RPGR

Chr XXLRX-linked

retinitis pigmentosa GTPase regulator

Also known as: COD1, CORDX1, CRD, PCDX, RP15, RP3, XLRP3, orf15

This gene encodes a guanine nucleotide exchange factor that activates RAB8A and RAB37, regulating ciliary trafficking and maintaining photoreceptor integrity in the retina. Mutations cause X-linked retinal dystrophies including retinitis pigmentosa, cone-rod dystrophy, and macular degeneration, with some cases associated with sinorespiratory infections and hearing loss. The gene is highly constrained against loss-of-function variants and follows X-linked recessive inheritance.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismXLR/X-linkedLOEUF 0.214 OMIM phenotypes
Clinical SummaryRPGR
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Gene-Disease Validity (ClinGen)
RPGR-related retinopathy · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
206 unique Pathogenic / Likely Pathogenic· 122 VUS of 500 total submissions
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Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available
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GeneReview available — RPGR
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.21LOEUF
pLI 0.998
Z-score 4.21
OE 0.04 (0.010.21)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
1.25Z-score
OE missense 0.82 (0.740.90)
294 obs / 360.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.04 (0.010.21)
00.351.4
Missense OE0.82 (0.740.90)
00.61.4
Synonymous OE1.16
01.21.6
LoF obs/exp: 1 / 22.6Missense obs/exp: 294 / 360.6Syn Z: -1.48

ClinVar Variant Classifications

500 submitted variants in ClinVar

Classification Summary

Pathogenic126
Likely Pathogenic80
VUS122
Likely Benign85
Benign6
Conflicting12
126
Pathogenic
80
Likely Pathogenic
122
VUS
85
Likely Benign
6
Benign
12
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
105
4
17
0
126
Likely Pathogenic
69
10
1
0
80
VUS
4
95
19
4
122
Likely Benign
0
12
26
47
85
Benign
0
2
3
1
6
Conflicting
12
Total1781236652431

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

RPGR · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

X-Linked Retinitis Pigmentosa

A Study Comparing Two Doses of AGTC-501 in Male Subjects With X-linked Retinitis Pigmentosa Caused by RPGR Mutations (SKYLINE)

ACTIVE NOT RECRUITING
NCT06333249Phase PHASE2Beacon TherapeuticsStarted 2021-04-13
rAAV2tYF-GRK1-RPGR
X-Linked Retinitis Pigmentosa

4D-125 in Patients With X-Linked Retinitis Pigmentosa (XLRP)

ACTIVE NOT RECRUITING
NCT04517149Phase PHASE1, PHASE24D Molecular TherapeuticsStarted 2020-06-09
4D-125 IVT InjectionObservational
X-Linked Retinitis Pigmentosa

A Follow-on Study for Second-Eye Treatment for Participants Previously Treated With Gene Therapy for X-Linked Retinitis Pigmentosa (XLRP)

ACTIVE NOT RECRUITING
NCT06646289Phase PHASE2Janssen Research & Development, LLCStarted 2024-10-10
AAV5-hRKp.RPGRNo intervention (Follow-Up assessment)
X-Linked Retinitis Pigmentosa

A Clinical Trial Evaluating the Safety and Efficacy of a Single Subretinal Injection of AGTC-501 in Participants With XLRP

ACTIVE NOT RECRUITING
NCT04850118Phase PHASE2, PHASE3Beacon TherapeuticsStarted 2024-03-14
rAAV2tYF-GRK1-hRPGRcoControl
X-Linked Retinitis Pigmentosa

A Study Comparing Two Doses of AGTC-501 in Male Participants With X-linked Retinitis Pigmentosa Caused by RPGR Mutations (DAWN)

ENROLLING BY INVITATION
NCT06275620Phase PHASE2Beacon TherapeuticsStarted 2023-11-14
AGTC-501 (high dose and standard corticosteroid regimen)AGTC-501 (low dose and standard corticosteroid regimen)AGTC-501 (high dose and modified corticosteroid regimen)
X-Linked Retinitis Pigmentosa

Safety and Efficacy of rAAV2tYF-GRK1-RPGR in Subjects With X-linked Retinitis Pigmentosa Caused by RPGR Mutations

ACTIVE NOT RECRUITING
NCT03316560Phase PHASE1, PHASE2Beacon TherapeuticsStarted 2018-04-16
rAAV2tYF-GRK1-RPGR
ChoroideremiaX-Linked Retinitis Pigmentosa

Long-term Safety and Efficacy Follow-up of BIIB111 for the Treatment of Choroideremia and BIIB112 for the Treatment of X-Linked Retinitis Pigmentosa

ENROLLING BY INVITATION
NCT03584165Phase PHASE3NightstaRx Ltd, a Biogen CompanyStarted 2018-06-04
BIIB111BIIB112
X-Linked Retinitis Pigmentosa

Follow-up Gene Therapy Trial for the Treatment of X-linked Retinitis Pigmentosa Associated With Variants in the RPGR Gene

ACTIVE NOT RECRUITING
NCT04794101Phase PHASE3Janssen Research & Development, LLCStarted 2020-12-04
Genetic: AAV5-hRKp.RPGR Intermediate DoseGenetic: AAV5-hRKp.RPGR Low Dose
X-Linked Retinitis Pigmentosa (XLRP)

A Phase 2 Open-label Study to Evaluate the Safety of Laruparetigene Zovaparvovec Administered Bilaterally in Male Participants With X-Linked Retinitis Pigmentosa

RECRUITING
NCT07174726Phase PHASE2Beacon TherapeuticsStarted 2025-09-10
Adeno-associated virus vector expressing a human RPGR gene
X-Linked Retinitis Pigmentosa (XLRP)

Gene Therapy for RPGR Gene Mutation-associated X-linked Retinitis Pigmentosa

RECRUITING
NCT06492850Phase PHASE1, PHASE2Frontera TherapeuticsStarted 2024-04-01
FT-002
Retinal DegenerationsRetinitis Pigmentosa (RP)Stargardt Disease

Inherited Retinal Diseases: Natural History and Genotype-Phenotype Correlations

NOT YET RECRUITING
NCT07265895IRCCS San RaffaeleStarted 2026-01-01
No Intervention: Observational Cohort
X-Linked Retinitis Pigmentosa

Gene Therapy for Subjects With RPGR Mutation-associated X-linked Retinitis Pigmentosa

RECRUITING
NCT05874310Phase EARLY_PHASE1Frontera TherapeuticsStarted 2023-02-01
FT-002
Clinical Literature
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