IMPG2

interphotoreceptor matrix proteoglycan 2

Basic information

Region (hg38): 3:101222546-101320575

Links

ENSG00000081148 ∙ NCBI:50939 ∙ OMIM:607056 ∙ HGNC:18362 ∙ Uniprot:Q9BZV3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• retinitis pigmentosa (Supportive), mode of inheritance: AD
• adult-onset foveomacular vitelliform dystrophy (Supportive), mode of inheritance: AD
• retinitis pigmentosa 56 (Strong), mode of inheritance: AR
• retinitis pigmentosa 56 (Definitive), mode of inheritance: AR
• vitelliform macular dystrophy 5 (Definitive), mode of inheritance: AD
• vitelliform macular dystrophy 5 (Limited), mode of inheritance: Unknown
• inherited retinal dystrophy (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Macular dystrophy, vitelliform, 5; Retinitis pigmentosa 56	AD/AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Ophthalmologic	20673862; 25085631

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IMPG2 gene.

• not_provided (772 variants)
• Inborn_genetic_diseases (151 variants)
• Retinal_dystrophy (134 variants)
• Retinitis_pigmentosa (70 variants)
• Retinitis_pigmentosa_56 (38 variants)
• Vitelliform_macular_dystrophy_5 (23 variants)
• IMPG2-related_disorder (20 variants)
• Autosomal_recessive_retinitis_pigmentosa (7 variants)
• not_specified (6 variants)
• Macular_dystrophy (3 variants)
• Vitelliform_macular_dystrophy_2 (3 variants)
• Retinitis_Pigmentosa,_Recessive (2 variants)
• IMPG2-related_recessive_retinopathy (1 variants)
• Cone-rod_dystrophy (1 variants)
• Vitelliform_macular_dystrophy_3 (1 variants)
• Prostate_cancer (1 variants)
• Bardet-Biedl_syndrome (1 variants)
• Abnormality_of_the_eye (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IMPG2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000016247.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			6	161	3	170
missense	1	12	477	18	1	509
nonsense	30	21				51
start loss						0
frameshift	37	17				54
splice donor/acceptor (+/-2bp)	5	25				30
Total	73	75	483	179	4

Highest pathogenic variant AF is 0.000158726

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IMPG2	protein_coding	protein_coding	ENST00000193391	19	98015

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.75e-13	1.00	125682	0	66	125748	0.000262

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.207	641	626	1.02	0.0000312	8159
Missense in Polyphen		110	137.93	0.79751		1937
Synonymous	-0.238	236	231	1.02	0.0000122	2372
Loss of Function	3.27	30	56.5	0.531	0.00000285	727

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000451	0.000449
Ashkenazi Jewish	0.00	0.00
East Asian	0.000762	0.000761
Finnish	0.0000925	0.0000924
European (Non-Finnish)	0.000282	0.000281
Middle Eastern	0.000762	0.000761
South Asian	0.000229	0.000229
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: 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. {ECO:0000269|PubMed:10702256}.
• Disease: DISEASE: Retinitis pigmentosa 56 (RP56) [MIM:613581]: A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. {ECO:0000269|PubMed:20673862}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Macular dystrophy, vitelliform, 5 (VMD5) [MIM:616152]: A form of macular dystrophy, a retinal disease in which various forms of deposits, pigmentary changes, and atrophic lesions are observed in the macula lutea. Vitelliform macular dystrophies are characterized by yellow, lipofuscin-containing deposits, usually localized at the center of the macula. VMD5 features include late- onset moderate visual impairment and preservation of retinal pigment epithelium reflectivity. {ECO:0000269|PubMed:20673862, ECO:0000269|PubMed:25085631}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.113

Intolerance Scores

• loftool: 0.864
• rvis_EVS: -0.84
• rvis_percentile_EVS: 11.45

Haploinsufficiency Scores

• pHI: 0.114
• hipred: N
• hipred_score: 0.251
• ghis: 0.415

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.112

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Impg2

Gene ontology

• Biological process: visual perception
• Cellular component: integral component of membrane;extracellular matrix;interphotoreceptor matrix;receptor complex
• Molecular function: extracellular matrix structural constituent;hyaluronic acid binding;heparin binding