CRYBB1

Summary

CRYBB1 (crystallin beta B1, HGNC:2397) is a protein-coding gene on chromosome 22q12.1, encoding Beta-crystallin B1 (P53674). 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 basic group member, undergoes extensive cleavage at its N-terminal extension during lens maturation. It is also a member of a gene cluster with beta-A4, beta-B2, and beta-B3.

Source: NCBI Gene 1414 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cataract 17 multiple types (Definitive, GenCC) — +3 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 18 total — 1 likely-pathogenic
• Phenotypes (HPO): 15
• MANE Select transcript: NM_001887

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2397
Approved symbol	CRYBB1
Name	crystallin beta B1
Location	22q12.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000100122
Ensembl biotype	protein_coding
OMIM	600929
Entrez	1414

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000647569, ENST00000647684, ENST00000872124, ENST00000872125, ENST00000872126, ENST00000927864, ENST00000927865, ENST00000946726

RefSeq mRNA: 1 — MANE Select: NM_001887 NM_001887

CCDS: CCDS13840

Canonical transcript exons

ENST00000647684 — 6 exons

Exon	Start	End
ENSE00000651921	26612072	26612190
ENSE00000879664	26616140	26616338
ENSE00001773373	26601879	26602021
ENSE00001784497	26599278	26599673
ENSE00002239510	26607889	26608021
ENSE00003836130	26617977	26618027

Expression profiles

Bgee: expression breadth ubiquitous, 154 present calls, max score 89.45.

FANTOM5 (CAGE): breadth broad, TPM avg 2.0928 / max 997.1068, expressed in 241 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
193433	1.6158	84
193434	0.4283	132
193432	0.0487	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.45	gold quality
prefrontal cortex	UBERON:0000451	71.84	gold quality
Brodmann (1909) area 10	UBERON:0013541	67.57	gold quality
parotid gland	UBERON:0001831	66.84	gold quality
vermiform appendix	UBERON:0001154	66.43	gold quality
frontal pole	UBERON:0002795	65.95	gold quality
middle frontal gyrus	UBERON:0002702	65.16	gold quality
paraflocculus	UBERON:0005351	65.11	gold quality
metanephric glomerulus	UBERON:0004736	64.74	gold quality
frontal cortex	UBERON:0001870	63.76	gold quality
right coronary artery	UBERON:0001625	62.22	gold quality
Brodmann (1909) area 9	UBERON:0013540	62.04	gold quality
spleen	UBERON:0002106	61.99	gold quality
neocortex	UBERON:0001950	61.94	gold quality
gall bladder	UBERON:0002110	61.66	gold quality
corpus epididymis	UBERON:0004359	61.59	gold quality
right adrenal gland	UBERON:0001233	61.35	gold quality
right adrenal gland cortex	UBERON:0035827	61.30	gold quality
caecum	UBERON:0001153	60.75	gold quality
right frontal lobe	UBERON:0002810	60.52	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	60.50	gold quality
anterior cingulate cortex	UBERON:0009835	60.25	gold quality
lymph node	UBERON:0000029	59.71	gold quality
smooth muscle tissue	UBERON:0001135	59.49	gold quality
omental fat pad	UBERON:0010414	59.38	gold quality
peritoneum	UBERON:0002358	59.33	gold quality
left adrenal gland	UBERON:0001234	58.76	gold quality
endometrium epithelium	UBERON:0004811	58.46	gold quality
adipose tissue of abdominal region	UBERON:0007808	58.40	gold quality
cerebral cortex	UBERON:0000956	58.20	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.95

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PAX6, PROX1, ZEB1

Literature-anchored findings (GeneRIF, showing 31)

• Mutation G220X is associated with autosomal dominant cataract. (PMID:12360425)
• 1.4 angstroms resolution crystal structure of a truncated version of human betaB1 that resembles an in vivo age-related truncation (PMID:14573871)
• The molecular characterization of a UK family with an autosomal dominant congenital cataract associated with microcornea is reported (PMID:16110300)
• fundamental transcriptional regulatory mechanism of the betaB1-crystallin gene has been well conserved between humans and zebrafish (PMID:16331646)
• the sequence of betaB2-crystallin appears well optimized for domain swapping (PMID:17327390)
• The dimeric intermediate may be a critical determinant for the life-long stability of the beta-crystallins and has important consequences on interactions with alpha-crystallin. (PMID:17448466)
• The current study showed that a different mutation in the same gene causes an autosomal recessive form of the disease. (PMID:17460281)
• study identified a novel mutation in CRYBB1 gene in a Chinese family with autosomal dominant congenital cataract; results provide strong evidence that CRYBB1 is a pathogenic gene for congenital cataract (PMID:17531125)
• This study has identified a novel nonsense mutation in CRYBB1 (p.Q223X) associated with autosomal dominant congenital nuclear cataract. (PMID:18432316)
• These data suggest a mechanism whereby a transient disulfide bond occurs between alphaA- and betaB1-crystallin followed by a disulfide exchange with cysteine 49 of a neighboring alphaA-crystallin subunit. (PMID:19071118)
• 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)
• study identified an initiation codon mutation in CRYBB1 in a family with autosomal recessive form of congenital cataract (nuclear pulverulent cataract) (PMID:19461930)
• Studies show that The major proteins in the lens–alpha, beta, and gamma-crystallins–are constantly subjected to age-related changes. (PMID:19463898)
• 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)
• Variant alleles of the CRYBB1 and CRYBB2 genes were found, none are considered pathogenic. (PMID:20565250)
• Data show a significant demixing of gammaD and betaB1 i.e., large difference of composition in the two coexisting phases. (PMID:20616077)
• Analyses of 20 Chinese families with hereditary nuclear congenital cataract revealed 3 novel mutations. Two of these mutations (V146M and I21N) affected betaB2-crystallin (CRYBB2). One mutation (R233H) was detected in betaB1-crystallin (CRYBB1). (PMID:21402992)
• The presence of significant amounts of small peptides derived from gammaS- and betaB1-crystallins in the water-insoluble fraction of the lens indicates that these interact tightly with cytoskeletal or membrane components. (PMID:21447408)
• study identified a novel heterozygous p.Ser129Arg mutation in CRYBB1 in a congenital cataract-microcornea syndrome family of Chinese origin (PMID:21972112)
• The formation of beta-crystallin heteromers not only stabilizes the unstable acidic beta-crystallin but also protects them against aggregation during refolding from the stress-denatured states. (PMID:22032798)
• Sequencing of this gene revealed a homozygous c.171del mutation (p.N58Tfs*107) with a shared haplotype in all 16 children. (PMID:22267527)
• Despite the disruption of betaB1-crystallin assembly, the thermal stability of betaB1-crystallin was increased by the mutation accompanied by the reduction of thermal aggregation at high temperatures (PMID:23159606)
• Congenital microcornea-cataract syndrome-causing mutation X253R increases betaB1-crystallin hydrophobicity to promote aggregate formation (PMID:27208166)
• Molecular dynamic simulation studies indicated that the mutation decreased the subunit binding energy and modified the distribution of surface electrostatic potentials. More importantly, the mutation separated two interacting loops in the C-terminal domain, which shielded the hydrophobic core from solvent in native betaB1-crystallin. (PMID:27318838)
• CRYBB1 partial duplication ad complete duplication of CRYBA4 identified in a family with autosomal dominant congenital cataract. (PMID:28272538)
• Our findings highlight the importance of the C-terminus in betaB1-crystallin in maintaining the crystalline function and stability, and provide a novel insight into the molecular mechanism underlying the pathogenesis of human autosomal dominant congenital cataract. (PMID:28928627)
• We examined a cohort of Chinese patients with congenital cataracts and studied the phenotypes and genotypes. Extralenticular abnormalities, such as microcornea and ocular coloboma, can also be found in patients with congenital cataracts. The phenotype of congenital cataracts associated with macular and optic disc coloboma was reported for the first time in this study. (PMID:29386872)
• A Novel Mutation p.S93R in CRYBB1 Associated with Dominant Congenital Cataract and Microphthalmia. (PMID:31566446)
• A novel missense mutation of CRYBB1 causes congenital cataract in a Chinese family. (PMID:32223445)
• Congenital cataract-causing mutation betaB1-L116P is prone to amyloid fibrils aggregation and protease degradation with low structural stability. (PMID:34896472)
• Cataract-causing Y204X mutation of crystallin protein CRYbetaB1 promotes its C-terminal degradation and higher-order oligomerization. (PMID:37356717)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	crybb1	ENSDARG00000068507
mus_musculus	Crybb1	ENSMUSG00000029343
rattus_norvegicus	Crybb1	ENSRNOG00000047653

Paralogs (14): CRYBG3 (ENSG00000080200), CRYBB3 (ENSG00000100053), CRYBA1 (ENSG00000108255), 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 B1 — P53674 (reviewed: P53674)

Alternative names: Beta-B1 crystallin

All UniProt accessions (1): P53674

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.

Post-translational modifications. Specific cleavages in the N-terminal arm occur during lens maturation and give rise to truncated forms, leading to impaired oligomerization and protein insolubilization.

Disease relevance. Cataract 17, multiple types (CTRCT17) [MIM:611544] 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. CTRCT17 includes nuclear and pulverulent cataracts, among others. Nuclear cataracts affect the central nucleus of the eye, are often not highly visually significant. The density of the opacities varies greatly from fine dots to a dense, white and chalk-like, central cataract. The condition is usually bilateral. Nuclear cataracts are often combined with opacified cortical fibers encircling the nuclear opacity, which are referred to as cortical riders. Pulverulent cataracts are characterized by a dust-like, ‘pulverised’ appearance of the opacities which can be found in any part of the lens. The disease is caused by variants affecting the gene represented in this entry. CRYBB1 mutations may be a cause of congenital cataract and microcornea syndrome, a disease characterized by the association of congenital cataract and microcornea without any other systemic anomaly or dysmorphism. Clinical findings include a corneal diameter inferior to 10 mm in both meridians in an otherwise normal eye, and an inherited cataract, which is most often bilateral posterior polar with opacification in the lens periphery. The cataract progresses to form a total cataract after visual maturity has been achieved, requiring cataract extraction in the first to third decade of life.

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_001878* (*=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 (40 total): strand 13, sequence variant 6, helix 5, domain 4, region of interest 4, turn 3, compositionally biased region 2, initiator methionine 1, chain 1, modified residue 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1OKI	X-RAY DIFFRACTION	1.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P53674-F1	82.13	0.70

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 (1): 2

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 79 (showing top): GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, GOBP_SENSORY_PERCEPTION, GOBP_SENSORY_ORGAN_DEVELOPMENT, GOBP_LENS_DEVELOPMENT_IN_CAMERA_TYPE_EYE, GOMF_STRUCTURAL_CONSTITUENT_OF_EYE_LENS, YOSHIMURA_MAPK8_TARGETS_UP, GOMF_STRUCTURAL_MOLECULE_ACTIVITY, MIKKELSEN_ES_LCP_WITH_H3K27ME3, SHEPARD_CRASH_AND_BURN_MUTANT_DN, GOBP_SENSORY_SYSTEM_DEVELOPMENT, CRX_NRL_DN.V1_UP, GSE13522_CTRL_VS_T_CRUZI_Y_STRAIN_INF_SKIN_IFNG_KO_UP, GSE13306_TREG_VS_TCONV_LAMINA_PROPRIA_DN, HP_ABNORMAL_CORNEA_MORPHOLOGY, HP_MICROCORNEA

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

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
camera-type eye development	1
anatomical structure development	1
sensory perception of light stimulus	1
structural molecule activity	1
binding	1

Protein interactions and networks

STRING

1446 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CRYBB1	BFSP2	Q13515	942
CRYBB1	GJA8	P48165	922
CRYBB1	GJA3	Q9Y6H8	919
CRYBB1	BFSP1	Q12934	857
CRYBB1	CRYAA	P02489	847
CRYBB1	CRYAB	P02511	824
CRYBB1	PITX3	O75364	787
CRYBB1	TMEM114	B3SHH9	744
CRYBB1	HSF4	Q9ULV5	726
CRYBB1	LIM2	P55344	708
CRYBB1	MYOC	Q99972	696
CRYBB1	FYCO1	Q9BQS8	646
CRYBB1	MIP	P30301	643
CRYBB1	CRYM	Q14894	629
CRYBB1	CHMP4B	Q9H444	623

IntAct

42 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
CRYBA4	CRYBB1	psi-mi:“MI:0915”(physical association)	0.730
CRYBA4	CRYBB1	psi-mi:“MI:0407”(direct interaction)	0.730
CRYBA4	CRYBB1	psi-mi:“MI:0914”(association)	0.730
CRYBB1	CRYBA4	psi-mi:“MI:0915”(physical association)	0.730
CRYBB1	AP1B1	psi-mi:“MI:0915”(physical association)	0.560
EXOC5	CRYBB1	psi-mi:“MI:0915”(physical association)	0.560
CRYBB1	DDIT4L	psi-mi:“MI:0915”(physical association)	0.560
GAS8	CRYBB1	psi-mi:“MI:0915”(physical association)	0.560
GPN3	POLR3A	psi-mi:“MI:0914”(association)	0.530
TERF1	CRYBB1	psi-mi:“MI:0915”(physical association)	0.510
CRYBB1	TERF2IP	psi-mi:“MI:0915”(physical association)	0.370
CRYBA1	CRYBB1	psi-mi:“MI:0915”(physical association)	0.370
CRYBB1	CRYBA1	psi-mi:“MI:0915”(physical association)	0.370
CRYBB1	CRYBB1	psi-mi:“MI:0915”(physical association)	0.370
CRYBB1	CRYBA2	psi-mi:“MI:0915”(physical association)	0.370
PCBP1	HSP90AA1	psi-mi:“MI:0914”(association)	0.350
DISC1	AGRN	psi-mi:“MI:0914”(association)	0.350
MRPS11	DBT	psi-mi:“MI:0914”(association)	0.350
MOCS2	CRYBB1	psi-mi:“MI:0914”(association)	0.350
CRYBB3	VWA8	psi-mi:“MI:0914”(association)	0.350

BioGRID (20): CRYBB1 (Two-hybrid), CRYBB1 (Two-hybrid), CRYBA1 (Two-hybrid), CRYBB1 (Affinity Capture-MS), PLA2G4C (Negative Genetic), LCK (Negative Genetic), LIG1 (Negative Genetic), PTK6 (Negative Genetic), CRYBB1 (Negative Genetic), CRYBB1 (Affinity Capture-MS), CRYBB1 (Two-hybrid), AP1B1 (Two-hybrid), GAS8 (Two-hybrid), DDIT4L (Two-hybrid), CRYBB1 (Affinity Capture-MS)

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

1 interactions.

A	Effect	B	Mechanism
CRYBB2	“up-regulates activity”	CRYBB1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	15
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1879550	NM_001887.4(CRYBB1):c.683C>A (p.Ser228Tyr)	Likely pathogenic

SpliceAI

616 predictions. Top by Δscore:

Variant	Effect	Δscore
22:26599669:CCCAT:C	acceptor_gain	1.0000
22:26599670:CCATC:C	acceptor_gain	1.0000
22:26599671:CAT:C	acceptor_gain	1.0000
22:26599673:TCTG:T	acceptor_loss	1.0000
22:26601877:A:AC	donor_gain	1.0000
22:26601877:ACGTT:A	donor_gain	1.0000
22:26601878:C:CA	donor_gain	1.0000
22:26601878:CGTT:C	donor_gain	1.0000
22:26601878:CGTTC:C	donor_gain	1.0000
22:26602018:CATC:C	acceptor_gain	1.0000
22:26607885:TCAC:T	donor_loss	1.0000
22:26607886:CACC:C	donor_loss	1.0000
22:26607887:ACCA:A	donor_loss	1.0000
22:26608019:CAG:C	acceptor_gain	1.0000
22:26608030:A:T	acceptor_gain	1.0000
22:26608039:CA:C	acceptor_gain	1.0000
22:26608040:A:C	acceptor_gain	1.0000
22:26612070:A:AC	donor_gain	1.0000
22:26612070:ACGGT:A	donor_gain	1.0000
22:26612071:C:CC	donor_gain	1.0000
22:26612071:CGGTC:C	donor_gain	1.0000
22:26599670:CCAT:C	acceptor_gain	0.9900
22:26599671:CATC:C	acceptor_gain	0.9900
22:26599672:AT:A	acceptor_gain	0.9900
22:26599674:C:CC	acceptor_gain	0.9900
22:26601874:CT:C	donor_loss	0.9900
22:26601875:TTACG:T	donor_loss	0.9900
22:26601877:ACG:A	donor_loss	0.9900
22:26601878:C:A	donor_loss	0.9900
22:26601878:CG:C	donor_gain	0.9900

AlphaMissense

1640 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:26612093:C:A	S93I	0.996
22:26607942:A:G	W127R	0.995
22:26607942:A:T	W127R	0.995
22:26608020:A:G	W101R	0.995
22:26608020:A:T	W101R	0.995
22:26612092:G:C	S93R	0.995
22:26612092:G:T	S93R	0.995
22:26612094:T:G	S93R	0.995
22:26612179:G:C	F64L	0.995
22:26612179:G:T	F64L	0.995
22:26612181:A:G	F64L	0.995
22:26599672:A:G	W193R	0.994
22:26599672:A:T	W193R	0.994
22:26607902:C:G	R140P	0.993
22:26599594:A:G	W219R	0.992
22:26599594:A:T	W219R	0.992
22:26601899:G:C	S185R	0.991
22:26601899:G:T	S185R	0.991
22:26601901:T:G	S185R	0.991
22:26608009:A:C	F104L	0.991
22:26608009:A:T	F104L	0.991
22:26608011:A:G	F104L	0.991
22:26599641:C:T	G203E	0.990
22:26607951:A:G	W124R	0.990
22:26607951:A:T	W124R	0.990
22:26607979:G:C	F114L	0.990
22:26607979:G:T	F114L	0.990
22:26607981:A:G	F114L	0.990
22:26612084:A:T	V96D	0.990
22:26599560:C:G	R230P	0.989

dbSNP variants (sampled 300 via entrez): RS1000106932 (22:26607990 C>A,G,T), RS1000307065 (22:26612508 CCCA>C), RS1000489042 (22:26611486 G>T), RS1000612265 (22:26613604 A>G), RS1000643517 (22:26613849 CA>C), RS1000675947 (22:26619852 G>A), RS1000961770 (22:26613559 C>A), RS1001084018 (22:26607782 G>A), RS1001088581 (22:26619558 G>A), RS1001616019 (22:26602982 G>A), RS1001618786 (22:26617869 C>T), RS1001686349 (22:26615344 T>C,G), RS1001697182 (22:26614752 G>T), RS1001731880 (22:26609102 A>G), RS1001784155 (22:26609471 T>C)

Disease associations

OMIM: gene MIM:600929 | disease phenotypes: MIM:181500, MIM:611544

GenCC curated gene-disease

Disease	Classification	Inheritance
cataract 17 multiple types	Definitive	Autosomal dominant
cataract - microcornea syndrome	Supportive	Autosomal dominant
pulverulent cataract	Supportive	Autosomal dominant
early-onset nuclear cataract	Supportive	Autosomal dominant

Mondo (5): schizophrenia (MONDO:0005090), cataract 17 multiple types (MONDO:0012688), cataract - microcornea syndrome (MONDO:0015300), pulverulent cataract (MONDO:0011430), early-onset nuclear cataract (MONDO:0020376)

Orphanet (2): Early onset non-syndromic cataract (Orphanet:91492), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140)

HPO phenotypes

15 total (16 of 15 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000482	Microcornea
HP:0000518	Cataract
HP:0000519	Developmental cataract
HP:0000545	Myopia
HP:0000612	Iris coloboma
HP:0000639	Nystagmus
HP:0000646	Amblyopia
HP:0001131	Corneal dystrophy
HP:0003577	Congenital onset
HP:0007663	Reduced visual acuity
HP:0007957	Corneal opacity
HP:0010693	Pulverulent cataract
HP:0100018	Nuclear cataract
HP:0100753	Schizophrenia

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST009391_1033	Metabolite levels	3.000000e-06
GCST009391_1387	Metabolite levels	4.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0009775	threonine measurement
EFO:0010368	lysophosphatidylethanolamine 18:1 measurement

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
C538287	Cataract microcornea syndrome (supp.)
C563333	Cataract, Age-Related Nuclear (supp.)
C566923	Cataract, Congenital Nuclear, Autosomal Recessive 3 (supp.)
C565133	Cataract, Coppock-Like (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	increases methylation	2
ethyl-p-hydroxybenzoate	increases expression	1
2-palmitoylglycerol	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
Amphotericin B	increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	increases methylation	1
Carmustine	decreases expression	1
Niclosamide	increases expression	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	PHASE4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	PHASE4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	PHASE4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	PHASE4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	PHASE4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	PHASE4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	PHASE4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	PHASE4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	PHASE4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	PHASE4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	PHASE4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	PHASE4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	PHASE4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	PHASE4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia
NCT00176436	PHASE4	COMPLETED	Atomoxetine for Treatment of Weight Gain in Olanzapine or Clozapine Patients
NCT00177008	PHASE4	COMPLETED	Aripiprazole for the Treatment of Schizophrenia With Co-Morbid Social Anxiety