NEK3

Chr 13

NIMA related kinase 3

Also known as: HSPK36

NCBI Gene: 4752ENSG00000136098UniProt: P51956OMIM: 604044

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.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.34
Clinical Summary— NEK3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
58 unique Pathogenic / Likely Pathogenic· 83 VUS of 177 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.34LOEUF
pLI 0.000
Z-score 0.14
OE 0.97 (0.71–1.34)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.20Z-score
OE missense 0.96 (0.87–1.07)
242 obs / 250.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.97 (0.71–1.34)
0≤0.351.4
Missense OE0.96 (0.87–1.07)
0≤0.61.4
Synonymous OE0.88
0≤1.21.6
LoF obs/exp: 27 / 27.8Missense obs/exp: 242 / 250.8Syn Z: 0.91
DN
0.6259th %ile
GOF
0.6737th %ile
LOF
0.4529th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

177 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic56
Likely Pathogenic2
VUS83
Likely Benign5
Benign2
56
Pathogenic
2
Likely Pathogenic
83
VUS
5
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
56
0
56
Likely Pathogenic
0
0
2
0
2
VUS
0
70
13
0
83
Likely Benign
0
4
0
1
5
Benign
1
1
0
0
2
Total175711148

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

NEK3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients