CRYGA

Summary

CRYGA (crystallin gamma A, HGNC:2408) is a protein-coding gene on chromosome 2q33.3, encoding Gamma-crystallin A (P11844). Crystallins are the dominant structural components of the vertebrate eye lens.

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.

Source: NCBI Gene 1418 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 49 total
• MANE Select transcript: NM_014617

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2408
Approved symbol	CRYGA
Name	crystallin gamma A
Location	2q33.3
Locus type	gene with protein product
Status	Approved
Aliases	CRYG5, CRY-g-A
Ensembl gene	ENSG00000168582
Ensembl biotype	protein_coding
OMIM	123660
Entrez	1418

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000304502

RefSeq mRNA: 1 — MANE Select: NM_014617 NM_014617

CCDS: CCDS33367

Canonical transcript exons

ENST00000304502 — 3 exons

Exon	Start	End
ENSE00001124023	208160740	208161076
ENSE00001124032	208163204	208163446
ENSE00001284812	208163548	208163589

Expression profiles

Bgee: expression breadth broad, 35 present calls, max score 83.13.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1376 / max 249.4038, expressed in 1 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
33433	0.1376	1

Top tissues by expression

241 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.13	gold quality
buccal mucosa cell	CL:0002336	62.15	gold quality
Brodmann (1909) area 9	UBERON:0013540	46.94	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	45.18	gold quality
prefrontal cortex	UBERON:0000451	44.00	gold quality
nucleus accumbens	UBERON:0001882	43.96	gold quality
anterior cingulate cortex	UBERON:0009835	43.40	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
frontal cortex	UBERON:0001870	42.97	gold quality
right frontal lobe	UBERON:0002810	42.97	gold quality
neocortex	UBERON:0001950	42.85	gold quality
primary visual cortex	UBERON:0002436	42.61	silver quality
secondary oocyte	CL:0000655	42.57	gold quality
putamen	UBERON:0001874	42.28	gold quality
cerebral cortex	UBERON:0000956	42.25	gold quality
occipital lobe	UBERON:0002021	41.89	silver quality
superior frontal gyrus	UBERON:0002661	41.77	silver quality
vastus lateralis	UBERON:0001379	41.41	gold quality
quadriceps femoris	UBERON:0001377	41.37	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
skin of hip	UBERON:0001554	41.11	silver quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality
mucosa of paranasal sinus	UBERON:0005030	40.98	gold quality
amygdala	UBERON:0001876	40.75	gold quality
amniotic fluid	UBERON:0000173	40.69	gold quality
jejunal mucosa	UBERON:0000399	40.59	gold quality
biceps brachii	UBERON:0001507	40.57	gold quality
epithelium of nasopharynx	UBERON:0001951	40.45	gold quality
myocardium	UBERON:0002349	40.45	gold quality
gingival epithelium	UBERON:0001949	40.43	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.80

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HSF1

Literature-anchored findings (GeneRIF, showing 4)

• This study establishes baseline frequency data for four SNPs in CRYGA and CRYGB genes for future case control studies on the role of these SNPs in the genetic basis of cataract. (PMID:19384013)
• Studies show that The major proteins in the lens–alpha, beta, and gamma-crystallins–are constantly subjected to age-related changes. (PMID:19463898)
• Cataract-causing mutation R48C increases gammaA-crystallin susceptibility to oxidative stress and ultraviolet radiation. (PMID:34826455)
• A novel cataract-causing mutation Ile82Met of gammaA crystallin trends to aggregate with unfolding intermediate. (PMID:35513103)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cryga	ENSMUSG00000044429
rattus_norvegicus	Cryga	ENSRNOG00000046343

Paralogs (14): CRYBG3 (ENSG00000080200), CRYBB3 (ENSG00000100053), CRYBB1 (ENSG00000100122), CRYBA1 (ENSG00000108255), CRYBG1 (ENSG00000112297), CRYGD (ENSG00000118231), CRYGN (ENSG00000127377), CRYGC (ENSG00000163254), CRYBA2 (ENSG00000163499), CRYBG2 (ENSG00000176092), CRYGB (ENSG00000182187), CRYBA4 (ENSG00000196431), CRYGS (ENSG00000213139), CRYBB2 (ENSG00000244752)

Protein

Protein identifiers

Gamma-crystallin A — P11844 (reviewed: P11844)

Alternative names: Gamma-A-crystallin, Gamma-crystallin 5

All UniProt accessions (2): P11844, A0A0S2A4T3

UniProt curated annotations — full annotation on UniProt →

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

Subunit / interactions. Monomer.

Domain organisation. Has a two-domain beta-structure, folded into four very similar Greek key motifs.

Similarity. Belongs to the beta/gamma-crystallin family.

RefSeq proteins (1): NP_055432* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001064	Beta/gamma_crystallin	Domain
IPR011024	G_crystallin-like	Homologous_superfamily
IPR050252	Beta/Gamma-Crystallin	Family

Pfam: PF00030

UniProt features (9 total): domain 4, sequence variant 3, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P11844-F1	96.14	0.95

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 44 (showing top): GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, MODULE_99, GOBP_SENSORY_PERCEPTION, GOBP_SENSORY_ORGAN_DEVELOPMENT, MODULE_287, LEE_AGING_CEREBELLUM_DN, MODULE_48, MODULE_95, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, GOBP_LENS_DEVELOPMENT_IN_CAMERA_TYPE_EYE, GOMF_STRUCTURAL_CONSTITUENT_OF_EYE_LENS, MODULE_248, YOSHIMURA_MAPK8_TARGETS_UP, GOMF_STRUCTURAL_MOLECULE_ACTIVITY, MIKKELSEN_IPS_HCP_WITH_H3_UNMETHYLATED

GO Biological Process (3): lens development in camera-type eye (GO:0002088), visual perception (GO:0007601), eye development (GO:0001654)

GO Molecular Function (1): structural constituent of eye lens (GO:0005212)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
camera-type eye development	1
anatomical structure development	1
sensory perception of light stimulus	1
sensory organ development	1
visual system development	1
structural molecule activity	1

Protein interactions and networks

STRING

388 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CRYGA	CRYAA	P02489	932
CRYGA	GJA8	P48165	655
CRYGA	TRNT1	Q96Q11	650
CRYGA	MYL1	P05976	649
CRYGA	GJA3	Q9Y6H8	633
CRYGA	BFSP2	Q13515	615
CRYGA	BFSP1	Q12934	613
CRYGA	TMEM114	B3SHH9	573
CRYGA	CRYAB	P02511	569
CRYGA	LIM2	P55344	506
CRYGA	GCNT2	Q8N0V5	505
CRYGA	GRIFIN	A4D1Z8	482
CRYGA	HSPB1	P04792	468
CRYGA	ASL	P04424	466
CRYGA	HSPB2	Q16082	459

IntAct

0 interactions, top by confidence:

BioGRID (6): TRAF1 (Two-hybrid), CRYGA (Two-hybrid), CRYGA (Two-hybrid), CRYGA (Two-hybrid), PSMB9 (Two-hybrid), CRYGA (Co-fractionation)

ESM2 similar proteins: A2IBY7, A3RLD7, A3RLD8, A3RLE1, A4L9I8, O35486, P02527, P02528, P02529, P02530, P02531, P04342, P04344, P04345, P06504, P07315, P07316, P07320, P08209, P0C5E9, P10065, P10066, P10067, P10068, P10112, P11844, P22914, P23005, P26444, P48646, P48647, P48649, P49152, P53673, P55164, P55940, P55941, Q03740, Q06254, Q06255

Diamond homologs: A2IBH5, A2IBY7, A2ICR5, A3RLD7, A3RLD8, A3RLE1, A3RLE2, A4L9I8, A4L9I9, A4QNB6, D3ZEG1, F6Q2R9, O35486, P02522, P02523, P02524, P02525, P02526, P02527, P02528, P02529, P02530, P02531, P04342, P04344, P04345, P05813, P06504, P07315, P07316, P07317, P07318, P07320, P07530, P08209, P0C5E9, P10042, P10043, P10065, P10066

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

49 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	41
Likely benign	4
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

253 predictions. Top by Δscore:

Variant	Effect	Δscore
2:208163202:A:AC	donor_gain	1.0000
2:208163203:C:CC	donor_gain	1.0000
2:208161072:CTGGT:C	acceptor_gain	0.9800
2:208161075:GTCTG:G	acceptor_loss	0.9800
2:208161076:TC:T	acceptor_loss	0.9800
2:208161077:C:CA	acceptor_loss	0.9800
2:208161078:T:C	acceptor_loss	0.9800
2:208161082:A:C	acceptor_gain	0.9800
2:208161088:A:AC	acceptor_gain	0.9800
2:208161073:TGGT:T	acceptor_gain	0.9700
2:208161074:GGT:G	acceptor_gain	0.9700
2:208161077:C:CC	acceptor_gain	0.9700
2:208161081:CA:C	acceptor_gain	0.9700
2:208161082:A:AC	acceptor_gain	0.9700
2:208161086:C:CT	acceptor_gain	0.9700
2:208161087:A:T	acceptor_gain	0.9700
2:208161088:A:C	acceptor_gain	0.9600
2:208161075:GT:G	acceptor_gain	0.9500
2:208163195:AAGAC:A	donor_loss	0.9500
2:208163196:AGACT:A	donor_loss	0.9500
2:208163197:GACT:G	donor_loss	0.9500
2:208163198:AC:A	donor_loss	0.9500
2:208163199:CTC:C	donor_loss	0.9500
2:208163200:TC:T	donor_loss	0.9500
2:208163201:C:CG	donor_loss	0.9500
2:208163202:A:AT	donor_loss	0.9500
2:208163203:C:A	donor_loss	0.9500
2:208163447:C:CC	acceptor_gain	0.9500
2:208163203:CATG:C	donor_gain	0.9400
2:208163452:G:C	acceptor_gain	0.9400

AlphaMissense

1138 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:208160938:A:G	W131R	0.962
2:208160938:A:T	W131R	0.962
2:208163353:A:G	S35P	0.957
2:208163329:A:G	W43R	0.951
2:208163329:A:T	W43R	0.951
2:208160936:C:A	W131C	0.945
2:208160936:C:G	W131C	0.945
2:208163420:A:C	F12L	0.942
2:208163420:A:T	F12L	0.942
2:208163422:A:G	F12L	0.942
2:208163221:A:G	C79R	0.939
2:208160860:A:G	W157R	0.932
2:208160860:A:T	W157R	0.932
2:208163322:A:T	L45H	0.928
2:208163352:G:A	S35F	0.928
2:208163445:A:G	I4T	0.928
2:208163439:A:G	F6S	0.925
2:208160944:C:G	G129R	0.916
2:208160934:A:T	V132D	0.912
2:208163416:C:A	G14C	0.911
2:208160858:C:A	W157C	0.909
2:208160858:C:G	W157C	0.909
2:208163251:A:G	W69R	0.909
2:208163251:A:T	W69R	0.909
2:208161060:A:G	L90S	0.906
2:208163359:A:G	C33R	0.904
2:208163346:C:G	R37P	0.903
2:208163445:A:C	I4S	0.903
2:208163219:G:C	C79W	0.901
2:208160833:A:G	S166P	0.900

dbSNP variants (sampled 300 via entrez): RS1000208666 (2:208160726 C>A,G), RS1000905478 (2:208160448 C>A,G,T), RS1000953143 (2:208161736 G>A), RS1001389914 (2:208161001 C>T), RS1001442791 (2:208160660 T>C), RS1003052650 (2:208162148 G>A,C), RS1003172031 (2:208162207 G>A), RS1003790668 (2:208161954 T>C), RS1004348112 (2:208160366 G>A,T), RS1005488989 (2:208162860 T>C), RS1006077279 (2:208164271 A>G), RS1006437983 (2:208163941 T>A,C), RS1006881873 (2:208162419 G>C), RS1007026802 (2:208160382 G>A,T), RS1007257710 (2:208164752 A>G)

Disease associations

OMIM: gene MIM:123660 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
tebuconazole	decreases expression	1
CGP 52608	affects binding, increases reaction	1
Resveratrol	affects cotreatment, decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.