Retinitis pigmentosa 56

Summary

Retinitis pigmentosa 56 (MONDO:0013314) is a disease caused by IMPG2 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: IMPG2 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 43

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	retinitis pigmentosa 56
Mondo ID	MONDO:0013314
OMIM	613581
DOID	DOID:0110371
UMLS	C3150819
MedGen	462169
GARD	0015678
Is cancer (heuristic)	no

Also known as: IMPG2 retinitis pigmentosa · retinitis pigmentosa 56 · retinitis pigmentosa caused by mutation in IMPG2 · retinitis pigmentosa type 56 · RP56

Data availability: 43 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 › inherited retinal dystrophy › retinitis pigmentosa › retinitis pigmentosa 56

Related subtypes (101): retinitis pigmentosa 6, cone-rod dystrophy 2, retinitis pigmentosa 1, retinitis pigmentosa 9, retinitis pigmentosa 10, dominant pericentral pigmentary retinopathy, late-adult onset retinitis pigmentosa, autosomal recessive pericentral pigmentary retinopathy, retinitis pigmentosa 3, retinitis pigmentosa 24, retinitis pigmentosa 23, retinitis pigmentosa 34, retinitis pigmentosa 2, retinitis pigmentosa Y-linked, retinitis pigmentosa 13, retinitis pigmentosa 12, retinitis pigmentosa 14, retinitis pigmentosa 11, retinitis pigmentosa 17, retinitis pigmentosa 18, retinitis pigmentosa 19, retinitis pigmentosa 22, retinitis pigmentosa 25, retinitis pigmentosa 28, retinitis pigmentosa 30, retinitis pigmentosa 7, retinitis pigmentosa 26, retinitis pigmentosa 32, retinitis pigmentosa 31, retinitis pigmentosa 35, retinitis pigmentosa 33, retinitis pigmentosa 36, retinitis pigmentosa 37, retinitis pigmentosa 41, retinitis pigmentosa 29, retinitis pigmentosa 46, retinitis pigmentosa 42, retinitis pigmentosa 50, retinitis pigmentosa 54, retinitis pigmentosa 51, retinitis pigmentosa 55, retinitis pigmentosa 57, retinitis pigmentosa 58, cone-rod dystrophy 15, retinitis pigmentosa 4, retinitis pigmentosa 27, retinitis pigmentosa 49, retinitis pigmentosa 47, retinitis pigmentosa 45, retinitis pigmentosa 44, retinitis pigmentosa 20, retinitis pigmentosa 40, retinitis pigmentosa 39, retinitis pigmentosa 43, retinitis pigmentosa 48, retinitis pigmentosa 59, retinitis pigmentosa 38, retinitis pigmentosa 60, retinitis pigmentosa 61, retinitis pigmentosa 62, retinitis pigmentosa 63, cone-rod dystrophy 16, retinitis pigmentosa 66, retinitis pigmentosa with or without situs inversus, retinitis pigmentosa 67, retinitis pigmentosa 68, retinitis pigmentosa 69, retinitis pigmentosa 70, retinal dystrophy and obesity, retinitis pigmentosa 71, retinitis pigmentosa 72, retinitis pigmentosa 73, retinitis pigmentosa 74, retinitis pigmentosa 75, retinitis pigmentosa 76, retinitis pigmentosa 77, retinitis pigmentosa 92, retinitis pigmentosa 93, retinitis pigmentosa 83, retinitis pigmentosa 84, retinitis pigmentosa 85, retinitis pigmentosa 86, retinitis pigmentosa 87 with choroidal involvement, retinitis pigmentosa 88, retinitis pigmentosa 90, retinitis pigmentosa 81, retinitis pigmentosa 78, retinitis pigmentosa 79, retinitis pigmentosa 80, retinitis pigmentosa 94, variable age at onset, retinitis pigmentosa 53, retinitis pigmentosa 65, retinitis pigmentosa 64, retinitis pigmentosa 95, retinitis pigmentosa 96, retinitis pigmentosa 97, retinitis pigmentosa 98, retinitis pigmentosa 99, retinitis pigmentosa 100, retinitis pigmentosa 101, retinitis pigmentosa 7, digenic

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

43 retrieved; paginated sample, class counts are floors:

12 uncertain significance, 11 pathogenic, 6 likely pathogenic, 5 pathogenic/likely pathogenic, 5 conflicting classifications of pathogenicity, 4 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1065646	NM_016247.4(IMPG2):c.2233del (p.Glu745fs)	IMPG2	Pathogenic	criteria provided, multiple submitters, no conflicts
1213852	NM_016247.4(IMPG2):c.2566C>T (p.Gln856Ter)	IMPG2	Pathogenic	criteria provided, multiple submitters, no conflicts
1213854	NM_016247.4(IMPG2):c.3405_3408del (p.Glu1137fs)	IMPG2	Pathogenic	criteria provided, single submitter
1517305	NM_016247.4(IMPG2):c.583+1G>C	IMPG2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2907341	NM_016247.4(IMPG2):c.828+1G>A	IMPG2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3384667	NM_016247.4(IMPG2):c.1491del (p.Leu498fs)	IMPG2	Pathogenic	criteria provided, single submitter
3546	NM_016247.4(IMPG2):c.635C>G (p.Ser212Ter)	IMPG2	Pathogenic	no assertion criteria provided
3548	NM_016247.4(IMPG2):c.2716C>T (p.Arg906Ter)	IMPG2	Pathogenic	criteria provided, multiple submitters, no conflicts
3549	NM_016247.4(IMPG2):c.2890C>T (p.Arg964Ter)	IMPG2	Pathogenic	criteria provided, multiple submitters, no conflicts
522455	NM_016247.4(IMPG2):c.85+2T>A	IMPG2	Pathogenic	no assertion criteria provided
522456	NM_016247.4(IMPG2):c.1826del (p.Val609fs)	IMPG2	Pathogenic	no assertion criteria provided
865937	NM_016247.4(IMPG2):c.1589C>A (p.Ser530Ter)	IMPG2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
866386	NM_016247.4(IMPG2):c.411G>A (p.Trp137Ter)	IMPG2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
866547	NM_016247.4(IMPG2):c.667-1G>A	IMPG2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
931179	NM_016247.4(IMPG2):c.1087C>T (p.Gln363Ter)	IMPG2	Pathogenic	criteria provided, multiple submitters, no conflicts
931664	NM_016247.4(IMPG2):c.1240-2A>G	IMPG2	Pathogenic	criteria provided, single submitter
2920627	NM_016247.4(IMPG2):c.1468del (p.Thr490fs)	IMPG2	Likely pathogenic	no assertion criteria provided
3547	NM_016247.4(IMPG2):c.887+430_908+274del	IMPG2	Likely pathogenic	criteria provided, single submitter
3775260	NM_016247.4(IMPG2):c.829-3_829-1delinsT	IMPG2	Likely pathogenic	criteria provided, single submitter
3775663	NM_016247.4(IMPG2):c.2344_2347del (p.Arg782fs)	IMPG2	Likely pathogenic	criteria provided, single submitter
3775729	NM_016247.4(IMPG2):c.2317_2318del (p.Leu773fs)	IMPG2	Likely pathogenic	criteria provided, single submitter
866757	NM_016247.4(IMPG2):c.1739T>G (p.Leu580Ter)	IMPG2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
194768	NM_016247.4(IMPG2):c.3423-7_3423-4del	IMPG2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3550	NM_016247.4(IMPG2):c.370T>C (p.Phe124Leu)	IMPG2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
813054	NM_016247.4(IMPG2):c.501+5G>A	IMPG2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
866317	NM_016247.4(IMPG2):c.3113G>T (p.Cys1038Phe)	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
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
1709485	NM_016247.4(IMPG2):c.452T>A (p.Met151Lys)	IMPG2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 2 · 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 recessive	retinitis pigmentosa 56	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

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
IMPG2	HGNC:18362	ENSG00000081148	Q9BZV3	Interphotoreceptor matrix proteoglycan 2	gencc,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.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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	1	1.8×	0.558

Per-gene assignment

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

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	1
pineal body	1
right uterine tube	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

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
IMPG2	516

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
IMPG2	Q9BZV3	54.28

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
retina morphogenesis in camera-type eye	1	1872.4×	0.002	IMPG2
extracellular matrix organization	1	122.1×	0.013	IMPG2
intracellular protein localization	1	104.7×	0.013	IMPG2
visual perception	1	79.5×	0.013	IMPG2

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 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

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; 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	1	IMPG2

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
IMPG2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.