Early-onset anterior polar cataract

Summary

Early-onset anterior polar cataract (MONDO:0020373) is a disease with 4 cohort genes.

At a glance

• Cohort genes: 4
• ClinVar variants: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	early-onset anterior polar cataract
Mondo ID	MONDO:0020373
Orphanet	98988
UMLS	C1855179
MedGen	340806
GARD	0001140
Is cancer (heuristic)	no

Also known as: cataract anterior polar · early-onset anterior subcapsular cataract

Data availability: 2 ClinVar variants · 4 GenCC gene-disease records.

Disease family

An umbrella term covering 1 Mondo subtype.

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 anterior polar cataract

Related subtypes (4): cataract 30, early-onset posterior subcapsular cataract, cerulean cataract, early-onset zonular cataract

Subtypes (1): cataract 24

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

2 retrieved; paginated sample, class counts are floors:

2 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
2515408	NM_057093.2(CRYBA2):c.571T>C (p.Ser191Pro)	CRYBA2	Uncertain significance	criteria provided, multiple submitters, no conflicts
3779182	NM_057093.2(CRYBA2):c.101C>A (p.Ala34Glu)	CRYBA2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 27 · Orphanet: 12 · 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
CRYAA	Definitive	Autosomal recessive	cataract 9 multiple types	8
CRYBB3	Definitive	Autosomal recessive	cataract 22 multiple types	9
CRYBA2	Strong	Autosomal dominant	cataract 42	5
CRYGB	Supportive	Autosomal dominant	early-onset lamellar cataract	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CRYBA2	Orphanet:98988	Early-onset anterior polar cataract
CRYBA2	Orphanet:98991	Early-onset nuclear cataract
CRYAA	Orphanet:1377	Cataract-microcornea syndrome
CRYAA	Orphanet:441452	Early-onset lamellar cataract
CRYAA	Orphanet:98988	Early-onset anterior polar cataract
CRYAA	Orphanet:98991	Early-onset nuclear cataract
CRYAA	Orphanet:98994	Total early-onset cataract
CRYBB3	Orphanet:98988	Early-onset anterior polar cataract
CRYBB3	Orphanet:98991	Early-onset nuclear cataract
CRYGB	Orphanet:441452	Early-onset lamellar cataract
CRYGB	Orphanet:98988	Early-onset anterior polar cataract
CRYGB	Orphanet:98994	Total early-onset cataract

Cohort genes → proteins

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CRYBA2	HGNC:2395	ENSG00000163499	P53672	Beta-crystallin A2	gencc,clinvar
CRYAA	HGNC:2388	ENSG00000160202	P02489	Alpha-crystallin A chain	gencc
CRYBB3	HGNC:2400	ENSG00000100053	P26998	Beta-crystallin B3	gencc
CRYGB	HGNC:2409	ENSG00000182187	P07316	Gamma-crystallin B	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CRYBA2	Beta-crystallin A2	Crystallins are the dominant structural components of the vertebrate eye lens.
CRYAA	Alpha-crystallin A chain	Contributes to the transparency and refractive index of the lens.
CRYBB3	Beta-crystallin B3	Crystallins are the dominant structural components of the vertebrate eye lens.
CRYGB	Gamma-crystallin B	Crystallins are the dominant structural components of the vertebrate eye lens.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 4 · 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	4	1.8×	0.097

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CRYBA2	Other/Unknown	no		Beta/gamma_crystallin, G_crystallin-like, Beta/Gamma-Crystallin
CRYAA	Other/Unknown	no		Alpha-crystallin/sHSP_animal, A-crystallin/Hsp20_dom, Alpha-crystallin_N
CRYBB3	Other/Unknown	no		Beta/gamma_crystallin, G_crystallin-like, Beta/Gamma-Crystallin
CRYGB	Other/Unknown	no		Beta/gamma_crystallin, G_crystallin-like, Beta/Gamma-Crystallin

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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	3
islet of Langerhans	1
primordial germ cell in gonad	1
adult mammalian kidney	1
liver	1
right lobe of liver	1
buccal mucosa cell	1
mucosa of transverse colon	1
skeletal muscle tissue of rectus abdominis	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CRYBA2	128	tissue_specific	marker	islet of Langerhans, primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis
CRYAA	42		marker	adult mammalian kidney, right lobe of liver, liver
CRYBB3	145	tissue_specific	yes	male germ line stem cell (sensu Vertebrata) in testis, buccal mucosa cell, mucosa of transverse colon
CRYGB	35	tissue_specific	yes	male germ line stem cell (sensu Vertebrata) in testis, sperm, skeletal muscle tissue of rectus abdominis

Protein interactions among cohort

Intra-cohort edges: 3.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CRYBB3	1,718
CRYAA	1,464
CRYBA2	759
CRYGB	435

Intra-cohort edges

A	B	Sources
CRYAA	CRYBA2	string_interaction
CRYAA	CRYBB3	intact, string_interaction
CRYAA	CRYGB	string_interaction

Structural data

PDB: 3 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CRYAA	P02489	5
CRYGB	P07316	2
CRYBB3	P26998	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CRYBA2	P53672	93.12

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 4 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 4 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	4	374.5×	9e-10	CRYBA2, CRYAA, CRYBB3, CRYGB
visual perception	4	79.5×	2e-07	CRYBA2, CRYAA, CRYBB3, CRYGB
lens fiber cell morphogenesis	2	1053.2×	8e-06	CRYAA, CRYGB
negative regulation of intracellular transport	1	1404.3×	0.004	CRYAA
response to UV-A	1	1053.2×	0.004	CRYAA
apoptotic process involved in morphogenesis	1	702.2×	0.005	CRYAA
tubulin complex assembly	1	421.3×	0.007	CRYAA
glutathione biosynthetic process	1	383.0×	0.007	CRYAA
embryonic camera-type eye morphogenesis	1	280.9×	0.008	CRYAA
microtubule-based process	1	247.8×	0.008	CRYAA
protein refolding	1	156.0×	0.012	CRYAA
response to hydrogen peroxide	1	117.0×	0.014	CRYAA
response to heat	1	105.3×	0.015	CRYAA
positive regulation of cell growth	1	45.8×	0.031	CRYAA
mitochondrion organization	1	38.0×	0.035	CRYAA
actin filament organization	1	29.7×	0.042	CRYAA
response to hypoxia	1	23.9×	0.048	CRYAA
negative regulation of gene expression	1	17.3×	0.062	CRYAA
protein stabilization	1	16.7×	0.062	CRYAA
negative regulation of apoptotic process	1	8.7×	0.110	CRYAA

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 4 evidence-associated genes (25%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CRYBA2	0	0
CRYAA	0	0
CRYBB3	0	0
CRYGB	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
CRYAA	25	Binding:25

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; 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	4	CRYBA2, CRYAA, CRYBB3, CRYGB

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CRYBA2	0	—
CRYAA	25	—
CRYBB3	0	—
CRYGB	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.