CRYAB

Chr 11ADAR

crystallin alpha B

Alpha-B crystallin functions as a molecular chaperone that prevents protein aggregation under stress conditions and contributes to lens transparency. Mutations cause autosomal dominant or recessive disorders including dilated cardiomyopathy, cataracts, and myofibrillar myopathies with either adult or infantile onset depending on the specific variant. The gene is not highly constrained against loss-of-function variation, reflecting its tolerance to certain types of genetic variants.

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismAD/ARLOEUF 1.434 OMIM phenotypes
Clinical SummaryCRYAB
Population Constraint (gnomAD)
Low constraint (pLI 0.02) — loss-of-function variants are relatively tolerated in the population.
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.43LOEUF
pLI 0.022
Z-score 0.93
OE 0.57 (0.261.43)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.48Z-score
OE missense 0.87 (0.731.03)
88 obs / 101.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.57 (0.261.43)
00.351.4
Missense OE0.87 (0.731.03)
00.61.4
Synonymous OE0.85
01.21.6
LoF obs/exp: 3 / 5.3Missense obs/exp: 88 / 101.5Syn Z: 0.72
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveCRYAB-related alpha-related B crystallinopathyDNAD
limitedCRYAB-related myopathy, myofibrillar, fatal infantile hypertonic, alpha-B crystallin-relatedLOFAR
limitedCRYAB-related cataract, multiple typesOTHERAR
DN
0.83top 10%
GOF
0.5955th %ile
LOF
0.3453th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median · 1 literature citation

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Literature Evidence

DNWe conclude that (1) despite its reduced expression, the mutant protein exerts a dominant negative effect; (2) mutations in alphaB-crystallin are an infrequent cause of myofibrillar myopathy; (3) alphaB-crystallin-related myopathies display phenotypic heterogeneity.PMID:14681890

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

CRYAB · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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