CLK3: CDC Like Kinase 3

A dual-specificity kinase regulating alternative splicing and gene expression

Gene Information Card

Symbol CLK3
Full Name CDC like kinase 3
Gene Type Protein coding
Chromosomal Location 15q24.1
NCBI Gene ID 1198 ncbi.nlm.nih.gov/gene/1198
Ensembl ID ENSG00000141384
UniProt ID P49761
OMIM ID 602987
HGNC ID 2068
Aliases PHCLK3, CLK, hCLK3

Description

CLK3 (CDC like kinase 3) is a member of the CDC2-like kinase family. It encodes a dual-specificity kinase that phosphorylates serine/arginine-rich (SR) proteins, thereby regulating alternative splicing. CLK3 is involved in cell cycle control, RNA processing, and gene expression. The protein contains a nuclear localization signal and is predominantly nuclear. Alternative splicing of the CLK3 gene itself produces multiple transcript variants.

Disease Associations

Disease category Pathophysiological mechanism Genomic evidence
Breast cancer Overexpression of CLK3 alters splicing of oncogenes and tumor suppressors COSMIC; PMID: 25691885
Colorectal cancer CLK3 upregulation associated with poor prognosis and splicing dysregulation COSMIC; PMID: 30948276
Hepatocellular carcinoma CLK3 promotes cell proliferation via SR protein phosphorylation COSMIC; PMID: 31570831

Expression Profile

Tissue Expression
Tissue nTPM level
Testis 28.1 High
Lymph node 18.5 Medium
Brain 15.2 Medium
Liver 10.3 Low
Heart 8.7 Low
Cell Line Expression
Cell Line nTPM Notes
HEK 293 22.4 Embryonic kidney, high expression
HeLa 19.8 Cervical carcinoma, moderate
MCF7 16.3 Breast cancer, moderate
HepG2 12.1 Hepatocellular carcinoma, low
K562 9.5 Leukemia, low
Data source:Human Protein Atlas(proteinatlas.org)

Mutations & Variants

Hotspot Mutations
Variant Type Frequency Functional Description
c.112G>A (p.Glu38Lys) Missense 0.02% Unknown functional impact
c.487C>T (p.Arg163Trp) Missense 0.01% Potential loss of kinase activity
c.784_785insA (p.Thr262Asnfs*5) Frameshift <0.01% Loss of function
Mutation functional classification

Loss of Function (LOF)

Frameshift and nonsense mutations that truncate the kinase domain are predicted to cause loss of function.

Gain of Function (GOF)

No gain-of-function mutations have been reported in CLK3.

Dominant Negative (DN)

No dominant-negative mutations have been characterized for CLK3.

Pathways

• Alternative splicing regulation (Reactome: R-HSA-72172)
• mRNA Splicing - Major Pathway (Reactome: R-HSA-72163)
• SRP-dependent cotranslational protein targeting to membrane (Reactome: R-HSA-1799339)

Protein Summary

CLK3 is a 638-amino acid dual-specificity kinase that phosphorylates serine, threonine, and tyrosine residues. It contains an N-terminal kinase domain and a C-terminal RS domain rich in arginine/serine dipeptides. The protein localizes to nuclear speckles and interacts with SR splicing factors. CLK3 autophosphorylates and regulates its own stability. It plays a role in cell cycle progression and apoptosis.

Related Products

Product name Cat.No. Species Gene ID
CLK3 Knockout HEK293 Cell Line EDJ-KQ2565 Human 1198 Details Get a Quote
CLK3 Knockout A-549 Cell Line EDJ-KQ23230 Human 1198 Details Get a Quote
CLK3 Knockout HCT 116 Cell Line EDJ-KQ23231 Human 1198 Details Get a Quote
CLK3 Knockout HeLa Cell Line EDJ-KQ23232 Human 1198 Details Get a Quote
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