NEK6
Chr 9NIMA related kinase 6
Also known as: SID6-1512
The protein is a kinase that regulates mitotic cell cycle progression by phosphorylating multiple substrates required for chromosome segregation, spindle formation, and cytokinesis. Loss-of-function mutations cause a neurodevelopmental disorder with intellectual disability, developmental delay, and seizures, inherited in an autosomal dominant pattern. The pathogenic mechanism involves dominant-negative effects that disrupt normal mitotic processes in developing neurons.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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
95 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 27 | 0 | 27 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 0 | 42 | 1 | 0 | 43 |
Likely Benign | 0 | 3 | 0 | 0 | 3 |
Benign | 0 | 0 | 0 | 1 | 1 |
| Total | 0 | 45 | 29 | 1 | 75 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
NEK6 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools