Pigmented paravenous retinochoroidal atrophy

Summary

Pigmented paravenous retinochoroidal atrophy (MONDO:0008246) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 253

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		100	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	pigmented paravenous retinochoroidal atrophy
Mondo ID	MONDO:0008246
MeSH	C566801
OMIM	172870
Orphanet	251295
DOID	DOID:0111541
ICD-11	1278139412
SNOMED CT	723450004
UMLS	C1868310
MedGen	401413
GARD	0017208
Is cancer (heuristic)	no

Also known as: pigmented paravenous chorioretinal atrophy · PPCRA · PPRCA

Data availability: 253 ClinVar variants · 2 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 › pigmented paravenous retinochoroidal atrophy

Related subtypes (104): retinal dystrophies primarily involving Bruch’s membrane, vitreoretinal dystrophy, dystrophies primarily involving the retinal pigment epithelium, retinal dystrophy in systemic or cerebroretinal lipidoses, age-related macular degeneration, helicoid peripapillary chorioretinal degeneration, Sorsby fundus dystrophy, microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability, retinoschisis, autosomal dominant, retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations, amaurosis-hypertrichosis syndrome, familial benign flecked retina, microcephaly and chorioretinopathy 1, ornithine aminotransferase deficiency, retinal degeneration-nanophthalmos-glaucoma syndrome, retinoschisis of fovea, Revesz syndrome, choroideremia, choroideremia-deafness-obesity syndrome, X-linked retinal dysplasia, X-linked retinoschisis, progressive bifocal chorioretinal atrophy, aceruloplasminemia, late-onset retinal degeneration, infantile cerebellar-retinal degeneration, progressive retinal dystrophy due to retinol transport defect, microcornea-myopic chorioretinal atrophy, retinal dystrophy with inner retinal dysfunction and ganglion cell anomalies, macular degeneration, early-onset, cone-rod dystrophy, ectopia lentis-chorioretinal dystrophy-myopia syndrome, foveal hypoplasia-presenile cataract syndrome, MRCS syndrome, X-linked intellectual disability-limb spasticity-retinal dystrophy-diabetes insipidus syndrome, Leber congenital amaurosis, oligocone trichromacy, Oguchi disease, retinitis pigmentosa, hereditary macular dystrophy, RPE65-related recessive retinopathy, RPGR-related retinopathy, AIPL1-related retinopathy, RP2-related retinopathy, RDH5-related retinopathy, RLBP1-related retinopathy, LCA5-related retinopathy, ATF6-related retinopathy, RAB28-related retinopathy, FLVCR1-related retinopathy with or without ataxia, RPE65-related dominant retinopathy, GUCY2D retinopathy, PDE6A-related retinopathy, ELOVL4-related maculopathy, MAK-related retinopathy, KIZ-related retinopathy, TOPORS-related retinopathy, PRPF8-related retinopathy, RD3-related retinopathy, BEST1-related dominant retinopathy, BEST1-related recessive retinopathy, IMPG2-related recessive retinopathy, IMPG2-related dominant retinopathy, CACNA1F-related retinopathy, CACNA2D4-related retinopathy, CDHR1-related retinopathy, GUCA1A-related retinopathy, RHO-related retinopathy, SNRNP200-related dominant retinopathy, RDH12-related recessive retinopathy, RDH12-related dominant retinopathy, NMNAT1-related retinopathy, CNGA3-related retinopathy, EYS-related retinopathy, GNAT2-related retinopathy, IDH3B-related retinopathy, MERTK-related retinopathy, PRPF31-related retinopathy, GPR179-related retinopathy, GRM6-related retinopathy, ADAM9-related retinopathy, RP1-related recessive retinopathy, RP1-related dominant retinopathy, CERKL-related retinopathy, TRPM1-related retinopathy, CNGB1-related retinopathy, PCARE-related retinopathy, CNGA1-related retinopathy, ABCA4-related retinopathy, NYX-related retinopathy, retinal dystrophy, X-linked, Gardner-Hardcastle type, PDE6C-related retinopathy, PDE6G-related retinopathy, LRIT3-related retinopathy, IMPG1-related dominant retinopathy, IMPG1-related recessive retinopathy, TTLL5-related retinopathy, HGSNAT-related retinopathy, IMPDH1-related retinopathy, PRPH2-related retinopathy, PROM1-related retinopathy, KCNV2-related retinopathy, CRX-related retinopathy, REEP6-related retinopathy, SPATA7-related retinopathy

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

253 retrieved; paginated sample, class counts are floors:

87 uncertain significance, 54 conflicting classifications of pathogenicity, 49 pathogenic/likely pathogenic, 21 pathogenic, 14 likely pathogenic, 11 likely benign, 11 benign/likely benign, 6 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1045903	NM_201253.3(CRB1):c.3686G>C (p.Cys1229Ser)	CRB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1065687	NM_201253.3(CRB1):c.3427del (p.Cys1143fs)	CRB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1065761	NM_201253.3(CRB1):c.3896del (p.Asp1299fs)	CRB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1073266	NM_201253.3(CRB1):c.1651C>T (p.Gln551Ter)	CRB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1074871	NM_201253.3(CRB1):c.1743_1755dup (p.Ser586fs)	CRB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1076789	NM_201253.3(CRB1):c.1831T>C (p.Ser611Pro)	CRB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1076902	NM_201253.3(CRB1):c.4006-1G>T	CRB1	Pathogenic	criteria provided, multiple submitters, no conflicts
1190977	NM_201253.3(CRB1):c.3144del (p.Ser1049fs)	CRB1	Pathogenic	criteria provided, multiple submitters, no conflicts
1319944	NM_201253.3(CRB1):c.3221T>C (p.Leu1074Ser)	CRB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1384992	NM_201253.3(CRB1):c.1660del (p.Val554fs)	CRB1	Pathogenic	criteria provided, multiple submitters, no conflicts
1388331	NM_201253.3(CRB1):c.2549G>T (p.Gly850Val)	CRB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
143167	NM_201253.3(CRB1):c.1576C>T (p.Arg526Ter)	CRB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1432716	NM_201253.3(CRB1):c.3419T>A (p.Leu1140Ter)	CRB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1439954	NM_201253.3(CRB1):c.358C>T (p.Gln120Ter)	CRB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1451950	NM_201253.3(CRB1):c.2252T>A (p.Leu751Ter)	CRB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1455373	NM_201253.3(CRB1):c.3988G>T (p.Glu1330Ter)	CRB1	Pathogenic	criteria provided, multiple submitters, no conflicts
1456203	NM_201253.3(CRB1):c.3442T>C (p.Cys1148Arg)	CRB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1484059	NM_201253.3(CRB1):c.652+1G>A	CRB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1490976	NM_201253.3(CRB1):c.3862G>A (p.Gly1288Ser)	CRB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
236473	NM_201253.3(CRB1):c.3017C>T (p.Ser1006Phe)	CRB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
236478	NM_201253.3(CRB1):c.2308G>A (p.Gly770Ser)	CRB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
265083	NM_201253.3(CRB1):c.584G>T (p.Cys195Phe)	CRB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2931827	NM_201253.3(CRB1):c.2129-2A>G	CRB1	Pathogenic	criteria provided, multiple submitters, no conflicts
2932631	NM_201253.3(CRB1):c.2129-1G>A	CRB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3233624	NM_201253.3(CRB1):c.1690G>T (p.Asp564Tyr)	CRB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
372352	NM_201253.3(CRB1):c.2506C>A (p.Pro836Thr)	CRB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
377183	NM_201253.3(CRB1):c.3988del (p.Glu1330fs)	CRB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
39614	NM_201253.3(CRB1):c.2843G>A (p.Cys948Tyr)	CRB1	Pathogenic	criteria provided, multiple submitters, no conflicts
427863	NM_201253.3(CRB1):c.2842T>C (p.Cys948Arg)	CRB1	Pathogenic	criteria provided, multiple submitters, no conflicts
438073	NM_201253.3(CRB1):c.2129A>T (p.Glu710Val)	CRB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 11 · Orphanet: 4 · 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
CRB1	Supportive	Autosomal dominant	pigmented paravenous retinochoroidal atrophy	11

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CRB1	Orphanet:251295	Pigmented paravenous retinochoroidal atrophy
CRB1	Orphanet:35612	Nanophthalmos
CRB1	Orphanet:65	Leber congenital amaurosis
CRB1	Orphanet:791	Retinitis pigmentosa

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
CRB1	HGNC:2343	ENSG00000134376	P82279	Protein crumbs homolog 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CRB1	Protein crumbs homolog 1	Plays a role in photoreceptor morphogenesis in the retina.

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)
CRB1	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, Laminin_G

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
endothelial cell	1
ganglionic eminence	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CRB1	163	broad	marker	ganglionic eminence, ventricular zone, endothelial cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CRB1	1,075

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CRB1	P82279	1

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
camera-type eye photoreceptor cell development	1	16852.0×	0.001	CRB1
post-embryonic retina morphogenesis in camera-type eye	1	8426.0×	0.001	CRB1
establishment of bipolar cell polarity involved in cell morphogenesis	1	5617.3×	0.001	CRB1
photoreceptor cell outer segment organization	1	1053.2×	0.003	CRB1
cellular response to light stimulus	1	1053.2×	0.003	CRB1
plasma membrane organization	1	887.0×	0.003	CRB1
glial cell differentiation	1	887.0×	0.003	CRB1
retina layer formation	1	648.1×	0.003	CRB1
detection of light stimulus involved in visual perception	1	648.1×	0.003	CRB1
establishment or maintenance of epithelial cell apical/basal polarity	1	581.1×	0.003	CRB1
establishment or maintenance of cell polarity	1	401.2×	0.004	CRB1
blood vessel remodeling	1	383.0×	0.004	CRB1
photoreceptor cell maintenance	1	358.6×	0.004	CRB1
heterophilic cell-cell adhesion	1	337.0×	0.004	CRB1
intracellular protein localization	1	104.7×	0.011	CRB1
gene expression	1	79.9×	0.013	CRB1
cell-cell signaling	1	69.6×	0.014	CRB1

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
CRB1	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	CRB1

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)
CRB1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.