CLK2

CDC like kinase 2, the group of CDC like kinases

Basic information

Region (hg38): 1:155262867-155278491

Links

ENSG00000176444 ∙ NCBI:1196 ∙ OMIM:602989 ∙ HGNC:2069 ∙ Uniprot:P49760 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CLK2 gene.

• Inborn genetic diseases (27 variants)
• not provided (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CLK2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous					1	1
missense			27	1		28
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	27	1	1

Variants in CLK2

This is a list of pathogenic ClinVar variants found in the CLK2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-155263271-G-A		not specified	Uncertain significance (Nov 06, 2023)
1-155263972-C-T			Likely benign (Dec 31, 2019)
1-155263973-G-A		not specified	Uncertain significance (May 25, 2022)
1-155263981-C-T		not specified	Uncertain significance (Jun 29, 2023)
1-155264014-C-A		not specified	Uncertain significance (Dec 01, 2022)
1-155264239-C-T		not specified	Uncertain significance (Apr 27, 2022)
1-155264254-C-G		not specified	Uncertain significance (Mar 24, 2023)
1-155264262-C-G		not specified	Uncertain significance (Mar 29, 2023)
1-155265882-T-C		not specified	Uncertain significance (Sep 28, 2022)
1-155266762-G-T		not specified	Uncertain significance (Jul 05, 2023)
1-155266765-G-A		not specified	Uncertain significance (Dec 21, 2022)
1-155268012-C-G		not specified	Uncertain significance (Jun 24, 2022)
1-155268031-T-C		not specified	Uncertain significance (Feb 23, 2023)
1-155268052-T-C		not specified	Uncertain significance (Feb 15, 2023)
1-155268115-C-T		not specified	Uncertain significance (May 23, 2023)
1-155269511-G-A		not specified	Uncertain significance (Dec 28, 2022)
1-155269517-G-A		not specified	Uncertain significance (Jan 22, 2024)
1-155269528-C-T		not specified	Uncertain significance (Nov 06, 2023)
1-155269553-G-A		not specified	Uncertain significance (May 30, 2023)
1-155269565-A-G		not specified	Uncertain significance (Dec 16, 2022)
1-155269579-C-T		not specified	Uncertain significance (Feb 21, 2024)
1-155269646-C-T		not specified	Uncertain significance (Apr 19, 2023)
1-155269652-G-A		not specified	Uncertain significance (Jul 05, 2023)
1-155269675-C-T		not specified	Uncertain significance (Jul 13, 2022)
1-155269681-T-C		not specified	Uncertain significance (Aug 19, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CLK2	protein_coding	protein_coding	ENST00000361168	12	15624

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000277	125745	0	3	125748	0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.20	226	340	0.665	0.0000244	3270
Missense in Polyphen		75	143.15	0.52394		1490
Synonymous	0.244	109	112	0.971	0.00000617	941
Loss of Function	5.45	2	38.4	0.0520	0.00000295	328

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000176	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

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. 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. Acts as a suppressor of hepatic gluconeogenesis and glucose output by repressing PPARGC1A transcriptional activity on gluconeogenic genes via its phosphorylation. Phosphorylates PPP2R5B thereby stimulating the assembly of PP2A phosphatase with the PPP2R5B-AKT1 complex leading to dephosphorylation of AKT1. Phosphorylates: PTPN1, SRSF1 and SRSF3. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells. {ECO:0000269|PubMed:10480872, ECO:0000269|PubMed:19168442, ECO:0000269|PubMed:8910305, ECO:0000269|PubMed:9637771}.
• Pathway: mRNA Processing (Consensus)

Recessive Scores

• pRec: 0.145

Intolerance Scores

• loftool: 0.0785
• rvis_EVS: -0.4
• rvis_percentile_EVS: 26.73

Haploinsufficiency Scores

• pHI: 0.350
• hipred: Y
• hipred_score: 0.783
• ghis: 0.615

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.973

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Clk2
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; liver/biliary system phenotype

Gene ontology

• Biological process: protein phosphorylation;response to ionizing radiation;peptidyl-tyrosine phosphorylation;response to retinoic acid;regulation of RNA splicing;negative regulation of gluconeogenesis;protein autophosphorylation
• Cellular component: nucleus;nucleoplasm;nuclear body;nuclear speck
• Molecular function: protein serine/threonine kinase activity;protein serine/threonine/tyrosine kinase activity;protein tyrosine kinase activity;protein binding;ATP binding;identical protein binding