Optic disk drusen

Summary

Optic disk drusen (MONDO:0001746) is a disease with 2 cohort genes and 3 clinical trials.

At a glance

• Cohort genes: 2
• ClinVar variants: 2
• Clinical trials: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	optic disk drusen
Mondo ID	MONDO:0001746
MeSH	D015594
DOID	DOID:13561
ICD-10-CM	H47.32
SNOMED CT	33629003
UMLS	C0029128
MedGen	14495
Is cancer (heuristic)	no

Also known as: drusen of optic disc · drusen of optic disk

Data availability: 2 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › optic nerve disorder › optic disk drusen

Related subtypes (7): optic nerve neoplasm, optic atrophy, optic neuritis, anterior ischemic optic neuropathy, low tension glaucoma, extensive peripapillary myelinated nerve fibers, isolated optic nerve aplasia

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

2 retrieved; paginated sample, class counts are floors:

1 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
523376	NM_000539.3(RHO):c.891C>G (p.Ser297Arg)	RHO	Pathogenic	criteria provided, multiple submitters, no conflicts
523395	NM_001039348.3(EFEMP1):c.1189T>C (p.Tyr397His)	EFEMP1	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 5 · 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
EFEMP1	Orphanet:75376	Familial drusen
EFEMP1	Orphanet:98977	Juvenile glaucoma

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RHO	HGNC:10012	ENSG00000163914	P08100	Rhodopsin	clinvar
EFEMP1	HGNC:3218	ENSG00000115380	Q12805	EGF-containing fibulin-like extracellular matrix protein 1	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.
EFEMP1	EGF-containing fibulin-like extracellular matrix protein 1	Binds EGFR, the EGF receptor, inducing EGFR autophosphorylation and the activation of downstream signaling pathways.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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	12.0×	0.164
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RHO	GPCR	yes		GPCR_Rhodpsn, Rhodopsin, Opsin
EFEMP1	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, EGF-like_Ca-bd_dom

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
diaphragm	1
neuron projection bundle connecting eye with brain	1
optic choroid	1
descending thoracic aorta	1
right coronary artery	1
thoracic aorta	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
EFEMP1	286	ubiquitous	marker	right coronary artery, thoracic aorta, descending thoracic aorta

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RHO	3,578
EFEMP1	2,988

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RHO	P08100	4

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
EFEMP1	Q12805	77.67

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. Enrichment computed across 2 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×	0.007	RHO
Activation of the phototransduction cascade	1	475.8×	0.007	RHO
The canonical retinoid cycle in rods (twilight vision)	1	259.6×	0.007	RHO
VxPx cargo-targeting to cilium	1	259.6×	0.007	RHO
Inactivation, recovery and regulation of the phototransduction cascade	1	158.6×	0.008	RHO
Molecules associated with elastic fibres	1	154.3×	0.008	EFEMP1
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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
thermotaxis	1	4213.0×	0.002	RHO
rod bipolar cell differentiation	1	4213.0×	0.002	RHO
post-embryonic eye morphogenesis	1	2808.7×	0.002	EFEMP1
detection of temperature stimulus involved in thermoception	1	2808.7×	0.002	RHO
visual perception	2	79.5×	0.002	RHO, EFEMP1
G protein-coupled opsin signaling pathway	1	1685.2×	0.002	RHO
absorption of visible light	1	1404.3×	0.002	RHO
response to light intensity	1	1053.2×	0.002	RHO
podosome assembly	1	1053.2×	0.002	RHO
embryonic eye morphogenesis	1	766.0×	0.003	EFEMP1
phototransduction, visible light	1	648.1×	0.003	RHO
cellular response to light stimulus	1	526.6×	0.003	RHO
negative regulation of chondrocyte differentiation	1	337.0×	0.005	EFEMP1
phototransduction	1	247.8×	0.006	RHO
peptidyl-tyrosine phosphorylation	1	210.7×	0.007	EFEMP1
camera-type eye development	1	179.3×	0.007	EFEMP1
photoreceptor cell maintenance	1	179.3×	0.007	RHO
epidermal growth factor receptor signaling pathway	1	123.9×	0.010	EFEMP1
microtubule cytoskeleton organization	1	60.6×	0.019	RHO
gene expression	1	39.9×	0.027	RHO
G protein-coupled receptor signaling pathway	1	18.1×	0.057	RHO
regulation of DNA-templated transcription	1	15.8×	0.062	EFEMP1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) 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
EFEMP1	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
RHO	1	Binding:1

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

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	1	RHO
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	EFEMP1

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)
RHO	1	—
EFEMP1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 3.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03957642	Not specified	UNKNOWN	Systematic Imaging Examination in ODD
NCT05305079	Not specified	COMPLETED	NA-AION Risk Factors: New Perspectives
NCT05736237	Not specified	COMPLETED	Identification and Verification of Candidate Genes Responsible for Optic Disc Drusen Development