Retinitis pigmentosa 3

Summary

Retinitis pigmentosa 3 (MONDO:0010227) is a disease caused by RPGR (GenCC Definitive), with 3 cohort genes.

At a glance

• Causal gene: RPGR (GenCC Definitive)
• Cohort genes: 3
• ClinVar variants: 270

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	retinitis pigmentosa 3
Mondo ID	MONDO:0010227
MeSH	C564520
OMIM	300029
DOID	DOID:0110414
UMLS	C1845667
MedGen	336999
GARD	0010381
Is cancer (heuristic)	no

Also known as: retinitis pigmentosa 3 · retinitis pigmentosa caused by mutation in RPGR · retinitis pigmentosa type 3 · RP3 · RPGR retinitis pigmentosa

Data availability: 270 ClinVar variants · 4 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 3

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 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 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

270 retrieved; paginated sample, class counts are floors:

106 pathogenic, 70 likely pathogenic, 42 pathogenic/likely pathogenic, 31 uncertain significance, 10 conflicting classifications of pathogenicity, 8 benign, 2 likely benign, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
975141	Single allele	CFAP47	Pathogenic	no assertion criteria provided
803987	NM_006915.3(RP2):c.158del (p.Leu53fs)	RP2	Pathogenic	criteria provided, single submitter
803989	NM_006915.3(RP2):c.932del (p.Cys311fs)	RP2	Pathogenic	criteria provided, single submitter
1065689	NM_001034853.2(RPGR):c.1754-3C>G	RPGR	Pathogenic	reviewed by expert panel
1065779	NM_001034853.2(RPGR):c.2071G>T (p.Glu691Ter)	RPGR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1172694	NM_001034853.2(RPGR):c.736_745dup (p.Ala249fs)	RPGR	Pathogenic	criteria provided, single submitter
1172696	NM_001034853.2(RPGR):c.2455_2468dup (p.Lys823_Gly824insTer)	RPGR	Pathogenic	reviewed by expert panel
1213920	NM_001034853.2(RPGR):c.779-2A>G	RPGR	Pathogenic	criteria provided, single submitter
1213921	NM_001034853.2(RPGR):c.2078_2148dup (p.Gln717delinsArgArgAsnTer)	RPGR	Pathogenic	criteria provided, single submitter
1213922	NM_001034853.2(RPGR):c.1541C>G (p.Ser514Ter)	RPGR	Pathogenic	reviewed by expert panel
1213924	NM_001034853.2(RPGR):c.934+2T>C	RPGR	Pathogenic	criteria provided, single submitter
1213925	NM_001034853.2(RPGR):c.897T>A (p.Tyr299Ter)	RPGR	Pathogenic	criteria provided, single submitter
1213926	NM_001034853.2(RPGR):c.665T>G (p.Leu222Ter)	RPGR	Pathogenic	criteria provided, single submitter
1275779	NM_001034853.2(RPGR):c.2218G>T (p.Glu740Ter)	RPGR	Pathogenic	reviewed by expert panel
1333218	NM_001034853.2(RPGR):c.1379del (p.Leu460fs)	RPGR	Pathogenic	criteria provided, single submitter
1351457	NM_001034853.2(RPGR):c.2894del (p.Glu965fs)	RPGR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1455429	NM_001034853.2(RPGR):c.2679_2680del (p.Glu894fs)	RPGR	Pathogenic	reviewed by expert panel
1685428	NM_001034853.2(RPGR):c.29-2A>G	RPGR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1686130	NM_001034853.2(RPGR):c.3184G>T (p.Glu1062Ter)	RPGR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1686131	NM_001034853.2(RPGR):c.2522_2525dup (p.Glu843fs)	RPGR	Pathogenic	criteria provided, single submitter
1686132	NM_001034853.2(RPGR):c.2470G>T (p.Gly824Ter)	RPGR	Pathogenic	criteria provided, multiple submitters, no conflicts
1687189	NM_001034853.2(RPGR):c.2237_2238del (p.Glu746fs)	RPGR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1687368	NM_001034853.2(RPGR):c.2257G>T (p.Gly753Ter)	RPGR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1691867	NM_001034853.2(RPGR):c.544_545del (p.Val182fs)	RPGR	Pathogenic	criteria provided, single submitter
1707409	NM_001034853.2(RPGR):c.1302dup (p.Leu435fs)	RPGR	Pathogenic	reviewed by expert panel
1802361	NM_001034853.2(RPGR):c.2455_2468del (p.Val819fs)	RPGR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1802367	NM_001034853.2(RPGR):c.2706_2707del (p.Glu903fs)	RPGR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1802373	NM_001034853.2(RPGR):c.2997_2998del (p.Glu1000fs)	RPGR	Pathogenic	reviewed by expert panel
183262	NM_001034853.2(RPGR):c.2426_2427del (p.Glu809fs)	RPGR	Pathogenic	reviewed by expert panel
2000840	NM_001034853.2(RPGR):c.2482G>T (p.Glu828Ter)	RPGR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 7 · 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
RPGR	Definitive	X-linked	retinitis pigmentosa 3	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RPGR	Orphanet:1872	Cone rod dystrophy
RPGR	Orphanet:244	Primary ciliary dyskinesia
RPGR	Orphanet:247522	Primary ciliary dyskinesia-retinitis pigmentosa syndrome
RPGR	Orphanet:49382	Achromatopsia
RPGR	Orphanet:791	Retinitis pigmentosa
RP2	Orphanet:791	Retinitis pigmentosa
CFAP47	Orphanet:137893	Male infertility due to large-headed multiflagellar polyploid spermatozoa

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RPGR	HGNC:10295	ENSG00000156313	Q92834	X-linked retinitis pigmentosa GTPase regulator	gencc,clinvar
RP2	HGNC:10274	ENSG00000102218	O75695	Protein XRP2	clinvar
CFAP47	HGNC:26708	ENSG00000165164	Q6ZTR5	Cilia- and flagella-associated protein 47	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RPGR	X-linked retinitis pigmentosa GTPase regulator	Acts as a guanine-nucleotide releasing factor (GEF) for RAB8A and RAB37 by promoting the conversion of inactive RAB-GDP to the active form RAB-GTP.
RP2	Protein XRP2	Acts as a GTPase-activating protein (GAP) involved in trafficking between the Golgi and the ciliary membrane.
CFAP47	Cilia- and flagella-associated protein 47	Plays a role in flagellar formation and sperm motility.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.33

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
Antibody/Immunoglobulin	1	9.7×	0.199
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RPGR	Other/Unknown	no		Reg_chr_condens, RCC1/BLIP-II, Signaling_Regulatory_Domain
RP2	Other/Unknown	no		CARP_motif, Tubulin-bd_cofactor_C_dom, CAP/MinC_C
CFAP47	Antibody/Immunoglobulin	yes		CH_dom, Ig-like_fold, CH_dom_sf

Expression context

Cohort genes with no expression data: 0.

3 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
bronchial epithelial cell	2
right uterine tube	1
sperm	1
leukocyte	1
monocyte	1
mononuclear cell	1
bronchus	1
oviduct epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RPGR	281	ubiquitous	marker	sperm, bronchial epithelial cell, right uterine tube
RP2	242	ubiquitous	marker	monocyte, mononuclear cell, leukocyte
CFAP47	95	tissue_specific	marker	bronchial epithelial cell, bronchus, oviduct epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RPGR	2,231
CFAP47	1,256
RP2	911

Structural data

PDB: 2 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RPGR	Q92834	3
RP2	O75695	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CFAP47	Q6ZTR5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 3 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
Trafficking of myristoylated proteins to the cilium	1	2284.0×	4e-04	RP2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
cilium assembly	3	73.6×	3e-05	RPGR, RP2, CFAP47
visual perception	2	53.0×	0.003	RPGR, RP2
protein localization to non-motile cilium	1	1404.3×	0.003	RPGR
post-Golgi vesicle-mediated transport	1	351.1×	0.009	RP2
eye photoreceptor cell development	1	280.9×	0.009	RPGR
intraciliary transport	1	187.2×	0.012	RPGR
sperm axoneme assembly	1	156.0×	0.012	CFAP47
positive regulation of autophagy	1	69.3×	0.023	RPGR
protein folding	1	34.5×	0.042	RP2
ubiquitin-dependent protein catabolic process	1	24.8×	0.052	RPGR
intracellular protein transport	1	21.6×	0.054	RPGR
protein transport	1	14.6×	0.071	RP2
protein ubiquitination	1	13.8×	0.071	RPGR

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 3 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
RPGR	0	0
RP2	0	0
CFAP47	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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	1	CFAP47
E	Difficult family or no structure, no drug	2	RPGR, RP2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
RPGR	0	—
RP2	0	—
CFAP47	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.