CIB1

Chr 15AR

calcium and integrin binding 1

Also known as: CIB, CIBP, EV3, KIP1, PRKDCIP, SIP2-28

NCBI Gene: 10519 ENSG00000185043 UniProt: Q99828 OMIM: 602293

This calcium-binding protein regulates diverse cellular processes including cell proliferation, migration, platelet function, and angiogenesis, and forms complexes with TMC6/EVER1 and TMC8/EVER2 proteins in lymphocytes and keratinocytes. Autosomal recessive mutations cause susceptibility to epidermodysplasia verruciformis, a rare disorder characterized by chronic human papillomavirus infections and increased risk of skin cancer. The gene shows tolerance to loss-of-function variation (LOEUF 1.148), consistent with the recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the EF-hand domain-containing calcium-binding superfamily. The encoded protein interacts with many other proteins, including the platelet integrin alpha-IIb-beta-3, DNA-dependent protein kinase, presenilin-2, focal adhesion kinase, p21 activated kinase, and protein kinase D. The encoded protein may be involved in cell survival and proliferation, and is associated with several disease states including cancer and Alzheimer's disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2013]

OMIM ResearchGenerating clinical summary…

MultiplemechanismARLOEUF 1.151 OMIM phenotype

Clinical Summary— CIB1

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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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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.15LOEUF

pLI 0.000

Z-score 1.22

OE 0.61 (0.35–1.15)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.06Z-score

OE missense 0.98 (0.84–1.15)

110 obs / 111.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.61 (0.35–1.15)

0≤0.351.4

Missense OE?0.98 (0.84–1.15)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 7 / 11.5Missense obs/exp: 110 / 111.8Syn Z: 0.48

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveCIB1-related epidermodysplasia verruciformisOTHERAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.79top 25%

GOF

0.82top 10%

LOF

0.2190th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.