CENPC

Chr 4Digenic dominantAR

centromere protein C

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

NCBI Gene: 1060ENSG00000145241UniProt: Q03188OMIM: 117139

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.

OMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismDigenic dominant/ARLOEUF 0.552 OMIM phenotypes
Clinical Summary— CENPC
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
17 unique Pathogenic / Likely Pathogenic· 130 VUS of 188 total submissions
Explore recent and relevant literature in Research Assistant →

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 OE0.36 (0.24–0.55)
0≤0.351.4
Missense OE0.90 (0.82–0.98)
0≤0.61.4
Synonymous OE0.98
0≤1.21.6
LoF obs/exp: 15 / 42.3Missense obs/exp: 379 / 422.8Syn Z: 0.19
DN
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

188 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic16
Likely Pathogenic1
VUS130
Likely Benign12
16
Pathogenic
1
Likely Pathogenic
130
VUS
12
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
16
0
16
Likely Pathogenic
0
0
1
0
1
VUS
0
119
11
0
130
Likely Benign
0
10
1
1
12
Benign
0
0
0
0
0
Total0129291159

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

View in ClinVar →

Protein Context — Lollipop Plot

CENPC · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients