NEK5

Chr 13

NIMA related kinase 5

NCBI Gene: 341676ENSG00000197168UniProt: Q6P3R8OMIM: 616731

NEK5 encodes a protein kinase predicted to function in chromatin remodeling and positive regulation of striated muscle cell differentiation. Mutations cause autosomal recessive primary ciliary dyskinesia, a disorder affecting respiratory cilia function leading to chronic respiratory infections, bronchiectasis, and potentially situs inversus. The gene shows no constraint against loss-of-function variants (pLI near 0), consistent with autosomal recessive inheritance where heterozygous carriers are typically unaffected.

OMIMResearchSummary from RefSeq
MultiplemechanismLOEUF 1.17
Clinical Summary— NEK5
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
59 unique Pathogenic / Likely Pathogenic· 108 VUS of 190 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
1.17LOEUF
pLI 0.000
Z-score 0.64
OE 0.89 (0.69–1.17)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.42Z-score
OE missense 0.94 (0.86–1.02)
346 obs / 368.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.89 (0.69–1.17)
0≤0.351.4
Missense OE0.94 (0.86–1.02)
0≤0.61.4
Synonymous OE0.95
0≤1.21.6
LoF obs/exp: 38 / 42.5Missense obs/exp: 346 / 368.8Syn Z: 0.45
DN
0.7131th %ile
GOF
0.73top 25%
LOF
0.4234th %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

190 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic56
Likely Pathogenic3
VUS108
Likely Benign10
56
Pathogenic
3
Likely Pathogenic
108
VUS
10
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
56
0
56
Likely Pathogenic
0
0
3
0
3
VUS
0
95
13
0
108
Likely Benign
0
8
1
1
10
Benign
0
0
0
0
0
Total0103731177

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

View in ClinVar →

Protein Context — Lollipop Plot

NEK5 · 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 3 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