NEK1

Chr 4ARADDigenic recessive

NIMA related kinase 1

Also known as: ALS24, NY-REN-55, OFD2, SRPS2, SRPS2A, SRTD6

NEK1 encodes a serine/threonine kinase that functions in DNA damage repair, cell cycle regulation, and cilium assembly. Mutations cause short-rib thoracic dysplasia with or without polydactyly, orofaciodigital syndrome type II, and contribute to amyotrophic lateral sclerosis susceptibility, with inheritance patterns including autosomal recessive, autosomal dominant, and digenic recessive depending on the condition. The gene shows very low constraint against loss-of-function variants, consistent with its association with recessive developmental disorders affecting skeletal development and ciliary function.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismAR/AD/Digenic recessiveLOEUF 0.863 OMIM phenotypes
Clinical SummaryNEK1
🧬
Gene-Disease Validity (ClinGen)
amyotrophic lateral sclerosis, susceptibility to, 24 · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.86LOEUF
pLI 0.000
Z-score 2.54
OE 0.68 (0.540.86)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.07Z-score
OE missense 0.88 (0.820.94)
542 obs / 616.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.68 (0.540.86)
00.351.4
Missense OE0.88 (0.820.94)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 51 / 74.7Missense obs/exp: 542 / 616.8Syn Z: -0.14
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveNEK1-related short rib-polydactyly syndromeLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6939th %ile
GOF
0.6247th %ile
LOF
0.3647th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Literature Evidence

LOFIn totality, we detected 9 variants, comprising 3 novel heterozygous loss-of-function mutations and 6 rare missense variants (MAF < 0.1%) in NEK1.PMID:30093141

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

NEK1 · 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

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →