CRYGD

crystallin gamma D, the group of Beta-gamma crystallins

Basic information

Region (hg38): 2:208121607-208124524

Previous symbols: [ "CRYG4" ]

Links

ENSG00000118231 ∙ NCBI:1421 ∙ OMIM:123690 ∙ HGNC:2411 ∙ Uniprot:P07320 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cataract 4 multiple types (Definitive), mode of inheritance: AD
• cataract 4 multiple types (Strong), mode of inheritance: AD
• cataract - microcornea syndrome (Supportive), mode of inheritance: AD
• pulverulent cataract (Supportive), mode of inheritance: AD
• cerulean cataract (Supportive), mode of inheritance: AD
• coralliform cataract (Supportive), mode of inheritance: AD
• early-onset nuclear cataract (Supportive), mode of inheritance: AD
• early-onset lamellar cataract (Supportive), mode of inheritance: AD
• cataract 4 multiple types (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cataract 4, multiple types	AD	General	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	Ophthalmologic	8733140; 10521291; 9927684; 10915766; 12567263; 12011157; 12676897; 17564961; 18587492; 19262743; 19633732; 19668596; 20508808; 21031598; 21552497; 21866214; 22219628; 22669729

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CRYGD gene.

• Aculeiform_cataract (40 variants)
• Cataract_4_multiple_types (32 variants)
• not_provided (24 variants)
• Inborn_genetic_diseases (18 variants)
• CRYGD-related_disorder (15 variants)
• not_specified (4 variants)
• Developmental_cataract (2 variants)
• Joubert_syndrome_17 (1 variants)
• High_myopia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CRYGD gene is commonly pathogenic or not. These statistics are base on transcript: NM_000006891.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	5	2	9
missense	4	4	32	7	3	50
nonsense	2	3			1	6
start loss						0
frameshift		2	3			5
splice donor/acceptor (+/-2bp)			1			1
Total	6	9	38	12	6

Highest pathogenic variant AF is 0.0000020593363

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CRYGD	protein_coding	protein_coding	ENST00000264376	3	2895

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000303	0.591	124179	19	1550	125748	0.00626

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0808	106	108	0.978	0.00000714	1138
Missense in Polyphen		31	27.035	1.1467		336
Synonymous	-0.520	48	43.6	1.10	0.00000287	325
Loss of Function	0.584	6	7.75	0.774	4.10e-7	79

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0327	0.0326
Ashkenazi Jewish	0.00441	0.00428
East Asian	0.00279	0.00278
Finnish	0.000326	0.000323
European (Non-Finnish)	0.00280	0.00274
Middle Eastern	0.00279	0.00278
South Asian	0.00157	0.00154
Other	0.00462	0.00457

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Crystallins are the dominant structural components of the vertebrate eye lens.
• Disease: DISEASE: Cataract 4, multiple types (CTRCT4) [MIM:115700]: 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. CTRCT4 includes crystalline aculeiform, congenital cerulean and non-nuclear polymorphic cataracts, among others. Crystalline aculeiform cataract is characterized by fiberglass-like or needle-like crystals projecting in different directions, through or close to the axial region of the lens. Non- nuclear polymorphic cataract is a partial opacity with variable location between the fetal nucleus of the lens and the equator. The fetal nucleus is normal. The opacities are irregular and look similar to a bunch of grapes and may be present simultaneously in different lens layers. Congenital cerulean cataract is characterized by peripheral bluish and white opacifications organized in concentric layers with occasional central lesions arranged radially. The opacities are observed in the superficial layers of the fetal nucleus as well as the adult nucleus of the lens. Involvement is usually bilateral. Visual acuity is only mildly reduced in childhood. In adulthood, the opacifications may progress, making lens extraction necessary. Histologically the lesions are described as fusiform cavities between lens fibers which contain a deeply staining granular material. Although the lesions may take on various colors, a dull blue is the most common appearance and is responsible for the designation cerulean cataract. {ECO:0000269|PubMed:10521291, ECO:0000269|PubMed:10688888, ECO:0000269|PubMed:10915766, ECO:0000269|PubMed:11371638, ECO:0000269|PubMed:12011157, ECO:0000269|PubMed:12676897, ECO:0000269|PubMed:15709761, ECO:0000269|PubMed:16943771, ECO:0000269|PubMed:17564961, ECO:0000269|PubMed:21031598, ECO:0000269|PubMed:9927684}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.147

Intolerance Scores

• loftool: 0.585
• rvis_EVS: 0.06
• rvis_percentile_EVS: 58.26

Haploinsufficiency Scores

• pHI: 0.290
• hipred: N
• hipred_score: 0.146
• ghis: 0.519

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.204

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Crygd
• Phenotype: vision/eye phenotype

Gene ontology

• Biological process: lens development in camera-type eye;visual perception;cellular response to reactive oxygen species;lens fiber cell differentiation
• Cellular component: nucleus;cytoplasm
• Molecular function: structural constituent of eye lens;protein binding