Cataract 16 multiple types

Summary

Cataract 16 multiple types (MONDO:0013411) is a disease caused by CRYAB (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: CRYAB (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 40

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cataract 16 multiple types
Mondo ID	MONDO:0013411
MeSH	C565134
OMIM	613763
DOID	DOID:0110250
UMLS	C3808377
MedGen	814707
GARD	0024920
Is cancer (heuristic)	no

Also known as: cataract 16, multiple types · CRYAB early-onset non-syndromic cataract · CTRCT16 · early-onset non-syndromic cataract caused by mutation in CRYAB

Data availability: 40 ClinVar variants · 3 GenCC gene-disease records.

Disease family

An umbrella term covering 2 Mondo subtypes.

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 › early-onset partial cataract › early-onset zonular cataract › cataract 16 multiple types

Related subtypes (2): early-onset sutural cataract, early-onset nuclear cataract

Subtypes (2): early-onset lamellar cataract, early-onset posterior polar 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

40 retrieved; paginated sample, class counts are floors:

21 uncertain significance, 9 conflicting classifications of pathogenicity, 3 pathogenic, 3 benign, 2 likely pathogenic, 2 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
16954	NM_001289808.2(CRYAB):c.450del (p.Lys150fs)	CRYAB	Pathogenic	no assertion criteria provided
41927	NM_001289808.2(CRYAB):c.418G>A (p.Asp140Asn)	CRYAB	Pathogenic	no assertion criteria provided
41928	NM_001289808.2(CRYAB):c.58C>T (p.Pro20Ser)	CRYAB	Pathogenic	no assertion criteria provided
1184448	NM_001289808.2(CRYAB):c.525del (p.Lys175fs)	CRYAB	Likely pathogenic	no assertion criteria provided
4687943	NM_001289808.2(CRYAB):c.527A>G (p.Ter176Trp)	CRYAB	Likely pathogenic	criteria provided, single submitter
475877	NM_004370.6(COL12A1):c.5467G>A (p.Val1823Ile)	COL12A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
178013	NM_001289808.2(CRYAB):c.116C>T (p.Pro39Leu)	CRYAB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
302430	NM_001289808.2(CRYAB):c.*38G>C	CRYAB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
302431	NM_001289808.2(CRYAB):c.375A>C (p.Pro125=)	CRYAB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
38963	NM_001289808.2(CRYAB):c.343del (p.Ser115fs)	CRYAB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
41926	NM_001289808.2(CRYAB):c.460G>A (p.Gly154Ser)	CRYAB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
41929	NM_001289808.2(CRYAB):c.166C>T (p.Arg56Trp)	CRYAB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
44232	NM_001289808.2(CRYAB):c.152C>T (p.Pro51Leu)	CRYAB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
44236	NM_001289808.2(CRYAB):c.3G>A (p.Met1Ile)	CRYAB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1044759	NM_001289808.2(CRYAB):c.37C>A (p.Pro13Thr)	CRYAB	Uncertain significance	criteria provided, multiple submitters, no conflicts
1388843	NM_001289808.2(CRYAB):c.85G>A (p.Gly29Arg)	CRYAB	Uncertain significance	criteria provided, multiple submitters, no conflicts
1410499	NM_001289808.2(CRYAB):c.319C>T (p.Arg107Cys)	CRYAB	Uncertain significance	criteria provided, multiple submitters, no conflicts
1486651	NM_001289808.2(CRYAB):c.148C>T (p.Arg50Trp)	CRYAB	Uncertain significance	criteria provided, multiple submitters, no conflicts
1507716	NM_001289808.2(CRYAB):c.362A>G (p.Lys121Arg)	CRYAB	Uncertain significance	criteria provided, multiple submitters, no conflicts
201688	NM_001289808.2(CRYAB):c.16C>T (p.His6Tyr)	CRYAB	Uncertain significance	criteria provided, multiple submitters, no conflicts
302428	NM_001289808.2(CRYAB):c.*107A>G	CRYAB	Uncertain significance	criteria provided, single submitter
302432	NM_001289808.2(CRYAB):c.102G>T (p.Glu34Asp)	CRYAB	Uncertain significance	criteria provided, multiple submitters, no conflicts
393088	NM_001289808.2(CRYAB):c.367C>T (p.Arg123Trp)	CRYAB	Uncertain significance	criteria provided, multiple submitters, no conflicts
41925	NM_001289808.2(CRYAB):c.470G>A (p.Arg157His)	CRYAB	Uncertain significance	criteria provided, multiple submitters, no conflicts
569482	NM_001289808.2(CRYAB):c.65G>A (p.Arg22His)	CRYAB	Uncertain significance	criteria provided, multiple submitters, no conflicts
571646	NM_001289808.2(CRYAB):c.115C>G (p.Pro39Ala)	CRYAB	Uncertain significance	criteria provided, multiple submitters, no conflicts
643345	NM_001289808.2(CRYAB):c.275A>G (p.Lys92Arg)	CRYAB	Uncertain significance	criteria provided, multiple submitters, no conflicts
657190	NM_001289808.2(CRYAB):c.115C>T (p.Pro39Ser)	CRYAB	Uncertain significance	criteria provided, multiple submitters, no conflicts
657757	NM_001289808.2(CRYAB):c.119C>T (p.Thr40Met)	CRYAB	Uncertain significance	criteria provided, multiple submitters, no conflicts
810752	NM_001289808.2(CRYAB):c.482T>C (p.Ile161Thr)	CRYAB	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 16 · Orphanet: 9 · 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
CRYAB	Strong	Autosomal dominant	cataract 16 multiple types	16

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CRYAB	Orphanet:154	Familial isolated dilated cardiomyopathy
CRYAB	Orphanet:280553	Fatal infantile hypertonic myofibrillar myopathy
CRYAB	Orphanet:399058	Alpha-B crystallin-related late-onset myopathy
CRYAB	Orphanet:441452	Early-onset lamellar cataract
CRYAB	Orphanet:98991	Early-onset nuclear cataract
CRYAB	Orphanet:98993	Early-onset posterior polar cataract
COL12A1	Orphanet:536516	Myopathic Ehlers-Danlos syndrome
COL12A1	Orphanet:610	Bethlem muscular dystrophy
COL12A1	Orphanet:75840	Ullrich congenital muscular dystrophy

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
CRYAB	HGNC:2389	ENSG00000109846	P02511	Alpha-crystallin B chain	gencc,clinvar
COL12A1	HGNC:2188	ENSG00000111799	Q99715	Collagen alpha-1(XII) chain	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CRYAB	Alpha-crystallin B chain	May contribute to the transparency and refractive index of the lens.
COL12A1	Collagen alpha-1(XII) chain	Type XII collagen interacts with type I collagen-containing fibrils, the COL1 domain could be associated with the surface of the fibrils, and the COL2 and NC3 domains may be localized in the perifibrillar matrix.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Antibody/Immunoglobulin	1	14.6×	0.135
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CRYAB	Other/Unknown	no		Alpha-crystallin/sHSP_animal, A-crystallin/Hsp20_dom, Alpha-crystallin_N
COL12A1	Antibody/Immunoglobulin	yes		VWF_A, FN3_dom, Collagen

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cardiac ventricle	1
left ventricle myocardium	1
middle frontal gyrus	1
calcaneal tendon	1
cartilage tissue	1
tibia	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CRYAB	289	ubiquitous	marker	middle frontal gyrus, left ventricle myocardium, cardiac ventricle
COL12A1	240	ubiquitous	marker	tibia, calcaneal tendon, cartilage tissue

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CRYAB	3,368
COL12A1	2,219

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CRYAB	P02511	21
COL12A1	Q99715	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. Enrichment computed across 2 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
HSF1-dependent transactivation	1	158.6×	0.012	CRYAB
Collagen chain trimerization	1	129.8×	0.012	COL12A1
Assembly of collagen fibrils and other multimeric structures	1	100.2×	0.012	COL12A1
Collagen degradation	1	87.8×	0.012	COL12A1
Collagen biosynthesis and modifying enzymes	1	85.2×	0.012	COL12A1

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
microtubule polymerization or depolymerization	1	8426.0×	0.003	CRYAB
negative regulation of intracellular transport	1	2808.7×	0.005	CRYAB
regulation of programmed cell death	1	1404.3×	0.005	CRYAB
apoptotic process involved in morphogenesis	1	1404.3×	0.005	CRYAB
tubulin complex assembly	1	842.6×	0.007	CRYAB
negative regulation of amyloid fibril formation	1	648.1×	0.007	CRYAB
negative regulation of reactive oxygen species metabolic process	1	468.1×	0.009	CRYAB
stress-activated MAPK cascade	1	351.1×	0.009	CRYAB
protein refolding	1	312.1×	0.009	CRYAB
cellular response to gamma radiation	1	300.9×	0.009	CRYAB
endodermal cell differentiation	1	247.8×	0.009	COL12A1
response to hydrogen peroxide	1	234.1×	0.009	CRYAB
negative regulation of protein-containing complex assembly	1	227.7×	0.009	CRYAB
response to heat	1	210.7×	0.009	CRYAB
lens development in camera-type eye	1	187.2×	0.010	CRYAB
glutathione metabolic process	1	175.5×	0.010	CRYAB
collagen fibril organization	1	112.3×	0.015	COL12A1
muscle contraction	1	104.0×	0.015	CRYAB
response to estradiol	1	99.1×	0.015	CRYAB
muscle organ development	1	83.4×	0.017	CRYAB
negative regulation of cell growth	1	72.0×	0.018	CRYAB
protein folding	1	51.7×	0.025	CRYAB
response to hypoxia	1	47.9×	0.025	CRYAB
negative regulation of gene expression	1	34.5×	0.033	CRYAB
protein stabilization	1	33.4×	0.033	CRYAB
cell adhesion	1	18.7×	0.057	COL12A1
negative regulation of apoptotic process	1	17.4×	0.059	CRYAB
negative regulation of DNA-templated transcription	1	15.8×	0.062	CRYAB

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CRYAB	0	0
COL12A1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
CRYAB	13	Binding:13

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

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	1	COL12A1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	CRYAB

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)
CRYAB	13	—
COL12A1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.