IMPG2

Chr 3ADAR

interphotoreceptor matrix proteoglycan 2

ENSG00000081148 UniProt: Q9BZV3 OMIM: 607056

IMPG2 encodes a chondroitin sulfate- and hyaluronan-binding proteoglycan that organizes the interphotoreceptor matrix and participates in maturation and maintenance of photoreceptor outer segments. Mutations cause macular dystrophy (vitelliform type 5) and retinitis pigmentosa 56, both progressive retinal degenerative disorders affecting vision. The gene shows both autosomal dominant and autosomal recessive inheritance patterns depending on the specific variant.

OMIM ResearchSummary from OMIM, UniProt

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. Binds heparin

OMIM ResearchGenerating clinical summary…

LOFmechanismAD/ARLOEUF 0.722 OMIM phenotypes

Clinical Summary— IMPG2

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Gene-Disease Validity (ClinGen)

IMPG2-related recessive retinopathy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.72LOEUF

pLI 0.000

Z-score 3.27

OE 0.53 (0.40–0.72)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.21Z-score

OE missense 1.02 (0.96–1.09)

641 obs / 626.4 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.53 (0.40–0.72)

0≤0.351.4

Missense OE?1.02 (0.96–1.09)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 30 / 56.5Missense obs/exp: 641 / 626.4Syn Z: -0.24

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveIMPG2-related macular dystrophy, vitelliformLOFAD

definitiveIMPG2-related retinitis pigmentosaLOFAR

This gene — mechanism propensity

0.6842th %ile

GOF

0.6150th %ile

LOF

0.2777th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.