CRYAB

Chr 11ADAR

crystallin alpha B

Also known as: CMD1II, CRYA2, CTPP2, CTRCT16, HEL-S-101, HSPB5, MFM2, MFM2A

NCBI Gene: 1410ENSG00000109846UniProt: P02511

Mammalian lens crystallins are divided into alpha, beta, and gamma families. Alpha crystallins are composed of two gene products: alpha-A and alpha-B, for acidic and basic, respectively. Alpha crystallins can be induced by heat shock and are members of the small heat shock protein (HSP20) family. They act as molecular chaperones although they do not renature proteins and release them in the fashion of a true chaperone; instead they hold them in large soluble aggregates. These heterogeneous aggregates consist of 30-40 subunits; the alpha-A and alpha-B subunits have a 3:1 ratio, respectively. Two additional functions of alpha crystallins are an autokinase activity and participation in the intracellular architecture. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. Alpha-A and alpha-B gene products are differentially expressed; alpha-A is preferentially restricted to the lens and alpha-B is expressed widely in many tissues and organs. Elevated expression of alpha-B crystallin occurs in many neurological diseases; a missense mutation cosegregated in a family with a desmin-related myopathy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2019]

Primary Disease Associations & Inheritance

Cardiomyopathy, dilated, 1IIMIM #615184
AD
Cataract 16, multiple typesMIM #613763
ADAR
Myopathy, myofibrillar, 2A, adult-onsetMIM #608810
AD
Myopathy, myofibrillar, 2B, infantile-onsetMIM #613869
AR
403
ClinVar variants
39
Pathogenic / LP
0.02
pLI score
0
Active trials
Clinical Summary— CRYAB
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.02) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
39 Pathogenic / Likely Pathogenic· 231 VUS of 403 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.
1.43LOEUF
pLI 0.022
Z-score 0.93
OE 0.57 (0.26–1.43)
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.
0.48Z-score
OE missense 0.87 (0.73–1.03)
88 obs / 101.5 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.0.57 (0.26–1.43)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.87 (0.73–1.03)
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.0.85
0≤1.21.6
LoF obs/exp: 3 / 5.3Missense obs/exp: 88 / 101.5Syn Z: 0.72

ClinVar Variant Classifications

403 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic33
Likely Pathogenic6
VUS231
Likely Benign105
Benign8
Conflicting16
33
Pathogenic
6
Likely Pathogenic
231
VUS
105
Likely Benign
8
Benign
16
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
7
5
21
0
33
Likely Pathogenic
4
1
1
0
6
VUS
13
187
29
2
231
Likely Benign
0
5
27
73
105
Benign
0
0
6
2
8
Conflicting
—16
Total241988477399

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

View 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.

Gene2Phenotype Curations

CRYAB-related alpha-related B crystallinopathy

definitive
ADDominant NegativeAltered Gene Product Structure
Dev. DisordersEyeCardiac
G2P ↗
stop lostmissense variantstop gained NMD escapingframeshift variant NMD escaping

CRYAB-related myopathy, myofibrillar, fatal infantile hypertonic, alpha-B crystallin-related

limited
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

CRYAB-related cataract, multiple types

limited
ARUndeterminedUncertain
Eye
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Cardiomyopathy, dilated, 1II

MIM #615184

Molecular basis of disorder known

Autosomal dominant

Cataract 16, multiple types

MIM #613763

Molecular basis of disorder known

Autosomal dominantAutosomal recessive

Myopathy, myofibrillar, 2A, adult-onset

MIM #608810

Molecular basis of disorder known

Autosomal dominant

Myopathy, myofibrillar, 2B, infantile-onset

MIM #613869

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Panorama of the distal myopathies.
Savarese M et al.·Acta Myol
2020Review
[Myofibrillar myopathy].
Hayashi YK·Brain Nerve
2011Review
New aspects of myofibrillar myopathies.
Kley RA et al.·Curr Opin Neurol
2016Review
Sex differences in the development of experimental diabetic retinopathy.
Chen Y et al.·Sci Rep
2024
Human Mutated MYOT and CRYAB Genes Cause a Myopathic Phenotype in Zebrafish.
Cannone E et al.·Int J Mol Sci
2023Functional
Myofibrillar myopathy in the genomic context.
Fichna JP et al.·J Appl Genet
2018Review
Integrative Analysis of Cuproptosis-Related Mitochondrial Depolarisation Genes for Prognostic Prediction in Non-Small Cell Lung Cancer.
Lyu G et al.·J Cell Mol Med
2025
Effects of the CRYAB gene on stem cell-like properties of colorectal cancer and its mechanism.
Dai A et al.·J Cancer Res Ther
2022Functional
CRYAB is upregulated and predicts clinical prognosis in kidney renal clear cell carcinoma.
Ren H et al.·IUBMB Life
2025
CRYAB stop-loss variant causes rare syndromic dilated cardiomyopathy with congenital cataract: expanding the phenotypic and mutational spectrum of alpha-B crystallinopathy.
Ha C et al.·J Hum Genet
2024
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