CABIN1

Chr 22

calcineurin binding protein 1

Also known as: CAIN, KB-318B8.7, PPP3IN

NCBI Gene: 23523ENSG00000099991UniProt: Q9Y6J0

Calcineurin plays an important role in the T-cell receptor-mediated signal transduction pathway. The protein encoded by this gene binds specifically to the activated form of calcineurin and inhibits calcineurin-mediated signal transduction. The encoded protein is found in the nucleus and contains a leucine zipper domain as well as several PEST motifs, sequences which confer targeted degradation to those proteins which contain them. Alternative splicing results in multiple transcript variants encoding two different isoforms. [provided by RefSeq, Jan 2011]

558
ClinVar variants
33
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— CABIN1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
33 Pathogenic / Likely Pathogenic· 330 VUS of 558 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.59LOEUF
pLI 0.000
Z-score 4.99
OE 0.46 (0.36–0.59)
Moderately constrained

More LoF-intolerant than ~75% 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.
1.92Z-score
OE missense 0.85 (0.80–0.89)
1059 obs / 1250.3 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.0.46 (0.36–0.59)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.85 (0.80–0.89)
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.1.01
0≤1.21.6
LoF obs/exp: 45 / 98.5Missense obs/exp: 1059 / 1250.3Syn Z: -0.21

ClinVar Variant Classifications

558 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic29
Likely Pathogenic4
VUS330
Likely Benign38
Benign4
Conflicting2
29
Pathogenic
4
Likely Pathogenic
330
VUS
38
Likely Benign
4
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
29
0
29
Likely Pathogenic
0
0
4
0
4
VUS
0
293
37
0
330
Likely Benign
0
13
10
15
38
Benign
0
2
2
0
4
Conflicting
—2
Total03088215407

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

View in ClinVar →

Protein Context — Lollipop Plot

CABIN1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

3 OMIM entries

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Human CABIN1 is a functional member of the human HIRA/UBN1/ASF1a histone H3.3 chaperone complex.
Rai TS et al.·Mol Cell Biol
2011Functional
A Molecular Prospective for HIRA Complex Assembly and H3.3-Specific Histone Chaperone Function.
Ricketts MD et al.·J Mol Biol
2017Review
Integrating rare pathogenic variant prioritization with gene-based association analysis to identify novel genes and relevant multimodal traits for Alzheimer's disease.
Cao J et al.·Alzheimers Dement
2025
Genome-Scale Methylation Analysis of Circulating Cell-Free DNA in Gastric Cancer Patients.
Ren J et al.·Clin Chem
2022Cohort
Functional activity of the H3.3 histone chaperone complex HIRA requires trimerization of the HIRA subunit.
Ray-Gallet D et al.·Nat Commun
2018Functional
Structural insights into the interaction of Hir2 and Hpc2 in the yeast Hir histone chaperone complex.
Tseng CH et al.·Structure
2025
DNA hypermethylation, Her-2/neu overexpression and p53 mutations in ovarian carcinoma.
Feng Q et al.·Gynecol Oncol
2008
HIRA complex deposition of histone H3.3 is driven by histone tetramerization and histone-DNA binding.
Vogt A et al.·J Biol Chem
2024
HIRA contributes to zygote formation in mice and is implicated in human 1PN zygote phenotype.
Smith R et al.·Reproduction
2021
Identification of an ubinuclein 1 region required for stability and function of the human HIRA/UBN1/CABIN1/ASF1a histone H3.3 chaperone complex.
Tang Y et al.·Biochemistry
2012
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.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools