NDC80
Chr 18NDC80 kinetochore complex component
Also known as: HEC, HEC1, HsHec1, KNTC2, TID3, hsNDC80
The NDC80 protein is a component of the essential kinetochore-associated NDC80 complex that organizes microtubule-kinetochore interactions and is required for proper chromosome segregation during cell division. Mutations cause autosomal recessive primary microcephaly with intellectual disability and seizures, typically presenting in infancy. This gene is highly intolerant to loss-of-function variants, reflecting its essential role in cell division.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
The highest-scoring mechanism for this gene is dominant-negative.
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
223 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 | 124 | 0 | 124 |
Likely Pathogenic | 0 | 0 | 2 | 0 | 2 |
VUS | 0 | 58 | 20 | 0 | 78 |
Likely Benign | 0 | 1 | 1 | 0 | 2 |
Benign | 0 | 0 | 1 | 2 | 3 |
| Total | 0 | 59 | 148 | 2 | 209 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
NDC80 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools