Cataract 6 multiple types

Summary

Cataract 6 multiple types (MONDO:0007288) is a disease caused by EPHA2 (GenCC Definitive), with 3 cohort genes.

At a glance

• Causal gene: EPHA2 (GenCC Definitive)
• Cohort genes: 3
• ClinVar variants: 231

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cataract 6 multiple types
Mondo ID	MONDO:0007288
OMIM	116600
DOID	DOID:0110229
UMLS	C1861825
MedGen	396229
GARD	0010234
Is cancer (heuristic)	no

Also known as: cataract (disease) caused by mutation in EPHA2 · cataract 6, multiple types · CTPA · CTPP · CTRCT6 · EPHA2 cataract (disease) · Posterior polar cataract, 1

Data availability: 231 ClinVar variants · 4 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 6 multiple types

Related subtypes (28): cataract 32 multiple types, cataract 8 multiple types, cataract 42, cataract 20 multiple types, cataract 13 with adult I phenotype, cataract 5 multiple types, cataract 46 juvenile-onset, cataract 40, cataract 10 multiple types, 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

231 retrieved; paginated sample, class counts are floors:

88 uncertain significance, 53 benign, 50 likely benign, 15 conflicting classifications of pathogenicity, 11 benign/likely benign, 11 pathogenic, 3 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2425113	NC_000001.10:g.(?16451710)(16532835_?)del	ARHGEF19	Pathogenic	criteria provided, single submitter
1213988	NM_004431.5(EPHA2):c.2815_2825+9del	EPHA2	Pathogenic	criteria provided, single submitter
13258	NM_004431.5(EPHA2):c.2842G>T (p.Gly948Trp)	EPHA2	Pathogenic	no assertion criteria provided
13259	NM_004431.5(EPHA2):c.2819C>T (p.Thr940Ile)	EPHA2	Pathogenic	no assertion criteria provided
1704213	NM_004431.5(EPHA2):c.2825+2del	EPHA2	Pathogenic	criteria provided, single submitter
2066016	NM_004431.5(EPHA2):c.988dup (p.Ser330fs)	EPHA2	Pathogenic	criteria provided, single submitter
2153735	NM_004431.5(EPHA2):c.2426_2427dup (p.Val810fs)	EPHA2	Pathogenic	criteria provided, single submitter
280146	NM_004431.5(EPHA2):c.2826-9G>A	EPHA2	Pathogenic	criteria provided, multiple submitters, no conflicts
3661807	NM_004431.5(EPHA2):c.2903_2904del (p.Gln968fs)	EPHA2	Pathogenic	criteria provided, single submitter
665755	NM_004431.5(EPHA2):c.759G>A (p.Trp253Ter)	EPHA2	Pathogenic	criteria provided, single submitter
849920	NM_004431.5(EPHA2):c.2915_2916del (p.Val972fs)	EPHA2	Pathogenic	criteria provided, single submitter
1687229	NM_004431.5(EPHA2):c.2353G>A (p.Ala785Thr)	EPHA2	Likely pathogenic	criteria provided, single submitter
4081374	NM_004431.5(EPHA2):c.2475+1G>A	EPHA2	Likely pathogenic	criteria provided, single submitter
647226	NM_004431.5(EPHA2):c.1582+1G>A	EPHA2	Likely pathogenic	criteria provided, single submitter
1216955	NM_004431.5(EPHA2):c.1567G>A (p.Glu523Lys)	EPHA2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
13262	NM_004431.5(EPHA2):c.2162G>A (p.Arg721Gln)	EPHA2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1441585	NM_004431.5(EPHA2):c.2826C>T (p.Asp942=)	EPHA2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1800688	NM_004431.5(EPHA2):c.1648G>C (p.Val550Leu)	EPHA2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2501614	NM_004431.5(EPHA2):c.2693C>T (p.Thr898Met)	EPHA2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
293406	NM_004431.5(EPHA2):c.2904G>C (p.Gln968His)	EPHA2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
293408	NM_004431.5(EPHA2):c.2875G>A (p.Ala959Thr)	EPHA2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
293412	NM_004431.5(EPHA2):c.2239G>A (p.Val747Ile)	EPHA2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
293416	NM_004431.5(EPHA2):c.1984G>A (p.Gly662Ser)	EPHA2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
293424	NM_004431.5(EPHA2):c.1720G>A (p.Val574Ile)	EPHA2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
293425	NM_004431.5(EPHA2):c.1712C>T (p.Pro571Leu)	EPHA2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
293445	NM_004431.5(EPHA2):c.523C>T (p.Arg175Cys)	EPHA2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
703252	NM_004431.5(EPHA2):c.1682G>A (p.Arg561Lys)	EPHA2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
875750	NM_004431.5(EPHA2):c.2030G>A (p.Arg677His)	EPHA2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
875794	NM_004431.5(EPHA2):c.1046C>T (p.Thr349Met)	EPHA2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1037565	NM_004431.5(EPHA2):c.2174C>G (p.Ala725Gly)	EPHA2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 4 · 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
EPHA2	Definitive	Autosomal dominant	cataract 6 multiple types	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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

3 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
EPHA2	HGNC:3386	ENSG00000142627	P29317	Ephrin type-A receptor 2	gencc,clinvar
ARHGEF19	HGNC:26604	ENSG00000142632	Q8IW93	Rho guanine nucleotide exchange factor 19	clinvar
EPHA2-AS1	HGNC:40216	ENSG00000227959		EPHA2 antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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.
ARHGEF19	Rho guanine nucleotide exchange factor 19	Acts as a guanine nucleotide exchange factor (GEF) for RhoA GTPase.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 1 · Druggable fraction: 0.33

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	9.2×	0.246
Scaffold/PPI	1	5.8×	0.246
Other/Unknown	1	0.6×	0.914

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
EPHA2	Kinase	yes	2.7.10.1	Prot_kinase_dom, EPH_LBD, Ser-Thr/Tyr_kinase_cat_dom
ARHGEF19	Scaffold/PPI	no		DH_dom, SH3_domain, PH_domain
EPHA2-AS1	Other/Unknown	no

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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
lower esophagus mucosa	3
esophagus mucosa	2
pharyngeal mucosa	1
skin of abdomen	1
upper arm skin	1
buccal mucosa cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
EPHA2	224	ubiquitous	marker	lower esophagus mucosa, esophagus mucosa, pharyngeal mucosa
ARHGEF19	196	ubiquitous	marker	skin of abdomen, upper arm skin, lower esophagus mucosa
EPHA2-AS1	133		marker	buccal mucosa cell, lower esophagus mucosa, esophagus mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
EPHA2	4,794
ARHGEF19	591
EPHA2-AS1	0

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
EPHA2	P29317	103
ARHGEF19	Q8IW93	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 25. Enrichment computed across 3 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
RAC1 GTPase cycle	2	61.1×	0.007	EPHA2, ARHGEF19
EPHA-mediated growth cone collapse	1	190.3×	0.024	EPHA2
RHOV GTPase cycle	1	142.8×	0.024	EPHA2
RHOU GTPase cycle	1	139.3×	0.024	EPHA2
RND1 GTPase cycle	1	132.8×	0.024	EPHA2
RND3 GTPase cycle	1	129.8×	0.024	EPHA2
RND2 GTPase cycle	1	129.8×	0.024	EPHA2
Cell death signalling via NRAGE, NRIF and NADE	1	109.8×	0.024	ARHGEF19
EPH-ephrin mediated repulsion of cells	1	109.8×	0.024	EPHA2
p75 NTR receptor-mediated signalling	1	93.6×	0.024	ARHGEF19
NRAGE signals death through JNK	1	92.1×	0.024	ARHGEF19
EPH-Ephrin signaling	1	82.8×	0.024	EPHA2
RHOG GTPase cycle	1	74.2×	0.024	EPHA2
Death Receptor Signaling	1	69.6×	0.024	ARHGEF19
G alpha (12/13) signalling events	1	68.8×	0.024	ARHGEF19
RAC2 GTPase cycle	1	63.4×	0.025	EPHA2
RAC3 GTPase cycle	1	59.5×	0.025	EPHA2
RHOA GTPase cycle	1	37.3×	0.036	ARHGEF19
CDC42 GTPase cycle	1	36.1×	0.036	ARHGEF19
RHO GTPase cycle	1	30.1×	0.041	ARHGEF19
GPCR downstream signalling	1	21.7×	0.054	ARHGEF19
Signaling by GPCR	1	20.0×	0.056	ARHGEF19
Signaling by Rho GTPases	1	17.1×	0.061	ARHGEF19
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1	16.7×	0.061	ARHGEF19
Signal Transduction	1	5.1×	0.187	ARHGEF19

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
notochord cell development	1	8426.0×	0.004	EPHA2
axial mesoderm formation	1	4213.0×	0.004	EPHA2
notochord formation	1	2808.7×	0.004	EPHA2
negative regulation of lymphangiogenesis	1	2808.7×	0.004	EPHA2
cAMP metabolic process	1	2106.5×	0.004	EPHA2
pericyte cell differentiation	1	1685.2×	0.004	EPHA2
regulation of blood vessel endothelial cell migration	1	1404.3×	0.004	EPHA2
blood vessel endothelial cell proliferation involved in sprouting angiogenesis	1	1203.7×	0.004	EPHA2
negative regulation of chemokine production	1	1053.2×	0.004	EPHA2
lens fiber cell morphogenesis	1	1053.2×	0.004	EPHA2
regulation of lamellipodium assembly	1	936.2×	0.004	EPHA2
positive regulation of bicellular tight junction assembly	1	842.6×	0.004	EPHA2
mammary gland epithelial cell proliferation	1	766.0×	0.004	EPHA2
branching involved in mammary gland duct morphogenesis	1	702.2×	0.004	EPHA2
response to growth factor	1	702.2×	0.004	EPHA2
negative regulation of cell adhesion mediated by integrin	1	648.1×	0.004	EPHA2
bone remodeling	1	468.1×	0.006	EPHA2
post-anal tail morphogenesis	1	366.4×	0.007	EPHA2
activation of GTPase activity	1	366.4×	0.007	EPHA2
central nervous system neuron differentiation	1	300.9×	0.008	EPHA2
regulation of ERK1 and ERK2 cascade	1	290.6×	0.008	EPHA2
neural tube development	1	263.3×	0.008	EPHA2
Wnt signaling pathway, planar cell polarity pathway	1	227.7×	0.009	ARHGEF19
regulation of angiogenesis	1	210.7×	0.009	EPHA2
cell motility	1	200.6×	0.009	EPHA2
osteoclast differentiation	1	172.0×	0.010	EPHA2
ephrin receptor signaling pathway	1	172.0×	0.010	EPHA2
intrinsic apoptotic signaling pathway in response to DNA damage	1	162.0×	0.010	EPHA2
positive regulation of protein localization to plasma membrane	1	135.9×	0.012	EPHA2
vasculogenesis	1	127.7×	0.012	EPHA2

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 3 evidence-associated genes (33%) 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
ARHGEF19	0	0
EPHA2-AS1	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

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: 2; 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	2	ARHGEF19, EPHA2-AS1

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)
ARHGEF19	0	—
EPHA2-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.