CLK1

Chr 2

CDC like kinase 1

Also known as: CLK, CLK/STY, STY

The protein is a dual specificity kinase that phosphorylates serine/arginine-rich proteins in the spliceosomal complex to regulate RNA splicing. Mutations cause autosomal recessive intellectual disability with seizures and spasticity, typically presenting in early childhood. The gene is not highly constrained against loss-of-function variants, which is consistent with the recessive inheritance pattern observed in affected individuals.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.77
Clinical SummaryCLK1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.77LOEUF
pLI 0.000
Z-score 2.54
OE 0.50 (0.330.77)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.47Z-score
OE missense 0.92 (0.841.02)
276 obs / 298.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.50 (0.330.77)
00.351.4
Missense OE0.92 (0.841.02)
00.61.4
Synonymous OE1.11
01.21.6
LoF obs/exp: 15 / 30.0Missense obs/exp: 276 / 298.8Syn Z: -0.82
DN
0.77top 25%
GOF
0.5367th %ile
LOF
0.2872th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

CLK1 · 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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