CDK5RAP1

protein-coding

CDK5 regulatory subunit associated protein 1, the group of Radical S-adenosylmethionine domain containing

Gene summary

This gene encodes a regulator of cyclin-dependent kinase 5 activity. This protein has also been reported to modify RNA by adding a methylthio-group and may thus have a dual function as an RNA methylthiotransferase and as an inhibitor of cyclin-dependent kinase 5 activity. Alternative splicing results in multiple transcript variants that encode different isoforms. [provided by RefSeq, May 2013]

Previous symbols:

C20orf34

MANE transcript

NM_016408.4

Inheritance

—

ClinVar variants

U:84B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.99

Max pathogenic AF

—

Genomic locus

chr20:33,358,839-33,401,561

External References & Databases

Ensembl (ENSG00000101391)

Transcript & Mutation Effects

hg38 • Region Span ~42.7 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 CDK5RAP1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 71

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_016408.4. 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			4 clinvar	1 clinvar		5
missense			72 clinvar	2 clinvar		74
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			7 clinvar			7
Total	0	0	84	3	0	87

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 93 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_016408.4	RefSeq	NP_057492.2	13	MANE Select
ENST00000346416.7	Ensembl	ENSP00000217372.2	13	MANE Select
NM_001278167.2	RefSeq	NP_001265096.1	13	Standard
NM_001278168.2	RefSeq	NP_001265097.1	12	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

miR-targeted genes in epithelium - TarBase
miR-targeted genes in leukocytes - TarBase
miR-targeted genes in lymphocytes - TarBase
miR-targeted genes in muscle cell - TarBase

Biological Process

brain development
tRNA methylthiolation
regulation of neuron differentiation
negative regulation of cyclin-dependent protein serine/threonine kinase activity
positive regulation of translational fidelity

Molecular Function

protein kinase binding
N6-isopentenyladenosine methylthiotransferase activity
protein-containing complex binding
metal ion binding
4 iron, 4 sulfur cluster binding

Cellular Component

cellular_component
mitochondrion

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000346416
Coding exons: 13
Length: 42723
Individuals with no LoFs: 125615
Homozygous LoFs: 0
Heterozygous LoFs: 133
Defined: 125748
p: 0.000529

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.25	277	342	0.810	0.0000192	3846
Missense (PolyPhen)		94	134.45	0.69914		1509
Synonymous	0.364	117	122	0.958	0.00000641	1154
Loss of Function	0.0555	28	28.3	0.989	0.00000137	337

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00043	0.00043	rare
Latino/Admixed American	0.00017	0.00017	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00071	0.00071	rare
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.00076	0.00076	rare
South Asian	0.00056	0.00056	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Specifically inhibits CDK5 activation by CDK5R1.;

Recessive Scores

pRec: 0.124

Intolerance Scores

LoFtool: 0.271
RVIS EVS: -0.8
RVIS percentile EVS: 12.46

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.974

Gene Damage Prediction

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