NEK1

Chr 4ARADDigenic recessive

NIMA related kinase 1

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

NCBI Gene: 4750 ENSG00000137601 UniProt: Q96PY6 OMIM: 604588

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a serine/threonine kinase involved in cell cycle regulation. The encoded protein is found in a centrosomal complex with FEZ1, a neuronal protein that plays a role in axonal development. Defects in this gene are a cause of polycystic kidney disease (PKD). Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2010]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Orofaciodigital syndrome IIMIM #252100

{Amyotrophic lateral sclerosis, susceptibility to, 24}MIM #617892

Short-rib thoracic dysplasia 6 with or without polydactylyMIM #263520

ARDigenic recessive

Clinical highlights

Gene-disease validity (ClinGen)

amyotrophic lateral sclerosis, susceptibility to, 24 · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.86

LOEUF

LOF

Mechanism· G2P

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GeneReview available — NEK1