Coats disease

Summary

Coats disease (MONDO:0010269) is a disease with 5 cohort genes and 5 clinical trials. Top therapeutic interventions include prednisolone acetate and ranibizumab.

At a glance

• Prevalence: <1 / 1 000 000 (United Kingdom) [Orphanet-validated]
• Cohort genes: 5
• ClinVar variants: 7
• Phenotypes (HPO): 8
• Clinical trials: 5

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Annual incidence	<1 / 1 000 000	0.09	United Kingdom	Validated

Signs & symptoms

Clinical features (HPO)

8 HPO clinical features (Orphanet curated; top 8 by frequency):

HPO ID	Term	Frequency
HP:0000486	Strabismus	Very frequent (80-99%)
HP:0008046	Abnormal retinal vascular morphology	Very frequent (80-99%)
HP:0000501	Glaucoma	Frequent (30-79%)
HP:0000541	Retinal detachment	Frequent (30-79%)
HP:0001103	Abnormal macular morphology	Frequent (30-79%)
HP:0000518	Cataract	Occasional (5-29%)
HP:0000593	Abnormal anterior chamber morphology	Occasional (5-29%)
HP:0008053	Aplasia/Hypoplasia of the iris	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Coats disease
Mondo ID	MONDO:0010269
MeSH	D058456
OMIM	300216
Orphanet	190
DOID	DOID:7765
ICD-11	2032707885
SNOMED CT	360455002
UMLS	C5964756
MedGen	1870587
GARD	0006121
MedDRA	10015901
NORD	981
Is cancer (heuristic)	no

Also known as: Coats disease · congenital retinal telangiectasia · exudative retinopathy · Leber miliary aneurysm

Data availability: 7 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › retinal disorder › retinal vascular disorder › retinal telangiectasia › Coats disease

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

7 retrieved; paginated sample, class counts are floors:

2 likely pathogenic, 2 pathogenic/likely pathogenic, 2 pathogenic, 1 uncertain significance

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
224622	NM_018191.4(RCBTB1):c.707del (p.Asn236fs)	RCBTB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
523376	NM_000539.3(RHO):c.891C>G (p.Ser297Arg)	RHO	Pathogenic	criteria provided, multiple submitters, no conflicts
619128	NM_016580.4(PCDH12):c.2008G>T (p.Glu670Ter)	PCDH12	Likely pathogenic	criteria provided, single submitter
224621	NM_018191.4(RCBTB1):c.1172+1G>A	RCBTB1	Likely pathogenic	criteria provided, single submitter
224623	NM_000266.4(NDP):c.-77A>G	NDP	Uncertain significance	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 13 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RHO	Orphanet:215	Congenital stationary night blindness
RHO	Orphanet:52427	Retinitis punctata albescens
RHO	Orphanet:791	Retinitis pigmentosa
RCBTB1	Orphanet:99002	Reticular dystrophy of the retinal pigment epithelium
FZD4	Orphanet:891	Familial exudative vitreoretinopathy
FZD4	Orphanet:90050	Retinopathy of prematurity
FZD4	Orphanet:91495	Persistent hyperplastic primary vitreous
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
PCDH12	Orphanet:319192	Diencephalic-mesencephalic junction dysplasia

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
RHO	HGNC:10012	ENSG00000163914	P08100	Rhodopsin	clinvar
RCBTB1	HGNC:18243	ENSG00000136144	Q8NDN9	RCC1 and BTB domain-containing protein 1	clinvar
FZD4	HGNC:4042	ENSG00000174804	Q9ULV1	Frizzled-4	clinvar
NDP	HGNC:7678	ENSG00000124479	Q00604	Norrin	clinvar
PCDH12	HGNC:8657	ENSG00000113555	Q9NPG4	Protocadherin-12	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RHO	Rhodopsin	Photoreceptor required for image-forming vision at low light intensity.
RCBTB1	RCC1 and BTB domain-containing protein 1	May be involved in cell cycle regulation by chromatin remodeling.
FZD4	Frizzled-4	Receptor for Wnt proteins.
NDP	Norrin	Activates the canonical Wnt signaling pathway through FZD4 and LRP5 coreceptor.
PCDH12	Protocadherin-12	Cellular adhesion molecule that may play an important role in cell-cell interactions at interendothelial junctions.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 3 · Druggable fraction: 0.4

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	2	9.6×	0.032
Other/Unknown	3	1.1×	0.608

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RHO	GPCR	yes		GPCR_Rhodpsn, Rhodopsin, Opsin
RCBTB1	Other/Unknown	no		BTB/POZ_dom, Reg_chr_condens, RCC1/BLIP-II
FZD4	GPCR	yes		Frizzled/Smoothened_7TM, Frizzled/SFRP, GPCR_2-like_7TM
NDP	Other/Unknown	no		Norrie_dis, Cys_knot_C, Glyco_hormone_CN
PCDH12	Other/Unknown	no		Cadherin-like_dom, Cadherin_N, Cadherin-like_sf

Expression context

Cohort genes with no expression data: 0.

4 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
decidua	2
diaphragm	1
neuron projection bundle connecting eye with brain	1
optic choroid	1
mucosa of paranasal sinus	1
pigmented layer of retina	1
adipose tissue	1
right lung	1
subcutaneous adipose tissue	1
caudate nucleus	1
cranial nerve II	1
olfactory bulb	1
tendon of biceps brachii	1
type B pancreatic cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RHO	38	tissue_specific	marker	optic choroid, neuron projection bundle connecting eye with brain, diaphragm
RCBTB1	280	ubiquitous	marker	mucosa of paranasal sinus, pigmented layer of retina, decidua
FZD4	243	ubiquitous	marker	adipose tissue, subcutaneous adipose tissue, right lung
NDP	197	broad	yes	cranial nerve II, decidua, caudate nucleus
PCDH12	217	broad	marker	tendon of biceps brachii, type B pancreatic cell, olfactory bulb

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RHO	3,578
FZD4	1,869
NDP	1,461
RCBTB1	1,081
PCDH12	657

Intra-cohort edges

A	B	Sources
FZD4	NDP	biogrid_interaction, intact, string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NDP	Q00604	12
FZD4	Q9ULV1	11
RHO	P08100	4

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
RCBTB1	Q8NDN9	92.98
PCDH12	Q9NPG4	66.22

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 14. Enrichment computed across 5 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
Opsins	1	634.4×	0.008	RHO
Signaling by RNF43 mutants	1	634.4×	0.008	FZD4
Activation of the phototransduction cascade	1	475.8×	0.008	RHO
WNT5A-dependent internalization of FZD4	1	380.7×	0.008	FZD4
The canonical retinoid cycle in rods (twilight vision)	1	259.6×	0.008	RHO
Regulation of FZD by ubiquitination	1	259.6×	0.008	FZD4
VxPx cargo-targeting to cilium	1	259.6×	0.008	RHO
Inactivation, recovery and regulation of the phototransduction cascade	1	158.6×	0.011	RHO
Asymmetric localization of PCP proteins	1	102.0×	0.014	FZD4
Class B/2 (Secretin family receptors)	1	95.2×	0.014	FZD4
Ca2+ pathway	1	89.2×	0.014	FZD4
Cargo recognition for clathrin-mediated endocytosis	1	52.4×	0.022	FZD4
Clathrin-mediated endocytosis	1	42.6×	0.025	FZD4
G alpha (i) signalling events	1	19.5×	0.051	RHO

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
extracellular matrix-cell signaling	2	1348.2×	3e-05	FZD4, NDP
Norrin signaling pathway	2	1348.2×	3e-05	FZD4, NDP
retinal blood vessel morphogenesis	2	963.0×	4e-05	FZD4, NDP
establishment of blood-brain barrier	2	561.7×	1e-04	FZD4, NDP
endothelial cell differentiation	2	449.4×	1e-04	FZD4, NDP
cerebellum vasculature morphogenesis	1	3370.4×	0.004	FZD4
progesterone secretion	1	1685.2×	0.005	FZD4
thermotaxis	1	1685.2×	0.005	RHO
retina blood vessel maintenance	1	1685.2×	0.005	NDP
rod bipolar cell differentiation	1	1685.2×	0.005	RHO
canonical Wnt signaling pathway	2	61.3×	0.005	FZD4, NDP
re-entry into mitotic cell cycle	1	1123.5×	0.006	NDP
detection of temperature stimulus involved in thermoception	1	1123.5×	0.006	RHO
Wnt signaling pathway, calcium modulating pathway	1	842.6×	0.007	FZD4
cone retinal bipolar cell differentiation	1	842.6×	0.007	NDP
neuron recognition	1	674.1×	0.007	PCDH12
G protein-coupled opsin signaling pathway	1	674.1×	0.007	RHO
retina vasculature morphogenesis in camera-type eye	1	674.1×	0.007	FZD4
glycine metabolic process	1	561.7×	0.007	NDP
absorption of visible light	1	561.7×	0.007	RHO
regulation of vascular endothelial growth factor receptor signaling pathway	1	561.7×	0.007	FZD4
establishment of blood-retinal barrier	1	561.7×	0.007	NDP
visual perception	2	31.8×	0.007	RHO, NDP
locomotion involved in locomotory behavior	1	481.5×	0.007	FZD4
response to light intensity	1	421.3×	0.007	RHO
labyrinthine layer development	1	421.3×	0.007	PCDH12
podosome assembly	1	421.3×	0.007	RHO
positive regulation of neuron projection arborization	1	421.3×	0.007	FZD4
retinal rod cell differentiation	1	374.5×	0.007	NDP
microglial cell proliferation	1	374.5×	0.007	NDP

Therapeutics

Drugs indicated for this disease

0 approved, 1 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Bevacizumab	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Anecortave Acetate.

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 5

Druggability breadth: 2 of 5 evidence-associated genes (40%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
RHO	0	0
RCBTB1	0	0
FZD4	0	0
NDP	0	0
PCDH12	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
FZD4	7	Functional:6, Binding:1
RHO	1	Binding:1

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

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	2	RHO, FZD4
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	3	RCBTB1, NDP, PCDH12

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
RHO	1	—
RCBTB1	0	—
FZD4	7	—
NDP	0	—
PCDH12	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 5.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	2
PHASE4	1
PHASE3	1
EARLY_PHASE1	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
NCT03940690	PHASE3	TERMINATED	Interest of Intravitreal Injections of Anti-VEGF as Initial and Adjuvant Treatment in Coats Disease
NCT05620901	EARLY_PHASE1	COMPLETED	DEXTENZA in Pediatric Patients Following Retinal Surgery or Laser Treatment Under Anesthesia
NCT04089995	Not specified	COMPLETED	Coats Plus Syndrome and LCC Syndrome: Series of 10 Pediatric Cases. Review of Literature and Natural History
NCT04310631	Not specified	COMPLETED	Evaluation of Retinal and Vascular Features in Coats Disease After Intravitreal Injections of Ranibizumab

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
PREDNISOLONE ACETATE	4	1
RANIBIZUMAB	4	1