CLK4

protein-coding

CDC like kinase 4, the group of CDC like kinases

Gene summary

The protein encoded by this gene belongs to the CDC2-like protein kinase (CLK) family. This protein kinase can interact with and phosphorylate the serine- and arginine-rich (SR) proteins, which are known to play an important role in the formation of spliceosomes, and thus may be involved in the regulation of alternative splicing. Studies in the Israeli sand rat Psammomys obesus suggested that the ubiquitin-like 5 (UBL5/BEACON), a highly conserved ubiquitin-like protein, may interact with and regulate the activity of this kinase. Multiple alternatively spliced transcript variants have been observed, but the full-length natures of which have not yet been determined. [provided by RefSeq, Jul 2008]

MANE transcript

NM_020666.3

Inheritance

—

ClinVar variants

U:52B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.42

Max pathogenic AF

—

Genomic locus

chr5:178,602,664-178,630,615

External References & Databases

Ensembl (ENSG00000113240)

Transcript & Mutation Effects

hg38 • Region Span ~28.0 kb

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GenCC 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 CLK4 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 47

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020666.3. 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 clinvar		1 clinvar	2
missense			49 clinvar	1 clinvar		50
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	52	1	1	54

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 38 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020666.3	RefSeq	NP_065717.1	12	MANE Select
ENST00000316308.9	Ensembl	ENSP00000316948.4	12	MANE Select
ENST00000520957.1	Ensembl	ENSP00000430892.1	1	Standard
ENST00000520957.2	Ensembl	ENSP00000430892.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

mRNA Processing

Biological Process

peptidyl-tyrosine phosphorylation
regulation of RNA splicing
protein autophosphorylation

Molecular Function

protein serine/threonine kinase activity
protein serine/threonine/tyrosine kinase activity
protein tyrosine kinase activity
protein binding
ATP binding

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000316308
Coding exons: 12
Length: 27952
Individuals with no LoFs: 125715
Homozygous LoFs: 0
Heterozygous LoFs: 33
Defined: 125748
p: 0.000131

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.11	181	280	0.645	0.0000161	3235
Missense (PolyPhen)		40	96.906	0.41277		1186
Synonymous	-0.0430	90	89.5	1.01	0.00000485	807
Loss of Function	2.87	12	28.6	0.420	0.00000159	346

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00026	0.00025	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.000051	0.000046	rare
European (Non-Finnish)	0.00018	0.00018	rare
South Asian	0.000098	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

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 and may be a constituent of a network of regulatory mechanisms that enable SR proteins to control RNA splicing. Phosphorylates SRSF1 and SRSF3. Required for the regulation of alternative splicing of MAPT/TAU. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells. {ECO:0000269|PubMed:11170754, ECO:0000269|PubMed:19168442}.;

Recessive Scores

pRec: 0.104

Intolerance Scores

LoFtool: 0.581
RVIS EVS: -0.05
RVIS percentile EVS: 50.22

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.973

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium