CENPU

Chr 4AR

centromere protein U

ENSG00000151725 UniProt: Q71F23 OMIM: 611509

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.

OMIM ResearchSummary from RefSeq, UniProt

Component of the CENPA-NAC (nucleosome-associated) complex, a complex that plays a central role in assembly of kinetochore proteins, mitotic progression and chromosome segregation. The CENPA-NAC complex recruits the CENPA-CAD (nucleosome distal) complex and may be involved in incorporation of newly synthesized CENPA into centromeres. Plays an important role in the correct PLK1 localization to the mitotic kinetochores. A scaffold protein responsible for the initial recruitment and maintenance of the kinetochore PLK1 population until its degradation. Involved in transcriptional repression

OMIM ResearchGenerating clinical summary…

DNmechanismARLOEUF 0.981 OMIM phenotype

Clinical Summary— CENPU

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.98LOEUF

pLI 0.000

Z-score 1.63

OE 0.64 (0.43–0.98)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.46Z-score

OE missense 1.09 (0.98–1.21)

232 obs / 213.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.64 (0.43–0.98)

0≤0.351.4

Missense OE?1.09 (0.98–1.21)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 15 / 23.5Missense obs/exp: 232 / 213.0Syn Z: -0.34

This gene — mechanism propensity

0.7325th %ile

GOF

0.3788th %ile

LOF

0.2968th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

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.