Vitelliform macular dystrophy 1

Summary

Vitelliform macular dystrophy 1 (MONDO:0007933) is a disease with 3 cohort genes.

At a glance

• Cohort genes: 3
• ClinVar variants: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	vitelliform macular dystrophy 1
Mondo ID	MONDO:0007933
MeSH	C537832
OMIM	153840
UMLS	C4551953
MedGen	1636950
GARD	0010120
Is cancer (heuristic)	no

Also known as: macular dystrophy, vitelliform, 1 · vitelliform macular dystrophy, atypical · VMD1

Data availability: 3 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › retinal disorder › retinal degeneration › macular degeneration › vitelliform macular dystrophy › adult-onset foveomacular vitelliform dystrophy › vitelliform macular dystrophy 1

Related subtypes (3): vitelliform macular dystrophy 4, vitelliform macular dystrophy 5, vitelliform macular dystrophy 3

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

3 retrieved; paginated sample, class counts are floors:

1 uncertain significance, 1 benign/likely benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2737	NM_004183.4(BEST1):c.728C>T (p.Ala243Val)	BEST1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1027943	NM_001563.4(IMPG1):c.1751T>C (p.Met584Thr)	IMPG1	Uncertain significance	criteria provided, multiple submitters, no conflicts
178438	NM_002473.6(MYH9):c.136C>T (p.Leu46Phe)	MYH9	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

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
BEST1	Orphanet:1243	Best vitelliform macular dystrophy
BEST1	Orphanet:139455	Autosomal recessive bestrophinopathy
BEST1	Orphanet:263347	MRCS syndrome
BEST1	Orphanet:3086	Autosomal dominant vitreoretinochoroidopathy
BEST1	Orphanet:35612	Nanophthalmos
BEST1	Orphanet:791	Retinitis pigmentosa
BEST1	Orphanet:99000	Adult-onset foveomacular vitelliform dystrophy
IMPG1	Orphanet:251287	Benign concentric annular macular dystrophy
IMPG1	Orphanet:791	Retinitis pigmentosa
IMPG1	Orphanet:99000	Adult-onset foveomacular vitelliform dystrophy
MYH9	Orphanet:182050	MYH9-related syndromic thrombocytopenia
MYH9	Orphanet:477742	Nodular fasciitis
MYH9	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA

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
BEST1	HGNC:12703	ENSG00000167995	O76090	Bestrophin-1	clinvar
IMPG1	HGNC:6055	ENSG00000112706	Q17R60	Interphotoreceptor matrix proteoglycan 1	clinvar
MYH9	HGNC:7579	ENSG00000100345	P35579	Myosin-9	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BEST1	Bestrophin-1	Ligand-gated anion channel that allows the movement of anions across cell membranes when activated by calcium (Ca2+).
IMPG1	Interphotoreceptor matrix proteoglycan 1	Chondroitin sulfate-, heparin- and hyaluronan-binding protein.
MYH9	Myosin-9	Cellular myosin that appears to play a role in cytokinesis, cell shape, and specialized functions such as secretion and capping.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 2 · 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
Scaffold/PPI	1	5.8×	0.327
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BEST1	Other/Unknown	no		Bestrophin, Bestrophin-like
IMPG1	Other/Unknown	no		SEA_dom, EGF, SEA_dom_sf
MYH9	Scaffold/PPI	no		IQ_motif_EF-hand-BS, Myosin_head_motor_dom-like, Myosin_tail

Expression context

Cohort genes with no expression data: 0.

3 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
inferior olivary complex	1
lateral globus pallidus	1
pigmented layer of retina	1
male germ line stem cell (sensu Vertebrata) in testis	1
nucleus accumbens	1
secondary oocyte	1
ascending aorta	1
stromal cell of endometrium	1
thoracic aorta	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BEST1	209	ubiquitous	marker	pigmented layer of retina, lateral globus pallidus, inferior olivary complex
IMPG1	155	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, nucleus accumbens, secondary oocyte
MYH9	279	ubiquitous	marker	stromal cell of endometrium, ascending aorta, thoracic aorta

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MYH9	5,533
BEST1	959
IMPG1	690

Intra-cohort edges

A	B	Sources
BEST1	IMPG1	string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
BEST1	O76090	19
MYH9	P35579	8

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
IMPG1	Q17R60	59.26

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 43. 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
CD163 mediating an anti-inflammatory response	1	571.0×	0.020	MYH9
Sema4D in semaphorin signaling	1	335.9×	0.020	MYH9
RHO GTPases activate CIT	1	300.5×	0.020	MYH9
RHO GTPases Activate ROCKs	1	300.5×	0.020	MYH9
Sema4D induced cell migration and growth-cone collapse	1	285.5×	0.020	MYH9
RHO GTPases activate PAKs	1	271.9×	0.020	MYH9
Semaphorin interactions	1	196.9×	0.020	MYH9
Anti-inflammatory response favouring Leishmania parasite infection	1	196.9×	0.020	MYH9
Leishmania parasite growth and survival	1	196.9×	0.020	MYH9
EPHA-mediated growth cone collapse	1	190.3×	0.020	MYH9
Parasite infection	1	173.0×	0.020	MYH9
Leishmania phagocytosis	1	173.0×	0.020	MYH9
RHO GTPases activate PKNs	1	158.6×	0.020	MYH9
Sensory processing of sound	1	154.3×	0.020	MYH9
Fcgamma receptor (FCGR) dependent phagocytosis	1	139.3×	0.020	MYH9
Signaling by ALK in cancer	1	135.9×	0.020	MYH9
Sensory processing of sound by outer hair cells of the cochlea	1	102.0×	0.023	MYH9
FCGR3A-mediated phagocytosis	1	93.6×	0.023	MYH9
Regulation of actin dynamics for phagocytic cup formation	1	92.1×	0.023	MYH9
EPH-Ephrin signaling	1	82.8×	0.023	MYH9
Leishmania infection	1	81.6×	0.023	MYH9
Sensory processing of sound by inner hair cells of the cochlea	1	81.6×	0.023	MYH9
Parasitic Infection Pathways	1	81.6×	0.023	MYH9
Translocation of SLC2A4 (GLUT4) to the plasma membrane	1	77.2×	0.023	MYH9
Signaling by ALK fusions and activated point mutants	1	75.1×	0.023	MYH9
Stimuli-sensing channels	1	68.0×	0.024	BEST1
Ion channel transport	1	48.0×	0.032	BEST1
Sensory Perception	1	47.6×	0.032	MYH9
RHO GTPase Effectors	1	34.0×	0.043	MYH9
Diseases of signal transduction by growth factor receptors and second messengers	1	28.4×	0.050	MYH9

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
uropod organization	1	2808.7×	0.003	MYH9
cortical granule exocytosis	1	2808.7×	0.003	MYH9
gamma-aminobutyric acid secretion, neurotransmission	1	2808.7×	0.003	BEST1
negative regulation of actin filament severing	1	2808.7×	0.003	MYH9
positive regulation of protein processing in phagocytic vesicle	1	2808.7×	0.003	MYH9
cytokinetic process	1	1872.4×	0.003	MYH9
regulation of plasma membrane repair	1	1872.4×	0.003	MYH9
visual perception	2	53.0×	0.003	BEST1, IMPG1
establishment of meiotic spindle localization	1	1404.3×	0.003	MYH9
cytoplasmic actin-based contraction involved in cell motility	1	1123.5×	0.004	MYH9
meiotic spindle organization	1	802.5×	0.005	MYH9
establishment of T cell polarity	1	624.1×	0.005	MYH9
transepithelial chloride transport	1	624.1×	0.005	BEST1
glutamate secretion	1	561.7×	0.005	BEST1
blood vessel endothelial cell migration	1	468.1×	0.006	MYH9
regulated exocytosis	1	295.6×	0.008	MYH9
actin filament-based movement	1	267.5×	0.008	MYH9
monocyte differentiation	1	267.5×	0.008	MYH9
regulation of calcium ion transport	1	267.5×	0.008	BEST1
platelet formation	1	234.1×	0.008	MYH9
phagocytosis, engulfment	1	224.7×	0.008	MYH9
protein complex oligomerization	1	224.7×	0.008	BEST1
membrane protein ectodomain proteolysis	1	216.1×	0.008	MYH9
detection of light stimulus involved in visual perception	1	216.1×	0.008	BEST1
leukocyte migration	1	208.1×	0.008	MYH9
myoblast fusion	1	200.6×	0.008	MYH9
plasma membrane repair	1	193.7×	0.008	MYH9
actomyosin structure organization	1	187.2×	0.008	MYH9
lysosome localization	1	175.5×	0.008	MYH9
endodermal cell differentiation	1	165.2×	0.009	MYH9

Therapeutics

Drug target analysis

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

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
MYH9	1	2
BEST1	0	0
IMPG1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	MYH9

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
MYH9	10	Binding:10

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

1 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)
MOLIBRESIB	2	MYH9

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	1	MYH9
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	BEST1, IMPG1

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)
BEST1	0	—
IMPG1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.