CYP1B1-related glaucoma with or without anterior segment dysgenesis

Summary

CYP1B1-related glaucoma with or without anterior segment dysgenesis (MONDO:0800472) is a disease caused by CYP1B1 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: CYP1B1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 59

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	CYP1B1-related glaucoma with or without anterior segment dysgenesis
Mondo ID	MONDO:0800472
GARD	0026571
Is cancer (heuristic)	no

Data availability: 59 ClinVar variants · 59 ClinGen variant curations · 1 GenCC gene-disease record.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › hereditary glaucoma › congenital glaucoma › primary congenital glaucoma › CYP1B1-related glaucoma with or without anterior segment dysgenesis

Related subtypes (2): glaucoma 3, primary congenital, C, glaucoma 3, primary congenital, D

Subtypes (2): glaucoma 3A, anterior segment dysgenesis 6

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

59 retrieved; paginated sample, class counts are floors:

26 pathogenic, 11 uncertain significance, 10 likely pathogenic, 8 benign, 4 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1120045	NM_000104.4(CYP1B1):c.434_443del (p.Arg145fs)	CYP1B1	Pathogenic	reviewed by expert panel
1254629	NM_000104.4(CYP1B1):c.1310C>T (p.Pro437Leu)	CYP1B1	Pathogenic	reviewed by expert panel
1322184	NM_000104.4(CYP1B1):c.517G>T (p.Glu173Ter)	CYP1B1	Pathogenic	reviewed by expert panel
1335387	NM_000104.4(CYP1B1):c.797GCAACTTCA[1] (p.Ser269_Phe271del)	CYP1B1	Pathogenic	reviewed by expert panel
1339135	NM_000104.4(CYP1B1):c.1044-2A>G	CYP1B1	Pathogenic	reviewed by expert panel
1339668	NM_000104.4(CYP1B1):c.1090G>A (p.Val364Met)	CYP1B1	Pathogenic	reviewed by expert panel
1412564	NM_000104.4(CYP1B1):c.1063C>T (p.Arg355Ter)	CYP1B1	Pathogenic	reviewed by expert panel
2203048	NM_000104.4(CYP1B1):c.1168C>A (p.Arg390Ser)	CYP1B1	Pathogenic	reviewed by expert panel
2577219	NM_000104.4(CYP1B1):c.317C>A (p.Ala106Asp)	CYP1B1	Pathogenic	reviewed by expert panel
282564	NM_000104.4(CYP1B1):c.1064_1076del (p.Arg355fs)	CYP1B1	Pathogenic	reviewed by expert panel
335952	NM_000104.4(CYP1B1):c.1168C>T (p.Arg390Cys)	CYP1B1	Pathogenic	reviewed by expert panel
3777763	NC_000002.12:g.38012214_38131522del	CYP1B1	Pathogenic	reviewed by expert panel
4530667	NM_000104.4(CYP1B1):c.784G>T (p.Glu262Ter)	CYP1B1	Pathogenic	reviewed by expert panel
4530669	NM_000104.4(CYP1B1):c.1044-1G>C	CYP1B1	Pathogenic	reviewed by expert panel
4530671	NM_000104.4(CYP1B1):c.1454C>T (p.Ser485Phe)	CYP1B1	Pathogenic	reviewed by expert panel
4530672	NM_000104.4(CYP1B1):c.1568G>C (p.Arg523Thr)	CYP1B1	Pathogenic	reviewed by expert panel
523943	NM_000104.4(CYP1B1):c.535del (p.Ala179fs)	CYP1B1	Pathogenic	reviewed by expert panel
592512	NM_000104.4(CYP1B1):c.1169G>A (p.Arg390His)	CYP1B1	Pathogenic	reviewed by expert panel
68466	NM_000104.4(CYP1B1):c.1200_1209dup (p.Thr404fs)	CYP1B1	Pathogenic	reviewed by expert panel
68468	NM_000104.4(CYP1B1):c.868dup (p.Arg290fs)	CYP1B1	Pathogenic	reviewed by expert panel
7730	NM_000104.4(CYP1B1):c.182G>A (p.Gly61Glu)	CYP1B1	Pathogenic	reviewed by expert panel
7733	NM_000104.4(CYP1B1):c.1405C>T (p.Arg469Trp)	CYP1B1	Pathogenic	reviewed by expert panel
7735	NM_000104.4(CYP1B1):c.1159G>A (p.Glu387Lys)	CYP1B1	Pathogenic	reviewed by expert panel
7736	NM_000104.4(CYP1B1):c.2T>C (p.Met1Thr)	CYP1B1	Pathogenic	reviewed by expert panel
7737	NM_000104.4(CYP1B1):c.171G>A (p.Trp57Ter)	CYP1B1	Pathogenic	reviewed by expert panel
845455	NM_000104.4(CYP1B1):c.1331G>A (p.Arg444Gln)	CYP1B1	Pathogenic	reviewed by expert panel
1331361	NM_000104.4(CYP1B1):c.1198C>T (p.Pro400Ser)	CYP1B1	Likely pathogenic	reviewed by expert panel
1338800	NM_000104.4(CYP1B1):c.710C>A (p.Ala237Glu)	CYP1B1	Likely pathogenic	reviewed by expert panel
1489392	NM_000104.4(CYP1B1):c.1102C>T (p.Arg368Cys)	CYP1B1	Likely pathogenic	reviewed by expert panel
2681127	NM_000104.4(CYP1B1):c.1027CTC[2] (p.Leu345del)	CYP1B1	Likely pathogenic	reviewed by expert panel

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
CYP1B1	Definitive	Autosomal recessive	CYP1B1-related glaucoma with or without anterior segment dysgenesis	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CYP1B1	Orphanet:708	Peters anomaly
CYP1B1	Orphanet:98976	Congenital glaucoma
CYP1B1	Orphanet:98977	Juvenile glaucoma

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CYP1B1	HGNC:2597	ENSG00000138061	Q16678	Cytochrome P450 1B1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CYP1B1	Cytochrome P450 1B1	A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CYP1B1	Other/Unknown	no		Cyt_P450, Cyt_P450_E_grp-I, Cyt_P450_CS

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cartilage tissue	1
pericardium	1
synovial joint	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CYP1B1	285	ubiquitous	marker	pericardium, cartilage tissue, synovial joint

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CYP1B1	2,883

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CYP1B1	Q16678	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective CYP1B1 causes Glaucoma	1	11420.0×	4e-04	CYP1B1
Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET)	1	1427.5×	0.001	CYP1B1
Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE)	1	1268.9×	0.001	CYP1B1
Endogenous sterols	1	393.8×	0.003	CYP1B1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
benzene-containing compound metabolic process	1	16852.0×	0.002	CYP1B1
trabecular meshwork development	1	8426.0×	0.002	CYP1B1
obsolete membrane lipid catabolic process	1	4213.0×	0.002	CYP1B1
endothelial cell-cell adhesion	1	4213.0×	0.002	CYP1B1
steroid catabolic process	1	2407.4×	0.002	CYP1B1
retinal blood vessel morphogenesis	1	2407.4×	0.002	CYP1B1
toxin metabolic process	1	2106.5×	0.002	CYP1B1
omega-hydroxylase P450 pathway	1	1532.0×	0.003	CYP1B1
blood vessel endothelial cell migration	1	1404.3×	0.003	CYP1B1
negative regulation of cell adhesion mediated by integrin	1	1296.3×	0.003	CYP1B1
retinal metabolic process	1	936.2×	0.003	CYP1B1
epoxygenase P450 pathway	1	887.0×	0.003	CYP1B1
intrinsic apoptotic signaling pathway in response to oxidative stress	1	842.6×	0.003	CYP1B1
sterol metabolic process	1	842.6×	0.003	CYP1B1
blood vessel morphogenesis	1	802.5×	0.003	CYP1B1
regulation of reactive oxygen species metabolic process	1	732.7×	0.003	CYP1B1
nitric oxide biosynthetic process	1	702.2×	0.003	CYP1B1
estrogen metabolic process	1	624.1×	0.003	CYP1B1
xenobiotic catabolic process	1	561.7×	0.003	CYP1B1
positive regulation of vascular endothelial growth factor production	1	495.6×	0.003	CYP1B1
retinol metabolic process	1	495.6×	0.003	CYP1B1
arachidonate metabolic process	1	481.5×	0.003	CYP1B1
positive regulation of receptor signaling pathway via JAK-STAT	1	432.1×	0.004	CYP1B1
endothelial cell migration	1	411.0×	0.004	CYP1B1
obsolete negative regulation of NF-kappaB transcription factor activity	1	358.6×	0.004	CYP1B1
steroid metabolic process	1	337.0×	0.004	CYP1B1
cellular response to hydrogen peroxide	1	234.1×	0.006	CYP1B1
collagen fibril organization	1	224.7×	0.006	CYP1B1
response to toxic substance	1	210.7×	0.006	CYP1B1
xenobiotic metabolic process	1	149.1×	0.008	CYP1B1

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
CYP1B1	PAZOPANIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CYP1B1	22	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PAZOPANIB	4	CYP1B1
INDACATEROL	4	CYP1B1
ESTRADIOL	4	CYP1B1
CANNABIDIOL	4	CYP1B1
BERBERINE	4	CYP1B1
MELATONIN	4	CYP1B1
ERYTHROMYCIN	4	CYP1B1
CARVEDILOL	4	CYP1B1
RESVERATROL	3	CYP1B1
BERGAPTEN	3	CYP1B1
QUERCETIN	3	CYP1B1
CANNABINOL	3	CYP1B1
LUTEOLIN	2	CYP1B1
FORMONONETIN	2	CYP1B1
FLAVONE	2	CYP1B1
2-METHOXYESTRADIOL	2	CYP1B1
PINOCEMBRIN	2	CYP1B1
KHELLIN	2	CYP1B1
BAICALEIN	2	CYP1B1
PTEROSTILBENE	2	CYP1B1
KAEMPFEROL	1	CYP1B1
PLUMBAGIN	1	CYP1B1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
CYP1B1	408	ADMET:281, Binding:127

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
CYP1B1	408

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

22 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
PAZOPANIB	4	CYP1B1
INDACATEROL	4	CYP1B1
ESTRADIOL	4	CYP1B1
CANNABIDIOL	4	CYP1B1
BERBERINE	4	CYP1B1
MELATONIN	4	CYP1B1
ERYTHROMYCIN	4	CYP1B1
CARVEDILOL	4	CYP1B1
RESVERATROL	3	CYP1B1
BERGAPTEN	3	CYP1B1
QUERCETIN	3	CYP1B1
CANNABINOL	3	CYP1B1
LUTEOLIN	2	CYP1B1
FORMONONETIN	2	CYP1B1
FLAVONE	2	CYP1B1
2-METHOXYESTRADIOL	2	CYP1B1
PINOCEMBRIN	2	CYP1B1
KHELLIN	2	CYP1B1
BAICALEIN	2	CYP1B1
PTEROSTILBENE	2	CYP1B1
KAEMPFEROL	1	CYP1B1
PLUMBAGIN	1	CYP1B1

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	CYP1B1
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 0.