Cataract 17 multiple types

Summary

Cataract 17 multiple types (MONDO:0012688) is a disease caused by CRYBB1 (GenCC Definitive), with 3 cohort genes.

At a glance

• Causal gene: CRYBB1 (GenCC Definitive)
• Cohort genes: 3
• ClinVar variants: 69

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cataract 17 multiple types
Mondo ID	MONDO:0012688
MeSH	C566923
OMIM	611544
DOID	DOID:0110270
UMLS	C3888124
MedGen	854781
GARD	0024881
Is cancer (heuristic)	no

Also known as: cataract 17, multiple types · CRYBB1 early-onset non-syndromic cataract · CTRCT17 · early-onset non-syndromic cataract caused by mutation in CRYBB1

Data availability: 69 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › disorder of orbital region › eye disorder › lens disorder › cataract › early-onset non-syndromic cataract › cataract 17 multiple types

Related subtypes (28): cataract 32 multiple types, cataract 8 multiple types, cataract 42, cataract 20 multiple types, cataract 6 multiple types, cataract 13 with adult I phenotype, cataract 5 multiple types, cataract 46 juvenile-onset, cataract 40, cataract 10 multiple types, cataract 14 multiple types, pulverulent cataract, cataract 31 multiple types, cataract 26 multiple types, cataract 22 multiple types, cataract 21 multiple types, cataract 23, cataract 11 multiple types, cataract 33, cataract 38, cataract 39 multiple types, cataract 15 multiple types, cataract 19 multiple types, cataract 43, cataract 44, cataract 45, early-onset partial cataract, total early-onset cataract

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

69 retrieved; paginated sample, class counts are floors:

39 uncertain significance, 9 likely benign, 6 conflicting classifications of pathogenicity, 6 likely pathogenic, 4 pathogenic, 2 benign, 2 benign/likely benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
419532	NM_001887.4(CRYBB1):c.171del (p.Asn58fs)	CRYBA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
427749	NM_001887.4(CRYBB1):c.387C>A (p.Ser129Arg)	CRYBA4	Pathogenic	no assertion criteria provided
574493	NM_001887.4(CRYBB1):c.585del (p.Tyr196fs)	CRYBA4	Pathogenic	criteria provided, single submitter
8687	NM_001887.4(CRYBB1):c.658G>T (p.Gly220Ter)	CRYBA4	Pathogenic	no assertion criteria provided
7730	NM_000104.4(CYP1B1):c.182G>A (p.Gly61Glu)	CYP1B1	Pathogenic	reviewed by expert panel
1679950	NM_001887.4(CRYBB1):c.419G>C (p.Arg140Pro)	CRYBA4	Likely pathogenic	criteria provided, single submitter
2737022	NM_001887.4(CRYBB1):c.698G>A (p.Arg233His)	CRYBA4	Likely pathogenic	criteria provided, single submitter
3065113	NM_001887.4(CRYBB1):c.2T>A (p.Met1Lys)	CRYBA4	Likely pathogenic	criteria provided, single submitter
3587868	NM_001887.4(CRYBB1):c.387C>G (p.Ser129Arg)	CRYBA4	Likely pathogenic	criteria provided, single submitter
3779548	NM_001887.4(CRYBB1):c.482del (p.Gly161fs)	CRYBA4	Likely pathogenic	criteria provided, single submitter
1879550	NM_001887.4(CRYBB1):c.683C>A (p.Ser228Tyr)	CRYBB1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1385307	NM_001887.4(CRYBB1):c.325T>C (p.Phe109Leu)	CRYBA4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2191216	NM_001887.4(CRYBB1):c.300C>T (p.Pro100=)	CRYBA4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
341042	NM_001887.4(CRYBB1):c.744A>G (p.Thr248=)	CRYBA4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
341047	NM_001887.4(CRYBB1):c.384G>A (p.Ser128=)	CRYBA4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
341049	NM_001887.4(CRYBB1):c.156G>A (p.Ala52=)	CRYBA4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
798218	NM_001887.4(CRYBB1):c.179G>C (p.Arg60Thr)	CRYBB1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1372249	NM_001887.4(CRYBB1):c.358G>A (p.Glu120Lys)	CRYBA4	Uncertain significance	criteria provided, single submitter
1450099	NM_001887.4(CRYBB1):c.394C>T (p.Arg132Cys)	CRYBA4	Uncertain significance	criteria provided, multiple submitters, no conflicts
1899847	NM_001887.4(CRYBB1):c.697C>T (p.Arg233Cys)	CRYBA4	Uncertain significance	criteria provided, multiple submitters, no conflicts
2118150	NM_001887.4(CRYBB1):c.305T>C (p.Val102Ala)	CRYBA4	Uncertain significance	criteria provided, single submitter
2154537	NM_001887.4(CRYBB1):c.640C>T (p.Arg214Trp)	CRYBA4	Uncertain significance	criteria provided, single submitter
2189716	NM_001887.4(CRYBB1):c.753dup (p.Lys252fs)	CRYBA4	Uncertain significance	criteria provided, single submitter
2416624	NM_001887.4(CRYBB1):c.512C>T (p.Ala171Val)	CRYBA4	Uncertain significance	criteria provided, single submitter
2574045	NM_001887.4(CRYBB1):c.508G>C (p.Asp170His)	CRYBA4	Uncertain significance	criteria provided, single submitter
341041	NM_001887.4(CRYBB1):c.*67C>G	CRYBA4	Uncertain significance	criteria provided, single submitter
341043	NM_001887.4(CRYBB1):c.576-3C>A	CRYBA4	Uncertain significance	criteria provided, single submitter
341044	NM_001887.4(CRYBB1):c.448A>G (p.Lys150Glu)	CRYBA4	Uncertain significance	criteria provided, multiple submitters, no conflicts
341045	NM_001887.4(CRYBB1):c.427A>G (p.Lys143Glu)	CRYBA4	Uncertain significance	criteria provided, single submitter
341046	NM_001887.4(CRYBB1):c.394C>G (p.Arg132Gly)	CRYBA4	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 8 · 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
CRYBB1	Definitive	Autosomal dominant	cataract 17 multiple types	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CRYBB1	Orphanet:1377	Cataract-microcornea syndrome
CRYBB1	Orphanet:98984	Pulverulent cataract
CRYBB1	Orphanet:98991	Early-onset nuclear cataract
CRYBA4	Orphanet:1377	Cataract-microcornea syndrome
CRYBA4	Orphanet:441452	Early-onset lamellar cataract
CYP1B1	Orphanet:708	Peters anomaly
CYP1B1	Orphanet:98976	Congenital glaucoma
CYP1B1	Orphanet:98977	Juvenile glaucoma

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CRYBB1	HGNC:2397	ENSG00000100122	P53674	Beta-crystallin B1	gencc,clinvar
CRYBA4	HGNC:2396	ENSG00000196431	P53673	Beta-crystallin A4	clinvar
CYP1B1	HGNC:2597	ENSG00000138061	Q16678	Cytochrome P450 1B1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CRYBB1	Beta-crystallin B1	Crystallins are the dominant structural components of the vertebrate eye lens.
CRYBA4	Beta-crystallin A4	Crystallins are the dominant structural components of the vertebrate eye lens.
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: 3 · 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	3	1.8×	0.174

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CRYBB1	Other/Unknown	no		Beta/gamma_crystallin, G_crystallin-like, Beta/Gamma-Crystallin
CRYBA4	Other/Unknown	no		Beta/gamma_crystallin, G_crystallin-like, Beta/Gamma-Crystallin
CYP1B1	Other/Unknown	no		Cyt_P450, Cyt_P450_E_grp-I, Cyt_P450_CS

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
primordial germ cell in gonad	2
Brodmann (1909) area 10	1
prefrontal cortex	1
frontal pole	1
male germ line stem cell (sensu Vertebrata) in testis	1
cartilage tissue	1
pericardium	1
synovial joint	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CRYBB1	154	broad	yes	primordial germ cell in gonad, prefrontal cortex, Brodmann (1909) area 10
CRYBA4	72	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, frontal pole
CYP1B1	285	ubiquitous	marker	pericardium, cartilage tissue, synovial joint

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CYP1B1	2,883
CRYBB1	1,508
CRYBA4	601

Intra-cohort edges

A	B	Sources
CRYBA4	CRYBB1	intact

Structural data

PDB: 3 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CYP1B1	Q16678	2
CRYBB1	P53674	1
CRYBA4	P53673	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. Enrichment computed across 3 evidence-associated genes (2 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 2 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	5710.0×	0.001	CYP1B1
Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET)	1	713.8×	0.004	CYP1B1
Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE)	1	634.4×	0.004	CYP1B1
Attenuation phase	1	203.9×	0.007	CRYBA4
Endogenous sterols	1	196.9×	0.007	CYP1B1
HSF1 activation	1	190.3×	0.007	CRYBA4
HSF1-dependent transactivation	1	158.6×	0.007	CRYBA4
Regulation of HSF1-mediated heat shock response	1	69.6×	0.014	CRYBA4

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
lens development in camera-type eye	2	249.7×	8e-04	CRYBB1, CRYBA4
benzene-containing compound metabolic process	1	5617.3×	0.003	CYP1B1
trabecular meshwork development	1	2808.7×	0.005	CYP1B1
visual perception	2	53.0×	0.005	CRYBB1, CRYBA4
obsolete membrane lipid catabolic process	1	1404.3×	0.005	CYP1B1
endothelial cell-cell adhesion	1	1404.3×	0.005	CYP1B1
steroid catabolic process	1	802.5×	0.006	CYP1B1
retinal blood vessel morphogenesis	1	802.5×	0.006	CYP1B1
toxin metabolic process	1	702.2×	0.006	CYP1B1
omega-hydroxylase P450 pathway	1	510.7×	0.008	CYP1B1
blood vessel endothelial cell migration	1	468.1×	0.008	CYP1B1
negative regulation of cell adhesion mediated by integrin	1	432.1×	0.008	CYP1B1
retinal metabolic process	1	312.1×	0.009	CYP1B1
epoxygenase P450 pathway	1	295.6×	0.009	CYP1B1
intrinsic apoptotic signaling pathway in response to oxidative stress	1	280.9×	0.009	CYP1B1
sterol metabolic process	1	280.9×	0.009	CYP1B1
blood vessel morphogenesis	1	267.5×	0.009	CYP1B1
regulation of reactive oxygen species metabolic process	1	244.2×	0.009	CYP1B1
nitric oxide biosynthetic process	1	234.1×	0.009	CYP1B1
estrogen metabolic process	1	208.1×	0.009	CYP1B1
xenobiotic catabolic process	1	187.2×	0.010	CYP1B1
positive regulation of vascular endothelial growth factor production	1	165.2×	0.010	CYP1B1
retinol metabolic process	1	165.2×	0.010	CYP1B1
arachidonate metabolic process	1	160.5×	0.010	CYP1B1
positive regulation of receptor signaling pathway via JAK-STAT	1	144.0×	0.011	CYP1B1
endothelial cell migration	1	137.0×	0.011	CYP1B1
obsolete negative regulation of NF-kappaB transcription factor activity	1	119.5×	0.012	CYP1B1
camera-type eye development	1	119.5×	0.012	CRYBA4
steroid metabolic process	1	112.3×	0.012	CYP1B1
cellular response to hydrogen peroxide	1	78.0×	0.017	CYP1B1

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 2

Druggability breadth: 1 of 3 evidence-associated genes (33%) 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
CRYBB1	0	0
CRYBA4	0	0

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: 3; 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	2	CRYBB1, CRYBA4

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CRYBB1	0	—
CRYBA4	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.