RPS6KC1

Chr 1AR

ribosomal protein S6 kinase C1

Also known as: NEDSCW, RPK118, RSKL1, S6K-delta-1, S6PKh1, humS6PKh1

This protein binds to sphingosine kinase and phosphatidylinositol 3-phosphate to transmit sphingosine-1-phosphate signaling and recruits peroxiredoxin-3 to early endosomes and mitochondria. Mutations in RPS6KC1 cause autosomal recessive developmental and epileptic encephalopathy with onset in early infancy. The gene is highly constrained against loss-of-function variants, suggesting that complete protein loss is not well tolerated.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismARLOEUF 0.481 OMIM phenotype
Clinical SummaryRPS6KC1
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.48LOEUF
pLI 0.001
Z-score 4.32
OE 0.31 (0.200.48)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.45Z-score
OE missense 0.95 (0.881.02)
519 obs / 548.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.31 (0.200.48)
00.351.4
Missense OE0.95 (0.881.02)
00.61.4
Synonymous OE1.00
01.21.6
LoF obs/exp: 14 / 45.4Missense obs/exp: 519 / 548.5Syn Z: 0.05
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
moderateRPS6KC1-related complex neurodevelopmental disorder with spasticity and hypoplasia of corpus callosumLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.7036th %ile
GOF
0.6443th %ile
LOF
0.3648th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

RPS6KC1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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