CIB1

Chr 15

calcium and integrin binding 1

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

NCBI Gene: 10519 ENSG00000185043 UniProt: Q99828

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.

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]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtEpidermodysplasia verruciformis 3

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.15

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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

Background carrier burden — how many people carry a rare variant somewhere in CIB1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 190

294 rare PASS variants

Rare truncating (LoF)

1 in 2,200

65 rare PASS variants

Rare synonymous (reference)

1 in 460

124 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CIB1. 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 260	1 in 2,100
South Asian	~43k	1 in 140	1 in 1,400
Remaining (unassigned)	~30k	1 in 130	1 in 1,600
European (Finnish)	~27k	1 in 350	1 in 3,600
Admixed American	~22k	1 in 270	1 in 1,100
African / African American	~21k	1 in 120	1 in 1,400
East Asian	~20k	1 in 220	1 in 1,300
Ashkenazi Jewish	~13k	1 in 670	none seen
Middle Eastern	~2,884	1 in 220	none seen

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): 6 of 7 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 7.? see exons ↓