Retinal macular dystrophy type 2

Summary

Retinal macular dystrophy type 2 (MONDO:0011957) is a disease caused by PROM1 (GenCC Definitive), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: PROM1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 131

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		5	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	retinal macular dystrophy type 2
Mondo ID	MONDO:0011957
MeSH	C562746
OMIM	608051
Orphanet	319640
DOID	DOID:0070517
UMLS	C4749334
MedGen	1666864
GARD	0017467
Is cancer (heuristic)	no

Also known as: macular dystrophy, retinal, 2 · macular dystrophy, retinal, type 2 · MCDR2

Data availability: 131 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › retinal disorder › retinal degeneration › inherited retinal dystrophy › hereditary macular dystrophy › macular dystrophy, retinal › retinal macular dystrophy type 2

Related subtypes (4): North Carolina macular dystrophy, macular dystrophy, retinal, 3, macular dystrophy, retinal, 5, macular dystrophy, retinal, 4

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

131 retrieved; paginated sample, class counts are floors:

61 conflicting classifications of pathogenicity, 44 uncertain significance, 12 benign, 4 likely pathogenic, 4 pathogenic/likely pathogenic, 3 benign/likely benign, 3 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1074912	NM_006017.3(PROM1):c.2215del (p.Thr739fs)	PROM1	Pathogenic	criteria provided, multiple submitters, no conflicts
2920638	NM_006017.3(PROM1):c.1709dup (p.Tyr570Ter)	PROM1	Pathogenic	criteria provided, single submitter
3780492	NM_006017.3(PROM1):c.154del (p.Ile52fs)	PROM1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
402237	NM_006017.3(PROM1):c.622del (p.Thr208fs)	PROM1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
5610	NM_006017.3(PROM1):c.1117C>T (p.Arg373Cys)	PROM1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
809626	NM_006017.3(PROM1):c.1142-1G>A	PROM1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
965933	NM_006017.3(PROM1):c.1682+3A>G	PROM1	Pathogenic	criteria provided, single submitter
2920637	NM_006017.3(PROM1):c.1975_1978del (p.Asn659fs)	PROM1	Likely pathogenic	no assertion criteria provided
3251979	NM_006017.3(PROM1):c.1984-1G>A	PROM1	Likely pathogenic	criteria provided, single submitter
3362528	NM_006017.3(PROM1):c.2366del (p.Asp789fs)	PROM1	Likely pathogenic	criteria provided, single submitter
965934	NM_006017.3(PROM1):c.2281-2A>G	PROM1	Likely pathogenic	criteria provided, single submitter
167535	NM_006017.3(PROM1):c.1497C>T (p.Ile499=)	PROM1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
191189	NM_006017.3(PROM1):c.604C>G (p.Arg202Gly)	PROM1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
194072	NM_006017.3(PROM1):c.1345G>A (p.Val449Met)	PROM1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
236524	NM_006017.3(PROM1):c.1632G>T (p.Gly544=)	PROM1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
287074	NM_006017.3(PROM1):c.1928C>G (p.Ala643Gly)	PROM1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
289314	NM_006017.3(PROM1):c.868A>C (p.Ser290Arg)	PROM1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
289616	NM_006017.3(PROM1):c.2271C>T (p.Ile757=)	PROM1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
347965	NM_006017.3(PROM1):c.*1052G>A	PROM1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
347967	NM_006017.3(PROM1):c.*684C>T	PROM1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
347971	NM_006017.3(PROM1):c.2578A>G (p.Thr860Ala)	PROM1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
347972	NM_006017.3(PROM1):c.2551G>A (p.Val851Ile)	PROM1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
347977	NM_006017.3(PROM1):c.2364C>T (p.Ile788=)	PROM1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
347978	NM_006017.3(PROM1):c.2309C>A (p.Pro770His)	PROM1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
347979	NM_006017.3(PROM1):c.2284A>G (p.Ser762Gly)	PROM1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
347981	NM_006017.3(PROM1):c.2211+7C>T	PROM1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
347984	NM_006017.3(PROM1):c.1911+14G>A	PROM1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
347987	NM_006017.3(PROM1):c.1683-3C>T	PROM1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
347988	NM_006017.3(PROM1):c.1579-6T>C	PROM1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
347989	NM_006017.3(PROM1):c.1578+9G>C	PROM1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 4 · 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
PROM1	Definitive	Autosomal dominant	retinal macular dystrophy type 2	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PROM1	Orphanet:1872	Cone rod dystrophy
PROM1	Orphanet:319640	Retinal macular dystrophy type 2
PROM1	Orphanet:791	Retinitis pigmentosa
PROM1	Orphanet:827	Stargardt disease

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
PROM1	HGNC:9454	ENSG00000007062	O43490	Prominin-1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PROM1	Prominin-1	May play a role in cell differentiation, proliferation and apoptosis.

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)
PROM1	Other/Unknown	no		Prominin

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
bronchial epithelial cell	1
bronchus	1
epithelium of bronchus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PROM1	252	broad	marker	bronchial epithelial cell, epithelium of bronchus, bronchus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PROM1	3,302

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PROM1	O43490	85.68

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
Developmental Lineage of Pancreatic Ductal Cells	1	228.4×	0.004	PROM1

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
glomerular parietal epithelial cell differentiation	1	8426.0×	6e-04	PROM1
positive regulation of nephron tubule epithelial cell differentiation	1	5617.3×	6e-04	PROM1
camera-type eye photoreceptor cell differentiation	1	3370.4×	7e-04	PROM1
retina morphogenesis in camera-type eye	1	1872.4×	9e-04	PROM1
podocyte differentiation	1	1404.3×	1e-03	PROM1
retina layer formation	1	648.1×	0.002	PROM1
photoreceptor cell maintenance	1	358.6×	0.003	PROM1

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PROM1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	PROM1

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)
PROM1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.