# RPS6KA3

Source: https://onco.cc/targets/rps6ka3/  
OnCo record `rps6ka3` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

Open 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.

## Fields

- Kind: Target
- Last checked: 2026-09-23
- Also known as: ribosomal protein S6 kinase A3; Ribosomal protein S6 kinase alpha-3; RSK2; HU-3; MRX19
- Tags: cancer-genes-wave
- Symbol: RPS6KA3
- Class: kinase
- 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).
- Where found: Hepatocellular carcinoma: Open Targets association 0.54 with hepatocellular carcinoma (MONDO_0007256); IntOGen driver in 4 cohorts (HCC)

## 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.

## Sources

- HGNC HGNC:10432: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:10432
- UniProt P51812: https://www.uniprot.org/uniprotkb/P51812/entry
- NCBI Gene 6197: https://www.ncbi.nlm.nih.gov/gene/6197
- Ensembl ENSG00000177189: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000177189

## Connected records

- collections: [IntOGen](https://onco.cc/collections/intogen/), [Open Targets Platform](https://onco.cc/collections/open-targets/)
- cancers: [Hepatocellular carcinoma](https://onco.cc/cancers/hcc/)

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JSON: https://onco.cc/api/v1/entities/rps6ka3.json