Exudative vitreoretinopathy 8

Summary

Exudative vitreoretinopathy 8 (MONDO:0979571) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	exudative vitreoretinopathy 8
Mondo ID	MONDO:0979571
OMIM	621268
UMLS	C6012752
MedGen	1876521
GARD	0028119
Is cancer (heuristic)	no

Data availability: 3 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › retinal disorder › retinal vascular disorder › exudative vitreoretinopathy › exudative vitreoretinopathy 8

Related subtypes (8): exudative vitreoretinopathy 2, X-linked, exudative vitreoretinopathy 3, exudative vitreoretinopathy 6, exudative vitreoretinopathy 7, LRP5-related exudative vitreoretinopathy, TSPAN12-related exudative vitreoretinopathy, dyneinopathy, FZD4-related exudative vitreoretinopathy

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

3 retrieved; paginated sample, class counts are floors:

3 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
4057214	LRP6, VAL743ALA (rs146852380)	LRP6	Pathogenic	no assertion criteria provided
4057215	LRP6, ARG1026HIS	LRP6	Pathogenic	no assertion criteria provided
4057216	G1309E	LRP6	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
LRP6	Orphanet:1810	Autosomal dominant hypohidrotic ectodermal dysplasia
LRP6	Orphanet:99798	Oligodontia

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
LRP6	HGNC:6698	ENSG00000070018	O75581	Low-density lipoprotein receptor-related protein 6	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
LRP6	Low-density lipoprotein receptor-related protein 6	Component of the Wnt-Fzd-LRP5-LRP6 complex that triggers beta-catenin signaling through inducing aggregation of receptor-ligand complexes into ribosome-sized signalosomes.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
LRP6	Other/Unknown	no		LDLR_classB_rpt, EGF, LDrepeatLR_classA_rpt

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	1
corpus callosum	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LRP6	139	ubiquitous	marker	calcaneal tendon, corpus callosum, ventricular zone

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LRP6	2,525

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
LRP6	O75581	30

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Signaling by RNF43 mutants	1	1268.9×	0.005	LRP6
Negative regulation of TCF-dependent signaling by WNT ligand antagonists	1	713.8×	0.005	LRP6
Signaling by WNT in cancer	1	601.0×	0.005	LRP6
Regulation of FZD by ubiquitination	1	519.1×	0.005	LRP6
Disassembly of the destruction complex and recruitment of AXIN to the membrane	1	356.9×	0.006	LRP6
TCF dependent signaling in response to WNT	1	117.7×	0.013	LRP6
Signaling by WNT	1	112.0×	0.013	LRP6
Diseases of signal transduction by growth factor receptors and second messengers	1	56.8×	0.022	LRP6
Disease	1	13.1×	0.085	LRP6
Signal Transduction	1	10.2×	0.098	LRP6

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
neural crest formation	1	1872.4×	0.004	LRP6
neural crest cell differentiation	1	1532.0×	0.004	LRP6
negative regulation of smooth muscle cell apoptotic process	1	1404.3×	0.004	LRP6
midbrain dopaminergic neuron differentiation	1	1203.7×	0.004	LRP6
cellular response to cholesterol	1	842.6×	0.004	LRP6
dopaminergic neuron differentiation	1	624.1×	0.005	LRP6
positive regulation of cell cycle	1	443.5×	0.006	LRP6
response to peptide hormone	1	391.9×	0.006	LRP6
canonical Wnt signaling pathway	1	153.2×	0.013	LRP6
positive regulation of cytosolic calcium ion concentration	1	117.0×	0.014	LRP6
protein localization to plasma membrane	1	108.7×	0.014	LRP6
cell-cell adhesion	1	101.5×	0.014	LRP6
Wnt signaling pathway	1	99.7×	0.014	LRP6
endocytosis	1	95.2×	0.014	LRP6
chemical synaptic transmission	1	77.3×	0.016	LRP6
nervous system development	1	45.9×	0.025	LRP6
positive regulation of DNA-templated transcription	1	27.9×	0.038	LRP6
positive regulation of transcription by RNA polymerase II	1	14.9×	0.067	LRP6

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
LRP6	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
LRP6	9	Binding:9

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	1	LRP6

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
LRP6	9	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.