CENPU
Chr 4centromere protein U
Also known as: CENP50, CENPU50, KLIP1, MLF1IP, PBIP1
The protein is a component of the CENPA-NAC complex that assembles kinetochore proteins and ensures proper chromosome segregation during mitosis, and serves as a scaffold for PLK1 localization to kinetochores. Mutations cause primary microcephaly with seizures and developmental delay, following an autosomal recessive inheritance pattern. This gene shows very low constraint against loss-of-function variants, which is consistent with the recessive disease mechanism.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Tolerant to missense variation
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
198 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 | 96 | 0 | 96 |
Likely Pathogenic | 0 | 0 | 9 | 0 | 9 |
VUS | 1 | 70 | 13 | 0 | 84 |
Likely Benign | 0 | 6 | 1 | 1 | 8 |
Benign | 0 | 0 | 1 | 0 | 1 |
| Total | 1 | 76 | 120 | 1 | 198 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
CENPU · 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
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools