CENPE

Chr 4AR

centromere protein E

Also known as: CENP-E, KIF10, MCPH13, PPP1R61

Centrosome-associated protein E is a kinesin-like motor protein that drives chromosome alignment during cell division by mediating chromosome movement along spindle microtubules and establishing stable kinetochore-microtubule attachments. Mutations cause autosomal recessive microcephaly with seizures and intellectual disability, with this gene being highly constrained against loss-of-function variants (LOEUF 0.308). The condition typically presents in early infancy with severe developmental delays and intractable epilepsy.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismARLOEUF 0.311 OMIM phenotype
Clinical SummaryCENPE
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Gene-Disease Validity (ClinGen)
autosomal recessive primary microcephaly · ARLimited

Limited evidence — not for standalone diagnostic reporting

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.23) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.31LOEUF
pLI 0.241
Z-score 8.44
OE 0.23 (0.170.31)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
1.27Z-score
OE missense 0.90 (0.850.94)
1113 obs / 1238.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.23 (0.170.31)
00.351.4
Missense OE0.90 (0.850.94)
00.61.4
Synonymous OE1.04
01.21.6
LoF obs/exp: 32 / 139.6Missense obs/exp: 1113 / 1238.3Syn Z: -0.64
DN
0.6744th %ile
GOF
0.6346th %ile
LOF
0.3259th %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.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

CENPE · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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