CRYGS

Chr 3

crystallin gamma S

Also known as: CRYG8, CTRCT20

Crystallins are separated into two classes: taxon-specific, or enzyme, and ubiquitous. The latter class constitutes the major proteins of vertebrate eye lens and maintains the transparency and refractive index of the lens. Since lens central fiber cells lose their nuclei during development, these crystallins are made and then retained throughout life, making them extremely stable proteins. Mammalian lens crystallins are divided into alpha, beta, and gamma families; beta and gamma crystallins are also considered as a superfamily. Alpha and beta families are further divided into acidic and basic groups. Seven protein regions exist in crystallins: four homologous motifs, a connecting peptide, and N- and C-terminal extensions. Gamma-crystallins are a homogeneous group of highly symmetrical, monomeric proteins typically lacking connecting peptides and terminal extensions. They are differentially regulated after early development. This gene encodes a protein initially considered to be a beta-crystallin but the encoded protein is monomeric and has greater sequence similarity to other gamma-crystallins. This gene encodes the most significant gamma-crystallin in adult eye lens tissue. Whether due to aging or mutations in specific genes, gamma-crystallins have been involved in cataract formation. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…
LOFmechanismLOEUF 0.98
Clinical SummaryCRYGS
Population Constraint (gnomAD)
Low constraint (pLI 0.02) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
7 unique Pathogenic / Likely Pathogenic· 43 VUS of 68 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
0.98LOEUF
pLI 0.023
Z-score 1.62
OE 0.43 (0.210.98)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
0.24Z-score
OE missense 0.93 (0.801.10)
102 obs / 109.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.43 (0.210.98)
00.351.4
Missense OE?0.93 (0.801.10)
00.61.4
Synonymous OE?0.76
01.21.6
LoF obs/exp: 4 / 9.3Missense obs/exp: 102 / 109.1Syn Z: 1.11
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveCRYGS-related cataract, multiple typesLOFAD

This gene — mechanism propensity

DN
0.75top 25%
GOF
0.4184th %ile
LOF
0.3549th %ile

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

DNprediction above median

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.

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

ClinVar Variant Classifications

68 submitted variants in ClinVar

Classification Summary

Pathogenic4
Likely Pathogenic3
VUS43
Likely Benign8
Benign6
Conflicting3
4
Pathogenic
3
Likely Pathogenic
43
VUS
8
Likely Benign
6
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
4
0
0
4
Likely Pathogenic
0
3
0
0
3
VUS
2
40
1
0
43
Likely Benign
0
1
5
2
8
Benign
0
0
4
2
6
Conflicting
3
Total24810467

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

View in ClinVar →

40 pathogenic / likely-pathogenic (of 45) ClinVar copy-number / structural variants overlap CRYGS — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

CRYGS · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →