CRYGB

protein-coding

crystallin gamma B, 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:

CRYG2

MANE transcript

NM_005210.4

Inheritance

ClinVar variants

P:1U:41B:13

Top phenotype

Cataract 39, multiple types

gnomAD constraint

pLI —, LoF o/e 1.18

Max pathogenic AF

—

Genomic locus

chr2:208,142,573-208,146,158

External References & Databases

Ensembl (ENSG00000182187)

Transcript & Mutation Effects

hg38 • Region Span ~3.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

cataract 39 multiple typesLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0014075

Submitter: G2P

early-onset lamellar cataractSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0018611

Submitter: Orphanet

cataract 39 multiple typesLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0014075

Submitter: Labcorp Genetics (formerly Invitae)

total early-onset cataractSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0021548

Submitter: Orphanet

early-onset anterior polar cataractSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0020373

Submitter: Orphanet

Clinical Genomic Database (CGD)

Cataract 39, multiple typesAD

Manifestation: Ophthalmologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 23288985

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CRYGB variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 32

Cataract 39 multiple typesTotal: 27

CRYGB-related disorderTotal: 5

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005210.4. 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	7 clinvar	2 clinvar	10
missense			38 clinvar	3 clinvar	1 clinvar	42
nonsense			1 clinvar			1
start loss						0
frameshift	1 clinvar		1 clinvar			2
splice donor/acceptor (+/-2bp)						0
Total	1	0	41	10	3	55

Highest pathogenic variant AF is 0.000003097878

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 4 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005210.4	RefSeq	NP_005201.2	3	MANE Select
ENST00000260988.5	Ensembl	ENSP00000260988.4	3	MANE Select
ENST00001139332.1	Ensembl	ENSP00000803086.1	3	Standard
XM_017003402.2	RefSeq	XP_016858891.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

visual perception
lens fiber cell morphogenesis

Molecular Function

structural constituent of eye lens

Cellular Component

cellular_component
nucleus
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000260988
Coding exons: 3
Length: 3596
Individuals with no LoFs: 125714
Homozygous LoFs: 0
Heterozygous LoFs: 33
Defined: 125747
p: 0.000131

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.454	120	107	1.12	0.00000625	1156
Missense (PolyPhen)		33	29.428	1.1214		351
Synonymous	-0.529	44	39.8	1.11	0.00000238	313
Loss of Function	-0.487	10	8.47	1.18	3.61e-7	94

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00037	0.00037	rare
Latino/Admixed American	0.00014	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000088	0.000088	rare
South Asian	0.00025	0.00023	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Crystallins are the dominant structural components of the vertebrate eye lens.;
Disease: DISEASE: Cataract 39, multiple types (CTRCT39) [MIM:615188]: An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function. CTRCT39 includes lamellar, anterior polar, and complete cataracts. {ECO:0000269|PubMed:23288985}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.115

Intolerance Scores

LoFtool: 0.703
RVIS EVS: 0.13
RVIS percentile EVS: 63

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.135

Gene Damage Prediction

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