Cataract 22 multiple types

disease

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Also known as cataract 22cataract 22, multiple typesCRYBB3 early-onset non-syndromic cataractCTRCT22early-onset non-syndromic cataract caused by mutation in CRYBB3

Summary

Cataract 22 multiple types (MONDO:0012336) is a disease caused by CRYBB3 (GenCC Definitive), with 1 cohort gene.

At a glance

Causal gene: CRYBB3 (GenCC Definitive)
Cohort genes: 1
ClinVar variants: 67

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cataract 22 multiple types
Mondo ID	MONDO:0012336
MeSH	C565725
OMIM	609741
DOID	DOID:0110268
UMLS	C1857853
MedGen	341862
GARD	0024861
Is cancer (heuristic)	no

Also known as: cataract 22 · cataract 22, multiple types · CRYBB3 early-onset non-syndromic cataract · CTRCT22 · early-onset non-syndromic cataract caused by mutation in CRYBB3

Data availability: 67 ClinVar variants · 6 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 22 multiple types

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

67 retrieved; paginated sample, class counts are floors:

36 uncertain significance, 11 conflicting classifications of pathogenicity, 7 likely benign, 5 benign/likely benign, 3 likely pathogenic, 3 benign, 2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
143233	NM_004076.5(CRYBB3):c.581T>A (p.Val194Glu)	CRYBB3	Pathogenic	no assertion criteria provided
16948	NM_004076.5(CRYBB3):c.493G>C (p.Gly165Arg)	CRYBB3	Pathogenic	no assertion criteria provided
2009486	NM_004076.5(CRYBB3):c.392T>G (p.Ile131Arg)	CRYBB3	Likely pathogenic	criteria provided, single submitter
3901180	NM_004076.5(CRYBB3):c.466G>C (p.Gly156Arg)	CRYBB3	Likely pathogenic	criteria provided, single submitter
4456860	NM_004076.5(CRYBB3):c.470+1G>A	CRYBB3	Likely pathogenic	criteria provided, single submitter
1955730	NM_004076.5(CRYBB3):c.96G>T (p.Glu32Asp)	CRYBB3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2819792	NM_004076.5(CRYBB3):c.287G>A (p.Arg96His)	CRYBB3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
340949	NM_004076.5(CRYBB3):c.38C>G (p.Ala13Gly)	CRYBB3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
340952	NM_004076.5(CRYBB3):c.213C>T (p.Ser71=)	CRYBB3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
340957	NM_004076.5(CRYBB3):c.584G>A (p.Arg195His)	CRYBB3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
4007160	NM_004076.5(CRYBB3):c.619C>T (p.Arg207Cys)	CRYBB3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
466361	NM_004076.5(CRYBB3):c.547G>T (p.Glu183Ter)	CRYBB3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
534700	NM_004076.5(CRYBB3):c.466G>A (p.Gly156Arg)	CRYBB3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
631888	NM_004076.5(CRYBB3):c.327+1G>T	CRYBB3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
902426	NM_004076.5(CRYBB3):c.125C>T (p.Ser42Leu)	CRYBB3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
903287	NM_004076.5(CRYBB3):c.235T>A (p.Phe79Ile)	CRYBB3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1000861	NM_004076.5(CRYBB3):c.503G>A (p.Gly168Glu)	CRYBB3	Uncertain significance	criteria provided, single submitter
1003766	NM_004076.5(CRYBB3):c.263G>A (p.Arg88His)	CRYBB3	Uncertain significance	criteria provided, single submitter
1381388	NM_004076.5(CRYBB3):c.157C>A (p.Leu53Met)	CRYBB3	Uncertain significance	criteria provided, single submitter
2425017	NC_000022.10:g.(?25601167)(25601349_?)dup	CRYBB3	Uncertain significance	criteria provided, single submitter
2893328	NM_004076.5(CRYBB3):c.159_160insTCG (p.Leu53_Glu54insSer)	CRYBB3	Uncertain significance	criteria provided, single submitter
340948	NM_004076.5(CRYBB3):c.25G>A (p.Glu9Lys)	CRYBB3	Uncertain significance	criteria provided, multiple submitters, no conflicts
340950	NM_004076.5(CRYBB3):c.144G>A (p.Leu48=)	CRYBB3	Uncertain significance	criteria provided, single submitter
340951	NM_004076.5(CRYBB3):c.174C>T (p.Ser58=)	CRYBB3	Uncertain significance	criteria provided, single submitter
340953	NM_004076.5(CRYBB3):c.313C>T (p.Arg105Trp)	CRYBB3	Uncertain significance	criteria provided, single submitter
340954	NM_004076.5(CRYBB3):c.379C>T (p.Arg127Cys)	CRYBB3	Uncertain significance	criteria provided, multiple submitters, no conflicts
340955	NM_004076.5(CRYBB3):c.506G>A (p.Arg169His)	CRYBB3	Uncertain significance	criteria provided, single submitter
340958	NM_004076.5(CRYBB3):c.603G>T (p.Lys201Asn)	CRYBB3	Uncertain significance	criteria provided, multiple submitters, no conflicts
340960	NM_004076.5(CRYBB3):c.*103C>T	CRYBB3	Uncertain significance	criteria provided, single submitter
340961	NM_004076.5(CRYBB3):c.*143C>T	CRYBB3	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · Orphanet: 2 · 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
CRYBB3	Definitive	Autosomal recessive	cataract 22 multiple types	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CRYBB3	Orphanet:98988	Early-onset anterior polar cataract
CRYBB3	Orphanet:98991	Early-onset nuclear cataract

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
CRYBB3	HGNC:2400	ENSG00000100053	P26998	Beta-crystallin B3	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CRYBB3	Beta-crystallin B3	Crystallins are the dominant structural components of the vertebrate eye lens.

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)
CRYBB3	Other/Unknown	no		Beta/gamma_crystallin, G_crystallin-like, Beta/Gamma-Crystallin

Expression context

Cohort genes with no expression data: 0.

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
buccal mucosa cell	1
male germ line stem cell (sensu Vertebrata) in testis	1
mucosa of transverse colon	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CRYBB3	145	tissue_specific	yes	male germ line stem cell (sensu Vertebrata) in testis, buccal mucosa cell, mucosa of transverse colon

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CRYBB3	1,718

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CRYBB3	P26998	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
lens development in camera-type eye	1	374.5×	0.005	CRYBB3
visual perception	1	79.5×	0.013	CRYBB3

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CRYBB3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
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	1	CRYBB3

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CRYBB3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: CRYBB3