Retinitis pigmentosa 13

Summary

Retinitis pigmentosa 13 (MONDO:0010806) is a disease caused by PRPF8 (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: PRPF8 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 71

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	retinitis pigmentosa 13
Mondo ID	MONDO:0010806
MeSH	C564008
OMIM	600059
DOID	DOID:0110403
UMLS	C1838702
MedGen	325486
GARD	0010388
Is cancer (heuristic)	no

Also known as: PRPF8 retinitis pigmentosa · retinitis pigmentosa 13 · retinitis pigmentosa caused by mutation in PRPF8 · retinitis pigmentosa type 13 · RP 13 · RP13

Data availability: 71 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 13

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 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 56, 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

71 retrieved; paginated sample, class counts are floors:

26 uncertain significance, 10 benign, 8 benign/likely benign, 8 pathogenic/likely pathogenic, 7 conflicting classifications of pathogenicity, 5 likely pathogenic, 4 likely benign, 3 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1433653	NM_006445.4(PRPF8):c.6978C>G (p.Tyr2326Ter)	PRPF8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
30666	NM_006445.4(PRPF8):c.6353C>T (p.Ser2118Phe)	PRPF8	Pathogenic	no assertion criteria provided
30667	NM_006445.4(PRPF8):c.6930G>C (p.Arg2310Ser)	PRPF8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3355	NM_006445.4(PRPF8):c.6926A>G (p.His2309Arg)	PRPF8	Pathogenic	criteria provided, multiple submitters, no conflicts
3356	NM_006445.4(PRPF8):c.6926A>C (p.His2309Pro)	PRPF8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3357	NM_006445.4(PRPF8):c.6929G>A (p.Arg2310Lys)	PRPF8	Pathogenic	criteria provided, multiple submitters, no conflicts
3359	NM_006445.4(PRPF8):c.6912C>G (p.Phe2304Leu)	PRPF8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
425117	NM_006445.4(PRPF8):c.6970dup (p.Glu2324fs)	PRPF8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
438226	NM_006445.4(PRPF8):c.6928A>G (p.Arg2310Gly)	PRPF8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
546782	NM_006445.4(PRPF8):c.5804G>A (p.Arg1935His)	PRPF8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
867014	NM_006445.4(PRPF8):c.5792C>T (p.Thr1931Met)	PRPF8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1034482	NM_006445.4(PRPF8):c.5377-1G>T	PRPF8	Likely pathogenic	criteria provided, single submitter
3235734	NM_006445.4(PRPF8):c.4367C>T (p.Thr1456Ile)	PRPF8	Likely pathogenic	criteria provided, single submitter
3358	NM_006445.4(PRPF8):c.6901C>A (p.Pro2301Thr)	PRPF8	Likely pathogenic	criteria provided, single submitter
3775792	NM_006445.4(PRPF8):c.6981dup (p.Ala2328fs)	PRPF8	Likely pathogenic	criteria provided, single submitter
803295	NM_006445.4(PRPF8):c.6994dup (p.Asp2332fs)	PRPF8	Likely pathogenic	criteria provided, single submitter
978991	NM_201253.3(CRB1):c.1463T>C (p.Phe488Ser)	CRB1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1065709	NM_006445.4(PRPF8):c.6926A>T (p.His2309Leu)	PRPF8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1430048	NM_006445.4(PRPF8):c.654-5C>T	PRPF8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3067921	NM_006445.4(PRPF8):c.4338+2T>C	PRPF8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
803296	NM_006445.4(PRPF8):c.6991G>A (p.Glu2331Lys)	PRPF8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
808181	NM_006445.4(PRPF8):c.5413G>A (p.Gly1805Arg)	PRPF8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
965683	NM_006445.4(PRPF8):c.6838A>G (p.Asn2280Asp)	PRPF8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1037910	NM_006445.4(PRPF8):c.1393A>G (p.Lys465Glu)	PRPF8	Uncertain significance	criteria provided, multiple submitters, no conflicts
1065678	NM_006445.4(PRPF8):c.6967G>T (p.Gly2323Trp)	PRPF8	Uncertain significance	criteria provided, single submitter
1065692	NM_006445.4(PRPF8):c.3368A>G (p.Glu1123Gly)	PRPF8	Uncertain significance	criteria provided, single submitter
1213885	NM_006445.4(PRPF8):c.6466A>C (p.Thr2156Pro)	PRPF8	Uncertain significance	criteria provided, multiple submitters, no conflicts
1213886	NM_006445.4(PRPF8):c.6837G>T (p.Trp2279Cys)	PRPF8	Uncertain significance	criteria provided, single submitter
1213887	NM_006445.4(PRPF8):c.1684G>A (p.Val562Met)	PRPF8	Uncertain significance	criteria provided, single submitter
1698943	NM_006445.4(PRPF8):c.6902C>T (p.Pro2301Leu)	PRPF8	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 6 · 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
PRPF8	Definitive	Autosomal dominant	retinitis pigmentosa 13	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PRPF8	Orphanet:528084	Non-specific syndromic intellectual disability
PRPF8	Orphanet:791	Retinitis pigmentosa
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

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PRPF8	HGNC:17340	ENSG00000174231	Q6P2Q9	Pre-mRNA-processing-splicing factor 8	gencc,clinvar
CRB1	HGNC:2343	ENSG00000134376	P82279	Protein crumbs homolog 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PRPF8	Pre-mRNA-processing-splicing factor 8	Plays a role in pre-mRNA splicing as core component of precatalytic, catalytic and postcatalytic spliceosomal complexes, both of the predominant U2-type spliceosome and the minor U12-type spliceosome.
CRB1	Protein crumbs homolog 1	Plays a role in photoreceptor morphogenesis in the retina.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PRPF8	Other/Unknown	no		JAMM/MPN+_dom, RNaseH-like_sf, PRO8NT
CRB1	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, Laminin_G

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ventricular zone	2
adenohypophysis	1
pituitary gland	1
endothelial cell	1
ganglionic eminence	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PRPF8	145	ubiquitous	marker	adenohypophysis, pituitary gland, ventricular zone
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
PRPF8	5,582
CRB1	1,075

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PRPF8	Q6P2Q9	101
CRB1	P82279	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 2 evidence-associated genes (1 with Reactome annotation).

Pathways 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.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
mRNA Splicing - Minor Pathway	1	223.9×	0.013	PRPF8
mRNA Splicing - Major Pathway	1	54.6×	0.022	PRPF8
Dengue Virus-Host Interactions	1	45.7×	0.022	PRPF8

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 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	8426.0×	0.003	CRB1
post-embryonic retina morphogenesis in camera-type eye	1	4213.0×	0.003	CRB1
establishment of bipolar cell polarity involved in cell morphogenesis	1	2808.7×	0.003	CRB1
spliceosomal tri-snRNP complex assembly	1	561.7×	0.007	PRPF8
photoreceptor cell outer segment organization	1	526.6×	0.007	CRB1
cellular response to light stimulus	1	526.6×	0.007	CRB1
plasma membrane organization	1	443.5×	0.007	CRB1
glial cell differentiation	1	443.5×	0.007	CRB1
retina layer formation	1	324.1×	0.007	CRB1
detection of light stimulus involved in visual perception	1	324.1×	0.007	CRB1
RNA splicing, via transesterification reactions	1	312.1×	0.007	PRPF8
establishment or maintenance of epithelial cell apical/basal polarity	1	290.6×	0.007	CRB1
establishment or maintenance of cell polarity	1	200.6×	0.009	CRB1
blood vessel remodeling	1	191.5×	0.009	CRB1
photoreceptor cell maintenance	1	179.3×	0.009	CRB1
heterophilic cell-cell adhesion	1	168.5×	0.009	CRB1
cellular response to tumor necrosis factor	1	81.8×	0.017	PRPF8
intracellular protein localization	1	52.3×	0.025	CRB1
cellular response to lipopolysaccharide	1	49.0×	0.026	PRPF8
mRNA splicing, via spliceosome	1	45.8×	0.026	PRPF8
RNA splicing	1	44.1×	0.026	PRPF8
gene expression	1	39.9×	0.026	CRB1
mRNA processing	1	39.4×	0.026	PRPF8
cell-cell signaling	1	34.8×	0.029	CRB1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PRPF8	1	2
CRB1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	PRPF8

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
PRPF8	8	Binding:8

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

1 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.

Compound	Max phase	Cohort target (bioactivity)
MOLIBRESIB	2	PRPF8

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	1	PRPF8
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.