CENPC

Chr 4

centromere protein C

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

NCBI Gene: 1060 ENSG00000145241 UniProt: Q03188 OMIM: 117141

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.

OMIM 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]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.55

LOEUF

Mechanism· predicted

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

Background carrier burden — how many people carry a rare variant somewhere in CENPC?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 46

1,083 rare PASS variants

Rare truncating (LoF)

1 in 1,900

131 rare PASS variants

Rare synonymous (reference)

1 in 150

357 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CENPC. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 77	1 in 2,300
South Asian	~43k	1 in 48	1 in 1,400
Remaining (unassigned)	~30k	1 in 43	1 in 2,000
European (Finnish)	~27k	1 in 130	1 in 1,700
Admixed American	~22k	1 in 36	1 in 1,000
African / African American	~21k	1 in 69	1 in 1,400
East Asian	~20k	1 in 72	1 in 1,500
Ashkenazi Jewish	~13k	1 in 150	1 in 2,100
Middle Eastern	~2,883	1 in 47	≈ 1 in 900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 7 of 19 coding exons well covered in gnomAD exomes; exons 1, 2, 4, 5, 7 and 7 more marginal. Genomes: all 19.? see exons ↓