CDK5R2

protein-coding

cyclin dependent kinase 5 regulatory subunit 2

Gene summary

The protein encoded by this gene is a neuron-specific activator of CDK5 kinase. It associates with CDK5 to form an active kinase. This protein and neuron-specific CDK5 activator CDK5R1/p39NCK5A both share limited similarity to cyclins, and thus may define a distinct family of cyclin-dependent kinase activating proteins. [provided by RefSeq, Jul 2008]

MANE transcript

NM_003936.5

Inheritance

—

ClinVar variants

U:40B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.13

Max pathogenic AF

—

Genomic locus

chr2:218,959,666-218,962,155

External References & Databases

Ensembl (ENSG00000171450)

Transcript & Mutation Effects

hg38 • Region Span ~2.5 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 CDK5R2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 41

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003936.5. 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
missense			39 clinvar	1 clinvar		40
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	40	2	0	42

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003936.5	RefSeq	NP_003927.1	1	MANE Select
ENST00000302625.6	Ensembl	ENSP00000304250.4	1	MANE Select

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
cdk5r2a	Danio rerio	Structure: retinal outer plexiform layer Quality: morphology abnormal

Gene / Model

Organism

Observed Phenotype

cdk5r2a

Danio rerio

Structure: retinal outer plexiform layer

Quality: morphology

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Lissencephaly gene (LIS1) in neuronal migration and development

Biological Process

regulation of cyclin-dependent protein serine/threonine kinase activity
neuron migration
cerebellum development
superior olivary nucleus maturation
hippocampus development

Molecular Function

actin binding
lipid binding
cyclin-dependent protein serine/threonine kinase activator activity

Cellular Component

cytoplasm
plasma membrane
membrane
protein kinase 5 complex
growth cone

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000302625
Coding exons: 1
Length: 2500
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.17	92	172	0.535	0.00000806	2259
Missense (PolyPhen)		23	57.949	0.3969		784
Synonymous	-0.193	85	82.8	1.03	0.00000408	843
Loss of Function	2.27	1	7.90	0.127	3.51e-7	92

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Activator of CDK5/TPKII.;

Recessive Scores

pRec: 0.112

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.856

Gene Damage Prediction

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