INCENP

Chr 11

inner centromere protein

NCBI Gene: 3619 ENSG00000149503 UniProt: Q9NQS7 OMIM: 604411

The protein acts as a scaffold component of the chromosomal passenger complex, which regulates chromosome alignment and segregation during cell division by controlling centromere function and spindle assembly. Mutations cause autosomal dominant neurodevelopmental disorders with intellectual disability, developmental delay, and seizures. This gene is highly constrained against loss-of-function variants in the general population.

OMIM ResearchSummary from RefSeq, UniProt

In mammalian cells, 2 broad groups of centromere-interacting proteins have been described: constitutively binding centromere proteins and 'passenger,' or transiently interacting, proteins (reviewed by Choo, 1997). The constitutive proteins include CENPA (centromere protein A; MIM 117139), CENPB (MIM 117140), CENPC1 (MIM 117141), and CENPD (MIM 117142). The term 'passenger proteins' encompasses a broad collection of proteins that localize to the centromere during specific stages of the cell cycle (Earnshaw and Mackay, 1994 [PubMed 8088460]). These include CENPE (MIM 117143); MCAK (MIM 604538); KID (MIM 603213); cytoplasmic dynein (e.g., MIM 600112); CliPs (e.g., MIM 179838); and CENPF/mitosin (MIM 600236). The inner centromere proteins (INCENPs) (Earnshaw and Cooke, 1991 [PubMed 1860899]), the initial members of the passenger protein group, display a broad localization along chromosomes in the early stages of mitosis but gradually become concentrated at centromeres as the cell cycle progresses into mid-metaphase. During telophase, the proteins are located within the midbody in the intercellular bridge, where they are discarded after cytokinesis (Cutts et al., 1999 [PubMed 10369859]).[supplied by OMIM, Mar 2008]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

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LOEUF

LOF

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 INCENP?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 34

1,169 rare PASS variants

Rare truncating (LoF)

1 in 1,800

100 rare PASS variants

Rare synonymous (reference)

1 in 81

525 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for INCENP. 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 53	1 in 2,100
South Asian	~43k	1 in 29	1 in 3,200
Remaining (unassigned)	~30k	1 in 27	1 in 890
European (Finnish)	~27k	1 in 130	1 in 3,200
Admixed American	~22k	1 in 36	1 in 630
African / African American	~21k	1 in 24	1 in 410
East Asian	~20k	1 in 34	1 in 720
Ashkenazi Jewish	~13k	1 in 180	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 39	≈ 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.