IMPG1

interphotoreceptor matrix proteoglycan 1

Basic information

Region (hg38): 6:75921114-76072678

Previous symbols: [ "SPACR" ]

Links

ENSG00000112706 ∙ NCBI:3617 ∙ OMIM:602870 ∙ HGNC:6055 ∙ Uniprot:Q17R60 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• retinitis pigmentosa (Moderate), mode of inheritance: AR
• retinitis pigmentosa (Moderate), mode of inheritance: AD
• adult-onset foveomacular vitelliform dystrophy (Supportive), mode of inheritance: AD
• vitelliform macular dystrophy 4 (Moderate), mode of inheritance: AD
• vitelliform macular dystrophy 4 (Definitive), mode of inheritance: AD
• vitelliform macular dystrophy 4 (Strong), mode of inheritance: AD
• inherited retinal dystrophy (Definitive), mode of inheritance: AD
• vitelliform macular dystrophy 4 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Macular dystrophy, vitelliform, 4; Retinitis pigmentosa 91; 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	23993198; 25085631; 30589393; 32817297

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IMPG1 gene.

• not provided (37 variants)
• Vitelliform macular dystrophy 4 (1 variants)
• Vitelliform macular dystrophy 2 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IMPG1 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			7	106	6	119
missense		1	310	6	15	332
nonsense	13	4	4			21
start loss			2			2
frameshift	22	1	1			24
inframe indel			4			4
splice donor/acceptor (+/-2bp)	3	11	3			17
splice region			18	24	2	44
non coding			1	52	2	55
Total	38	17	332	164	23

Highest pathogenic variant AF is 0.0000460

Variants in IMPG1

This is a list of pathogenic ClinVar variants found in the IMPG1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
6-75922092-A-G		Retinal dystrophy	Conflicting classifications of pathogenicity (Oct 22, 2023)
6-75922100-C-T			Uncertain significance (Mar 10, 2022)
6-75922106-C-T		Retinal dystrophy	Benign (Jan 30, 2024)
6-75922107-T-C			Likely benign (Oct 10, 2023)
6-75922119-T-A			Uncertain significance (Dec 19, 2023)
6-75922121-C-A		Vitelliform macular dystrophy 4	Uncertain significance (Jan 11, 2023)
6-75922133-C-T		not specified	Conflicting classifications of pathogenicity (Jan 25, 2024)
6-75922139-G-A			Likely benign (Apr 19, 2023)
6-75922144-TC-T			Uncertain significance (Sep 15, 2022)
6-75922158-A-G			Likely benign (Sep 04, 2020)
6-75922159-C-T		not specified	Uncertain significance (Feb 24, 2022)
6-75922166-C-T			Uncertain significance (Oct 22, 2023)
6-75922168-TGAAAGA-T			Uncertain significance (Apr 02, 2022)
6-75922180-A-C			Likely benign (Jun 04, 2022)
6-75923626-G-T			Likely benign (Dec 11, 2022)
6-75923627-A-AT			Benign (Jan 15, 2024)
6-75923634-C-T			Uncertain significance (Jul 02, 2022)
6-75923645-G-A			Uncertain significance (Oct 04, 2022)
6-75923647-T-TGATTTTGGAACTTTTTTTTTTTTTTTTTTTTTTTTTNNNNNNNNNNCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCGCCCCCCCCCCCCGGGAGCGGGAGAGGGAGAGG			Uncertain significance (May 24, 2023)
6-75923656-A-G			Uncertain significance (Nov 03, 2023)
6-75923657-A-C		not specified	Uncertain significance (Mar 01, 2023)
6-75923658-C-A			Uncertain significance (Jul 25, 2022)
6-75923667-A-G			Likely benign (Feb 08, 2022)
6-75923668-C-T		Retinal dystrophy	Benign (Jan 31, 2024)
6-75923705-A-G			Likely benign (Jul 01, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IMPG1	protein_coding	protein_coding	ENST00000369950	17	151564

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.37e-29	0.0000339	125670	0	78	125748	0.000310

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.937	476	422	1.13	0.0000211	5242
Missense in Polyphen		106	97.698	1.085		1337
Synonymous	0.0878	154	155	0.991	0.00000863	1509
Loss of Function	-0.295	43	41.0	1.05	0.00000225	471

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000754	0.000631
Ashkenazi Jewish	0.0000997	0.0000992
East Asian	0.000435	0.000435
Finnish	0.00	0.00
European (Non-Finnish)	0.000356	0.000352
Middle Eastern	0.000435	0.000435
South Asian	0.000439	0.000425
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May interact with hyaluronan which may serve to form a basic macromolecular scaffold comprising the insoluble interphotoreceptor matrix. {ECO:0000269|PubMed:9813076}.
• Disease: DISEASE: Macular dystrophy, vitelliform, 4 (VMD4) [MIM:616151]: 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. VMD4 features include late- onset moderate visual impairment, small satellite drusen-like lesions in the foveal area, and preservation of retinal pigment epithelium reflectivity. {ECO:0000269|PubMed:23993198}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.0918

Intolerance Scores

• loftool: 0.964
• rvis_EVS: 0.69
• rvis_percentile_EVS: 85.29

Haploinsufficiency Scores

• pHI: 0.269
• hipred: N
• hipred_score: 0.112

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0100

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Impg1

Gene ontology

• Biological process: visual perception
• Cellular component: extracellular matrix
• Molecular function: extracellular matrix structural constituent