RPS6KA3

Chr X

ribosomal protein S6 kinase A3

Also known as: CLS, HU-3, ISPK-1, MAPKAPK1B, MRX19, RSK, RSK2, S6K-alpha3

NCBI Gene: 6197ENSG00000177189UniProt: P51812

This gene encodes a member of the RSK (ribosomal S6 kinase) family of serine/threonine kinases. This kinase contains 2 non-identical kinase catalytic domains and phosphorylates various substrates, including members of the mitogen-activated kinase (MAPK) signalling pathway. The activity of this protein has been implicated in controlling cell growth and differentiation. Mutations in this gene have been associated with Coffin-Lowry syndrome (CLS). [provided by RefSeq, Jul 2008]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtCoffin-Lowry syndrome
UniProtIntellectual developmental disorder, X-linked 19

Clinical highlights

Gene-disease validity (ClinGen)
Coffin-Lowry syndrome · XLDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.
1
Active trials
19
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.09
LOEUF· LoF intol.
LOF
Mechanism· G2P
📖
GeneReview available — RPS6KA3
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?
0.09LOEUF
pLI 1.000
Z-score 5.41
OE 0.00 (0.00–0.09)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?
4.52Z-score
OE missense 0.23 (0.19–0.29)
64 obs / 275.0 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?
LoF OE?0.00 (0.00–0.09)
0≤0.351.4
Missense OE?0.23 (0.19–0.29)
0≤0.61.4
Synonymous OE?0.81
0≤1.21.6
LoF obs/exp: 0 / 34.1Missense obs/exp: 64 / 275.0Syn Z: 1.41

ClinVar Variant Classifications

0 submitted variants in ClinVar

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.

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients