CABP2

Chr 11AR

calcium binding protein 2

Also known as: DFNB93

NCBI Gene: 51475ENSG00000167791UniProt: Q9NPB3

This gene belongs to a subfamily of calcium binding proteins that share similarity to calmodulin. Like calmodulin, these family members can likely stimulate calmodulin-dependent kinase II and the protein phosphatase calcineurin. Calcium binding proteins are an important component of calcium mediated cellular signal transduction. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2016]

Primary Disease Associations & Inheritance

Deafness, autosomal recessive 93MIM #614899
AR
160
ClinVar variants
23
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— CABP2
🧬
Gene-Disease Validity (ClinGen)
nonsyndromic genetic hearing loss · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
23 Pathogenic / Likely Pathogenic· 71 VUS of 160 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.
0.97LOEUF
pLI 0.003
Z-score 1.64
OE 0.49 (0.27–0.97)
Tolerant

Typical tolerance to LoF variation

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.
0.03Z-score
OE missense 0.99 (0.87–1.14)
152 obs / 153.0 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.0.49 (0.27–0.97)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.99 (0.87–1.14)
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.1.08
0≤1.21.6
LoF obs/exp: 6 / 12.2Missense obs/exp: 152 / 153.0Syn Z: -0.48

ClinVar Variant Classifications

160 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic12
Likely Pathogenic11
VUS71
Likely Benign49
Benign10
Conflicting7
12
Pathogenic
11
Likely Pathogenic
71
VUS
49
Likely Benign
10
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
11
0
12
Likely Pathogenic
6
0
4
1
11
VUS
1
61
9
0
71
Likely Benign
0
9
27
13
49
Benign
0
2
8
0
10
Conflicting
—7
Total7735914160

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

View in ClinVar →

Protein Context — Lollipop Plot

CABP2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

CABP2-related deafness

strong
ARLoss Of FunctionAbsent Gene Product
Ear
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Deafness, autosomal recessive 93

MIM #614899

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
A Novel Pathogenic Variant in the CABP2 Gene Causes Severe Nonsyndromic Hearing Loss in a Consanguineous Iranian Family.
Koohiyan M et al.·Audiol Neurootol
2019
First reported CABP2-related non-syndromic hearing loss in Northern Europe.
Sheyanth IN et al.·Mol Genet Genomic Med
2021Case report
Autosomal recessive nonsyndromic hearing impairment in two Finnish families due to the population enriched CABP2 c.637+1G>T variant.
Bharadwaj T et al.·Mol Genet Genomic Med
2022
Structure-Function Diversity of Calcium-Binding Proteins (CaBPs): Key Roles in Cell Signalling and Disease.
Morris VS et al.·Cells
2025Review
Homozygous mutations in Pakistani consanguineous families with prelingual nonsyndromic hearing loss.
Park HR et al.·Mol Biol Rep
2020
Mutations in eight small DFNB genes are not a frequent cause of non-syndromic hereditary hearing loss in Czech patients.
Marková S et al.·Int J Pediatr Otorhinolaryngol
2016Cohort
Clinical and genetic characterisation of childhood-onset sensorineural hearing loss reveal associated phenotypes and enrichment of pathogenic founder mutations in the Finnish population.
Kraatari-Tiri M et al.·Int J Audiol
2025
Comprehensive Characterization of a Subfamily of Ca(2+)-Binding Proteins in Mouse and Human Retinal Neurons at Single-Cell Resolution.
Liu JB et al.·eNeuro
2024Functional
Spectrum and frequencies of non GJB2 gene mutations in Czech patients with early non-syndromic hearing loss detected by gene panel NGS and whole-exome sequencing.
Safka Brozkova D et al.·Clin Genet
2020Cohort
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