NEK4

protein-coding

NIMA related kinase 4

Gene summary

The protein encoded by this gene is a serine/threonine protein kinase required for normal entry into replicative senescence. The encoded protein also is involved in cell cycle arrest in response to double-stranded DNA damage. Finally, this protein plays a role in maintaining cilium integrity, and defects in this gene have been associated with ciliopathies. [provided by RefSeq, Jan 2017]

Previous symbols:

STK2

MANE transcript

NM_003157.6

Inheritance

—

ClinVar variants

P:1U:117B:13

Top phenotype

EBV-positive nodal T- and NK-cell lymphoma

gnomAD constraint

pLI —, LoF o/e 0.89

Max pathogenic AF

—

Genomic locus

chr3:52,708,444-52,770,946

External References & Databases

Ensembl (ENSG00000114904)

Transcript & Mutation Effects

hg38 • Region Span ~62.5 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 NEK4 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 113

not providedTotal: 2

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

CiliopathyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003157.6. 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			2 clinvar	1 clinvar		3
missense			111 clinvar	12 clinvar		123
nonsense			1 clinvar			1
start loss						0
frameshift		1 clinvar				1
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	1	117	13	0	131

Highest pathogenic variant AF is 0.000009368851

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 58 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003157.6	RefSeq	NP_003148.2	16	MANE Select
ENST00000233027.10	Ensembl	ENSP00000233027.5	16	MANE Select
NM_001193533.3	RefSeq	NP_001180462.1	15	Standard
NM_001348412.2	RefSeq	NP_001335341.1	15	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

mitotic cell cycle
protein phosphorylation
cellular response to DNA damage stimulus
signal transduction by protein phosphorylation
stress-activated protein kinase signaling cascade

Molecular Function

protein serine/threonine kinase activity
ATP binding
manganese ion binding

Cellular Component

cytoplasm
cytosol
ciliary rootlet
ciliary transition zone
ciliary basal body

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000233027
Coding exons: 16
Length: 60166
Individuals with no LoFs: 125520
Homozygous LoFs: 1
Heterozygous LoFs: 227
Defined: 125748
p: 0.000907

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.883	381	433	0.881	0.0000226	5448
Missense (PolyPhen)		115	142.52	0.80692		1796
Synonymous	1.06	141	158	0.893	0.00000766	1630
Loss of Function	0.675	43	48.0	0.895	0.00000303	541

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00037	0.00037	rare
Latino/Admixed American	0.00084	0.00084	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0019	0.0019	notable
Finnish	0.00023	0.00023	rare
European (Non-Finnish)	0.0010	0.0010	notable
South Asian	0.00079	0.00078	rare
Other	0.0020	0.0020	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Protein kinase that seems to act exclusively upon threonine residues (By similarity). Required for normal entry into proliferative arrest after a limited number of cell divisions, also called replicative senescence. Required for normal cell cycle arrest in response to double-stranded DNA damage. {ECO:0000250|UniProtKB:Q9Z1J2, ECO:0000269|PubMed:22851694}.;

Recessive Scores

pRec: 0.0739

Intolerance Scores

LoFtool: 0.993
RVIS EVS: -0.35
RVIS percentile EVS: 29.43

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.257

Gene Damage Prediction

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