CRYBA2

Summary

CRYBA2 (crystallin beta A2, HGNC:2395) is a protein-coding gene on chromosome 2q35, encoding Beta-crystallin A2 (P53672). 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 the vertebrate eye, which function to maintain 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 defined 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. Beta-crystallins, the most heterogeneous, differ by the presence of the C-terminal extension (present in the basic group but absent in the acidic group). Beta-crystallins form aggregates of different sizes and are able to form homodimers through self-association or heterodimers with other beta-crystallins. This gene is a beta acidic group member. Three alternatively spliced transcript variants encoding identical proteins have been reported.

Source: NCBI Gene 1412 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cataract 42 (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 6
• Clinical variants (ClinVar): 45 total
• Phenotypes (HPO): 7
• MANE Select transcript: NM_057093

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2395
Approved symbol	CRYBA2
Name	crystallin beta A2
Location	2q35
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000163499
Ensembl biotype	protein_coding
OMIM	600836
Entrez	1412

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000295728, ENST00000392096, ENST00000453769, ENST00000487181, ENST00000490678, ENST00000496566, ENST00000941879, ENST00000941880

RefSeq mRNA: 2 — MANE Select: NM_057093 NM_057093, NM_057094

CCDS: CCDS2429

Canonical transcript exons

ENST00000295728 — 4 exons

Exon	Start	End
ENSE00001075316	218992102	218992243
ENSE00001349578	218993016	218993422
ENSE00003556851	218990852	218990994
ENSE00003589095	218990190	218990399

Expression profiles

Bgee: expression breadth ubiquitous, 128 present calls, max score 95.22.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3861 / max 230.5905, expressed in 74 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
34008	0.3861	74

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
islet of Langerhans	UBERON:0000006	95.22	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.62	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.93	gold quality
adenohypophysis	UBERON:0002196	85.19	gold quality
pancreas	UBERON:0001264	84.92	gold quality
pituitary gland	UBERON:0000007	83.76	gold quality
body of pancreas	UBERON:0001150	82.24	gold quality
mucosa of transverse colon	UBERON:0004991	75.17	gold quality
lower esophagus mucosa	UBERON:0035834	74.89	gold quality
rectum	UBERON:0001052	74.72	gold quality
right testis	UBERON:0004534	70.18	gold quality
left testis	UBERON:0004533	69.44	gold quality
testis	UBERON:0000473	66.39	gold quality
small intestine Peyer’s patch	UBERON:0003454	65.41	gold quality
body of stomach	UBERON:0001161	64.62	gold quality
putamen	UBERON:0001874	63.61	gold quality
small intestine	UBERON:0002108	63.50	gold quality
transverse colon	UBERON:0001157	63.24	gold quality
duodenum	UBERON:0002114	60.94	gold quality
stomach	UBERON:0000945	60.79	gold quality
mucosa of sigmoid colon	UBERON:0004993	60.63	gold quality
fundus of stomach	UBERON:0001160	60.44	gold quality
caudate nucleus	UBERON:0001873	59.27	gold quality
anterior cingulate cortex	UBERON:0009835	58.81	gold quality
cingulate cortex	UBERON:0003027	58.77	gold quality
Brodmann (1909) area 9	UBERON:0013540	58.50	gold quality
right frontal lobe	UBERON:0002810	58.00	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	56.85	gold quality
colonic mucosa	UBERON:0000317	56.41	gold quality
intestine	UBERON:0000160	56.11	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-MTAB-5061	yes	3234.62
E-GEOD-81547	yes	2954.61
E-HCAD-31	yes	2039.48
E-GEOD-125970	yes	1259.92
E-GEOD-81608	yes	226.60
E-GEOD-83139	yes	156.75
E-ENAD-27	yes	13.03
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 4)

• RhoGAP19D inhibits Cdc42 laterally to control epithelial cell shape and prevent invasion. (PMID:33646271)
• The cell-stress molecules alphaB-crystallin and iNOS are overexpressed in GNE myopathy muscle and may identify early disease mechanisms. (PMID:23496965)
• Whole exome sequencing in dominant cataract identifies a new causative factor, CRYBA2, and a variety of novel alleles in known genes. (PMID:23508780)
• A novel missense mutation in the CRYBA2 caused autosomal dominant presenile cataract in a Chinese family. (PMID:37438446)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cryba2a	ENSDARG00000030349
danio_rerio	cryba2b	ENSDARG00000041925
mus_musculus	Cryba2	ENSMUSG00000006546
rattus_norvegicus	Cryba2	ENSRNOG00000017996

Paralogs (14): CRYBG3 (ENSG00000080200), CRYBB3 (ENSG00000100053), CRYBB1 (ENSG00000100122), CRYBA1 (ENSG00000108255), CRYBG1 (ENSG00000112297), CRYGD (ENSG00000118231), CRYGN (ENSG00000127377), CRYGC (ENSG00000163254), CRYGA (ENSG00000168582), CRYBG2 (ENSG00000176092), CRYGB (ENSG00000182187), CRYBA4 (ENSG00000196431), CRYGS (ENSG00000213139), CRYBB2 (ENSG00000244752)

Protein

Protein identifiers

Beta-crystallin A2 — P53672 (reviewed: P53672)

Alternative names: Beta-A2 crystallin

All UniProt accessions (2): P53672, C9JDH2

UniProt curated annotations — full annotation on UniProt →

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

Subunit / interactions. Homo/heterodimer, or complexes of higher-order. The structure of beta-crystallin oligomers seems to be stabilized through interactions between the N-terminal arms.

Disease relevance. Cataract 42 (CTRCT42) [MIM:115900] 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. 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 (2): NP_476434, NP_476435 (=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 (10 total): domain 4, region of interest 2, sequence variant 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P53672-F1	93.12	0.88

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 76 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, BENPORATH_ES_WITH_H3K27ME3, PEREZ_TP63_TARGETS, GGGTGGRR_PAX4_03, AP1_Q4_01, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, BACH2_01, TGANTCA_AP1_C, NRF2_Q4, GOBP_SENSORY_PERCEPTION, SABATES_COLORECTAL_ADENOMA_DN, GOBP_SENSORY_ORGAN_DEVELOPMENT, GOBP_LENS_DEVELOPMENT_IN_CAMERA_TYPE_EYE, NRSF_01, AP1FJ_Q2

GO Biological Process (2): lens development in camera-type eye (GO:0002088), visual perception (GO:0007601)

GO Molecular Function (3): structural constituent of eye lens (GO:0005212), identical protein binding (GO:0042802), protein binding (GO:0005515)

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
structural molecule activity	1
protein binding	1
binding	1

Protein interactions and networks

STRING

624 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CRYBA2	CRYAB	P02511	720
CRYBA2	BFSP1	Q12934	716
CRYBA2	CRYAA	P02489	706
CRYBA2	GJA3	Q9Y6H8	600
CRYBA2	CFAP65	Q6ZU64	599
CRYBA2	GJA8	P48165	577
CRYBA2	BFSP2	Q13515	569
CRYBA2	GRIFIN	A4D1Z8	512
CRYBA2	LGSN	Q5TDP6	490
CRYBA2	LIM2	P55344	480
CRYBA2	FOXE3	Q13461	469
CRYBA2	MAK16	Q9BXY0	435
CRYBA2	PITX3	O75364	413
CRYBA2	IFT38	Q96AJ1	413
CRYBA2	UBB	P02248	411

IntAct

108 interactions, top by confidence:

A	B	Type	Score
CRYBA2	TRIP13	psi-mi:“MI:0915”(physical association)	0.700
CRYBA2	ATXN1	psi-mi:“MI:0915”(physical association)	0.610
ATXN1	CRYBA2	psi-mi:“MI:0915”(physical association)	0.610
CRYBA2	LASP1	psi-mi:“MI:0915”(physical association)	0.600
LASP1	CRYBA2	psi-mi:“MI:0915”(physical association)	0.600
PIK3R3	CRYBA2	psi-mi:“MI:0915”(physical association)	0.570
CRYBA2	PIK3R3	psi-mi:“MI:0915”(physical association)	0.570
CRYBA2	TRAF2	psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	CRYBA2	psi-mi:“MI:0915”(physical association)	0.560
CRYBA2	VAC14	psi-mi:“MI:0915”(physical association)	0.560
CRYBA2	OXER1	psi-mi:“MI:0915”(physical association)	0.560
CRYBA2	C22orf39	psi-mi:“MI:0915”(physical association)	0.560
	CRYBA2	psi-mi:“MI:0915”(physical association)	0.560
CRYBA2	BPIFA1	psi-mi:“MI:0915”(physical association)	0.560
CRYBA2	UNKL	psi-mi:“MI:0915”(physical association)	0.560
CRYBA2	KRTAP11-1	psi-mi:“MI:0915”(physical association)	0.560
CRYBA2	RUSC1	psi-mi:“MI:0915”(physical association)	0.560
CRYBA2	FHL3	psi-mi:“MI:0915”(physical association)	0.560
CRYBA2	C10orf55	psi-mi:“MI:0915”(physical association)	0.560
CRYBA2	ARID5A	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (27): CALCOCO1 (Two-hybrid), CRYBA2 (Two-hybrid), CRYBA2 (Affinity Capture-Luminescence), CRYBA2 (Two-hybrid), CRYBA2 (Two-hybrid), CRYBA2 (Two-hybrid), CRYBA2 (Two-hybrid), CRYBA2 (Two-hybrid), CRYBA2 (Two-hybrid), CRYBA2 (Two-hybrid), CRYBA2 (Two-hybrid), CRYBA2 (Two-hybrid), CRYBA2 (Two-hybrid), CRYBA2 (Two-hybrid), CRYBA2 (Two-hybrid)

ESM2 similar proteins: A2IBH5, A2IBY7, A3KGF7, A4D1Z8, A8MX76, E7F9T0, F6Q2R9, O88644, O89040, P02522, P02523, P02524, P07318, P07530, P13943, P19141, P26998, P43320, P49221, P50281, P53672, P53674, P53690, P55165, P62696, P62697, P62698, Q007T1, Q05714, Q10739, Q2LEC2, Q3UW68, Q4V8Q1, Q5BK10, Q5EF38, Q5RES1, Q6J756, Q6MZZ7, Q91318, Q91320

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	4
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

691 predictions. Top by Δscore:

Variant	Effect	Δscore
2:218990850:A:AC	donor_gain	1.0000
2:218990851:C:CC	donor_gain	1.0000
2:218990851:CG:C	donor_gain	1.0000
2:218990882:T:TA	donor_gain	1.0000
2:218990995:C:CC	acceptor_gain	1.0000
2:218991001:C:CT	acceptor_gain	1.0000
2:218991004:A:T	acceptor_gain	1.0000
2:218991012:C:CT	acceptor_gain	1.0000
2:218992096:GCTCA:G	donor_loss	1.0000
2:218992097:CTCA:C	donor_loss	1.0000
2:218992098:TCACC:T	donor_loss	1.0000
2:218992099:CACCG:C	donor_loss	1.0000
2:218992100:A:AC	donor_gain	1.0000
2:218992100:A:AT	donor_loss	1.0000
2:218992101:C:CA	donor_loss	1.0000
2:218992101:C:CC	donor_gain	1.0000
2:218992101:CCG:C	donor_gain	1.0000
2:218992101:CCGCG:C	donor_gain	1.0000
2:218992239:CCCAA:C	acceptor_gain	1.0000
2:218992240:CCAA:C	acceptor_gain	1.0000
2:218992240:CCAAC:C	acceptor_gain	1.0000
2:218992241:CAA:C	acceptor_gain	1.0000
2:218992241:CAAC:C	acceptor_gain	1.0000
2:218992242:AA:A	acceptor_gain	1.0000
2:218992242:AAC:A	acceptor_loss	1.0000
2:218992244:C:CC	acceptor_gain	1.0000
2:218992244:CTGG:C	acceptor_loss	1.0000
2:218993010:A:AC	donor_gain	1.0000
2:218993011:C:CC	donor_gain	1.0000
2:218993014:A:AC	donor_gain	1.0000

AlphaMissense

1293 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:218990398:A:G	W150R	0.990
2:218990398:A:T	W150R	0.990
2:218992231:A:C	F58L	0.989
2:218992231:A:T	F58L	0.989
2:218992233:A:G	F58L	0.989
2:218990271:A:T	I192N	0.988
2:218992242:A:G	W55R	0.987
2:218992242:A:T	W55R	0.987
2:218990368:C:G	G160R	0.986
2:218993034:A:T	V48D	0.986
2:218990262:A:T	V195D	0.985
2:218990367:C:A	G160V	0.985
2:218990396:C:A	W150C	0.985
2:218990396:C:G	W150C	0.985
2:218990965:A:C	F111L	0.984
2:218990965:A:T	F111L	0.984
2:218990967:A:G	F111L	0.984
2:218990264:T:A	R194S	0.983
2:218990264:T:G	R194S	0.983
2:218990895:A:G	W135R	0.983
2:218990895:A:T	W135R	0.983
2:218992118:C:G	R96P	0.983
2:218992164:A:G	W81R	0.983
2:218992164:A:T	W81R	0.983
2:218990274:G:A	S191F	0.980
2:218992124:G:A	S94F	0.980
2:218992201:G:C	F68L	0.980
2:218992201:G:T	F68L	0.980
2:218992203:A:G	F68L	0.980
2:218993038:A:G	S47P	0.980

dbSNP variants (sampled 300 via entrez): RS1000017858 (2:218991844 G>A,T), RS1000466540 (2:218993445 C>A,G), RS1000679252 (2:218994527 G>A,T), RS1001341845 (2:218994131 A>C), RS1001741980 (2:218994601 G>A,T), RS1002512351 (2:218991445 C>A,T), RS1003707203 (2:218991227 G>A), RS1003777585 (2:218992540 C>T), RS1003800629 (2:218991518 T>C), RS1004132811 (2:218992913 G>A), RS1004933066 (2:218990925 C>G,T), RS1005709520 (2:218993758 T>G), RS1005971732 (2:218992479 GAA>G), RS1006218728 (2:218994026 G>A), RS1006271476 (2:218989812 C>G)

Disease associations

OMIM: gene MIM:600836 | disease phenotypes: MIM:115900

GenCC curated gene-disease

Disease	Classification	Inheritance
cataract 42	Strong	Autosomal dominant
early-onset anterior polar cataract	Supportive	Autosomal dominant
early-onset nuclear cataract	Supportive	Autosomal dominant

Mondo (3): early-onset anterior polar cataract (MONDO:0020373), cataract 42 (MONDO:0007283), early-onset nuclear cataract (MONDO:0020376)

Orphanet (2): Early-onset anterior polar cataract (Orphanet:98988), Early onset non-syndromic cataract (Orphanet:91492)

HPO phenotypes

7 total (7 of 7 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000501	Glaucoma
HP:0000518	Cataract
HP:0000519	Developmental cataract
HP:0000545	Myopia
HP:0003577	Congenital onset
HP:0011462	Young adult onset

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST000175_19	Height	1.000000e-06
GCST006976_54	Macular thickness	2.000000e-10
GCST007829_6	Systolic blood pressure	3.000000e-07
GCST008839_385	Height	6.000000e-12
GCST009380_12	Type 2 diabetes (adjusted for BMI)	7.000000e-09
GCST90002399_127	Neutrophil percentage of white cells	2.000000e-16

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006944	systolic blood pressure change measurement
EFO:0007990	neutrophil percentage of leukocytes

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C563333	Cataract, Age-Related Nuclear (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
methylmercuric chloride	increases expression	1
beta-lapachone	increases expression	1
tebuconazole	decreases expression	1
CGP 52608	affects binding, increases reaction	1
Resveratrol	affects cotreatment, decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Plant Extracts	decreases expression, affects cotreatment	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Cyclosporine	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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