RP2

Chr XX-linked

RP2 activator of ARL3 GTPase

Also known as: DELXp11.3, NM23-H10, NME10, TBCCD2, XRP2

NCBI Gene: 6102ENSG00000102218UniProt: O75695OMIM: 300757

The RP2 locus has been implicated as one cause of X-linked retinitis pigmentosa. The predicted gene product shows homology with human cofactor C, a protein involved in the ultimate step of beta-tubulin folding. Progressive retinal degeneration may therefore be due to the accumulation of incorrectly-folded photoreceptor or neuron-specific tubulin isoforms followed by progressive cell death [provided by RefSeq, Jul 2008]

GeneReviewsOMIMResearch
LOFmechanismX-linkedLOEUF 0.312 OMIM phenotypes
Clinical Summary— RP2
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Gene-Disease Validity (ClinGen)
RP2-related retinopathy · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.96). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
150 unique Pathogenic / Likely Pathogenic· 101 VUS of 400 total submissions
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Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
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GeneReview available — RP2
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.31LOEUF
pLI 0.956
Z-score 2.90
OE 0.00 (0.00–0.31)
Highly constrained

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

Missense Constraint
0.63Z-score
OE missense 0.85 (0.72–0.99)
112 obs / 132.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.00–0.31)
0≤0.351.4
Missense OE0.85 (0.72–0.99)
0≤0.61.4
Synonymous OE0.83
0≤1.21.6
LoF obs/exp: 0 / 9.8Missense obs/exp: 112 / 132.5Syn Z: 0.93
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveRP2-related retinitis pigmentosaLOFXLR
DN
0.2698th %ile
GOF
0.2497th %ile
LOF
0.65top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 68% of P/LP variants are LoF · LOEUF 0.31

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

400 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic117
Likely Pathogenic33
VUS101
Likely Benign70
Benign26
Conflicting11
117
Pathogenic
33
Likely Pathogenic
101
VUS
70
Likely Benign
26
Benign
11
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
78
5
34
0
117
Likely Pathogenic
24
4
5
0
33
VUS
2
87
12
0
101
Likely Benign
0
3
22
45
70
Benign
0
8
5
13
26
Conflicting
—11
Total1041077858358

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

View in ClinVar →

Protein Context — Lollipop Plot

RP2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Secondary punctate inner choroidopathy in an RP2 associated retinopathy female carrier.
Roig-Ferreruela G et al.·J Ophthalmic Inflamm Infect
2026
A de novo splice-site variant in the retinitis pigmentosa 2 (RP2) gene identified in a symptomatic carrier woman.
Domoto A et al.·Ophthalmic Genet
2026
A novel PDPN antagonist peptide CY12-RP2 inhibits melanoma growth via Wnt/β-catenin and modulates the immune cells.
Feng C et al.·J Exp Clin Cancer Res
2024Open Access
RP2-Associated X-linked Retinopathy: Clinical Findings, Molecular Genetics, and Natural History in a Large Cohort of Female Carriers.
Georgiou M et al.·Am J Ophthalmol
2024Open AccessCohort
A Novel Arg120Pro Mutation in the RP2 Gene in an Iranian Family with X-linked Retinitis Pigmentosa: A Case Report.
Mansouri N et al.·Iran J Med Sci
2023Open AccessCase report
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients