INCENP

Chr 11

inner centromere protein

NCBI Gene: 3619ENSG00000149503UniProt: Q9NQS7

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]

0
ClinVar variants
0
Pathogenic / LP
0.89
pLI score
0
Active trials
Clinical Summary— INCENP
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.89) — some intolerance to loss-of-function variants.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.34LOEUF
pLI 0.886
Z-score 5.11
OE 0.19 (0.12–0.34)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.77Z-score
OE missense 0.91 (0.85–0.98)
545 obs / 597.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.19 (0.12–0.34)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.91 (0.85–0.98)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.99
0≤1.21.6
LoF obs/exp: 9 / 46.7Missense obs/exp: 545 / 597.7Syn Z: 0.09

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

INCENP · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Revisiting the question: When is a centromere not a kinetochore?
Corless S et al.·Chromosome Res
2025Review
Survivin's dual role: an export's view.
Knauer SK et al.·Cell Cycle
2007Review
Survivin and the inner centromere protein INCENP show similar cell-cycle localization and gene knockout phenotype.
Uren AG et al.·Curr Biol
2000
A Preliminary Investigation of PVT1 on the Effect and Mechanisms of Hepatocellular Carcinoma: Evidence from Clinical Data, a Meta-Analysis of 840 Cases, and In Vivo Validation.
Zhang Y et al.·Cell Physiol Biochem
2018Meta-analysis
Investigations of survivin: the past, present and future.
Cheung CH et al.·Front Biosci (Landmark Ed)
2011Review
High Inner Centromere Protein Expression Correlates with Aggressive Features and Predicts Poor Prognosis in Patients with Invasive Breast Cancer.
Ibrahim A et al.·Pathobiology
2023Cohort
Recapitulation of the Roberts syndrome cellular phenotype by inhibition of INCENP, ZWINT-1 and ZW10 genes.
Musio A et al.·Gene
2004
Establishing a Proteomics-Based Signature of AKR1C3-Related Genes for Predicting the Prognosis of Prostate Cancer.
Cui X et al.·Int J Mol Sci
2023
A comprehensive review on Aurora kinase: Small molecule inhibitors and clinical trial studies.
Borisa AC et al.·Eur J Med Chem
2017Review
Basal-Type Breast Cancer Stem Cells Over-Express Chromosomal Passenger Complex Proteins.
Schwarz-Cruz Y Celis A et al.·Cells
2020
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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External Resources

Links to major genomics databases and tools