Vitelliform macular dystrophy 5

Summary

Vitelliform macular dystrophy 5 (MONDO:0014509) is a disease caused by IMPG2 (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: IMPG2 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 28

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	vitelliform macular dystrophy 5
Mondo ID	MONDO:0014509
OMIM	616152
UMLS	C4015343
MedGen	863780
GARD	0016065
Is cancer (heuristic)	no

Also known as: IMPG2 vitelliform macular dystrophy · macular dystrophy, vitelliform, 5 · macular dystrophy, vitelliform, type 5 · vitelliform macular dystrophy caused by mutation in IMPG2 · VMD5

Data availability: 28 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 5

Related subtypes (3): vitelliform macular dystrophy 1, vitelliform macular dystrophy 4, 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

28 retrieved; paginated sample, class counts are floors:

11 uncertain significance, 4 benign, 4 likely pathogenic, 4 pathogenic, 3 conflicting classifications of pathogenicity, 2 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
143151	NM_016247.4(IMPG2):c.3262C>T (p.Arg1088Ter)	IMPG2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
191180	NM_016247.4(IMPG2):c.2274G>A (p.Trp758Ter)	IMPG2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
191181	NM_016247.4(IMPG2):c.513T>G (p.Tyr171Ter)	IMPG2	Pathogenic	criteria provided, multiple submitters, no conflicts
3548	NM_016247.4(IMPG2):c.2716C>T (p.Arg906Ter)	IMPG2	Pathogenic	criteria provided, multiple submitters, no conflicts
959814	NM_016247.4(IMPG2):c.1658del (p.Val553fs)	IMPG2	Pathogenic	criteria provided, multiple submitters, no conflicts
978983	NM_016247.4(IMPG2):c.2346_2347del (p.Arg782fs)	IMPG2	Pathogenic	criteria provided, single submitter
162138	NM_016247.4(IMPG2):c.3230G>T (p.Cys1077Phe)	IMPG2	Likely pathogenic	criteria provided, single submitter
191182	NM_016247.4(IMPG2):c.380G>C (p.Arg127Pro)	IMPG2	Likely pathogenic	criteria provided, single submitter
2627610	NM_016247.4(IMPG2):c.3047T>C (p.Phe1016Ser)	IMPG2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
599088	NM_016247.4(IMPG2):c.2816T>A (p.Leu939His)	IMPG2	Likely pathogenic	no assertion criteria provided
3550	NM_016247.4(IMPG2):c.370T>C (p.Phe124Leu)	IMPG2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
866736	NM_016247.4(IMPG2):c.727G>C (p.Ala243Pro)	IMPG2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
902880	NM_016247.4(IMPG2):c.745C>T (p.Leu249Phe)	IMPG2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1368693	NM_001563.4(IMPG1):c.1079G>C (p.Ser360Thr)	IMPG1	Uncertain significance	criteria provided, single submitter
1032727	NM_016247.4(IMPG2):c.2636G>C (p.Ser879Thr)	IMPG2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1044355	NM_016247.4(IMPG2):c.2897A>G (p.Lys966Arg)	IMPG2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1509063	NM_016247.4(IMPG2):c.2887A>G (p.Ser963Gly)	IMPG2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1801828	NM_016247.4(IMPG2):c.86-8C>G	IMPG2	Uncertain significance	criteria provided, single submitter
191183	NM_016247.4(IMPG2):c.101C>G (p.Ser34Cys)	IMPG2	Uncertain significance	criteria provided, single submitter
1960816	NM_016247.4(IMPG2):c.2050G>A (p.Gly684Arg)	IMPG2	Uncertain significance	criteria provided, multiple submitters, no conflicts
3891387	NM_016247.4(IMPG2):c.1498G>A (p.Val500Met)	IMPG2	Uncertain significance	criteria provided, single submitter
853888	NM_016247.4(IMPG2):c.1300C>T (p.Pro434Ser)	IMPG2	Uncertain significance	criteria provided, multiple submitters, no conflicts
95748	NM_016247.4(IMPG2):c.2524C>A (p.Leu842Met)	IMPG2	Uncertain significance	criteria provided, multiple submitters, no conflicts
957924	NM_016247.4(IMPG2):c.2056G>A (p.Ala686Thr)	IMPG2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1167430	NM_016247.4(IMPG2):c.828+17_828+18insC	IMPG2	Benign	criteria provided, multiple submitters, no conflicts
1300072	NM_016247.4(IMPG2):c.85+25T>G	IMPG2	Benign	criteria provided, multiple submitters, no conflicts
342337	NM_016247.4(IMPG2):c.3381C>T (p.Leu1127=)	IMPG2	Benign	criteria provided, multiple submitters, no conflicts
95747	NM_016247.4(IMPG2):c.2021C>T (p.Thr674Ile)	IMPG2	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 5 · 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
IMPG2	Definitive	Autosomal dominant	vitelliform macular dystrophy 5	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
IMPG2	Orphanet:791	Retinitis pigmentosa
IMPG2	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

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
IMPG2	HGNC:18362	ENSG00000081148	Q9BZV3	Interphotoreceptor matrix proteoglycan 2	gencc,clinvar
IMPG1	HGNC:6055	ENSG00000112706	Q17R60	Interphotoreceptor matrix proteoglycan 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
IMPG2	Interphotoreceptor matrix proteoglycan 2	Chondroitin sulfate- and hyaluronan-binding proteoglycan involved in the organization of interphotoreceptor matrix; may participate in the maturation and maintenance of the light-sensitive photoreceptor outer segment.
IMPG1	Interphotoreceptor matrix proteoglycan 1	Chondroitin sulfate-, heparin- and hyaluronan-binding protein.

Protein-family classification

Druggable: 0 · Difficult: 0 · 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
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
IMPG2	Other/Unknown	no		SEA_dom, EGF, SEA_dom_sf
IMPG1	Other/Unknown	no		SEA_dom, EGF, SEA_dom_sf

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
male germ line stem cell (sensu Vertebrata) in testis	2
pineal body	1
right uterine tube	1
nucleus accumbens	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
IMPG2	81	tissue_specific	marker	right uterine tube, male germ line stem cell (sensu Vertebrata) in testis, pineal body
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
IMPG2	516

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
IMPG1	Q17R60	59.26
IMPG2	Q9BZV3	54.28

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 2 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 2 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	2	122.1×	3e-04	IMPG2, IMPG1
visual perception	2	79.5×	3e-04	IMPG2, IMPG1
retina morphogenesis in camera-type eye	1	936.2×	0.001	IMPG2
intracellular protein localization	1	52.3×	0.019	IMPG2

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 2 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
IMPG2	0	0
IMPG1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	IMPG2, 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)
IMPG2	0	—
IMPG1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.