CLK1

Chr 2

CDC like kinase 1

Also known as: CLK, CLK/STY, STY

NCBI Gene: 1195ENSG00000013441UniProt: P49759

This gene encodes a member of the CDC2-like (or LAMMER) family of dual specificity protein kinases. In the nucleus, the encoded protein phosphorylates serine/arginine-rich proteins involved in pre-mRNA processing, releasing them into the nucleoplasm. The choice of splice sites during pre-mRNA processing may be regulated by the concentration of transacting factors, including serine/arginine rich proteins. Therefore, the encoded protein may play an indirect role in governing splice site selection. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2009]

105
ClinVar variants
33
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— CLK1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
33 Pathogenic / Likely Pathogenic· 69 VUS of 105 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.77LOEUF
pLI 0.000
Z-score 2.54
OE 0.50 (0.33–0.77)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.47Z-score
OE missense 0.92 (0.84–1.02)
276 obs / 298.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.50 (0.33–0.77)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.92 (0.84–1.02)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.11
0≤1.21.6
LoF obs/exp: 15 / 30.0Missense obs/exp: 276 / 298.8Syn Z: -0.82

ClinVar Variant Classifications

105 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic32
Likely Pathogenic1
VUS69
Likely Benign3
32
Pathogenic
1
Likely Pathogenic
69
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
32
0
32
Likely Pathogenic
0
0
1
0
1
VUS
0
67
2
0
69
Likely Benign
0
3
0
0
3
Benign
0
0
0
0
0
Total070350105

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View 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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
CDC-LIKE KINASE 1; CLK1
MIM #601951 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Urinary Complement proteome strongly linked to diabetic kidney disease progression.
Md Dom ZI et al.·Nat Commun
2025
Regulatory interplay between SR proteins governs CLK1 kinase splice variants production.
Shkreta L et al.·RNA
2024
Targeting CLK1/SRSF7 axis-dependent alternative splicing sensitizes pancreatic ductal adenocarcinoma to chemotherapy and immunotherapy.
Zhang C et al.·Drug Resist Updat
2025
Machine learning-based selection of immune cell markers in osteosarcoma: prognostic determination and validation of CLK1 in disease progression.
Zhang N et al.·Front Immunol
2024
Discovery of novel 5-methoxybenzothiophene hydrazides as metabolically stable Clk1 inhibitors with high potency and unprecedented Clk1 isoenzyme selectivity.
El-Gamil DS et al.·Eur J Med Chem
2023
YTHDC1 orchestrates oncogenic splicing via the CLK1-SRSF1 splicing machinery to regulate castration-resistant prostate cancer progression.
Gupta P et al.·Mol Cell Biochem
2025
Structural and functional diversity of collectins and ficolins and their relationship to disease.
Howard M et al.·Semin Immunopathol
2018Review
Clk1-regulated aerobic glycolysis is involved in glioma chemoresistance.
Zhang L et al.·J Neurochem
2017
Phosphoproteomic analysis identifies CLK1 as a novel therapeutic target in gastric cancer.
Babu N et al.·Gastric Cancer
2020
The antitumor mechanisms of Huangqin Houpo decoction and its effect on chemotherapy-induced toxicity in colorectal cancer.
Qiu Z et al.·Phytomedicine
2026Functional
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
CLK1 Promotes Myeloid-Derived Suppressor Cell Trafficking and Reprograms the Tumor Microenvironment by activating Hippo/YAP signaling in Colorectal Cancer.
Li P et al.·Cancer Immunol Res
2026
CLK1 is a potential tumor suppressor for NSCLC by regulating cell proliferation and immune infiltration.
Ma R et al.·Front Cell Dev Biol
2026🔓 Open Access
Regulation of CLK1 Isoform Expression by Alternative Splicing in Activated Human Monocytes Contributes to Activation-Associated TNF Production.
van Haaren MJH et al.·Cells
2025🔓 Open Access
Genome-wide CRISPR-Cas9 screening identifies CLK1 inhibition as a strategy to restore PARP inhibitor sensitivity via ERCC1 isoform switching.
Chaohua L et al.·Protein Cell
2025
Discovery and Characterization of Cell-Permeable Inhibitors of Leishmania mexicana CLK1 Using an In-Cell Target Engagement Assay.
Catta-Preta CMC et al.·ACS Infect Dis
2025
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools