Occult macular dystrophy

Summary

Occult macular dystrophy (MONDO:0013316) is a disease caused by RP1L1 (GenCC Definitive), with 3 cohort genes.

At a glance

• Prevalence: Unknown (Worldwide)
• Causal gene: RP1L1 (GenCC Definitive)
• Cohort genes: 3
• ClinVar variants: 452

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	occult macular dystrophy
Mondo ID	MONDO:0013316
OMIM	613587
Orphanet	247834
DOID	DOID:0050578
ICD-11	863463706
UMLS	C3150833
MedGen	462183
GARD	0017200
Is cancer (heuristic)	no

Also known as: occult macular dystrophy · OCMD · OMD

Data availability: 452 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › retinal disorder › retinal degeneration › macular degeneration › occult macular dystrophy

Related subtypes (8): vitelliform macular dystrophy, degeneration of macula and posterior pole, macular retinal edema, autosomal recessive bestrophinopathy, macular degeneration, early-onset, Stargardt disease, patterned macular dystrophy, isolated macular dystrophy

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

452 retrieved; paginated sample, class counts are floors:

134 benign, 123 uncertain significance, 85 conflicting classifications of pathogenicity, 78 benign/likely benign, 26 likely benign, 2 pathogenic, 2 pathogenic/likely pathogenic, 2 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1065635	NM_178857.6(RP1L1):c.6530T>G (p.Leu2177Ter)	RP1L1	Pathogenic	criteria provided, multiple submitters, no conflicts
2193	NM_178857.6(RP1L1):c.133C>T (p.Arg45Trp)	RP1L1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3765542	NM_178857.6(RP1L1):c.2116G>T (p.Gly706Ter)	RP1L1	Pathogenic	criteria provided, single submitter
865995	NM_178857.6(RP1L1):c.1189C>T (p.Arg397Ter)	RP1L1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3249352	NM_178857.6(RP1L1):c.5540_5541del (p.Glu1847fs)	RP1L1	Likely pathogenic	criteria provided, single submitter
992970	NM_178857.6(RP1L1):c.5033del (p.Ala1678fs)	RP1L1	Likely pathogenic	no assertion criteria provided
1065636	NM_178857.6(RP1L1):c.4020_4021del (p.Glu1340fs)	RP1L1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
225459	NM_178857.6(RP1L1):c.3956_3957insAAGAAGAGAG (p.Val1320fs)	RP1L1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
225460	NM_178857.6(RP1L1):c.324_325insT (p.Pro109fs)	RP1L1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
283503	NM_178857.6(RP1L1):c.3200G>C (p.Gly1067Ala)	RP1L1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3155809	NM_178857.6(RP1L1):c.2011C>T (p.Arg671Cys)	RP1L1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
361216	NM_178857.6(RP1L1):c.6603A>T (p.Ala2201=)	RP1L1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
361218	NM_178857.6(RP1L1):c.6597A>G (p.Pro2199=)	RP1L1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
361224	NM_178857.6(RP1L1):c.6380C>T (p.Pro2127Leu)	RP1L1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
361227	NM_178857.6(RP1L1):c.6322G>A (p.Gly2108Arg)	RP1L1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
361237	NM_178857.6(RP1L1):c.5821C>T (p.Gln1941Ter)	RP1L1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
361241	NM_178857.6(RP1L1):c.5713G>A (p.Gly1905Ser)	RP1L1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
361245	NM_178857.6(RP1L1):c.5618A>T (p.Asp1873Val)	RP1L1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
361251	NM_178857.6(RP1L1):c.5483A>C (p.Gln1828Pro)	RP1L1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
361255	NM_178857.6(RP1L1):c.5284G>A (p.Glu1762Lys)	RP1L1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
361256	NM_178857.6(RP1L1):c.5224G>A (p.Glu1742Lys)	RP1L1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
361258	NM_178857.6(RP1L1):c.5138C>A (p.Thr1713Asn)	RP1L1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
361266	NM_178857.6(RP1L1):c.4795C>G (p.Leu1599Val)	RP1L1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
361273	NM_178857.6(RP1L1):c.4594G>A (p.Ala1532Thr)	RP1L1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
361297	NM_178857.6(RP1L1):c.3971A>G (p.Glu1324Gly)	RP1L1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
361316	NM_178857.6(RP1L1):c.3263C>T (p.Ala1088Val)	RP1L1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
361322	NM_178857.6(RP1L1):c.3022C>G (p.Gln1008Glu)	RP1L1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
361325	NM_178857.6(RP1L1):c.2991C>G (p.Asp997Glu)	RP1L1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
361328	NM_178857.6(RP1L1):c.2923T>A (p.Leu975Met)	RP1L1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
361333	NM_178857.6(RP1L1):c.2791G>C (p.Gly931Arg)	RP1L1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 11 · Orphanet: 6 · 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
RP1L1	Definitive	Autosomal dominant	occult macular dystrophy	11

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RP1L1	Orphanet:247834	Occult macular dystrophy
RP1L1	Orphanet:791	Retinitis pigmentosa
RHO	Orphanet:215	Congenital stationary night blindness
RHO	Orphanet:52427	Retinitis punctata albescens
RHO	Orphanet:791	Retinitis pigmentosa
CAPN5	Orphanet:329211	Autosomal dominant neovascular inflammatory vitreoretinopathy

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RP1L1	HGNC:15946	ENSG00000183638	Q8IWN7	Retinitis pigmentosa 1-like 1 protein	gencc,clinvar
RHO	HGNC:10012	ENSG00000163914	P08100	Rhodopsin	clinvar
CAPN5	HGNC:1482	ENSG00000149260	O15484	Calpain-5	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RP1L1	Retinitis pigmentosa 1-like 1 protein	Required for the differentiation of photoreceptor cells.
RHO	Rhodopsin	Photoreceptor required for image-forming vision at low light intensity.
CAPN5	Calpain-5	Calcium-regulated non-lysosomal thiol-protease.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.67

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
Protease	1	12.2×	0.180
GPCR	1	8.0×	0.180
Other/Unknown	1	0.6×	0.914

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RP1L1	Other/Unknown	no		Doublecortin_dom, Doublecortin_dom_sf
RHO	GPCR	yes		GPCR_Rhodpsn, Rhodopsin, Opsin
CAPN5	Protease	yes	3.4.22.B25	C2_dom, Pept_cys_AS, Peptidase_C2_calpain_cat

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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
bone marrow cell	1
buccal mucosa cell	1
primordial germ cell in gonad	1
diaphragm	1
neuron projection bundle connecting eye with brain	1
optic choroid	1
gall bladder	1
mucosa of transverse colon	1
rectum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RP1L1	30	tissue_specific	yes	primordial germ cell in gonad, buccal mucosa cell, bone marrow cell
RHO	38	tissue_specific	marker	optic choroid, neuron projection bundle connecting eye with brain, diaphragm
CAPN5	224	ubiquitous	marker	mucosa of transverse colon, rectum, gall bladder

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RHO	3,578
RP1L1	1,004
CAPN5	972

Structural data

PDB: 2 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RHO	P08100	4
CAPN5	O15484	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
RP1L1	Q8IWN7	38.97

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. Enrichment computed across 3 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
Activation of the phototransduction cascade	1	475.8×	0.008	RHO
The canonical retinoid cycle in rods (twilight vision)	1	259.6×	0.008	RHO
VxPx cargo-targeting to cilium	1	259.6×	0.008	RHO
Inactivation, recovery and regulation of the phototransduction cascade	1	158.6×	0.010	RHO
Degradation of the extracellular matrix	1	58.9×	0.023	CAPN5
Extracellular matrix organization	1	31.6×	0.036	CAPN5
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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
photoreceptor cell maintenance	2	239.0×	5e-04	RP1L1, RHO
thermotaxis	1	2808.7×	0.002	RHO
rod bipolar cell differentiation	1	2808.7×	0.002	RHO
detection of temperature stimulus involved in thermoception	1	1872.4×	0.002	RHO
visual perception	2	53.0×	0.002	RP1L1, RHO
photoreceptor cell development	1	1404.3×	0.003	RP1L1
G protein-coupled opsin signaling pathway	1	1123.5×	0.003	RHO
absorption of visible light	1	936.2×	0.003	RHO
response to light intensity	1	702.2×	0.003	RHO
podosome assembly	1	702.2×	0.003	RHO
phototransduction, visible light	1	432.1×	0.005	RHO
photoreceptor cell outer segment organization	1	351.1×	0.005	RP1L1
cellular response to light stimulus	1	351.1×	0.005	RHO
axoneme assembly	1	181.2×	0.009	RP1L1
phototransduction	1	165.2×	0.009	RHO
retina development in camera-type eye	1	85.1×	0.016	RP1L1
microtubule cytoskeleton organization	1	40.4×	0.032	RHO
gene expression	1	26.6×	0.045	RHO
intracellular signal transduction	1	12.7×	0.089	RP1L1
G protein-coupled receptor signaling pathway	1	12.1×	0.089	RHO
proteolysis	1	11.4×	0.089	CAPN5
signal transduction	1	5.3×	0.176	CAPN5

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 3 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
RP1L1	0	0
RHO	0	0
CAPN5	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
RHO	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CAPN5	3.4.22.B25

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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, CAPN5
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	RP1L1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
RP1L1	0	—
RHO	1	—
CAPN5	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.