RPS6KA3","role":["tumour-suppressor"],"evidenceTier":"cohort-driver","sources":[{"label":"HGNC HGNC:10432","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:10432","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt P51812","url":"https://www.uniprot.org/uniprotkb/P51812/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"Open Targets ENSG00000177189","url":"https://platform.opentargets.org/target/ENSG00000177189/associations","note":"association with cancer (MONDO_0004992) 0.54; per-cancer scores at or above 0.5: hepatocellular carcinoma 0.54 (GraphQL API, CC0)"},{"label":"IntOGen RPS6KA3","url":"https://www.intogen.org/search?gene=RPS6KA3","note":"driver in 4 cohorts (Act 0, LoF 4); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"hgnc":"HGNC:10432","ensembl":"ENSG00000177189","uniprot":"P51812","entrez":"6197","biology":"Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signalling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 and EIF4B phosphorylation, and mediates cellular proliferation, survival, and differentiation by modulating mTOR signalling and repressing pro-apoptotic function of BAD and DAPK1. In fibroblast, is required for EGF-stimulated phosphorylation of CREB1 and histone H3 at 'Ser-10', which results in the subsequent transcriptional activation of several immediate-early genes. In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP. Upon insulin-derived signal, acts indirectly on the transcription regulation of several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting its activity. Phosphorylates RPS6 in response to serum or EGF via an mTOR-independent mechanism and promotes translation initiation by facilitating assembly of the preinitiation complex. In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and stimulating cap-dependent translation. Location: Nucleus; Cytoplasm (UniProt). Locus Xp22.12 (HGNC).","whereFound":["Hepatocellular carcinoma: Open Targets association 0.54 with hepatocellular carcinoma (MONDO_0007256); IntOGen driver in 4 cohorts (HCC)"],"targetClass":"kinase","prevalence":[]},"route":"/targets/rps6ka3/","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":"hcc","kind":"cancer","name":"Hepatocellular carcinoma","route":"/cancers/hcc/"}]}}