CENPO
Chr 2centromere protein O
Also known as: CENP-O, ICEN-36, MCM21R
The protein is a component of the interphase centromere complex that localizes to centromeres throughout the cell cycle and is required for bipolar spindle assembly, chromosome segregation, and checkpoint signaling during mitosis. Mutations cause primary microcephaly with seizures and developmental delay, following autosomal recessive inheritance. The gene shows minimal constraint against loss-of-function variants (very low pLI), consistent with the recessive inheritance pattern observed clinically.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
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
157 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 | 1 | 0 | 19 | 0 | 20 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 2 | 59 | 14 | 0 | 75 |
Likely Benign | 1 | 7 | 7 | 20 | 35 |
Benign | 0 | 0 | 3 | 2 | 5 |
| Total | 4 | 66 | 44 | 22 | 136 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
CENPO · 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