Exudative vitreoretinopathy

Summary

Exudative vitreoretinopathy (MONDO:0019516) is a disease (an umbrella term covering 9 Mondo subtypes) caused by CTNNB1 (GenCC Definitive), with 7 cohort genes and 3 clinical trials. Top therapeutic interventions include bromfenac sodium.

At a glance

• Prevalence: Unknown (Worldwide)
• Causal gene: CTNNB1 (GenCC Definitive)
• Umbrella term: 9 Mondo subtypes
• Cohort genes: 7
• ClinVar variants: 17
• Phenotypes (HPO): 27
• Clinical trials: 3

Clinical features

Signs & symptoms

Clinical features (HPO)

27 HPO clinical features (Orphanet curated; top 27 by frequency):

HPO ID	Term	Frequency
HP:0007773	Vitreoretinopathy	Obligate (100%)
HP:0007685	Peripheral retinal avascularization	Very frequent (80-99%)
HP:0001493	Falciform retinal fold	Frequent (30-79%)
HP:0007663	Reduced visual acuity	Frequent (30-79%)
HP:0007917	Tractional retinal detachment	Frequent (30-79%)
HP:0012795	Abnormality of the optic disc	Frequent (30-79%)
HP:0030666	Retinal neovascularization	Frequent (30-79%)
HP:0031526	Subretinal fluid	Frequent (30-79%)
HP:0000252	Microcephaly	Occasional (5-29%)
HP:0000365	Hearing impairment	Occasional (5-29%)
HP:0000518	Cataract	Occasional (5-29%)
HP:0000533	Chorioretinal atrophy	Occasional (5-29%)
HP:0000568	Microphthalmia	Occasional (5-29%)
HP:0000618	Blindness	Occasional (5-29%)
HP:0001004	Lymphedema	Occasional (5-29%)
HP:0001141	Severely reduced visual acuity	Occasional (5-29%)
HP:0001256	Intellectual disability, mild	Occasional (5-29%)
HP:0001270	Motor delay	Occasional (5-29%)
HP:0004349	Reduced bone mineral density	Occasional (5-29%)
HP:0007902	Vitreous hemorrhage	Occasional (5-29%)
HP:0011342	Mild global developmental delay	Occasional (5-29%)
HP:0012230	Rhegmatogenous retinal detachment	Occasional (5-29%)
HP:0030496	Macular exudate	Occasional (5-29%)
HP:0030503	Macular telangiectasia	Occasional (5-29%)
HP:0040049	Macular edema	Occasional (5-29%)
HP:0100014	Epiretinal membrane	Occasional (5-29%)
HP:0100832	Vitreous floaters	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	exudative vitreoretinopathy
Mondo ID	MONDO:0019516
MeSH	C580083
OMIM	133780
Orphanet	891
DOID	DOID:0050535
SNOMED CT	232063007
UMLS	C0339539
MedGen	573220
GARD	0001613
Is cancer (heuristic)	no

Also known as: Criswick-Schepens syndrome · exudative vitreoretinopathy, familial · familial exudative vitreoretinopathy · FEVR

Data availability: 17 ClinVar variants · 9 GenCC gene-disease records · 1 cell line.

Disease family

An umbrella term covering 9 Mondo subtypes.

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

Related subtypes (11): retinal microaneurysm, retinal vascular occlusion, retinal hemangioblastoma, retinal telangiectasia, diabetic retinopathy, retinal vasculitis, retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations, familial retinal arterial macroaneurysm, vasoproliferative tumor of retina, arteriosclerotic retinopathy, perifoveal exudative vascular anomalous complex

Subtypes (9): exudative vitreoretinopathy 2, X-linked, exudative vitreoretinopathy 3, exudative vitreoretinopathy 6, exudative vitreoretinopathy 7, LRP5-related exudative vitreoretinopathy, TSPAN12-related exudative vitreoretinopathy, exudative vitreoretinopathy 8, 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

17 retrieved; paginated sample, class counts are floors:

6 uncertain significance, 5 pathogenic, 3 likely pathogenic, 2 pathogenic/likely pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
224624	NM_012193.4(FZD4):c.313A>G (p.Met105Val)	FZD4	Pathogenic	criteria provided, multiple submitters, no conflicts
224625	NM_012193.4(FZD4):c.1282_1285del (p.Asp428fs)	FZD4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
441133	NM_012193.4(FZD4):c.40_49del (p.Pro14fs)	FZD4	Pathogenic	criteria provided, multiple submitters, no conflicts
2429188	NC_000011.9:g.(?68080076)(68216744_?)del	LRP5	Pathogenic	criteria provided, single submitter
6287	NM_002335.4(LRP5):c.4488+2T>G	LRP5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
236067	NM_012338.4(TSPAN12):c.542G>T (p.Cys181Phe)	TSPAN12	Pathogenic	criteria provided, multiple submitters, no conflicts
812466	NM_024741.3(ZNF408):c.1697T>A (p.Leu566His)	ZNF408	Pathogenic	no assertion criteria provided
812323	NM_012193.4(FZD4):c.349T>C (p.Cys117Arg)	FZD4	Likely pathogenic	no assertion criteria provided
3721066	NM_002335.4(LRP5):c.1042C>T (p.Arg348Trp)	LRP5	Likely pathogenic	criteria provided, multiple submitters, no conflicts
224621	NM_018191.4(RCBTB1):c.1172+1G>A	RCBTB1	Likely pathogenic	criteria provided, single submitter
1722379	NM_002335.4(LRP5):c.3763+2T>C	LRP5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1386515	NM_012193.4(FZD4):c.50T>C (p.Val17Ala)	FZD4	Uncertain significance	criteria provided, single submitter
437991	NM_002335.4(LRP5):c.1265C>T (p.Ala422Val)	LRP5	Uncertain significance	criteria provided, single submitter
437992	NM_002335.4(LRP5):c.3242T>G (p.Leu1081Arg)	LRP5	Uncertain significance	criteria provided, single submitter
224623	NM_000266.4(NDP):c.-77A>G	NDP	Uncertain significance	no assertion criteria provided
437962	NM_012338.4(TSPAN12):c.225_227del (p.Ile76del)	TSPAN12	Uncertain significance	criteria provided, single submitter
812465	NM_024741.3(ZNF408):c.1174T>C (p.Ser392Pro)	ZNF408	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 74 · Orphanet: 33 · 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
CTNNB1	Definitive	Autosomal dominant	exudative vitreoretinopathy	9
FZD4	Definitive	Semidominant	exudative vitreoretinopathy 1	7
LRP5	Definitive	Semidominant	exudative vitreoretinopathy 4	26
NDP	Definitive	X-linked	exudative vitreoretinopathy 2, X-linked	9
TSPAN12	Definitive	Autosomal dominant	exudative vitreoretinopathy 5	5
ZNF408	Strong	Autosomal dominant	exudative vitreoretinopathy 6	10
RCBTB1	Limited	Autosomal dominant	exudative vitreoretinopathy	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RCBTB1	Orphanet:99002	Reticular dystrophy of the retinal pigment epithelium
ZNF408	Orphanet:791	Retinitis pigmentosa
ZNF408	Orphanet:891	Familial exudative vitreoretinopathy
TSPAN12	Orphanet:891	Familial exudative vitreoretinopathy
FZD4	Orphanet:891	Familial exudative vitreoretinopathy
FZD4	Orphanet:90050	Retinopathy of prematurity
FZD4	Orphanet:91495	Persistent hyperplastic primary vitreous
LRP5	Orphanet:178377	Osteosclerosis-developmental delay-craniosynostosis syndrome
LRP5	Orphanet:2783	Autosomal dominant osteopetrosis type 1
LRP5	Orphanet:2788	Osteoporosis-pseudoglioma syndrome
LRP5	Orphanet:2790	Endosteal hyperostosis, Worth type
LRP5	Orphanet:2924	Isolated polycystic liver disease
LRP5	Orphanet:3416	Hyperostosis corticalis generalisata
LRP5	Orphanet:498481	LRP5-related primary osteoporosis
LRP5	Orphanet:891	Familial exudative vitreoretinopathy
LRP5	Orphanet:90050	Retinopathy of prematurity
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
CTNNB1	Orphanet:1501	Adrenocortical carcinoma
CTNNB1	Orphanet:210159	Adult hepatocellular carcinoma
CTNNB1	Orphanet:2780	Osteopathia striata-cranial sclerosis syndrome
CTNNB1	Orphanet:33402	Pediatric hepatocellular carcinoma
CTNNB1	Orphanet:404473	Intellectual disability-eye abnormalities-microcephaly-peripheral spasticity syndrome
CTNNB1	Orphanet:54595	Craniopharyngioma
CTNNB1	Orphanet:569248	Microcystic stromal tumor
CTNNB1	Orphanet:689430	Adenoid ameloblastoma
CTNNB1	Orphanet:873	Desmoid tumor
CTNNB1	Orphanet:891	Familial exudative vitreoretinopathy
CTNNB1	Orphanet:91414	Pilomatrixoma
CTNNB1	Orphanet:952	Acrofacial dysostosis, Weyers type

Cohort genes → proteins

7 cohort genes, 7 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	7

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RCBTB1	HGNC:18243	ENSG00000136144	Q8NDN9	RCC1 and BTB domain-containing protein 1	gencc,clinvar
ZNF408	HGNC:20041	ENSG00000175213	Q9H9D4	Zinc finger protein 408	gencc,clinvar
TSPAN12	HGNC:21641	ENSG00000106025	O95859	Tetraspanin-12	gencc,clinvar
FZD4	HGNC:4042	ENSG00000174804	Q9ULV1	Frizzled-4	gencc,clinvar
LRP5	HGNC:6697	ENSG00000162337	O75197	Low-density lipoprotein receptor-related protein 5	gencc,clinvar
NDP	HGNC:7678	ENSG00000124479	Q00604	Norrin	gencc,clinvar
CTNNB1	HGNC:2514	ENSG00000168036	P35222	Catenin beta-1	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RCBTB1	RCC1 and BTB domain-containing protein 1	May be involved in cell cycle regulation by chromatin remodeling.
ZNF408	Zinc finger protein 408	May be involved in transcriptional regulation.
TSPAN12	Tetraspanin-12	Regulator of cell surface receptor signal transduction.
FZD4	Frizzled-4	Receptor for Wnt proteins.
LRP5	Low-density lipoprotein receptor-related protein 5	Acts as a coreceptor with members of the frizzled family of seven-transmembrane spanning receptors to transduce signal by Wnt proteins.
NDP	Norrin	Activates the canonical Wnt signaling pathway through FZD4 and LRP5 coreceptor.
CTNNB1	Catenin beta-1	Key downstream component of the canonical Wnt signaling pathway.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 5 · Druggable fraction: 0.14

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
GPCR	1	3.4×	0.499
Other/Unknown	5	1.3×	0.499
Transcription factor	1	1.2×	0.595

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RCBTB1	Other/Unknown	no		BTB/POZ_dom, Reg_chr_condens, RCC1/BLIP-II
ZNF408	Transcription factor	no		SET_dom, Znf_C2H2_type, Znf_C2H2_sf
TSPAN12	Other/Unknown	no		Tetraspanin_animals, Tetraspanin_EC2_sf, Tetraspanin/Peripherin
FZD4	GPCR	yes		Frizzled/Smoothened_7TM, Frizzled/SFRP, GPCR_2-like_7TM
LRP5	Other/Unknown	no		LDLR_classB_rpt, EGF, LDrepeatLR_classA_rpt
NDP	Other/Unknown	no		Norrie_dis, Cys_knot_C, Glyco_hormone_CN
CTNNB1	Other/Unknown	no		Armadillo, ARM-like, Beta-catenin

Expression context

Cohort genes with no expression data: 0.

5 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)	7
unknown	0

Top tissues across cohort

Tissue	Cohort genes
decidua	2
mucosa of paranasal sinus	1
pigmented layer of retina	1
cervix squamous epithelium	1
endothelial cell	1
tendon of biceps brachii	1
nephron tubule	1
oocyte	1
secondary oocyte	1
adipose tissue	1
right lung	1
subcutaneous adipose tissue	1
ascending aorta	1
mucosa of transverse colon	1
right lobe of liver	1
caudate nucleus	1
cranial nerve II	1
adrenal tissue	1
periodontal ligament	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RCBTB1	280	ubiquitous	marker	mucosa of paranasal sinus, pigmented layer of retina, decidua
ZNF408	224	ubiquitous	yes	endothelial cell, tendon of biceps brachii, cervix squamous epithelium
TSPAN12	267	ubiquitous	marker	oocyte, nephron tubule, secondary oocyte
FZD4	243	ubiquitous	marker	adipose tissue, subcutaneous adipose tissue, right lung
LRP5	224	ubiquitous	marker	right lobe of liver, mucosa of transverse colon, ascending aorta
NDP	197	broad	yes	cranial nerve II, decidua, caudate nucleus
CTNNB1	295	ubiquitous	marker	adrenal tissue, ventricular zone, periodontal ligament

Protein interactions among cohort

Intra-cohort edges: 13.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CTNNB1	15,668
LRP5	2,619
FZD4	1,869
ZNF408	1,700
NDP	1,461
RCBTB1	1,081
TSPAN12	686

Intra-cohort edges

A	B	Sources
CTNNB1	NDP	string_interaction
FZD4	LRP5	string_interaction
FZD4	NDP	biogrid_interaction, intact, string_interaction
FZD4	TSPAN12	string_interaction
FZD4	ZNF408	string_interaction
LRP5	NDP	intact, string_interaction
LRP5	TSPAN12	string_interaction
LRP5	ZNF408	string_interaction
NDP	TSPAN12	intact, string_interaction
NDP	ZNF408	string_interaction
RCBTB1	TSPAN12	string_interaction
RCBTB1	ZNF408	string_interaction
TSPAN12	ZNF408	string_interaction

Structural data

PDB: 4 · AlphaFold-only: 3 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CTNNB1	P35222	50
NDP	Q00604	12
FZD4	Q9ULV1	11
TSPAN12	O95859	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
RCBTB1	Q8NDN9	92.98
LRP5	O75197	78.65
ZNF408	Q9H9D4	56.25

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 60. Enrichment computed across 7 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
Signaling by RNF43 mutants	2	845.9×	1e-04	FZD4, LRP5
Regulation of FZD by ubiquitination	2	346.1×	3e-04	FZD4, LRP5
Disassembly of the destruction complex and recruitment of AXIN to the membrane	2	237.9×	5e-04	LRP5, CTNNB1
Ca2+ pathway	2	119.0×	0.001	FZD4, CTNNB1
TCF dependent signaling in response to WNT	2	78.5×	0.003	LRP5, CTNNB1
LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production	1	761.3×	0.010	CTNNB1
Signaling by LRP5 mutants	1	543.8×	0.010	LRP5
CDH11 homotypic and heterotypic interactions	1	543.8×	0.010	CTNNB1
Regulation of CDH19 Expression and Function	1	475.8×	0.010	CTNNB1
InlA-mediated entry of Listeria monocytogenes into host cells	1	423.0×	0.010	CTNNB1
Binding of TCF/LEF:CTNNB1 to target gene promoters	1	380.7×	0.010	CTNNB1
RUNX3 regulates WNT signaling	1	380.7×	0.010	CTNNB1
Apoptotic cleavage of cell adhesion proteins	1	346.1×	0.010	CTNNB1
Regulation of CDH11 function	1	346.1×	0.010	CTNNB1
Regulation of CDH1 Function	1	317.2×	0.010	CTNNB1
Formation of axial mesoderm	1	271.9×	0.010	CTNNB1
WNT5A-dependent internalization of FZD4	1	253.8×	0.010	FZD4
Signaling by GSK3beta mutants	1	253.8×	0.010	CTNNB1
CTNNB1 S33 mutants aren’t phosphorylated	1	253.8×	0.010	CTNNB1
CTNNB1 S37 mutants aren’t phosphorylated	1	253.8×	0.010	CTNNB1
CTNNB1 S45 mutants aren’t phosphorylated	1	253.8×	0.010	CTNNB1
CTNNB1 T41 mutants aren’t phosphorylated	1	253.8×	0.010	CTNNB1
Negative regulation of TCF-dependent signaling by WNT ligand antagonists	1	237.9×	0.010	LRP5
Formation of definitive endoderm	1	237.9×	0.010	CTNNB1
Beta-catenin phosphorylation cascade	1	223.9×	0.010	CTNNB1
Germ layer formation at gastrulation	1	223.9×	0.010	CTNNB1
Formation of the nephric duct	1	211.5×	0.010	CTNNB1
Specification of the neural plate border	1	211.5×	0.010	CTNNB1
Signaling by WNT in cancer	1	200.3×	0.010	LRP5
Regulation of MITF-M-dependent genes involved in cell cycle and proliferation	1	190.3×	0.010	CTNNB1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 7 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
Norrin signaling pathway	4	1925.9×	1e-11	TSPAN12, FZD4, LRP5, NDP
establishment of blood-brain barrier	4	802.5×	7e-10	FZD4, LRP5, NDP, CTNNB1
extracellular matrix-cell signaling	3	1444.5×	4e-08	FZD4, LRP5, NDP
establishment of blood-retinal barrier	3	1203.7×	6e-08	LRP5, NDP, CTNNB1
retinal blood vessel morphogenesis	3	1031.8×	8e-08	FZD4, LRP5, NDP
canonical Wnt signaling pathway	4	87.5×	3e-06	FZD4, LRP5, NDP, CTNNB1
endothelial cell differentiation	2	321.0×	6e-04	FZD4, NDP
gastrulation with mouth forming second	2	267.5×	7e-04	LRP5, CTNNB1
retina layer formation	2	185.2×	0.001	TSPAN12, NDP
positive regulation of mesenchymal cell proliferation	2	172.0×	0.001	LRP5, CTNNB1
positive regulation of DNA-templated transcription	4	16.0×	0.001	FZD4, LRP5, NDP, CTNNB1
regulation of angiogenesis	2	120.4×	0.002	TSPAN12, CTNNB1
angiogenesis	3	26.8×	0.003	TSPAN12, FZD4, NDP
embryonic digit morphogenesis	2	86.0×	0.004	LRP5, CTNNB1
glial cell fate determination	1	2407.4×	0.006	CTNNB1
canonical Wnt signaling pathway involved in mesenchymal stem cell differentiation	1	2407.4×	0.006	CTNNB1
cerebellum vasculature morphogenesis	1	2407.4×	0.006	FZD4
cranial ganglion development	1	2407.4×	0.006	CTNNB1
positive regulation of osteoblast differentiation	2	64.2×	0.006	LRP5, CTNNB1
neural plate development	1	1203.7×	0.006	CTNNB1
negative regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis	1	1203.7×	0.006	CTNNB1
regulation of centriole-centriole cohesion	1	1203.7×	0.006	CTNNB1
progesterone secretion	1	1203.7×	0.006	FZD4
negative regulation of mitotic cell cycle, embryonic	1	1203.7×	0.006	CTNNB1
regulation of timing of anagen	1	1203.7×	0.006	CTNNB1
positive regulation of branching involved in lung morphogenesis	1	1203.7×	0.006	CTNNB1
renal vesicle formation	1	1203.7×	0.006	CTNNB1
renal inner medulla development	1	1203.7×	0.006	CTNNB1
renal outer medulla development	1	1203.7×	0.006	CTNNB1
nephron tubule formation	1	1203.7×	0.006	CTNNB1

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 6

Druggability breadth: 3 of 7 evidence-associated genes (43%) 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
CTNNB1	DITHIAZANINE IODIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CTNNB1	4	4
RCBTB1	0	0
ZNF408	0	0
TSPAN12	0	0
FZD4	0	0
LRP5	0	0
NDP	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
DITHIAZANINE IODIDE	4	CTNNB1
QUERCETIN	3	CTNNB1
SALINOMYCIN	2	CTNNB1
DALOSIRVAT	2	CTNNB1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
CTNNB1	361	Binding:358, Functional:3
FZD4	7	Functional:6, Binding:1
LRP5	1	Binding:1

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
CTNNB1	361

Pharmacogenomics

Cohort genes with a PharmGKB record: 7; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

4 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)
DITHIAZANINE IODIDE	4	CTNNB1
QUERCETIN	3	CTNNB1
SALINOMYCIN	2	CTNNB1
DALOSIRVAT	2	CTNNB1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	CTNNB1
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	FZD4
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	5	RCBTB1, ZNF408, TSPAN12, LRP5, NDP

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
RCBTB1	0	—
ZNF408	0	—
TSPAN12	0	—
FZD4	7	—
LRP5	1	—
NDP	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 3.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE4	1
PHASE2	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06520410	PHASE4	RECRUITING	Safety and Efficacy of 18 mm Short Vitrectomy Probe for Pediatric Vitreoretinal Surgeries
NCT05107921	PHASE2	UNKNOWN	Bromfenac Sodium Hydrate Eye Drops in Familial Exudative Vitreoretinopathy
NCT00106756	Not specified	COMPLETED	Clinical and Genetic Studies of Familial Exudative Vitreoretinopathy

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
BROMFENAC SODIUM	4	1