Vitelliform macular dystrophy 4

Summary

Vitelliform macular dystrophy 4 (MONDO:0014508) is a disease caused by IMPG1 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: IMPG1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 23

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	vitelliform macular dystrophy 4
Mondo ID	MONDO:0014508
OMIM	616151
UMLS	C4015342
MedGen	863779
GARD	0016064
Is cancer (heuristic)	no

Also known as: IMPG1 vitelliform macular dystrophy · macular dystrophy, vitelliform, 4 · macular dystrophy, vitelliform, type 4 · vitelliform macular dystrophy caused by mutation in IMPG1 · VMD4

Data availability: 23 ClinVar variants · 3 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 › vitelliform macular dystrophy › adult-onset foveomacular vitelliform dystrophy › vitelliform macular dystrophy 4

Related subtypes (3): vitelliform macular dystrophy 1, 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

23 retrieved; paginated sample, class counts are floors:

9 uncertain significance, 5 pathogenic, 3 conflicting classifications of pathogenicity, 3 pathogenic/likely pathogenic, 2 benign, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1240016	NM_001563.4(IMPG1):c.807+5G>A	IMPG1	Pathogenic	criteria provided, single submitter
1240018	NM_001563.4(IMPG1):c.1824+1G>A	IMPG1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1240019	NM_001563.4(IMPG1):c.960T>A (p.Ser320Arg)	IMPG1	Pathogenic	no assertion criteria provided
162133	NM_001563.4(IMPG1):c.713T>G (p.Leu238Arg)	IMPG1	Pathogenic	no assertion criteria provided
162134	NM_001563.4(IMPG1):c.807+1G>T	IMPG1	Pathogenic	no assertion criteria provided
162135	NM_001563.4(IMPG1):c.1519C>T (p.Arg507Ter)	IMPG1	Pathogenic	criteria provided, single submitter
2955296	NM_001563.4(IMPG1):c.1428del (p.Pro477fs)	IMPG1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
620263	NM_001563.4(IMPG1):c.175C>T (p.Arg59Ter)	IMPG1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1701925	NM_001563.4(IMPG1):c.1530del (p.Gly511fs)	IMPG1	Likely pathogenic	criteria provided, single submitter
1032753	NM_001563.4(IMPG1):c.1836T>G (p.Tyr612Ter)	IMPG1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
162136	NM_001563.4(IMPG1):c.461T>C (p.Leu154Pro)	IMPG1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
846627	NM_001563.4(IMPG1):c.773A>G (p.Tyr258Cys)	IMPG1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3779768	NC_000008.11:g.75728605_75728647del		Uncertain significance	criteria provided, single submitter
3779769	NC_000008.11:g.75819624_75819627dup		Uncertain significance	criteria provided, single submitter
1026278	NM_001563.4(IMPG1):c.1897G>A (p.Val633Met)	IMPG1	Uncertain significance	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
1054275	NM_001563.4(IMPG1):c.332G>A (p.Arg111Gln)	IMPG1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1056230	NM_001563.4(IMPG1):c.1982G>A (p.Arg661His)	IMPG1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1810752	NM_001563.4(IMPG1):c.2362G>T (p.Glu788Ter)	IMPG1	Uncertain significance	criteria provided, single submitter
3061945	NM_001563.4(IMPG1):c.710_727del (p.Glu237_Leu242del)	IMPG1	Uncertain significance	criteria provided, single submitter
957728	NM_001563.4(IMPG1):c.1228C>A (p.Pro410Thr)	IMPG1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1098856	NM_001563.4(IMPG1):c.2132G>A (p.Arg711His)	IMPG1	Benign	criteria provided, multiple submitters, no conflicts
1165049	NM_001563.4(IMPG1):c.1552C>G (p.His518Asp)	IMPG1	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 3 · 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
IMPG1	Definitive	Autosomal dominant	vitelliform macular dystrophy 4	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
IMPG1	Orphanet:251287	Benign concentric annular macular dystrophy
IMPG1	Orphanet:791	Retinitis pigmentosa
IMPG1	Orphanet:99000	Adult-onset foveomacular vitelliform dystrophy

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
IMPG1	HGNC:6055	ENSG00000112706	Q17R60	Interphotoreceptor matrix proteoglycan 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
IMPG1	Interphotoreceptor matrix proteoglycan 1	Chondroitin sulfate-, heparin- and hyaluronan-binding protein.

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)
IMPG1	Other/Unknown	no		SEA_dom, EGF, SEA_dom_sf

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
male germ line stem cell (sensu Vertebrata) in testis	1
nucleus accumbens	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
IMPG1	155	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, nucleus accumbens, secondary oocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
IMPG1	690

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
IMPG1	Q17R60	59.26

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
extracellular matrix organization	1	122.1×	0.013	IMPG1
visual perception	1	79.5×	0.013	IMPG1

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
IMPG1	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	IMPG1

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)
IMPG1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.