CRYBA1

Summary

CRYBA1 (crystallin beta A1, HGNC:2394) is a protein-coding gene on chromosome 17q11.2, encoding Beta-crystallin A3 (P05813). 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. Beta-crystallins, the most heterogeneous, differ by the presence of the C-terminal extension (present in the basic group, none in the acidic group). Beta-crystallins form aggregates of different sizes and are able to self-associate to form dimers or to form heterodimers with other beta-crystallins. This gene, a beta acidic group member, encodes two proteins (crystallin, beta A3 and crystallin, beta A1) from a single mRNA, the latter protein is 17 aa shorter than crystallin, beta A3 and is generated by use of an alternate translation initiation site. Deletion of exons 3 and 4 causes the autosomal dominant disease ‘zonular cataract with sutural opacities’.

Source: NCBI Gene 1411 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cataract 10 multiple types (Definitive, GenCC) — +4 more curated relationships
• GWAS associations: 4
• Clinical variants (ClinVar): 96 total — 4 pathogenic, 9 likely-pathogenic
• Phenotypes (HPO): 6
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_005208

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2394
Approved symbol	CRYBA1
Name	crystallin beta A1
Location	17q11.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000108255
Ensembl biotype	protein_coding
OMIM	123610
Entrez	1411

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 nonsense_mediated_decay

ENST00000225387, ENST00000484605

RefSeq mRNA: 1 — MANE Select: NM_005208 NM_005208

CCDS: CCDS11249

Canonical transcript exons

ENST00000225387 — 6 exons

Exon	Start	End
ENSE00000707483	29252064	29252205
ENSE00001053092	29246859	29246894
ENSE00002339519	29250182	29250300
ENSE00002392275	29254202	29254494
ENSE00002417572	29249142	29249206
ENSE00003672966	29253640	29253782

Expression profiles

Bgee: expression breadth ubiquitous, 138 present calls, max score 95.16.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.6753 / max 493.9772, expressed in 65 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
160086	0.6753	65

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lens of camera-type eye	UBERON:0000965	95.16	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	92.18	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.14	gold quality
granulocyte	CL:0000094	64.57	gold quality
monocyte	CL:0000576	56.16	gold quality
leukocyte	CL:0000738	55.12	gold quality
corpus callosum	UBERON:0002336	52.83	gold quality
calcaneal tendon	UBERON:0003701	51.96	gold quality
colonic epithelium	UBERON:0000397	51.37	gold quality
lower esophagus mucosa	UBERON:0035834	50.51	gold quality
frontal pole	UBERON:0002795	50.41	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
blood	UBERON:0000178	50.27	gold quality
paraflocculus	UBERON:0005351	50.18	gold quality
Brodmann (1909) area 10	UBERON:0013541	50.18	gold quality
buccal mucosa cell	CL:0002336	50.14	gold quality
bone marrow cell	CL:0002092	49.36	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
cerebellar vermis	UBERON:0004720	49.25	gold quality
choroid plexus epithelium	UBERON:0003911	48.89	gold quality
ascending aorta	UBERON:0001496	48.29	gold quality
thoracic aorta	UBERON:0001515	48.26	gold quality
metanephric glomerulus	UBERON:0004736	47.83	gold quality
right lung	UBERON:0002167	47.78	gold quality
renal glomerulus	UBERON:0000074	47.64	gold quality
nephron tubule	UBERON:0001231	47.59	gold quality
tendon	UBERON:0000043	47.44	gold quality
periodontal ligament	UBERON:0008266	47.14	gold quality
endometrium epithelium	UBERON:0004811	46.85	gold quality
islet of Langerhans	UBERON:0000006	46.84	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.70

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MAFA, PPARD

miRNA regulators (miRDB)

14 targeting CRYBA1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-5701	98.97	69.54	1502
HSA-MIR-4752	98.71	68.04	833
HSA-MIR-4468	98.01	66.85	1187
HSA-MIR-432-5P	98.00	68.13	989
HSA-MIR-890	97.47	68.67	982
HSA-MIR-8056	97.15	64.49	769
HSA-MIR-4757-3P	88.86	63.55	51
HSA-MIR-487B-3P	88.08	68.35	83

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 31)

• A deletion mutation in the betaA1/A3 crystallin gene is associated with autosomal dominant congenital nuclear cataract (PMID:14598164)
• comprehensive description of the biophysical consequences of a mutant beta-crystallin protein that is associated with human inherited cataract. (PMID:15016766)
• The DeltaG91 mutation in CRYBA3/A1 is associated with an autosomal dominant congenital nuclear lactescent cataract (PMID:15111599)
• The glutamine residues at the Q180 and the Q85 were substituted with glutamic acid residues by site-directed mutagenesis. These structural changes led to decreased stability during unfolding in urea and increased precipitation during heat denaturation. (PMID:17616172)
• Delta91 mutation arise in a relatively mutation-prone sequence of the CRYBA1 gene. (PMID:17653060)
• This study confirmed the interactions between a low molecular weight peptide derived from betaA3/A1-crystallin found in aged and cataract lenses and alphaB-crystallin. (PMID:18401461)
• Deamidation destabilizes and triggers aggregation of crystallin beta A3. (PMID:18567786)
• mixed betaB1- and betaA3-crystallins associate predominantly into heterotetramers in equilibrium with heterodimers (PMID:18823128)
• A serine-type betaA3-crystallin proteinase existed in an inactive state in the alpha-crystallin fraction and was activated by detergents. (PMID:18949065)
• deamidation decreased formation of hetero-oligomers between beta-crystallin subunits; excess accumulation of deamidated beta-crystallins in vivo may disrupt normal protein-protein interactions and diminish the stabilizing effects between them (PMID:19190732)
• the motifs III and IV of betaA3-crystallin were interactive with alphaA-crystallin, and motifs II and III of betaA3-crystallin primarily interacted with alphaB-crystallin (PMID:19401464)
• Results suggest that the N-terminal arm of betaB1-crystallin interacts with betaA3-crystallin during heterooligomerization, and the solubility of betaB1-crystallin and the heterooligomer are dependent on the intact C-terminal domain of betaB1-crystallin. (PMID:19548648)
• This study is the first report relating a mutation of CRYBA1/A3 to posterior polar cataract. (PMID:20142846)
• Mutations involved in congenital cataracts and deamidation in aged lenses commonly altered protein-protein interaction between human lens betaA3-crystallins. (PMID:20300566)
• A serine-type protease activity of betaA3-crystalllin was responsible for its autodegradation. (PMID:21139689)
• This is the first report of a phenotype of progressive nuclear and cortical cataracts related to the CRYBA3/A1 mutation IVS3+1 G>A. (PMID:21139983)
• The c.279-281delGAG mutation in CRYBA1 is responsible for the autosomal dominant congenital nuclear cataract disease in this Chinese family. (PMID:21686330)
• A G–>T splice site mutation of CRYBA1/A3 associated with autosomal dominant suture cataracts in a Chinese family. (PMID:21850182)
• ThebetaA3-crystallin and betaB1-crystallin homomers and the betaA3/betaB1-crystallin heteromer all undergo similar five-state folding pathways which include one dimeric and two monomeric intermediates. (PMID:22032798)
• A novel splice site mutation in CRYBA1/A3 is associated with autosomal dominant nuclear cataracts in a Chinese family. (PMID:22665976)
• A splice site mutation (c.215+1G>A) at the first base of intron 3 of the crystallin beta A3/A1 (CRYBA3/A1) gene has been identified in Chinese congenital polymorphic cataract patients. (PMID:22919269)
• association between a frameshift mutation in exon 6 of CRYBA1/A3 and congenital cataracts (PMID:24926697)
• Data indicate that alpha-crystallin B chain and beta-crystallin A3-cyrstallins dissociate to the monomers upon racemization of d-aspartic acids (Asp). (PMID:25450505)
• The findings suggest that impaired endolysosomal signaling in ocular astrocytes can cause PFV disease, by adversely affecting the vascular remodeling processes essential to ocular development, including regression of the fetal vasculature. [review] (PMID:26022148)
• This study investigated the mechanism of cataracts caused by a c.215 + 1G > A splice mutation in CRYBA1. The mutant beta A3/A1 crystallin causes toxicity and degeneration of differentiating lens cells. The mutant beta A3/A1 crystallin acts by inducing the unfolded protein response culminating in apoptosis. (PMID:26851658)
• We identified a de novo in-frame 3-bp deletion in the proband with an autosomal dominant congenital cataract, but not in her parents, in an Iranian family. This mutation has occurred de novo on a paternal gamete during spermatogenesis. The in-silico results predicted the interaction of CRYBA1 protein with the other CRY as well as proteins responsible for eye cell signaling. (PMID:28120589)
• A recurrent DeltaG91CRYBA1/A3 mutation occurs independently in 6.4% of the Chinese families with autosomal dominant nuclear cataracts and most likely represents a mutational hot spot, which underscores the relations between nonprogressive nuclear cataract and CRYBA1/A3. (PMID:29364738)
• CRYBA1 showed lower expression in cataract lenses than in control lenses. The deleted form (p.G91del) of CRYBA1 showed lower expression and was more aggregate to the cell membrane than the wild-type CRYBA1. (PMID:31488069)
• A novel missense mutation of CRYBA1 in a northern Chinese family with inherited coronary cataract with blue punctate opacities. (PMID:33827296)
• Pathogenic mechanism of congenital cataract caused by the CRYBA1/A3-G91del variant and related intervention strategies. (PMID:34419537)
• Cataract-causing G91del mutant destabilised betaA3 heteromers formation linking with structural stability and cellular viability. (PMID:34489339)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cryba1a	ENSDARG00000041141
mus_musculus	Cryba1	ENSMUSG00000000724
rattus_norvegicus	Cryba1	ENSRNOG00000008700

Paralogs (14): CRYBG3 (ENSG00000080200), CRYBB3 (ENSG00000100053), CRYBB1 (ENSG00000100122), CRYBG1 (ENSG00000112297), CRYGD (ENSG00000118231), CRYGN (ENSG00000127377), CRYGC (ENSG00000163254), CRYBA2 (ENSG00000163499), CRYGA (ENSG00000168582), CRYBG2 (ENSG00000176092), CRYGB (ENSG00000182187), CRYBA4 (ENSG00000196431), CRYGS (ENSG00000213139), CRYBB2 (ENSG00000244752)

Protein

Protein identifiers

Beta-crystallin A3 — P05813 (reviewed: P05813)

All UniProt accessions (2): P05813, J3QRT1

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. Interacts with CRYBA1.

Post-translational modifications. Specific cleavages in the N-terminal arm occur during lens maturation and give rise to several truncated forms. Cleavages do not seem to have adverse effects on solubility. S-methylation and glutathionylation occur in normal young lenses and do not seem to be detrimental.

Disease relevance. Cataract 10, multiple types (CTRCT10) [MIM:600881] 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. CTRCT10 includes congenital zonular with sutural opacities, among others. This is a form of zonular cataract with an erect Y-shaped anterior and an inverted Y-shaped posterior sutural opacities. Zonular or lamellar cataracts are opacities, broad or narrow, usually consisting of powdery white dots affecting only certain layers or zones between the cortex and nucleus of an otherwise clear lens. The opacity may be so dense as to render the entire central region of the lens completely opaque, or so translucent that vision is hardly if at all impeded. Zonular cataracts generally do not involve the embryonic nucleus, though sometimes they involve the fetal nucleus. Usually sharply separated from a clear cortex outside them, they may have projections from their outer edges known as riders or spokes. 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.

Isoforms (2)

UniProt ID	Names	Canonical?
P05813-1	A3	yes
P05813-2	A1

RefSeq proteins (1): NP_005199* (*=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 (27 total): modified residue 7, sequence conflict 5, chain 4, domain 4, region of interest 3, compositionally biased region 1, splice variant 1, sequence variant 1, initiator methionine 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P05813-F1	88.27	0.81

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (7): 1, 82, 82, 117, 117, 185, 2

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 91 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, GOBP_NEGATIVE_REGULATION_OF_ERK1_AND_ERK2_CASCADE, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_VESICLE_MEDIATED_TRANSPORT, chr17q11, GOBP_NEGATIVE_REGULATION_OF_MAPK_CASCADE, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_PHOSPHATIDYLINOSITOL_3_KINASE_PROTEIN_KINASE_B_SIGNAL_TRANSDUCTION, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, TGCTGAY_UNKNOWN, GOBP_NEGATIVE_REGULATION_OF_TOR_SIGNALING, GOBP_PHOSPHATIDYLINOSITOL_3_KINASE_PROTEIN_KINASE_B_SIGNAL_TRANSDUCTION, GOBP_CYTOKINE_PRODUCTION

GO Biological Process (9): negative regulation of cytokine production (GO:0001818), lens development in camera-type eye (GO:0002088), phagocytosis (GO:0006909), visual perception (GO:0007601), regulation of autophagy (GO:0010506), negative regulation of TOR signaling (GO:0032007), negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051898), negative regulation of ERK1 and ERK2 cascade (GO:0070373), positive regulation of anoikis (GO:2000210)

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

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
negative regulation of intracellular signal transduction	2
cytokine production	1
regulation of cytokine production	1
negative regulation of gene expression	1
negative regulation of multicellular organismal process	1
camera-type eye development	1
anatomical structure development	1
endocytosis	1
sensory perception of light stimulus	1
autophagy	1
regulation of catabolic process	1
TOR signaling	1
regulation of TOR signaling	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
negative regulation of MAPK cascade	1
ERK1 and ERK2 cascade	1
regulation of ERK1 and ERK2 cascade	1
positive regulation of apoptotic process	1
anoikis	1
regulation of anoikis	1
structural molecule activity	1
binding	1

Protein interactions and networks

STRING

810 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CRYBA1	CRYAA	P02489	943
CRYBA1	GJA3	Q9Y6H8	813
CRYBA1	GJA8	P48165	812
CRYBA1	BFSP2	Q13515	777
CRYBA1	GALK1	P51570	774
CRYBA1	CRYAB	P02511	756
CRYBA1	BFSP1	Q12934	752
CRYBA1	LIM2	P55344	693
CRYBA1	HSF4	Q9ULV5	668
CRYBA1	PITX3	O75364	648
CRYBA1	CHMP4B	Q9H444	605
CRYBA1	TMEM114	B3SHH9	598
CRYBA1	THRA	P10827	580
CRYBA1	FOXE3	Q13461	558
CRYBA1	CRYM	Q14894	548

IntAct

79 interactions, top by confidence:

A	B	Type	Score
CRYBB1	CRYBA1	psi-mi:“MI:0915”(physical association)	0.780
CRYBA1	CRYBB1	psi-mi:“MI:0915”(physical association)	0.780
CRYBA1	CRYBB3	psi-mi:“MI:0915”(physical association)	0.720
CRYBB3	CRYBA1	psi-mi:“MI:0915”(physical association)	0.720
RBPMS	CRYBA1	psi-mi:“MI:0915”(physical association)	0.560
RHOXF2	CRYBA1	psi-mi:“MI:0915”(physical association)	0.560
CRYBA1	RBPMS	psi-mi:“MI:0915”(physical association)	0.560
CRYBA1	LASP1	psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	CRYBA1	psi-mi:“MI:0915”(physical association)	0.560
CRYBA1	CRYBB2	psi-mi:“MI:0915”(physical association)	0.560
CRYBA1	BANF2	psi-mi:“MI:0915”(physical association)	0.560
CRYBA1	VAC14	psi-mi:“MI:0915”(physical association)	0.560
FOXH1	CRYBA1	psi-mi:“MI:0915”(physical association)	0.560
CRYBA1	ARID5A	psi-mi:“MI:0915”(physical association)	0.560
CRYBA1	CHCHD2	psi-mi:“MI:0915”(physical association)	0.560
	CRYBA1	psi-mi:“MI:0915”(physical association)	0.560
CRYBA1	KRTAP11-1	psi-mi:“MI:0915”(physical association)	0.560
PROP1	CRYBA1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (36): CRYBB1 (Two-hybrid), CRYBB3 (Two-hybrid), RBPMS (Two-hybrid), RHOXF2 (Two-hybrid), CRYBB1 (Two-hybrid), CRYBA1 (Reconstituted Complex), CRYBA1 (FRET), CRYBA1 (Two-hybrid), CRYBA1 (Two-hybrid), CRYBA1 (Two-hybrid), CRYBA1 (Two-hybrid), CRYBA1 (Two-hybrid), CRYBA1 (Two-hybrid), CRYBA1 (Two-hybrid), CRYBA1 (Two-hybrid)

ESM2 similar proteins: A2IBY7, A2ICR5, A3RLD8, A3RLE2, A4L9I8, A4L9I9, O35486, P02525, P02526, P02528, P02529, P02531, P04342, P04344, P05813, P06504, P07315, P07316, P07317, P07320, P08209, P0C5E9, P10042, P10067, P10068, P10112, P11842, P11843, P11844, P14881, P22914, P23005, P26444, P49152, P53672, P53673, P55164, P56374, Q03740, Q28088

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

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	9
Uncertain significance	43
Likely benign	14
Benign	13

Top pathogenic / likely-pathogenic (13)

Variant ID	HGVS	Classification
1073011	NM_005208.5(CRYBA1):c.215+1G>C	Pathogenic
3382052	NM_005208.5(CRYBA1):c.279C>A (p.Tyr93Ter)	Pathogenic
4695766	NM_005208.5(CRYBA1):c.340C>T (p.Arg114Cys)	Pathogenic
560445	NM_005208.5(CRYBA1):c.607_608del (p.Gln203fs)	Pathogenic
1184515	NM_005208.5(CRYBA1):c.626C>G (p.Ser209Trp)	Likely pathogenic
1209931	NM_005208.5(CRYBA1):c.500+1G>C	Likely pathogenic
1324178	NM_005208.5(CRYBA1):c.258del (p.Phe86fs)	Likely pathogenic
1803183	NM_005208.5(CRYBA1):c.501-2_522del	Likely pathogenic
191293	NM_005208.5(CRYBA1):c.588_591del (p.Arg196fs)	Likely pathogenic
225328	NM_005208.5(CRYBA1):c.500+1G>A	Likely pathogenic
3354229	NM_005208.5(CRYBA1):c.530del (p.Arg177fs)	Likely pathogenic
4081298	NM_005208.5(CRYBA1):c.96+2T>A	Likely pathogenic
464096	NM_005208.5(CRYBA1):c.530_538del (p.Arg177_Tyr179del)	Likely pathogenic

SpliceAI

700 predictions. Top by Δscore:

Variant	Effect	Δscore
17:29250296:GGCGC:G	donor_gain	1.0000
17:29250297:GCGC:G	donor_gain	1.0000
17:29250297:GCGCG:G	donor_gain	1.0000
17:29250299:GC:G	donor_gain	1.0000
17:29250301:G:GG	donor_gain	1.0000
17:29252203:GCT:G	donor_gain	1.0000
17:29253630:T:TA	acceptor_gain	1.0000
17:29253633:A:AG	acceptor_gain	1.0000
17:29253637:C:G	acceptor_gain	1.0000
17:29253637:CA:C	acceptor_loss	1.0000
17:29253638:A:AC	acceptor_loss	1.0000
17:29253638:A:AG	acceptor_gain	1.0000
17:29253639:G:GC	acceptor_gain	1.0000
17:29253639:GA:G	acceptor_gain	1.0000
17:29253639:GAA:G	acceptor_gain	1.0000
17:29253639:GAAT:G	acceptor_gain	1.0000
17:29253639:GAATC:G	acceptor_gain	1.0000
17:29253778:GGGGC:G	donor_gain	1.0000
17:29253779:GGGC:G	donor_gain	1.0000
17:29253779:GGGCG:G	donor_gain	1.0000
17:29253780:GGC:G	donor_gain	1.0000
17:29253780:GGCG:G	donor_gain	1.0000
17:29253781:GC:G	donor_gain	1.0000
17:29253781:GCG:G	donor_gain	1.0000
17:29253783:G:GG	donor_gain	1.0000
17:29253784:T:TC	donor_loss	1.0000
17:29253787:G:GG	donor_gain	1.0000
17:29254200:A:AG	acceptor_gain	1.0000
17:29254200:AGCT:A	acceptor_gain	1.0000
17:29254200:AGCTG:A	acceptor_gain	1.0000

AlphaMissense

1439 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:29254234:G:A	G178E	1.000
17:29252065:T:A	W73R	0.999
17:29252065:T:C	W73R	0.999
17:29252096:G:A	G83E	0.999
17:29252096:G:T	G83V	0.999
17:29252143:T:A	W99R	0.999
17:29252143:T:C	W99R	0.999
17:29254203:T:A	W168R	0.999
17:29254203:T:C	W168R	0.999
17:29254233:G:A	G178R	0.999
17:29254233:G:C	G178R	0.999
17:29254233:G:T	G178W	0.999
17:29254234:G:T	G178V	0.999
17:29254293:T:A	W198R	0.999
17:29254293:T:C	W198R	0.999
17:29254333:G:C	R211P	0.999
17:29250278:T:C	S65P	0.998
17:29252071:G:C	G75R	0.998
17:29252072:G:A	G75D	0.998
17:29252095:G:T	G83W	0.998
17:29254209:T:C	C170R	0.998
17:29254231:G:C	R177P	0.998
17:29254327:C:G	S209W	0.998
17:29254332:C:A	R211S	0.998
17:29250212:G:C	G43R	0.997
17:29250213:G:T	G43V	0.997
17:29252095:G:A	G83R	0.997
17:29252095:G:C	G83R	0.997
17:29252111:T:C	L88P	0.997
17:29252125:T:G	Y93D	0.997

dbSNP variants (sampled 300 via entrez): RS1000194053 (17:29253262 A>T), RS1000315519 (17:29249321 G>A,T), RS1000374804 (17:29254959 G>A,C), RS1001529572 (17:29246710 A>G), RS1001699075 (17:29253591 T>C), RS1001828864 (17:29249390 G>A), RS1002090551 (17:29248260 CAA>C), RS1002168378 (17:29249653 C>T), RS1002169759 (17:29246288 A>G), RS1002769316 (17:29250926 A>ACC), RS1003210545 (17:29250619 A>G), RS1003338836 (17:29254805 C>T), RS1003438032 (17:29248047 C>T), RS1003608729 (17:29248525 C>T), RS1003975950 (17:29254403 A>G)

Disease associations

OMIM: gene MIM:123610 | disease phenotypes: MIM:600881

GenCC curated gene-disease

Disease	Classification	Inheritance
cataract 10 multiple types	Definitive	Autosomal dominant
early-onset lamellar cataract	Supportive	Autosomal dominant
early-onset sutural cataract	Supportive	Autosomal dominant
early-onset nuclear cataract	Supportive	Autosomal dominant
early-onset posterior polar cataract	Supportive	Autosomal dominant

Mondo (5): cataract 10 multiple types (MONDO:0010948), early-onset lamellar cataract (MONDO:0018611), early-onset sutural cataract (MONDO:0020372), early-onset nuclear cataract (MONDO:0020376), early-onset posterior polar cataract (MONDO:0020378)

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

HPO phenotypes

6 total (6 of 6 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000519	Developmental cataract
HP:0003577	Congenital onset
HP:0008031	Posterior Y-sutural cataract
HP:0010920	Zonular cataract
HP:0100018	Nuclear cataract

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST003542_68	Night sleep phenotypes	9.000000e-06
GCST005839_44	Depression	9.000000e-09
GCST009600_135	Anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, or Tourette syndrome (pleiotropy)	8.000000e-09
GCST90002396_614	Mean reticulocyte volume	4.000000e-15

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007827	nighttime rest measurement
EFO:0010701	mean reticulocyte volume

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C563333	Cataract, Age-Related Nuclear (supp.)
C563435	Cataract, Congenital Zonular, with Sutural Opacities (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression	5
Panobinostat	affects cotreatment, decreases expression	2
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	decreases expression	1
perfluorooctanoic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
perfluorohexanesulfonic acid	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
licochalcone B	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Rotenone	decreases expression	1
Silicon Dioxide	increases expression	1
Gold Compounds	increases expression	1
Lactic Acid	increases expression	1

Clinical trials (associated diseases)

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