CENPS

Chr 1

centromere protein S

Also known as: APITD1, CENP-S, FAAP16, MHF1

NCBI Gene: 378708 ENSG00000175279 UniProt: Q8N2Z9 OMIM: 609130

The protein is a DNA-binding component of the Fanconi anemia core complex required for DNA damage response and also functions as part of the kinetochore complex essential for proper chromosome segregation during cell division. Mutations cause Fanconi anemia, an autosomal recessive disorder characterized by bone marrow failure, developmental abnormalities, and increased cancer predisposition. The gene shows low constraint against loss-of-function variants, consistent with the recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, UniProt

This gene was identified in the neuroblastoma tumor suppressor candidate region on chromosome 1p36. It contains a TFIID-31 domain, similar to that found in TATA box-binding protein-associated factor, TAF(II)31, which is required for p53-mediated transcription activation. This gene was expressed at very low levels in neuroblastoma tumors, and was shown to reduce cell growth in neuroblastoma cells, suggesting that it may have a role in a cell death pathway. The protein is a component of multiple complexes, including the Fanconi anemia (FA) core complex, the APITD1/CENPS complex, and the CENPA-CAD (nucleosome distal) complex. Known functions include an involvement with chromatin associations of the FA core complex, and a role in the stable assembly of the outer kinetochore. Alternative splicing of this gene results in multiple transcript variants. Naturally occurring read-through transcripts also exist between this gene and the downstream cortistatin (CORT) gene, as represented in GeneID:100526739. An APITD1-related pseudogene has been identified on chromosome 7. [provided by RefSeq, Nov 2010]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

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LOEUF

Mechanism· predicted

Some data sources returned errors (1)

gnomad: Error: gnomAD API error: 400

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

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

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 420

234 rare PASS variants

Rare truncating (LoF)

1 in 1,100

63 rare PASS variants

Rare synonymous (reference)

1 in 590

75 rare PASS variants

Rare missense and truncating variants are carried at similar rates in CENPS; this gene does not show strong loss-of-function constraint by this measure. 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 750	1 in 1,300
South Asian	~43k	1 in 310	1 in 530
Remaining (unassigned)	~30k	1 in 340	1 in 990
European (Finnish)	~27k	1 in 450	≈ 1 in 13,000
Admixed American	~22k	1 in 820	1 in 690
African / African American	~21k	1 in 300	1 in 720
East Asian	~20k	1 in 430	1 in 950
Ashkenazi Jewish	~13k	≈ 1 in 13,000	1 in 400
Middle Eastern	~2,884	1 in 460	≈ 1 in 720

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): All 5 coding exons well covered in gnomAD exomes and genomes.? see exons ↓