CRYGC

Chr 2AD

crystallin gamma C

Also known as: CCL, CRYG3, CTRCT2

NCBI Gene: 1420ENSG00000163254UniProt: P07315

This gene encodes a member of the beta/gamma-crystallin family of proteins. Crystallins constitute the major proteins of vertebrate eye lens and maintain the transparency and refractive index of the lens. This gene and several family members are present in a gene cluster on chromosome 2. Mutations in this gene have been shown to cause multiple types of cataract, including Coppock-like cataract and zonular pulverulent cataract, among others. [provided by RefSeq, Jan 2015]

Primary Disease Associations & Inheritance

Cataract 2, multiple typesMIM #604307
AD
145
ClinVar variants
51
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— CRYGC
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
51 Pathogenic / Likely Pathogenic· 60 VUS of 145 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.
1.31LOEUF
pLI 0.001
Z-score 0.93
OE 0.67 (0.36–1.31)
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.
-0.60Z-score
OE missense 1.16 (1.01–1.35)
127 obs / 109.2 exp
Tolerant

Tolerant to missense variation

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.0.67 (0.36–1.31)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.16 (1.01–1.35)
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.1.12
0≤1.21.6
LoF obs/exp: 6 / 9.0Missense obs/exp: 127 / 109.2Syn Z: -0.63

ClinVar Variant Classifications

145 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic42
Likely Pathogenic9
VUS60
Likely Benign15
Benign13
Conflicting5
42
Pathogenic
9
Likely Pathogenic
60
VUS
15
Likely Benign
13
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
7
3
32
0
42
Likely Pathogenic
2
1
6
0
9
VUS
5
44
11
0
60
Likely Benign
0
3
9
3
15
Benign
0
2
7
4
13
Conflicting
—5
Total1453657144

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

View in ClinVar →

Protein Context — Lollipop Plot

CRYGC · protein map & ClinVar variants

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

Gene2Phenotype Curations

CRYGC-related congenital cataract

definitive
ADLoss Of FunctionAbsent Gene Product
Dev. DisordersEye
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Cataract 2, multiple types

MIM #604307

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genetic architecture of congenital cataracts: correlation of pathogenic variants with morphology and clinical outcomes.
Guo D et al.·Prog Retin Eye Res
2025Review
Microphthalmia and anterior segment dysgenesis due to a double gene variant in GJA8 and CRYGC.
Zhou L et al.·Eur J Ophthalmol
2024Case report
Novel CRYGC Mutation in Conserved Ultraviolet-Protective Tryptophan (p.Trp131Arg) Is Linked to Autosomal Dominant Congenital Cataract.
Delas F et al.·Int J Mol Sci
2023Case report
A nonsense mutation in CRYGC associated with autosomal dominant congenital nuclear cataract in a Chinese family.
Yao K et al.·Mol Vis
2008
Mutation analysis of CRYAA, CRYGC, and CRYGD associated with autosomal dominant congenital cataract in Brazilian families.
Santana A et al.·Mol Vis
2009
Genome sequencing reveals novel variants in a diverse population with congenital anterior segment anomalies.
Hussain A et al.·Sci Rep
2025
The genetic landscape of crystallins in congenital cataract.
Berry V et al.·Orphanet J Rare Dis
2020
Mutation screening and genotype phenotype correlation of α-crystallin, γ-crystallin and GJA8 gene in congenital cataract.
Kumar M et al.·Mol Vis
2011
A novel CRYGC E128* mutation underlying an autosomal dominant nuclear cataract in a south Indian kindred.
Kandaswamy DK et al.·Ophthalmic Genet
2020Case report
Genetic Analysis in a Swiss Cohort of Bilateral Congenital Cataract.
Rechsteiner D et al.·JAMA Ophthalmol
2021Cohort
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