CLK3
protein-codingCDC like kinase 3, the group of CDC like kinases
Gene summary
This gene encodes a protein belonging to the serine/threonine type protein kinase family. This protein is a nuclear dual-specificity kinase that regulates the intranuclear distribution of the serine/arginine-rich (SR) family of splicing factors. Two transcript variants encoding different isoforms have been found for this gene. Related pseudogenes are located on chromosomes 1 and 9. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~46.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CLK3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001130028.2. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | ||||
| missense | 75 | 75 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 81 | 0 | 0 | 81 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001123500.2 | 12 | MANE Select | |
| Ensembl | ENSP00000378505.4 | 12 | MANE Select | |
| RefSeq | NP_003983.2 | 12 | Standard | |
| Ensembl | ENSP00000344112.4 | 12 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- mRNA Processing
Biological Process
- protein phosphorylation
- peptidyl-tyrosine phosphorylation
- regulation of RNA splicing
- protein autophosphorylation
Molecular Function
- RNA binding
- protein serine/threonine kinase activity
- protein serine/threonine/tyrosine kinase activity
- protein tyrosine kinase activity
- protein binding
Cellular Component
- acrosomal vesicle
- nucleus
- nucleoplasm
- membrane
- nuclear speck
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000395066
- Coding exons
- 13
- Length
- 41217
- Individuals with no LoFs
- 125732
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 15
- Defined
- 125747
- p
- 0.0000596
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.03 | 228 | 332 | 0.686 | 0.0000225 | 4104 |
| Missense (PolyPhen) | 60 | 121.16 | 0.49523 | 1339 | ||
| Synonymous | 0.128 | 118 | 120 | 0.985 | 0.00000687 | 1286 |
| Loss of Function | 4.09 | 8 | 33.6 | 0.238 | 0.00000221 | 365 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.000059 | 0.000058 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000080 | 0.000079 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Dual specificity kinase acting on both serine/threonine and tyrosine-containing substrates. Phosphorylates serine- and arginine-rich (SR) proteins of the spliceosomal complex. May be a constituent of a network of regulatory mechanisms that enable SR proteins to control RNA splicing and can cause redistribution of SR proteins from speckles to a diffuse nucleoplasmic distribution. Phosphorylates SRSF1 and SRSF3. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells. {ECO:0000269|PubMed:19168442, ECO:0000269|PubMed:9637771}.;
Recessive Scores
- pRec
- 0.109
Intolerance Scores
- LoFtool
- 0.682
- RVIS EVS
- -0.67
- RVIS percentile EVS
- 15.62
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.983
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |