CENPC

Chr 4

centromere protein C

Also known as: CENP-C, CENPC1, MIF2, hcp-4

NCBI Gene: 1060 ENSG00000145241 UniProt: Q03188

Centromere protein C is a component of the inner kinetochore plate that is essential for proper chromosome segregation during cell division and recruits DNA methylation machinery to centromeric regions. Mutations cause immunodeficiency-centromeric instability-facial anomalies syndrome 1 through autosomal recessive inheritance and contribute to facioscapulohumeral muscular dystrophy 4 through digenic dominant inheritance. The gene is highly constrained against loss-of-function variants, reflecting its essential role in cell division.

ResearchSummary from RefSeq, OMIM, UniProt

Centromere protein C 1 is a centromere autoantigen and a component of the inner kinetochore plate. The protein is required for maintaining proper kinetochore size and a timely transition to anaphase. A putative pseudogene exists on chromosome 12. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

DNmechanismLOEUF 0.55

Clinical Summary— CENPC

⚡

Population Constraint (gnomAD)

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

📋

ClinVar Variants

119 VUS of 159 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.55LOEUF

pLI 0.000

Z-score 3.88

OE 0.36 (0.24–0.55)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.76Z-score

OE missense 0.90 (0.82–0.98)

379 obs / 422.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.36 (0.24–0.55)

0≤0.351.4

Missense OE?0.90 (0.82–0.98)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 15 / 42.3Missense obs/exp: 379 / 422.8Syn Z: 0.19

This gene — mechanism propensity

0.6355th %ile

GOF

0.2597th %ile

LOF

0.4627th %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

159 submitted variants in ClinVar

ClinVar

Classification Summary

VUS119

Likely Benign11

119

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	119	0	119
Likely Benign	10	1	11
Benign	0	0	0
Total	129	1	130

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

17 pathogenic / likely-pathogenic (of 29) ClinVar copy-number / structural variants overlap CENPC — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →