CDKL2

protein-coding

cyclin dependent kinase like 2, the group of Cyclin dependent kinases

Gene summary

This gene product is a member of a large family of CDC2-related serine/threonine protein kinases. It accumulates primarily in the cytoplasm, with lower levels in the nucleus. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001330724.2

Inheritance

—

ClinVar variants

P:1U:76B:5

Top phenotype

CDKL2-related condition

gnomAD constraint

pLI —, LoF o/e 1.02

Max pathogenic AF

—

Genomic locus

chr4:75,576,496-75,630,716

External References & Databases

Ensembl (ENSG00000138769)

Transcript & Mutation Effects

hg38 • Region Span ~54.2 kb

Loading mutation effect viewer...

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 CDKL2 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 73

not providedTotal: 2

CDKL2-related conditionTotal: 1

CDKL2-related disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001330724.2. 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						0
missense		1 clinvar	73 clinvar	5 clinvar		79
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	1	76	5	0	82

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 28 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001330724.2	RefSeq	NP_001317653.1	12	MANE Select
ENST00000307465.9	Ensembl	ENSP00000306340.4	12	MANE Select
NM_003948.5	RefSeq	NP_003939.1	10	Standard
ENST00000429927.6	Ensembl	ENSP00000412365.2	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

EMT transition in Colorectal Cancer

Biological Process

protein phosphorylation
signal transduction
sex differentiation
regulation of cell cycle

Molecular Function

protein kinase activity
cyclin-dependent protein serine/threonine kinase activity
ATP binding

Cellular Component

nucleus
cytoplasm
centrosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000429927
Coding exons: 10
Length: 52686
Individuals with no LoFs: 123331
Homozygous LoFs: 18
Heterozygous LoFs: 2398
Defined: 125747
p: 0.00965

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.246	263	252	1.04	0.0000118	3271
Missense (PolyPhen)		70	73.715	0.9496		966
Synonymous	-0.0988	91	89.8	1.01	0.00000457	894
Loss of Function	-0.113	25	24.4	1.02	0.00000138	319

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0023	0.0022	notable
Latino/Admixed American	0.0057	0.0048	notable
Ashkenazi Jewish	0.0043	0.0040	notable
East Asian	0.0044	0.0041	notable
Finnish	0.022	0.022	notable
European (Non-Finnish)	0.014	0.013	notable
South Asian	0.0016	0.0014	notable
Other	0.013	0.012	notable

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.178

Intolerance Scores

LoFtool: 0.714
RVIS EVS: -0.07
RVIS percentile EVS: 48.54

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0385

Gene Damage Prediction

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