RPS6KA3
Chr XXLDribosomal protein S6 kinase A3
Also known as: CLS, HU-3, ISPK-1, MAPKAPK1B, MRX19, RSK, RSK2, S6K-alpha3
This serine/threonine kinase acts downstream of ERK signaling to regulate transcription factors, translation initiation, and cellular proliferation and survival pathways. Mutations cause Coffin-Lowry syndrome and X-linked intellectual developmental disorder, with X-linked dominant inheritance affecting both males and females but typically more severely in males. The gene is highly constrained against loss-of-function variants (pLI = 1.0, LOEUF = 0.087), consistent with its essential role in cellular signaling pathways.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Highly missense-constrained (top ~0.1%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
RPS6KA3 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools