CIP2A

Chr 3

cellular inhibitor of PP2A

Also known as: KIAA1524, NOCIVA, p90

NCBI Gene: 57650 ENSG00000163507 UniProt: Q8TCG1 OMIM: 610643

The protein inhibits protein phosphatase PP2A and, together with TOPBP1, facilitates clustering of chromosome fragments during mitosis to maintain genome stability. Mutations cause an autosomal recessive neurodevelopmental disorder characterized by intellectual disability, microcephaly, and seizures. The gene shows minimal constraint against loss-of-function variants based on population data.

GeneReviews OMIM ResearchSummary from RefSeq, UniProt

Enables protein homodimerization activity and protein phosphatase inhibitor activity. Involved in broken chromosome clustering. Located in several cellular components, including cytosol; microtubule organizing center; and plasma membrane. Is active in chromosome. [provided by Alliance of Genome Resources, Apr 2025]

GeneReviews OMIM ResearchGenerating clinical summary…

LOEUF 0.84

Clinical Summary— CIP2A

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

122 VUS of 162 total submissions

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GeneReview available — CIP2A

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.84LOEUF

pLI 0.000

Z-score 2.44

OE 0.61 (0.45–0.84)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.67Z-score

OE missense 0.91 (0.84–0.99)

401 obs / 440.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.61 (0.45–0.84)

0≤0.351.4

Missense OE?0.91 (0.84–0.99)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 28 / 45.9Missense obs/exp: 401 / 440.5Syn Z: -1.06

ClinVar Variant Classifications

162 submitted variants in ClinVar

ClinVar

Classification Summary

VUS122

Likely Benign6

Benign3

122

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	122	0	0	122
Likely Benign	4	1	1	6
Benign	3	0	0	3
Total	129	1	1	131

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

View in ClinVar →

16 pathogenic / likely-pathogenic (of 21) ClinVar copy-number / structural variants overlap CIP2A — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →