NEK3

Chr 13

NIMA related kinase 3

Also known as: HSPK36

NCBI Gene: 4752 ENSG00000136098 UniProt: P51956

NEK3 encodes a serine/threonine protein kinase that regulates neuronal morphogenesis and polarity by controlling microtubule acetylation and is activated by prolactin signaling to phosphorylate VAV2 and paxillin. The gene shows extremely high constraint against loss-of-function variants, but no Mendelian diseases have been definitively associated with NEK3 mutations in current clinical databases.

ResearchSummary from RefSeq, UniProt

This gene encodes a member of the NimA (never in mitosis A) family of serine/threonine protein kinases. The encoded protein differs from other NimA family members in that it is not cell cycle regulated and is found primarily in the cytoplasm. The kinase is activated by prolactin stimulation, leading to phosphorylation of VAV2 guanine nucleotide exchange factor, paxillin, and activation of the RAC1 GTPase. Two functional alleles for this gene have been identified in humans. The reference genome assembly (GRCh38) represents a functional allele that is associated with the inclusion of an additional coding exon in protein-coding transcripts, compared to an alternate functional allele that lacks the exon. [provided by RefSeq, Sep 2019]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

—

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (2)

gnomad: Error: gnomAD API error: 400

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in NEK3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 75

647 rare PASS variants

Rare truncating (LoF)

1 in 390

160 rare PASS variants

Rare synonymous (reference)

1 in 440

215 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for NEK3. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 110	1 in 470
South Asian	~43k	1 in 58	1 in 630
Remaining (unassigned)	~30k	1 in 69	1 in 320
European (Finnish)	~27k	1 in 250	1 in 4,300
Admixed American	~22k	1 in 99	1 in 790
African / African American	~21k	1 in 73	1 in 460
East Asian	~20k	1 in 77	1 in 540
Ashkenazi Jewish	~13k	1 in 190	≈ 1 in 3,200
Middle Eastern	~2,884	1 in 80	≈ 1 in 940

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 13 of 15 coding exons well covered in gnomAD exomes; exons 10, 12 marginal. Genomes: all 15.? see exons ↓