CRYGB

Summary

CRYGB (crystallin gamma B, HGNC:2409) is a protein-coding gene on chromosome 2q33.3, encoding Gamma-crystallin B (P07316). 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 1419 — RefSeq curated summary.

At a glance

• Gene–disease (curated): early-onset lamellar cataract (Supportive, GenCC) — +3 more curated relationships
• Clinical variants (ClinVar): 66 total — 1 pathogenic
• Phenotypes (HPO): 5
• MANE Select transcript: NM_005210

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2409
Approved symbol	CRYGB
Name	crystallin gamma B
Location	2q33.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000182187
Ensembl biotype	protein_coding
OMIM	123670
Entrez	1419

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000260988

RefSeq mRNA: 1 — MANE Select: NM_005210 NM_005210

CCDS: CCDS2380

Canonical transcript exons

ENST00000260988 — 3 exons

Exon	Start	End
ENSE00000469896	208142573	208142913
ENSE00000796723	208145774	208146016
ENSE00001072773	208146112	208146158

Expression profiles

Bgee: expression breadth broad, 35 present calls, max score 86.40.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0475 / max 81.1007, expressed in 2 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
33432	0.0425	1
33431	0.0049	2

Top tissues by expression

234 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	86.40	silver quality
sperm	CL:0000019	49.88	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
gingival epithelium	UBERON:0001949	42.32	gold quality
vastus lateralis	UBERON:0001379	41.71	gold quality
quadriceps femoris	UBERON:0001377	41.66	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
trigeminal ganglion	UBERON:0001675	41.30	gold quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality
gingiva	UBERON:0001828	41.07	gold quality
mucosa of paranasal sinus	UBERON:0005030	40.98	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
skin of hip	UBERON:0001554	40.49	silver quality
epithelium of nasopharynx	UBERON:0001951	40.45	gold quality
myocardium	UBERON:0002349	40.45	gold quality
germinal epithelium of ovary	UBERON:0001304	40.33	gold quality
esophagus squamous epithelium	UBERON:0006920	40.29	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	40.27	gold quality
jejunum	UBERON:0002115	40.18	gold quality
substantia nigra	UBERON:0002038	40.17	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	40.12	gold quality
midbrain	UBERON:0001891	40.08	gold quality
spinal cord	UBERON:0002240	40.07	gold quality
cartilage tissue	UBERON:0002418	40.06	gold quality
oviduct epithelium	UBERON:0004804	40.03	gold quality
mammary duct	UBERON:0001765	39.98	gold quality
mucosa of sigmoid colon	UBERON:0004993	39.95	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.98

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HSF1, JUN, PGR

Literature-anchored findings (GeneRIF, showing 8)

• In gammaD-crystallin, methylation is exclusively at Cys 110, whereas in gammaC- and gammaB-crystallins, the principal methylation site is Cys 22 with minor methylation at Cys 79 (PMID:12876325)
• Possible sites for posttranslational modifications in gamma B crystallin. (PMID:14517968)
• 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)
• The alphaB-crystallin oligomers formed long-lived stable complexes with their gammaD-crystallin substrates. (PMID:20621668)
• -47C allele of rs2289917 in CRYGB showed the strongest association with cataract. (PMID:21941057)
• Complex heterogeneous mutations in the gammaB crystallin gene have been described resulting in autosomal dominant congenital cataracts with three distinct phenotypes (lamellar, anterior polar, and complete cataracts) in the same family. (PMID:23288985)
• Allelic variant frequency of the gamma-crystallin promoter (g(-47) ->a) affects the level of its expression in platelets from cataract patients. (PMID:26552302)
• Glycation of human gammaB-crystallin (PMID:28013006)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
mus_musculus	Crygb	ENSMUSG00000073658

Paralogs (14): CRYBG3 (ENSG00000080200), CRYBB3 (ENSG00000100053), CRYBB1 (ENSG00000100122), CRYBA1 (ENSG00000108255), CRYBG1 (ENSG00000112297), CRYGD (ENSG00000118231), CRYGN (ENSG00000127377), CRYGC (ENSG00000163254), CRYBA2 (ENSG00000163499), CRYGA (ENSG00000168582), CRYBG2 (ENSG00000176092), CRYBA4 (ENSG00000196431), CRYGS (ENSG00000213139), CRYBB2 (ENSG00000244752)

Protein

Protein identifiers

Gamma-crystallin B — P07316 (reviewed: P07316)

Alternative names: Gamma-B-crystallin, Gamma-crystallin 1-2

All UniProt accessions (1): P07316

UniProt curated annotations — full annotation on UniProt →

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

Subunit / interactions. Monomer.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry.

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_005201* (*=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 (32 total): strand 15, turn 5, domain 4, helix 3, sequence variant 3, chain 1, region of interest 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2JDF	X-RAY DIFFRACTION	1.7
2JDG	X-RAY DIFFRACTION	2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P07316-F1	96.86	0.97

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 70 (showing top): GOBP_LENS_FIBER_CELL_DIFFERENTIATION, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_EPITHELIAL_CELL_DEVELOPMENT, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, BYSTRYKH_HEMATOPOIESIS_STEM_CELL_AND_BRAIN_QTL_TRANS, RYTTCCTG_ETS2_B, GOBP_SENSORY_PERCEPTION, GOBP_SENSORY_ORGAN_DEVELOPMENT, GOBP_SENSORY_ORGAN_MORPHOGENESIS, FOXJ2_02, GOBP_LENS_MORPHOGENESIS_IN_CAMERA_TYPE_EYE, GOBP_CAMERA_TYPE_EYE_MORPHOGENESIS, YNGTTNNNATT_UNKNOWN, TTCNRGNNNNTTC_HSF_Q6

GO Biological Process (5): lens development in camera-type eye (GO:0002088), visual perception (GO:0007601), lens fiber cell morphogenesis (GO:0070309), eye development (GO:0001654), lens fiber cell development (GO:0070307)

GO Molecular Function (2): structural constituent of eye lens (GO:0005212), protein binding (GO:0005515)

GO Cellular Component (2): nucleus (GO:0005634), cytoplasm (GO:0005737)

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
cell morphogenesis	1
lens morphogenesis in camera-type eye	1
lens fiber cell development	1
sensory organ development	1
visual system development	1
epithelial cell development	1
lens fiber cell differentiation	1
structural molecule activity	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

426 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CRYGB	CRYAA	P02489	788
CRYGB	TRNT1	Q96Q11	762
CRYGB	CRYAB	P02511	662
CRYGB	GJA3	Q9Y6H8	650
CRYGB	GJA8	P48165	634
CRYGB	BFSP1	Q12934	602
CRYGB	ASL	P04424	595
CRYGB	BFSP2	Q13515	587
CRYGB	HSPB2	Q16082	515
CRYGB	LIM2	P55344	479
CRYGB	COL3A1	P02461	470
CRYGB	TMEM114	B3SHH9	465
CRYGB	HSPB1	P04792	456
CRYGB	GRIFIN	A4D1Z8	450
CRYGB	HSPB3	Q12988	434

IntAct

4 interactions, top by confidence:

A	B	Type	Score
CRYGC	CRYGB	psi-mi:“MI:0915”(physical association)	0.590
KCNK4	CRYGB	psi-mi:“MI:0914”(association)	0.350

BioGRID (5): CRYGB (Affinity Capture-MS), CRYGB (Affinity Capture-MS), CRYGB (Affinity Capture-MS), CRYGB (Affinity Capture-MS), CRYGB (Affinity Capture-MS)

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

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	36
Likely benign	9
Benign	18

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
41987	NM_005210.4(CRYGB):c.72del (p.Asn25fs)	Pathogenic

SpliceAI

229 predictions. Top by Δscore:

Variant	Effect	Δscore
2:208145770:TCA:T	donor_loss	1.0000
2:208145771:CA:C	donor_loss	1.0000
2:208145772:A:AC	donor_gain	1.0000
2:208145773:C:CG	donor_gain	1.0000
2:208145773:CCG:C	donor_gain	1.0000
2:208145773:CCGG:C	donor_gain	1.0000
2:208145773:CCGGG:C	donor_gain	1.0000
2:208142913:GC:G	acceptor_loss	0.9900
2:208142914:C:CA	acceptor_loss	0.9900
2:208142919:G:GC	acceptor_gain	0.9900
2:208142923:C:CT	acceptor_gain	0.9900
2:208142934:C:CT	acceptor_gain	0.9900
2:208145772:AC:A	donor_gain	0.9900
2:208145773:CC:C	donor_gain	0.9900
2:208146107:CTTA:C	donor_loss	0.9900
2:208146108:TTA:T	donor_loss	0.9900
2:208146109:TA:T	donor_loss	0.9900
2:208146111:C:G	donor_loss	0.9900
2:208142909:GAGTG:G	acceptor_gain	0.9800
2:208142910:AGTG:A	acceptor_gain	0.9800
2:208142911:GTG:G	acceptor_gain	0.9800
2:208142912:TG:T	acceptor_gain	0.9800
2:208142914:C:CC	acceptor_gain	0.9800
2:208142919:G:C	acceptor_gain	0.9800
2:208142924:A:T	acceptor_gain	0.9800
2:208142927:C:CT	acceptor_gain	0.9800
2:208142928:A:T	acceptor_gain	0.9800
2:208142936:C:CT	acceptor_gain	0.9800
2:208142937:A:T	acceptor_gain	0.9800
2:208142941:G:GC	acceptor_gain	0.9800

AlphaMissense

1165 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:208142772:A:G	W132R	0.995
2:208142772:A:T	W132R	0.995
2:208145923:A:G	S35P	0.994
2:208145899:A:G	W43R	0.989
2:208145899:A:T	W43R	0.989
2:208145922:G:A	S35F	0.988
2:208145986:C:G	G14R	0.987
2:208145927:G:C	C33W	0.985
2:208145929:A:G	C33R	0.985
2:208146009:A:G	F6S	0.985
2:208145928:C:T	C33Y	0.984
2:208142742:C:G	G142R	0.983
2:208142742:C:T	G142R	0.983
2:208145821:A:G	W69R	0.983
2:208145821:A:T	W69R	0.983
2:208145869:C:G	G53R	0.983
2:208145890:A:C	Y46D	0.983
2:208145990:G:C	F12L	0.983
2:208145990:G:T	F12L	0.983
2:208145992:A:G	F12L	0.983
2:208142741:C:T	G142E	0.982
2:208142694:A:G	W158R	0.981
2:208142694:A:T	W158R	0.981
2:208142741:C:A	G142V	0.981
2:208142778:C:G	G130R	0.981
2:208145986:C:A	G14C	0.981
2:208146007:A:C	Y7D	0.980
2:208145853:A:G	L58P	0.979
2:208145985:C:A	G14V	0.979
2:208142667:A:G	S167P	0.978

dbSNP variants (sampled 300 via entrez): RS1000752205 (2:208143694 G>A,T), RS1000831739 (2:208145411 G>A), RS1001101187 (2:208143428 G>A), RS1001534127 (2:208145305 C>A,G,T), RS1001920488 (2:208144169 C>A,T), RS1001984945 (2:208145461 G>A), RS1002374426 (2:208144517 C>T), RS1002605806 (2:208146906 C>T), RS1003969555 (2:208145335 C>A,T), RS1004397474 (2:208147407 C>T), RS1004449627 (2:208147714 T>A,C), RS1004734604 (2:208145917 T>C,G), RS1004783980 (2:208146273 G>A), RS1005307731 (2:208146222 C>A), RS1006319741 (2:208143014 C>A,G,T)

Disease associations

OMIM: gene MIM:123670 | disease phenotypes: MIM:615188

GenCC curated gene-disease

Disease	Classification	Inheritance
early-onset lamellar cataract	Supportive	Autosomal dominant
early-onset anterior polar cataract	Supportive	Autosomal dominant
total early-onset cataract	Supportive	Autosomal dominant
cataract 39 multiple types	Limited	Autosomal dominant

Mondo (4): cataract 39 multiple types (MONDO:0014075), early-onset lamellar cataract (MONDO:0018611), early-onset anterior polar cataract (MONDO:0020373), total early-onset cataract (MONDO:0021548)

Orphanet (1): Early onset non-syndromic cataract (Orphanet:91492)

HPO phenotypes

5 total (5 of 5 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000519	Developmental cataract
HP:0001134	Anterior polar cataract
HP:0003577	Congenital onset
HP:0007971	Lamellar cataract

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

2 total (human), top 2 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
pirinixic acid	increases activity, affects binding, decreases expression	1
Benzo(a)pyrene	increases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT06068348	Not specified	ACTIVE_NOT_RECRUITING	Liquid Biopsy Collection Study