IMPG1

Chr 6ADAR

interphotoreceptor matrix proteoglycan 1

NCBI Gene: 3617ENSG00000112706UniProt: Q17R60

Chondroitin sulfate-, heparin- and hyaluronan-binding protein (By similarity). May serve to form a basic macromolecular scaffold comprising the insoluble interphotoreceptor matrix (PubMed:9813076)

Primary Disease Associations & Inheritance

Macular dystrophy, vitelliform, 4MIM #616151
ADAR
Retinitis pigmentosa 91MIM #153870
AD
520
ClinVar variants
61
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— IMPG1
🧬
Gene-Disease Validity (ClinGen)
IMPG1-related dominant retinopathy · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
61 Pathogenic / Likely Pathogenic· 272 VUS of 520 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.35LOEUF
pLI 0.000
Z-score -0.30
OE 1.05 (0.82–1.35)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.94Z-score
OE missense 1.13 (1.05–1.22)
476 obs / 421.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.1.05 (0.82–1.35)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.13 (1.05–1.22)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.99
0≤1.21.6
LoF obs/exp: 43 / 41.0Missense obs/exp: 476 / 421.9Syn Z: 0.09

ClinVar Variant Classifications

520 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic42
Likely Pathogenic19
VUS272
Likely Benign155
Benign23
Conflicting9
42
Pathogenic
19
Likely Pathogenic
272
VUS
155
Likely Benign
23
Benign
9
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
16
2
24
0
42
Likely Pathogenic
15
0
4
0
19
VUS
5
230
29
8
272
Likely Benign
0
2
66
87
155
Benign
0
14
4
5
23
Conflicting
—9
Total36248127100520

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

IMPG1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

IMPG1-related macular dystrophy, vitelliform

definitive
ADLoss Of FunctionAbsent Gene Product
Eye
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Macular dystrophy, vitelliform, 4

MIM #616151

Molecular basis of disorder known

Autosomal dominantAutosomal recessive

Retinitis pigmentosa 91

MIM #153870

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Prevalence of IMPG1 and IMPG2 Mutations Leading to Retinitis Pigmentosa or Vitelliform Macular Dystrophy in a Cohort of Patients with Inherited Retinal Dystrophies.
Yuan M et al.·Genes (Basel)
2025Cohort
Pathogenic variants in IMPG1 cause autosomal dominant and autosomal recessive retinitis pigmentosa.
Olivier G et al.·J Med Genet
2021
Frequency and clinical pattern of vitelliform macular dystrophy caused by mutations of interphotoreceptor matrix IMPG1 and IMPG2 genes.
Meunier I et al.·Ophthalmology
2014
Clinical manifestations of dual-gene variants involving ABCA4 in retinal dystrophies.
Wolfram L et al.·BMC Ophthalmol
2025
Adult-onset foveomacular vitelliform dystrophy: A fresh perspective.
Chowers I et al.·Prog Retin Eye Res
2015Review
Expanding the Genetic Spectrum in IMPG1 and IMPG2 Retinopathy.
Al-Khuzaei S et al.·Genes (Basel)
2025
Critical Roles of SEA Domains.
Salido EM·Adv Exp Med Biol
2025Review
Photoreceptor and Retinal Pigment Epithelium Relationships in Eyes With Vitelliform Macular Dystrophy Revealed by Multimodal Adaptive Optics Imaging.
Liu T et al.·Invest Ophthalmol Vis Sci
2022
Molecular genetic analysis of two functional candidate genes in the autosomal recessive retinitis pigmentosa, RP25, locus.
Abd El-Aziz MM et al.·Curr Eye Res
2005Functional
Mutations in IMPG1 cause vitelliform macular dystrophies.
Manes G et al.·Am J Hum Genet
2013
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools