Anterior segment dysgenesis 6

Summary

Anterior segment dysgenesis 6 (MONDO:0015016) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 96

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	anterior segment dysgenesis 6
Mondo ID	MONDO:0015016
OMIM	617315
DOID	DOID:0080611
UMLS	C4310623
MedGen	934590
GARD	0025051
Is cancer (heuristic)	no

Also known as: anterior segment dysgenesis 6 · anterior segment dysgenesis 6, multiple subtypes · anterior segment dysgenesis type 6 · ASGD6

Data availability: 96 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › anterior segment dysgenesis › anterior segment dysgenesis 6

Related subtypes (7): anterior segment dysgenesis 1, anterior segment dysgenesis 7, iridogoniodysgenesis, Peters anomaly, congenital primary aphakia, anterior segment dysgenesis 8, isolated iridoschisis

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

96 retrieved; paginated sample, class counts are floors:

32 likely pathogenic, 29 pathogenic, 12 pathogenic/likely pathogenic, 9 uncertain significance, 8 conflicting classifications of pathogenicity, 5 benign, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1076484	NM_000104.4(CYP1B1):c.840C>A (p.Cys280Ter)	CYP1B1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
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
1324202	NM_000104.4(CYP1B1):c.1390dup (p.Ser464fs)	CYP1B1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1335387	NM_000104.4(CYP1B1):c.797GCAACTTCA[1] (p.Ser269_Phe271del)	CYP1B1	Pathogenic	reviewed by expert panel
1339668	NM_000104.4(CYP1B1):c.1090G>A (p.Val364Met)	CYP1B1	Pathogenic	reviewed by expert panel
1339669	NM_000104.4(CYP1B1):c.970_971dup (p.Thr325fs)	CYP1B1	Pathogenic	criteria provided, multiple submitters, no conflicts
1412564	NM_000104.4(CYP1B1):c.1063C>T (p.Arg355Ter)	CYP1B1	Pathogenic	reviewed by expert panel
1442930	NM_000104.4(CYP1B1):c.55C>T (p.Gln19Ter)	CYP1B1	Pathogenic	criteria provided, multiple submitters, no conflicts
2203048	NM_000104.4(CYP1B1):c.1168C>A (p.Arg390Ser)	CYP1B1	Pathogenic	reviewed by expert panel
2203049	NM_000104.4(CYP1B1):c.988_989delinsTT (p.Ala330Phe)	CYP1B1	Pathogenic	criteria provided, multiple submitters, no conflicts
2577219	NM_000104.4(CYP1B1):c.317C>A (p.Ala106Asp)	CYP1B1	Pathogenic	reviewed by expert panel
2637448	NM_000104.4(CYP1B1):c.277_306delinsGG (p.Pro93fs)	CYP1B1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
265390	NM_000104.4(CYP1B1):c.830del (p.Phe276_Leu277insTer)	CYP1B1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2681125	NM_000104.4(CYP1B1):c.1075G>T (p.Glu359Ter)	CYP1B1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2681129	NM_000104.4(CYP1B1):c.346_363del (p.Asp116_Ala121del)	CYP1B1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2681130	NM_000104.4(CYP1B1):c.872A>G (p.Asp291Gly)	CYP1B1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2681133	NM_000104.4(CYP1B1):c.575A>T (p.Asp192Val)	CYP1B1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2681137	NM_000104.4(CYP1B1):c.868del (p.Arg290fs)	CYP1B1	Pathogenic	criteria provided, multiple submitters, no conflicts
2681138	NM_000104.4(CYP1B1):c.1140dup (p.Val381fs)	CYP1B1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2681139	NM_000104.4(CYP1B1):c.1023G>A (p.Trp341Ter)	CYP1B1	Pathogenic	criteria provided, multiple submitters, no conflicts
2734165	NM_000104.4(CYP1B1):c.243C>G (p.Tyr81Ter)	CYP1B1	Pathogenic	criteria provided, multiple submitters, no conflicts
282564	NM_000104.4(CYP1B1):c.1064_1076del (p.Arg355fs)	CYP1B1	Pathogenic	reviewed by expert panel
2860750	NM_000104.4(CYP1B1):c.218C>A (p.Ser73Ter)	CYP1B1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2996356	NM_000104.4(CYP1B1):c.1223_1224del (p.Ser408fs)	CYP1B1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
335952	NM_000104.4(CYP1B1):c.1168C>T (p.Arg390Cys)	CYP1B1	Pathogenic	reviewed by expert panel
523782	NM_000104.4(CYP1B1):c.1330C>T (p.Arg444Ter)	CYP1B1	Pathogenic	criteria provided, multiple submitters, no conflicts
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

Genes & proteins

Mendelian disease overlap and somatic drivers

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

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	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.