Cataract 10 multiple types

Summary

Cataract 10 multiple types (MONDO:0010948) is a disease caused by CRYBA1 (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: CRYBA1 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 50

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cataract 10 multiple types
Mondo ID	MONDO:0010948
MeSH	C563435
OMIM	600881
DOID	DOID:0110258
UMLS	C1833229
MedGen	318817
GARD	0024764
Is cancer (heuristic)	no

Also known as: cataract 10, multiple types · CRYBA1 early-onset non-syndromic cataract · CTRCT10 · early-onset non-syndromic cataract caused by mutation in CRYBA1

Data availability: 50 ClinVar variants · 3 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 10 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 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 17 multiple types, 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

50 retrieved; paginated sample, class counts are floors:

16 uncertain significance, 7 likely pathogenic, 6 likely benign, 6 benign, 5 benign/likely benign, 4 pathogenic, 3 conflicting classifications of pathogenicity, 3 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1073011	NM_005208.5(CRYBA1):c.215+1G>C	CRYBA1	Pathogenic	criteria provided, single submitter
3382052	NM_005208.5(CRYBA1):c.279C>A (p.Tyr93Ter)	CRYBA1	Pathogenic	criteria provided, single submitter
425127	NM_005208.5(CRYBA1):c.269GAG[1] (p.Gly91del)	CRYBA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4695766	NM_005208.5(CRYBA1):c.340C>T (p.Arg114Cys)	CRYBA1	Pathogenic	criteria provided, single submitter
521851	NM_005208.5(CRYBA1):c.215+1G>A	CRYBA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
560445	NM_005208.5(CRYBA1):c.607_608del (p.Gln203fs)	CRYBA1	Pathogenic	no assertion criteria provided
572809	NM_005208.5(CRYBA1):c.215+1G>T	CRYBA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1184515	NM_005208.5(CRYBA1):c.626C>G (p.Ser209Trp)	CRYBA1	Likely pathogenic	no assertion criteria provided
1209931	NM_005208.5(CRYBA1):c.500+1G>C	CRYBA1	Likely pathogenic	criteria provided, single submitter
1324178	NM_005208.5(CRYBA1):c.258del (p.Phe86fs)	CRYBA1	Likely pathogenic	criteria provided, single submitter
1803183	NM_005208.5(CRYBA1):c.501-2_522del	CRYBA1	Likely pathogenic	criteria provided, single submitter
225328	NM_005208.5(CRYBA1):c.500+1G>A	CRYBA1	Likely pathogenic	criteria provided, single submitter
4081298	NM_005208.5(CRYBA1):c.96+2T>A	CRYBA1	Likely pathogenic	criteria provided, single submitter
464096	NM_005208.5(CRYBA1):c.530_538del (p.Arg177_Tyr179del)	CRYBA1	Likely pathogenic	criteria provided, single submitter
1126851	NM_005208.5(CRYBA1):c.464A>G (p.Asn155Ser)	CRYBA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1334473	NM_005208.5(CRYBA1):c.500+1G>T	CRYBA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
665795	NM_005208.5(CRYBA1):c.590_591del (p.Glu197fs)	CRYBA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3131899	NM_001693.4(ATP6V1B2):c.14C>A (p.Ala5Glu)	ATP6V1B2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1025844	NM_005208.5(CRYBA1):c.465C>A (p.Asn155Lys)	CRYBA1	Uncertain significance	criteria provided, single submitter
1031516	NM_005208.5(CRYBA1):c.367G>A (p.Glu123Lys)	CRYBA1	Uncertain significance	criteria provided, single submitter
1376037	NM_005208.5(CRYBA1):c.548T>A (p.Leu183Ter)	CRYBA1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1377037	NM_005208.5(CRYBA1):c.490_491del (p.Gln164fs)	CRYBA1	Uncertain significance	criteria provided, single submitter
1430646	NM_005208.5(CRYBA1):c.344C>T (p.Pro115Leu)	CRYBA1	Uncertain significance	criteria provided, single submitter
1435605	NM_005208.5(CRYBA1):c.548T>C (p.Leu183Ser)	CRYBA1	Uncertain significance	criteria provided, single submitter
1440392	NC_000017.10:g.(?27579473)(27581294_?)del	CRYBA1	Uncertain significance	criteria provided, single submitter
2118967	NM_005208.5(CRYBA1):c.310G>A (p.Ala104Thr)	CRYBA1	Uncertain significance	criteria provided, single submitter
2598608	NM_005208.5(CRYBA1):c.117G>C (p.Glu39Asp)	CRYBA1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2748316	NM_005208.5(CRYBA1):c.215+5G>A	CRYBA1	Uncertain significance	criteria provided, single submitter
2787126	NM_005208.5(CRYBA1):c.101C>T (p.Thr34Ile)	CRYBA1	Uncertain significance	criteria provided, single submitter
3661236	NM_005208.5(CRYBA1):c.519T>A (p.Tyr173Ter)	CRYBA1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 7 · 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
CRYBA1	Definitive	Autosomal dominant	cataract 10 multiple types	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CRYBA1	Orphanet:441452	Early-onset lamellar cataract
CRYBA1	Orphanet:98985	Early-onset sutural cataract
CRYBA1	Orphanet:98991	Early-onset nuclear cataract
CRYBA1	Orphanet:98993	Early-onset posterior polar cataract
ATP6V1B2	Orphanet:3473	Zimmermann-Laband syndrome
ATP6V1B2	Orphanet:79499	Autosomal dominant deafness-onychodystrophy syndrome
ATP6V1B2	Orphanet:79500	DOORS syndrome

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CRYBA1	HGNC:2394	ENSG00000108255	P05813	Beta-crystallin A3	gencc,clinvar
ATP6V1B2	HGNC:854	ENSG00000147416	P21281	V-type proton ATPase subunit B, brain isoform	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CRYBA1	Beta-crystallin A3	Crystallins are the dominant structural components of the vertebrate eye lens.
ATP6V1B2	V-type proton ATPase subunit B, brain isoform	Non-catalytic subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CRYBA1	Other/Unknown	no		Beta/gamma_crystallin, G_crystallin-like, Beta/Gamma-Crystallin
ATP6V1B2	Other/Unknown	no		ATPase_F1/V1/A1_a/bsu_nucl-bd, ATPase_F1/V1/A1_a/bsu_N, ATPase_V1-cplx_bsu

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
lens of camera-type eye	1
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1
lateral nuclear group of thalamus	1
monocyte	1
pons	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CRYBA1	138	tissue_specific	yes	lens of camera-type eye, primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis
ATP6V1B2	300	ubiquitous	marker	pons, monocyte, lateral nuclear group of thalamus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ATP6V1B2	2,898
CRYBA1	925

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ATP6V1B2	P21281	8

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CRYBA1	P05813	88.27

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. Enrichment computed across 2 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
Regulation of MITF-M-dependent genes involved in lysosome biogenesis and autophagy	1	671.8×	0.004	ATP6V1B2
Insulin receptor recycling	1	380.7×	0.004	ATP6V1B2
Transferrin endocytosis and recycling	1	368.4×	0.004	ATP6V1B2
ROS and RNS production in phagocytes	1	335.9×	0.004	ATP6V1B2
Amino acids regulate mTORC1	1	200.3×	0.006	ATP6V1B2
Ion channel transport	1	96.0×	0.010	ATP6V1B2

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of anoikis	1	936.2×	0.010	CRYBA1
synaptic vesicle lumen acidification	1	468.1×	0.010	ATP6V1B2
vacuolar acidification	1	366.4×	0.010	ATP6V1B2
negative regulation of TOR signaling	1	280.9×	0.010	CRYBA1
negative regulation of cytokine production	1	255.3×	0.010	CRYBA1
ATP metabolic process	1	234.1×	0.010	ATP6V1B2
lens development in camera-type eye	1	187.2×	0.010	CRYBA1
proton transmembrane transport	1	156.0×	0.010	ATP6V1B2
regulation of macroautophagy	1	147.8×	0.010	ATP6V1B2
negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1	131.7×	0.010	CRYBA1
phagocytosis	1	120.4×	0.010	CRYBA1
regulation of autophagy	1	120.4×	0.010	CRYBA1
negative regulation of ERK1 and ERK2 cascade	1	108.0×	0.010	CRYBA1
visual perception	1	39.8×	0.025	CRYBA1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) 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
ATP6V1B2	ENOXACIN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ATP6V1B2	1	4
CRYBA1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
ENOXACIN	4	ATP6V1B2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
ATP6V1B2	3	Binding:3

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

1 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)
ENOXACIN	4	ATP6V1B2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	ATP6V1B2
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	CRYBA1

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)
CRYBA1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.