CIB1

Chr 15AR

calcium and integrin binding 1

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

NCBI Gene: 10519ENSG00000185043UniProt: Q99828

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]

Primary Disease Associations & Inheritance

{Epidermodysplasia verruciformis, susceptibility to, 3}MIM #618267
AR
321
ClinVar variants
54
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— CIB1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
54 Pathogenic / Likely Pathogenic· 155 VUS of 321 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
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?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.
0.06Z-score
OE missense 0.98 (0.84–1.15)
110 obs / 111.8 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.0.61 (0.35–1.15)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.98 (0.84–1.15)
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.0.91
0≤1.21.6
LoF obs/exp: 7 / 11.5Missense obs/exp: 110 / 111.8Syn Z: 0.48

ClinVar Variant Classifications

321 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic45
Likely Pathogenic9
VUS155
Likely Benign95
Benign15
Conflicting2
45
Pathogenic
9
Likely Pathogenic
155
VUS
95
Likely Benign
15
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
7
0
38
0
45
Likely Pathogenic
5
0
4
0
9
VUS
0
144
11
0
155
Likely Benign
0
9
42
44
95
Benign
0
2
10
3
15
Conflicting
—2
Total1215510547321

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

View in ClinVar →

Protein Context — Lollipop Plot

CIB1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

CIB1-related epidermodysplasia verruciformis

definitive
ARUndeterminedAltered Gene Product Structure
Skin
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

{Epidermodysplasia verruciformis, susceptibility to, 3}

MIM #618267

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Research Advances of Calcium-and Integrin-binding Protein 1 in Tumors.
Hui L et al.·Zhongguo Yi Xue Ke Xue Yuan Xue Bao
2017Review
Identification of key genes and immune infiltration in peripheral blood biomarker analysis of delayed cerebral ischemia: Valproic acid as a potential therapeutic drug.
Wu Z et al.·Int Immunopharmacol
2024
Monogenic etiologies of persistent human papillomavirus infections: A comprehensive systematic review.
Biglari S et al.·Genet Med
2024Review
Expression of a TMC6-TMC8-CIB1 heterotrimeric complex in lymphocytes is regulated by each of the components.
Wu CJ et al.·J Biol Chem
2020
Role of calcium integrin-binding protein 1 in the mechanobiology of the liver endothelium.
Wang C et al.·J Cell Physiol
2024
Gene expression is stable in a complete CIB1 knockout keratinocyte model.
Imahorn E et al.·Sci Rep
2020Functional
Integrative public data-mining pipeline for the validation of novel independent prognostic biomarkers for lung adenocarcinoma.
Ghandili S et al.·Biomark Med
2020Meta-analysis
Human genetic dissection of papillomavirus-driven diseases: new insight into their pathogenesis.
Béziat V·Hum Genet
2020Review
Whole transcriptome-based skin virome profiling in typical epidermodysplasia verruciformis reveals α-, β-, and γ-HPV infections.
Saeidian AH et al.·JCI Insight
2023
Aldehyde Dehydrogenase 1B1 Is Implicated in DNA Damage Response in Human Colorectal Adenocarcinoma.
Tsochantaridis I et al.·Cells
2022
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
No evidence for restriction of Beta-HPV8 gene expression by epidermodysplasia verruciformis susceptibility genes CIB1, TMC6, or TMC8 in keratinocytes.
Rehm TM et al.·Tumour Virus Res
2025🔓 Open Access
CIB1 and platelet integrin αIIbβ3: Molecular mechanisms, disruption strategies and antithrombotic opportunities.
Kamel EM et al.·Thromb Res
2025Functional
Establishment of a CIB1 knockout human pluripotent stem cell line via CRISPR/Cas9 genome editing technology.
Gong T et al.·Stem Cell Res
2024
In silico fragment-based discovery of CIB1-directed anti-tumor agents by FRASE-bot.
An Y et al.·Nat Commun
2024🔓 Open Access
High CIB1 expression in colorectal cancer liver metastases correlates with worse survival and the replacement histopathological growth pattern.
Fan S et al.·Mol Ther Oncol
2024🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools