RP9

Chr 7AD

RP9 pre-mRNA splicing factor

Also known as: PAP-1, PAP1

The protein encoded by RP9 localizes to nuclear speckles and functions in pre-mRNA splicing, where it can be phosphorylated by PIM1 kinase and interacts with splicing factors. Mutations cause autosomal dominant retinitis pigmentosa-9, a progressive retinal degeneration affecting photoreceptors. The gene shows relatively low constraint against loss-of-function variants (pLI 0.02, LOEUF 0.80), consistent with its autosomal dominant inheritance pattern.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismADLOEUF 0.802 OMIM phenotypes
Clinical SummaryRP9
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Gene-Disease Validity (ClinGen)
retinitis pigmentosa 9 · ADLimited

Limited evidence — not for standalone diagnostic reporting

Population Constraint (gnomAD)
Low constraint (pLI 0.02) — loss-of-function variants are relatively tolerated in the population.
📖
GeneReview available — RP9
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.80LOEUF
pLI 0.019
Z-score 2.07
OE 0.38 (0.200.80)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.69Z-score
OE missense 0.81 (0.680.97)
84 obs / 103.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.38 (0.200.80)
00.351.4
Missense OE0.81 (0.680.97)
00.61.4
Synonymous OE0.82
01.21.6
LoF obs/exp: 5 / 13.1Missense obs/exp: 84 / 103.9Syn Z: 0.85
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongRP9-related retinitis pigmentosaOTHERAD
DN
0.77top 25%
GOF
0.73top 25%
LOF
0.3357th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

RP9 · 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

No active trials found for this gene.

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Clinical Literature
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