exudative vitreoretinopathy 2, X-linked

Summary

exudative vitreoretinopathy 2, X-linked (MONDO:0010588) is a disease caused by NDP (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: NDP (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 10

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	exudative vitreoretinopathy 2, X-linked
Mondo ID	MONDO:0010588
MeSH	C564428
OMIM	305390
DOID	DOID:0111413
UMLS	C1844579
MedGen	337030
GARD	0015292
Is cancer (heuristic)	no

Also known as: EVR2 · exudative vitreoretinopathy 2, X-linked · exudative vitreoretinopathy 2, X-linked, X-linked recessive, X-linked dominant · exudative vitreoretinopathy caused by mutation in NDP · NDP exudative vitreoretinopathy

Data availability: 10 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › X-linked disease › exudative vitreoretinopathy 2, X-linked

Related subtypes (49): X-linked Opitz G/BBB syndrome, X-linked immunoneurologic disorder, X-linked adrenal hypoplasia congenita, X-linked lissencephaly with abnormal genitalia, X-linked severe congenital neutropenia, X-linked distal spinal muscular atrophy type 3, epilepsy, X-linked 1, with variable learning disabilities and behavior disorders, Aland island eye disease, X-linked erythropoietic protoporphyria, X-linked central congenital hypothyroidism with late-onset testicular enlargement, X-linked colobomatous microphthalmia-microcephaly-intellectual disability-short stature syndrome, X-linked acrogigantism due to Xq26 microduplication, Wiskott-Aldrich syndrome, X-linked Alport syndrome, X-linked mandibulofacial dysostosis, X-linked chondrodysplasia punctata, choroideremia, cone dystrophy, X-linked, with tapetal-like sheen, diabetes insipidus, nephrogenic, X-linked, Dyggve-Melchior-Clausen syndrome, X-linked, dyskeratosis congenita, X-linked, X-linked hypohidrotic ectodermal dysplasia, X-linked Ehlers-Danlos syndrome, epidermodysplasia verruciformis, X-linked, Aarskog-Scott syndrome, X-linked, hemophilia A, X-linked hydrocephalus with stenosis of the aqueduct of Sylvius, hyper-IgM syndrome type 1, X-linked lymphoproliferative syndrome, macular dystrophy, X-linked, X-linked Emery-Dreifuss muscular dystrophy, X-linked myotubular myopathy, X-linked lethal multiple pterygium syndrome, X-linked retinoschisis, spondyloepiphyseal dysplasia tarda, X-linked, X-linked cerebellar ataxia, adrenoleukodystrophy, Charcot-Marie-Tooth disease type X, X-linked dominant disease, X-linked recessive disease, X-linked hypophosphatemic rickets, X-linked sideroblastic anemia 1, X-linked deafness, X-linked cone-rod dystrophy, X-linked congenital stationary night blindness, X-linked congenital hemolytic anemia, X-linked complex neurodevelopmental disorder, X-linked intellectual disability, leukemia, acute, X-linked

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

10 retrieved; paginated sample, class counts are floors:

5 pathogenic, 4 likely pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
10691	NM_000266.4(NDP):c.125A>G (p.His42Arg)	NDP	Pathogenic	criteria provided, multiple submitters, no conflicts
10695	NM_000266.4(NDP):c.362G>T (p.Arg121Leu)	NDP	Pathogenic	no assertion criteria provided
3237510	NM_000266.4(NDP):c.199G>T (p.Gly67Trp)	NDP	Pathogenic	criteria provided, single submitter
10684	NM_000266.4(NDP):c.370C>T (p.Leu124Phe)	NDP-AS1	Pathogenic	criteria provided, single submitter
10688	NM_000266.4(NDP):c.361C>T (p.Arg121Trp)	NDP-AS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
10694	NM_000266.4(NDP):c.328T>G (p.Cys110Gly)	NDP-AS1	Pathogenic	no assertion criteria provided
10680	NM_000266.4(NDP):c.224C>G (p.Ser75Cys)	NDP	Likely pathogenic	criteria provided, single submitter
3382646	NM_000266.4(NDP):c.334_349dup (p.Thr117fs)	NDP	Likely pathogenic	criteria provided, single submitter
3382653	NM_000266.4(NDP):c.279del (p.His94fs)	NDP	Likely pathogenic	criteria provided, single submitter
522928	NM_000266.4(NDP):c.200G>T (p.Gly67Val)	NDP-AS1	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · Orphanet: 5 · 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
NDP	Definitive	X-linked	exudative vitreoretinopathy 2, X-linked	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NDP	Orphanet:190	Coats disease
NDP	Orphanet:649	Norrie disease
NDP	Orphanet:891	Familial exudative vitreoretinopathy
NDP	Orphanet:90050	Retinopathy of prematurity
NDP	Orphanet:91495	Persistent hyperplastic primary vitreous

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
NDP	HGNC:7678	ENSG00000124479	Q00604	Norrin	gencc,clinvar
NDP-AS1	HGNC:40395	ENSG00000236276		NDP antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NDP	Norrin	Activates the canonical Wnt signaling pathway through FZD4 and LRP5 coreceptor.

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)
NDP	Other/Unknown	no		Norrie_dis, Cys_knot_C, Glyco_hormone_CN
NDP-AS1	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

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
caudate nucleus	1
cranial nerve II	1
decidua	1
endometrium	1
ganglionic eminence	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NDP	197	broad	yes	cranial nerve II, decidua, caudate nucleus
NDP-AS1	67		yes	ganglionic eminence, ventricular zone, endometrium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NDP	1,461
NDP-AS1	0

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NDP	Q00604	12

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 2 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
retina blood vessel maintenance	1	8426.0×	0.002	NDP
re-entry into mitotic cell cycle	1	5617.3×	0.002	NDP
cone retinal bipolar cell differentiation	1	4213.0×	0.002	NDP
extracellular matrix-cell signaling	1	3370.4×	0.002	NDP
Norrin signaling pathway	1	3370.4×	0.002	NDP
glycine metabolic process	1	2808.7×	0.002	NDP
establishment of blood-retinal barrier	1	2808.7×	0.002	NDP
retinal blood vessel morphogenesis	1	2407.4×	0.002	NDP
retinal rod cell differentiation	1	1872.4×	0.002	NDP
microglial cell proliferation	1	1872.4×	0.002	NDP
ubiquitin-dependent endocytosis	1	1872.4×	0.002	NDP
retinal pigment epithelium development	1	1685.2×	0.002	NDP
L-serine metabolic process	1	1685.2×	0.002	NDP
vacuole organization	1	1532.0×	0.002	NDP
microglia differentiation	1	1532.0×	0.002	NDP
establishment of blood-brain barrier	1	1404.3×	0.002	NDP
optic nerve development	1	1203.7×	0.002	NDP
dendritic spine development	1	1203.7×	0.002	NDP
endothelial cell differentiation	1	1123.5×	0.002	NDP
retinal ganglion cell axon guidance	1	766.0×	0.003	NDP
decidualization	1	674.1×	0.003	NDP
retina layer formation	1	648.1×	0.003	NDP
exploration behavior	1	648.1×	0.003	NDP
protein targeting to lysosome	1	624.1×	0.003	NDP
tricarboxylic acid cycle	1	510.7×	0.003	NDP
response to axon injury	1	510.7×	0.003	NDP
blood vessel remodeling	1	383.0×	0.004	NDP
lens development in camera-type eye	1	374.5×	0.004	NDP
action potential	1	358.6×	0.004	NDP
glutathione metabolic process	1	351.1×	0.004	NDP

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 2 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
NDP	0	0
NDP-AS1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; 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	2	NDP, NDP-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)
NDP	0	—
NDP-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.