CRYGA

protein-coding

crystallin gamma A, the group of Beta-gamma crystallins

Gene summary

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. Four gamma-crystallin genes (gamma-A through gamma-D) and three pseudogenes (gamma-E, gamma-F, gamma-G) are tandemly organized in a genomic segment as a gene cluster. Whether due to aging or mutations in specific genes, gamma-crystallins have been involved in cataract formation. [provided by RefSeq, Jul 2008]

Previous symbols:

CRYG1

MANE transcript

NM_014617.4

Inheritance

—

ClinVar variants

U:41B:8

Top phenotype

CRYGA-related disorder

gnomAD constraint

pLI —, LoF o/e 1.22

Max pathogenic AF

—

Genomic locus

chr2:208,160,740-208,163,589

External References & Databases

Ensembl (ENSG00000168582)

Transcript & Mutation Effects

hg38 • Region Span ~2.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CRYGA variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 41

CRYGA-related disorderTotal: 6

not providedTotal: 2

Developmental cataractTotal: 1

See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014617.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				1 clinvar	1 clinvar	2
missense			41 clinvar	4 clinvar	1 clinvar	46
nonsense					1 clinvar	1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	41	5	3	49

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014617.4	RefSeq	NP_055432.2	3	MANE Select
ENST00000304502.5	Ensembl	ENSP00000302105.4	3	MANE Select

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

lens development in camera-type eye
visual perception

Molecular Function

structural constituent of eye lens

Cellular Component

cellular_component

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000304502
Coding exons: 3
Length: 2837
Individuals with no LoFs: 124900
Homozygous LoFs: 16
Heterozygous LoFs: 830
Defined: 125746
p: 0.00337

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.651	136	116	1.17	0.00000782	1134
Missense (PolyPhen)		49	35.988	1.3615		386
Synonymous	-0.326	49	46.2	1.06	0.00000306	329
Loss of Function	-0.677	13	10.6	1.22	7.10e-7	92

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00074	0.00074	rare
Latino/Admixed American	0.023	0.023	notable
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00033	0.00033	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00018	0.00018	rare
South Asian	0.00013	0.00013	rare
Other	0.0033	0.0033	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Crystallins are the dominant structural components of the vertebrate eye lens.;

Recessive Scores

pRec: 0.137

Intolerance Scores

LoFtool: 0.692
RVIS EVS: 0.02
RVIS percentile EVS: 55.22

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.307

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium