CABP2

Chr 11

calcium binding protein 2

Also known as: DFNB93

NCBI Gene: 51475 ENSG00000167791 UniProt: Q9NPB3

The protein is required for sound encoding at inner hair cell synapses, likely by preventing inactivation of voltage-gated calcium channels, and is also necessary for normal light signal transfer through the retina. Mutations cause autosomal recessive deafness (ARNSHL 93). The gene shows low constraint to loss-of-function variants, consistent with its recessive inheritance pattern.

ResearchSummary from RefSeq, OMIM, UniProt

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]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtDeafness, autosomal recessive, 93

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · nonsyndromic genetic hearing loss · AR · ClinGen 2020

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.97

LOEUF

LOF

Mechanism· G2P

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?

0.97LOEUF

pLI 0.003

Z-score 1.64

OE 0.49 (0.27–0.97)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.03Z-score

OE missense 0.99 (0.87–1.14)

152 obs / 153.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.49 (0.27–0.97)

0≤0.351.4

Missense OE?0.99 (0.87–1.14)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 6 / 12.2Missense obs/exp: 152 / 153.0Syn Z: -0.48

Background carrier burden — how many people carry a rare variant somewhere in CABP2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 90

370 rare PASS variants

Rare truncating (LoF)

1 in 1,900

55 rare PASS variants

Rare synonymous (reference)

1 in 360

163 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CABP2. 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 150	1 in 2,200
South Asian	~43k	1 in 66	1 in 5,200
Remaining (unassigned)	~30k	1 in 100	1 in 520
European (Finnish)	~27k	1 in 430	≈ 1 in 13,000
Admixed American	~22k	1 in 100	1 in 1,500
African / African American	~21k	1 in 95	1 in 610
East Asian	~20k	1 in 170	1 in 1,600
Ashkenazi Jewish	~13k	1 in 410	≈ 1 in 3,100
Middle Eastern	~2,884	1 in 83	≈ 1 in 2,900

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): All 7 coding exons well covered in gnomAD exomes and genomes.? see exons ↓