CRYBA4

Chr 22AD

crystallin beta A4

NCBI Gene: 1413ENSG00000196431UniProt: P53673

Crystallins are the dominant structural components of the vertebrate eye lens

Primary Disease Associations & Inheritance

Cataract 23MIM #610425
AD
UniProtCataract 23, multiple types
259
ClinVar variants
0
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— CRYBA4
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
259 total variants — no pathogenic classifications of 259 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.
1.39LOEUF
pLI 0.000
Z-score 0.41
OE 0.89 (0.59–1.39)
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.
0.69Z-score
OE missense 0.83 (0.70–0.97)
105 obs / 127.0 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.0.89 (0.59–1.39)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.83 (0.70–0.97)
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.1.05
0≤1.21.6
LoF obs/exp: 14 / 15.8Missense obs/exp: 105 / 127.0Syn Z: -0.29

ClinVar Variant Classifications

259 submitted variants in ClinVar

ClinVar

Classification Summary

Protein Context — Lollipop Plot

CRYBA4 · protein map & ClinVar variants

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

Gene2Phenotype Curations

CRYBA4-related cataract with or wihout microcornea or microphthalmia

definitive
ADUndetermined Non-Loss-Of-FunctionAltered Gene Product Structure
Dev. DisordersEye
G2P ↗
missense variantinframe deletioninframe insertion

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Cataract 23

MIM #610425

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Sex differences in the development of experimental diabetic retinopathy.
Chen Y et al.·Sci Rep
2024
A missense mutation in CRYBA4 associated with congenital cataract and microcornea.
Zhou G et al.·Mol Vis
2010
Biochemical characterization of G64W mutant of acidic beta-crystallin 4.
Li W et al.·Exp Eye Res
2019
A novel missense variant c.71G > T (p.Gly24Val) of the CRYBA4 gene contributes to autosomal-dominant congenital cataract in a Chinese family.
Zhang X et al.·Int Ophthalmol
2023
CRYBA4, a novel human cataract gene, is also involved in microphthalmia.
Billingsley G et al.·Am J Hum Genet
2006
In silico analysis and high-risk pathogenic phenotype predictions of non-synonymous single nucleotide polymorphisms in human Crystallin beta A4 gene associated with congenital cataract.
Wang Z et al.·PLoS One
2020
Identification of mutations associated with congenital cataracts in nineteen Chinese families.
Sun HS et al.·BMC Ophthalmol
2025
Partial duplication of the CRYBB1-CRYBA4 locus is associated with autosomal dominant congenital cataract.
Siggs OM et al.·Eur J Hum Genet
2017
Clinical and genetic characteristics of Chinese patients with familial or sporadic pediatric cataract.
Li J et al.·Orphanet J Rare Dis
2018Cohort
Genetics of crystallins: cataract and beyond.
Graw J·Exp Eye Res
2009Review
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