CYP1B1

cytochrome P450 family 1 subfamily B member 1, the group of Cytochrome P450 family 1

Basic information

Region (hg38): 2:38066972-38109902

Previous symbols: [ "GLC3A" ]

Links

ENSG00000138061 ∙ NCBI:1545 ∙ OMIM:601771 ∙ HGNC:2597 ∙ Uniprot:Q16678 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• glaucoma 3A (Definitive), mode of inheritance: AR
• anterior segment dysgenesis 6 (Strong), mode of inheritance: AD
• Peters anomaly (Supportive), mode of inheritance: AD
• congenital glaucoma (Supportive), mode of inheritance: AD
• glaucoma 3A (Definitive), mode of inheritance: AR
• glaucoma 3A (Strong), mode of inheritance: AR
• CYP1B1-related glaucoma with or without anterior segment dysgenesis (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Glaucoma 3A, primary congenital, A; Anterior segment dysgenesis 6	AR	Ophthalmologic; Pharmacogenomic	Early diagnosis and treatment with surgery (with the use of pre and postoperative agents to control intraocular pressure), or, if surgery is not effective, drainage implants or cyclodestruction, may be effective to decrease morbidity and mortality related to vision loss; Agents that may contribute to glaucoma, as well as alpha-2-agonists, should be avoided	Ophthalmologic	9097971; 9463332; 9497261; 10227395; 10655546; 11730663; 11403040; 12372064; 11774072; 15342693; 15733270; 17718864; 19807744; 19643970; 20301314; 21081970; 21600657; 22128238; 22942166; 23218701; 23363883; 24227805; 27839872
Severe and difficult to treat glaucoma has been reported in many individuals with Peters anomaly; heterozygous variants may increase susceptibility to glaucoma; Digenic inheritance (with MYOC) has been reported; Variants may also act as disease modifiers (eg, related to Glaucoma, age of onset)

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CYP1B1 gene.

• Glaucoma 3A (141 variants)
• Congenital glaucoma (134 variants)
• Irido-corneo-trabecular dysgenesis (125 variants)
• not provided (63 variants)
• Anterior segment dysgenesis 6 (60 variants)
• not specified (37 variants)
• Primary congenital glaucoma (31 variants)
• Inborn genetic diseases (20 variants)
• Glaucoma 3A;Glaucoma 3, primary infantile, B;Anterior segment dysgenesis 6 (10 variants)
• Anterior segment dysgenesis 6;Glaucoma 3A;Glaucoma 3, primary infantile, B (9 variants)
• CYP1B1-related condition (6 variants)
• Anterior segment dysgenesis (5 variants)
• CYP1B1-Related Disorders (4 variants)
• Congenital ocular coloboma (4 variants)
• Glaucoma 3, primary infantile, B;Anterior segment dysgenesis 6;Glaucoma 3A (4 variants)
• Glaucoma, primary open angle, juvenile-onset (2 variants)
• Anterior segment dysgenesis 6;Glaucoma 3A (1 variants)
• Primary open angle glaucoma (1 variants)
• Glaucoma 3, primary infantile, B;Glaucoma 3A;Anterior segment dysgenesis 6 (1 variants)
• Glaucoma, early-onset, digenic (1 variants)
• Glaucoma of childhood (1 variants)
• Irido-corneo-trabecular dysgenesis;Glaucoma 3A (1 variants)
• Glaucoma 3A;Anterior segment dysgenesis 6;Glaucoma 3, primary infantile, B (1 variants)
• Myopathy, centronuclear, 5 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CYP1B1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			6	50	5	61
missense	10	18	66	7	2	103
nonsense	8	8				16
start loss	1	2				3
frameshift	13	10				23
inframe indel		3				3
splice donor/acceptor (+/-2bp)		1	1			2
splice region			2			2
non coding			69	11	13	93
Total	32	42	142	68	20

Highest pathogenic variant AF is 0.000223

Variants in CYP1B1

This is a list of pathogenic ClinVar variants found in the CYP1B1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-38067636-A-T		Irido-corneo-trabecular dysgenesis • Glaucoma 3A	Uncertain significance (Jan 13, 2018)
2-38067644-C-T		Glaucoma 3A • Irido-corneo-trabecular dysgenesis	Uncertain significance (Jan 13, 2018)
2-38067658-T-A		Glaucoma 3A • Irido-corneo-trabecular dysgenesis	Uncertain significance (Jan 13, 2018)
2-38067698-A-G		Glaucoma 3A • Irido-corneo-trabecular dysgenesis	Uncertain significance (Jan 12, 2018)
2-38067962-G-T		Irido-corneo-trabecular dysgenesis • Glaucoma 3A	Uncertain significance (Jan 13, 2018)
2-38068062-A-T		Glaucoma 3A • Irido-corneo-trabecular dysgenesis	Uncertain significance (Jan 12, 2018)
2-38068125-T-C		Irido-corneo-trabecular dysgenesis • Glaucoma 3A	Uncertain significance (Mar 30, 2018)
2-38068223-A-G		Irido-corneo-trabecular dysgenesis • Glaucoma 3A	Uncertain significance (Jan 13, 2018)
2-38068224-A-G		Irido-corneo-trabecular dysgenesis • Glaucoma 3A	Uncertain significance (Jan 13, 2018)
2-38068313-T-A		Glaucoma 3A • Irido-corneo-trabecular dysgenesis	Benign (Jan 13, 2018)
2-38068351-A-G		Irido-corneo-trabecular dysgenesis • Glaucoma 3A	Likely benign (Apr 27, 2017)
2-38068373-C-T		Irido-corneo-trabecular dysgenesis • Glaucoma 3A	Uncertain significance (Jan 12, 2018)
2-38068389-C-T		Primary congenital glaucoma • Irido-corneo-trabecular dysgenesis	Uncertain significance (Jun 14, 2016)
2-38068407-T-TA		Irido-corneo-trabecular dysgenesis • Primary congenital glaucoma	Uncertain significance (Jun 14, 2016)
2-38068418-T-G		Glaucoma 3A • Irido-corneo-trabecular dysgenesis	Uncertain significance (Jan 13, 2018)
2-38068433-C-A		Irido-corneo-trabecular dysgenesis • Glaucoma 3A	Uncertain significance (Jan 13, 2018)
2-38068461-T-G		Irido-corneo-trabecular dysgenesis • Glaucoma 3A	Likely benign (Jan 13, 2018)
2-38068513-T-C		Glaucoma 3A • Irido-corneo-trabecular dysgenesis	Uncertain significance (Jan 12, 2018)
2-38068515-C-T		Irido-corneo-trabecular dysgenesis • Glaucoma 3A	Uncertain significance (Jan 13, 2018)
2-38068564-A-G		Glaucoma 3A • Irido-corneo-trabecular dysgenesis	Likely benign (Jan 13, 2018)
2-38068571-A-G		Irido-corneo-trabecular dysgenesis • Primary congenital glaucoma	Uncertain significance (Jun 14, 2016)
2-38068761-C-G		Irido-corneo-trabecular dysgenesis • Glaucoma 3A	Uncertain significance (Jan 13, 2018)
2-38068766-T-C		Glaucoma 3A • Irido-corneo-trabecular dysgenesis	Uncertain significance (Jan 12, 2018)
2-38068784-C-T		Glaucoma 3A • Irido-corneo-trabecular dysgenesis	Uncertain significance (Jan 13, 2018)
2-38068812-T-C		Irido-corneo-trabecular dysgenesis • Glaucoma 3A	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CYP1B1	protein_coding	protein_coding	ENST00000260630	2	42929

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000220	0.744	125543	0	203	125746	0.000808

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.748	356	318	1.12	0.0000155	3494
Missense in Polyphen		139	133.73	1.0394		1509
Synonymous	-1.92	171	142	1.21	0.00000711	1138
Loss of Function	1.10	9	13.4	0.674	7.10e-7	120

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00133	0.00132
Ashkenazi Jewish	0.000101	0.0000992
East Asian	0.000442	0.000435
Finnish	0.000185	0.000185
European (Non-Finnish)	0.00122	0.00113
Middle Eastern	0.000442	0.000435
South Asian	0.000332	0.000327
Other	0.00147	0.00147

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, retinoid and xenobiotics. Preferentially oxidizes 17beta- estradiol to the carcinogenic 4-hydroxy derivative, and a variety of procarcinogenic compounds to their activated forms, including polycyclic aromatic hydrocarbons. Promotes angiogenesis by removing cellular oxygenation products, thereby decreasing oxidative stress, release of antiangiogenic factor THBS2, then allowing endothelial cells migration, cell adhesion and capillary morphogenesis. These changes are concommitant with the endothelial nitric oxide synthase activity and nitric oxide synthesis. Plays an important role in the regulation of perivascular cell proliferation, migration, and survival through modulation of the intracellular oxidative state and NF-kappa-B expression and/or activity, during angiogenesis. Contributes to oxidative homeostasis and ultrastructural organization and function of trabecular meshwork tissue through modulation of POSTN expression. {ECO:0000269|PubMed:10426814, ECO:0000269|PubMed:15258110, ECO:0000269|PubMed:22888116, ECO:0000269|PubMed:23821647}.
• Disease: DISEASE: Anterior segment dysgenesis 6 (ASGD6) [MIM:617315]: A form of anterior segment dysgenesis, a group of defects affecting anterior structures of the eye including cornea, iris, lens, trabecular meshwork, and Schlemm canal. Anterior segment dysgeneses result from abnormal migration or differentiation of the neural crest derived mesenchymal cells that give rise to components of the anterior chamber during eye development. Different anterior segment anomalies may exist alone or in combination, including iris hypoplasia, enlarged or reduced corneal diameter, corneal vascularization and opacity, posterior embryotoxon, corectopia, polycoria, abnormal iridocorneal angle, ectopia lentis, and anterior synechiae between the iris and posterior corneal surface. Clinical conditions falling within the phenotypic spectrum of anterior segment dysgeneses include aniridia, Axenfeld anomaly, Reiger anomaly/syndrome, Peters anomaly, and iridogoniodysgenesis. ASGD6 patients predominantly manifest Peters anomaly. Peters anomaly consists of corneal leukoma, defects in the posterior structures of the cornea such as absence of the posterior corneal stroma and Descemet membrane, and a variable degree of iridocorneal and/or keratolenticular adhesions. Over 50% of patients develop glaucoma in childhood. {ECO:0000269|PubMed:11403040}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Glaucoma 3, primary congenital, A (GLC3A) [MIM:231300]: An autosomal recessive form of primary congenital glaucoma (PCG). PCG is characterized by marked increase of intraocular pressure at birth or early childhood, large ocular globes (buphthalmos) and corneal edema. It results from developmental defects of the trabecular meshwork and anterior chamber angle of the eye that prevent adequate drainage of aqueous humor. {ECO:0000269|PubMed:10227395, ECO:0000269|PubMed:10655546, ECO:0000269|PubMed:11184479, ECO:0000269|PubMed:11527932, ECO:0000269|PubMed:11774072, ECO:0000269|PubMed:11980847, ECO:0000269|PubMed:12036985, ECO:0000269|PubMed:12525557, ECO:0000269|PubMed:14635112, ECO:0000269|PubMed:14640114, ECO:0000269|PubMed:15255109, ECO:0000269|PubMed:15342693, ECO:0000269|PubMed:15475877, ECO:0000269|PubMed:16490498, ECO:0000269|PubMed:16688110, ECO:0000269|PubMed:16735994, ECO:0000269|PubMed:16862072, ECO:0000269|PubMed:18470941, ECO:0000269|PubMed:9463332, ECO:0000269|PubMed:9497261}. Note=The disease is caused by mutations affecting distinct genetic loci, including the gene represented in this entry.; DISEASE: Glaucoma 1, open angle, A (GLC1A) [MIM:137750]: A form of primary open angle glaucoma (POAG). POAG is characterized by a specific pattern of optic nerve and visual field defects. The angle of the anterior chamber of the eye is open, and usually the intraocular pressure is increased. However, glaucoma can occur at any intraocular pressure. The disease is generally asymptomatic until the late stages, by which time significant and irreversible optic nerve damage has already taken place. {ECO:0000269|PubMed:11774072}. Note=The gene represented in this entry acts as a disease modifier. Digenic mutations in CYP1B1 and MYOC have been found in a family segregating both primary adult- onset and juvenile forms of open angle glaucoma (PubMed:11774072). All affected family members with mutations in both MYOC and CYP1B1 had juvenile glaucoma, whereas those with only the MYOC mutation had the adult-onset form (PubMed:11774072). {ECO:0000269|PubMed:11774072}.
• Pathway: Amodiaquine Pathway, Pharmacokinetics;Tryptophan metabolism - Homo sapiens (human);Steroid hormone biosynthesis - Homo sapiens (human);Metabolism of xenobiotics by cytochrome P450 - Homo sapiens (human);Chemical carcinogenesis - Homo sapiens (human);MicroRNAs in cancer - Homo sapiens (human);Ovarian steroidogenesis - Homo sapiens (human);Estrogen Metabolism Pathway;Taxane Pathway, Pharmacokinetics;miR-targeted genes in adipocytes - TarBase;miR-targeted genes in epithelium - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;Sulindac Metabolic Pathway;Aryl Hydrocarbon Receptor;Aryl Hydrocarbon Receptor Pathway;Estrogen Receptor Pathway;Nuclear Receptors Meta-Pathway;Melatonin metabolism and effects;Liver steatosis AOP;Oxidation by Cytochrome P450;Tryptophan metabolism;Tamoxifen metabolism;Benzo(a)pyrene metabolism;Estrogen metabolism;Metapathway biotransformation Phase I and II;Phase I - Functionalization of compounds;Metabolism of lipids;Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE);Arachidonic acid metabolism;Endogenous sterols;Tyrosine metabolism;Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET);Androgen and estrogen biosynthesis and metabolism;Cytochrome P450 - arranged by substrate type;Leukotriene metabolism;Biological oxidations;Metabolism;Fatty acid metabolism;Linoleate metabolism;C21-steroid hormone biosynthesis and metabolism;Xenobiotics metabolism;Tryptophan degradation;superpathway of tryptophan utilization;melatonin degradation I;superpathway of melatonin degradation;Arachidonic acid metabolism (Consensus)

Recessive Scores

• pRec: 0.620

Intolerance Scores

• loftool: 0.351
• rvis_EVS: 0.44
• rvis_percentile_EVS: 77.91

Haploinsufficiency Scores

• pHI: 0.108
• hipred: N
• hipred_score: 0.300
• ghis: 0.394

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.893

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Cyp1b1
• Phenotype: neoplasm; vision/eye phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: angiogenesis;trabecular meshwork development;cellular aromatic compound metabolic process;xenobiotic metabolic process;nitric oxide biosynthetic process;cell adhesion;visual perception;steroid metabolic process;estrogen metabolic process;negative regulation of cell population proliferation;intrinsic apoptotic signaling pathway in response to oxidative stress;toxin metabolic process;positive regulation of vascular endothelial growth factor production;sterol metabolic process;arachidonic acid metabolic process;epoxygenase P450 pathway;collagen fibril organization;negative regulation of cell migration;negative regulation of NF-kappaB transcription factor activity;negative regulation of cell adhesion mediated by integrin;retinol metabolic process;retinal metabolic process;positive regulation of apoptotic process;endothelial cell migration;positive regulation of angiogenesis;positive regulation of JAK-STAT cascade;membrane lipid catabolic process;blood vessel morphogenesis;oxidation-reduction process;retinal blood vessel morphogenesis;cellular response to hydrogen peroxide;cellular response to organic cyclic compound;endothelial cell-cell adhesion;omega-hydroxylase P450 pathway;regulation of reactive oxygen species metabolic process
• Cellular component: mitochondrion;endoplasmic reticulum membrane;organelle membrane
• Molecular function: monooxygenase activity;iron ion binding;oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen;oxygen binding;heme binding;aromatase activity