Early-onset posterior subcapsular cataract

Summary

Early-onset posterior subcapsular cataract (MONDO:0018610) is a disease with 5 cohort genes.

At a glance

• Cohort genes: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	early-onset posterior subcapsular cataract
Mondo ID	MONDO:0018610
Orphanet	441447
UMLS	C5681190
MedGen	1842187
GARD	0021846
Is cancer (heuristic)	no

Data availability: 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 › early-onset partial cataract › early-onset posterior subcapsular cataract

Related subtypes (4): cataract 30, early-onset anterior polar cataract, cerulean cataract, early-onset zonular 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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 44 · Orphanet: 18 · 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
CRYBB2	Definitive	Autosomal dominant	cataract 3 multiple types	11
EPHA2	Definitive	Autosomal dominant	cataract 6 multiple types	10
CHMP4B	Strong	Autosomal dominant	cataract 31 multiple types	5
LEMD2	Strong	Autosomal recessive	cataract 46 juvenile-onset	10
UNC45B	Strong	Autosomal dominant	cataract 43	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
UNC45B	Orphanet:441447	Early-onset posterior subcapsular cataract
UNC45B	Orphanet:98991	Early-onset nuclear cataract
CHMP4B	Orphanet:441447	Early-onset posterior subcapsular cataract
CHMP4B	Orphanet:98993	Early-onset posterior polar cataract
LEMD2	Orphanet:441447	Early-onset posterior subcapsular cataract
LEMD2	Orphanet:659873	Wormian bones-micrognathia-abnormal dentition-progeroid syndrome
LEMD2	Orphanet:98994	Total early-onset cataract
CRYBB2	Orphanet:1377	Cataract-microcornea syndrome
CRYBB2	Orphanet:441447	Early-onset posterior subcapsular cataract
CRYBB2	Orphanet:98984	Pulverulent cataract
CRYBB2	Orphanet:98985	Early-onset sutural cataract
CRYBB2	Orphanet:98989	Cerulean cataract
CRYBB2	Orphanet:98991	Early-onset nuclear cataract
CRYBB2	Orphanet:98994	Total early-onset cataract
EPHA2	Orphanet:441447	Early-onset posterior subcapsular cataract
EPHA2	Orphanet:98991	Early-onset nuclear cataract
EPHA2	Orphanet:98993	Early-onset posterior polar cataract
EPHA2	Orphanet:98994	Total early-onset cataract

Cohort genes → proteins

5 cohort genes, 5 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	5

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
UNC45B	HGNC:14304	ENSG00000141161	Q8IWX7	Protein unc-45 homolog B	gencc
CHMP4B	HGNC:16171	ENSG00000101421	Q9H444	Charged multivesicular body protein 4b	gencc
LEMD2	HGNC:21244	ENSG00000161904	Q8NC56	LEM domain-containing protein 2	gencc
CRYBB2	HGNC:2398	ENSG00000244752	P43320	Beta-crystallin B2	gencc
EPHA2	HGNC:3386	ENSG00000142627	P29317	Ephrin type-A receptor 2	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
UNC45B	Protein unc-45 homolog B	Acts as a co-chaperone for HSP90 and is required for proper folding of the myosin motor domain.
CHMP4B	Charged multivesicular body protein 4b	Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) which is involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs.
LEMD2	LEM domain-containing protein 2	Nuclear lamina-associated inner nuclear membrane protein that is involved in nuclear structure organization, maintenance of nuclear envelope (NE) integrity and NE reformation after mitosis.
CRYBB2	Beta-crystallin B2	Crystallins are the dominant structural components of the vertebrate eye lens.
EPHA2	Ephrin type-A receptor 2	Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 4 · Druggable fraction: 0.2

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
Kinase	1	5.5×	0.269
Other/Unknown	4	1.4×	0.269

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
UNC45B	Other/Unknown	no		Armadillo, ARM-like, TPR-like_helical_dom_sf
CHMP4B	Other/Unknown	no		Snf7_fam
LEMD2	Other/Unknown	no		LEM_dom, LEM/LEM-like_dom_sf, Man1/Src1-like_C
CRYBB2	Other/Unknown	no		Beta/gamma_crystallin, G_crystallin-like, Beta/Gamma-Crystallin
EPHA2	Kinase	yes	2.7.10.1	Prot_kinase_dom, EPH_LBD, Ser-Thr/Tyr_kinase_cat_dom

Expression context

Cohort genes with no expression data: 0.

3 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)	5
unknown	0

Top tissues across cohort

Tissue	Cohort genes
tibialis anterior	2
cardiac muscle of right atrium	1
left ventricle myocardium	1
ileal mucosa	1
upper arm skin	1
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1
gluteal muscle	1
trabecular bone tissue	1
triceps brachii	1
esophagus mucosa	1
lower esophagus mucosa	1
pharyngeal mucosa	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
UNC45B	111	tissue_specific	yes	left ventricle myocardium, cardiac muscle of right atrium, tibialis anterior
CHMP4B	259	ubiquitous	marker	ileal mucosa, upper arm skin, tibialis anterior
LEMD2	186	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
CRYBB2	144	tissue_specific	yes	triceps brachii, gluteal muscle, trabecular bone tissue
EPHA2	224	ubiquitous	marker	lower esophagus mucosa, esophagus mucosa, pharyngeal mucosa

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
EPHA2	4,794
CHMP4B	3,043
LEMD2	2,340
UNC45B	1,273
CRYBB2	548

Intra-cohort edges

A	B	Sources
CHMP4B	CRYBB2	string_interaction

Structural data

PDB: 3 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
EPHA2	P29317	103
CHMP4B	Q9H444	4
CRYBB2	P43320	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
UNC45B	Q8IWX7	88.38
LEMD2	Q8NC56	71.49

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 31. Enrichment computed across 5 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Sealing of the nuclear envelope (NE) by ESCRT-III	2	230.7×	8e-04	CHMP4B, LEMD2
Translation of Replicase and Assembly of the Replication Transcription Complex	1	292.8×	0.020	CHMP4B
Translation of Replicase and Assembly of the Replication Transcription Complex	1	271.9×	0.020	CHMP4B
Depolymerization of the Nuclear Lamina	1	253.8×	0.020	LEMD2
Initiation of Nuclear Envelope (NE) Reformation	1	200.3×	0.020	LEMD2
Nuclear Envelope Breakdown	1	152.3×	0.020	LEMD2
Pyroptosis	1	141.0×	0.020	CHMP4B
Budding and maturation of HIV virion	1	135.9×	0.020	CHMP4B
EPHA-mediated growth cone collapse	1	126.9×	0.020	EPHA2
Mitotic Prophase	1	122.8×	0.020	LEMD2
Endosomal Sorting Complex Required For Transport (ESCRT)	1	122.8×	0.020	CHMP4B
Late endosomal microautophagy	1	108.8×	0.020	CHMP4B
Nuclear Envelope (NE) Reassembly	1	97.6×	0.020	LEMD2
RHOV GTPase cycle	1	95.2×	0.020	EPHA2
RHOU GTPase cycle	1	92.8×	0.020	EPHA2
RND1 GTPase cycle	1	88.5×	0.020	EPHA2
RND3 GTPase cycle	1	86.5×	0.020	EPHA2
RND2 GTPase cycle	1	86.5×	0.020	EPHA2
EPH-ephrin mediated repulsion of cells	1	73.2×	0.022	EPHA2
EPH-Ephrin signaling	1	55.2×	0.028	EPHA2
RHOG GTPase cycle	1	49.4×	0.030	EPHA2
RAC2 GTPase cycle	1	42.3×	0.033	EPHA2
RAC3 GTPase cycle	1	39.6×	0.033	EPHA2
Macroautophagy	1	38.5×	0.033	CHMP4B
HCMV Late Events	1	32.8×	0.035	CHMP4B
Mitotic Metaphase and Anaphase	1	32.3×	0.035	LEMD2
Mitotic Anaphase	1	32.3×	0.035	LEMD2
M Phase	1	22.0×	0.050	LEMD2
RAC1 GTPase cycle	1	20.4×	0.052	EPHA2
Cell Cycle, Mitotic	1	16.1×	0.063	LEMD2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 5 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	149.8×	0.006	UNC45B, CRYBB2
notochord cell development	1	3370.4×	0.012	EPHA2
axial mesoderm formation	1	1685.2×	0.012	EPHA2
notochord formation	1	1123.5×	0.012	EPHA2
negative regulation of lymphangiogenesis	1	1123.5×	0.012	EPHA2
cAMP metabolic process	1	842.6×	0.012	EPHA2
heart formation	1	674.1×	0.012	LEMD2
obsolete ubiquitin-independent protein catabolic process via the multivesicular body sorting pathway	1	674.1×	0.012	CHMP4B
pericyte cell differentiation	1	674.1×	0.012	EPHA2
regulation of blood vessel endothelial cell migration	1	561.7×	0.012	EPHA2
blood vessel endothelial cell proliferation involved in sprouting angiogenesis	1	481.5×	0.012	EPHA2
nuclear membrane organization	1	481.5×	0.012	LEMD2
negative regulation of chemokine production	1	421.3×	0.012	EPHA2
maintenance of lens transparency	1	421.3×	0.012	CHMP4B
lens fiber cell morphogenesis	1	421.3×	0.012	EPHA2
regulation of lamellipodium assembly	1	374.5×	0.012	EPHA2
viral budding	1	374.5×	0.012	CHMP4B
positive regulation of bicellular tight junction assembly	1	337.0×	0.012	EPHA2
late endosome to vacuole transport via multivesicular body sorting pathway	1	306.4×	0.012	CHMP4B
mammary gland epithelial cell proliferation	1	306.4×	0.012	EPHA2
vesicle fusion with vacuole	1	306.4×	0.012	CHMP4B
post-translational protein targeting to endoplasmic reticulum membrane	1	280.9×	0.012	CHMP4B
branching involved in mammary gland duct morphogenesis	1	280.9×	0.012	EPHA2
multivesicular body-lysosome fusion	1	280.9×	0.012	CHMP4B
response to growth factor	1	280.9×	0.012	EPHA2
negative regulation of cell adhesion mediated by integrin	1	259.3×	0.012	EPHA2
viral budding from plasma membrane	1	259.3×	0.012	CHMP4B
nervous system process	1	240.7×	0.013	CHMP4B
vesicle budding from membrane	1	224.7×	0.013	CHMP4B
exit from mitosis	1	210.7×	0.013	CHMP4B

Therapeutics

Drug target analysis

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

Druggability breadth: 3 of 5 evidence-associated genes (60%) 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
EPHA2	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
EPHA2	50	4
UNC45B	0	0
CHMP4B	0	0
LEMD2	0	0
CRYBB2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PONATINIB	4	EPHA2
FEDRATINIB	4	EPHA2
TIVOZANIB	4	EPHA2
SORAFENIB	4	EPHA2
DASATINIB ANHYDROUS	4	EPHA2
REGORAFENIB	4	EPHA2
CABOZANTINIB	4	EPHA2
VANDETANIB	4	EPHA2
NILOTINIB	4	EPHA2
BOSUTINIB	4	EPHA2
TOVORAFENIB	4	EPHA2
NINTEDANIB	4	EPHA2
DASATINIB	4	EPHA2
CRIZOTINIB	4	EPHA2
SARACATINIB	3	EPHA2
LINIFANIB	3	EPHA2
TESEVATINIB	3	EPHA2
ALVOCIDIB	3	EPHA2
ALISERTIB	3	EPHA2
LESTAURTINIB	3	EPHA2
DORAMAPIMOD	2	EPHA2
NEFLAMAPIMOD	2	EPHA2
FORETINIB	2	EPHA2
ILORASERTIB	2	EPHA2
CEP-32496	2	EPHA2
BAFETINIB	2	EPHA2
SAPITINIB	2	EPHA2
OSI-632	2	EPHA2
GOLVATINIB	2	EPHA2
PEXMETINIB	2	EPHA2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
EPHA2	567	Binding:565, Functional:1, ADMET:1
CRYBB2	9	Binding:9
CHMP4B	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
EPHA2	2.7.10.1	receptor protein-tyrosine kinase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
EPHA2	567

Pharmacogenomics

Cohort genes with a PharmGKB record: 5; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

30 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)
PONATINIB	4	EPHA2
FEDRATINIB	4	EPHA2
TIVOZANIB	4	EPHA2
SORAFENIB	4	EPHA2
DASATINIB ANHYDROUS	4	EPHA2
REGORAFENIB	4	EPHA2
CABOZANTINIB	4	EPHA2
VANDETANIB	4	EPHA2
NILOTINIB	4	EPHA2
BOSUTINIB	4	EPHA2
TOVORAFENIB	4	EPHA2
NINTEDANIB	4	EPHA2
DASATINIB	4	EPHA2
CRIZOTINIB	4	EPHA2
SARACATINIB	3	EPHA2
LINIFANIB	3	EPHA2
TESEVATINIB	3	EPHA2
ALVOCIDIB	3	EPHA2
ALISERTIB	3	EPHA2
LESTAURTINIB	3	EPHA2
DORAMAPIMOD	2	EPHA2
NEFLAMAPIMOD	2	EPHA2
FORETINIB	2	EPHA2
ILORASERTIB	2	EPHA2
CEP-32496	2	EPHA2
BAFETINIB	2	EPHA2
SAPITINIB	2	EPHA2
OSI-632	2	EPHA2
GOLVATINIB	2	EPHA2
PEXMETINIB	2	EPHA2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	EPHA2
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	UNC45B, CHMP4B, LEMD2, CRYBB2

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)
UNC45B	0	—
CHMP4B	1	—
LEMD2	0	—
CRYBB2	9	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.