RP9

Chr 7AD

RP9 pre-mRNA splicing factor

Also known as: PAP-1, PAP1

NCBI Gene: 6100ENSG00000164610UniProt: Q8TA86

The protein encoded by this gene can be bound and phosphorylated by the protooncogene PIM1 product, a serine/threonine protein kinase . This protein localizes in nuclear speckles containing the splicing factors, and has a role in pre-mRNA splicing. CBF1-interacting protein (CIR), a corepressor of CBF1, can also bind to this protein and effects alternative splicing. Mutations in this gene result in autosomal dominant retinitis pigmentosa-9. This gene has a pseudogene (GeneID: 441212), which is located in tandem array approximately 166 kb distal to this gene. [provided by RefSeq, Sep 2009]

Primary Disease Associations & Inheritance

?Retinitis pigmentosa 9MIM #180104
AD
?Retinitis pigmentosa 9MIM #180104
AD
199
ClinVar variants
26
Pathogenic / LP
0.02
pLI score
0
Active trials
Clinical Summary— RP9
🧬
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.
📋
ClinVar Variants
26 Pathogenic / Likely Pathogenic· 115 VUS of 199 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.80LOEUF
pLI 0.019
Z-score 2.07
OE 0.38 (0.20–0.80)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.69Z-score
OE missense 0.81 (0.68–0.97)
84 obs / 103.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.38 (0.20–0.80)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.81 (0.68–0.97)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.82
0≤1.21.6
LoF obs/exp: 5 / 13.1Missense obs/exp: 84 / 103.9Syn Z: 0.85

ClinVar Variant Classifications

199 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21
Likely Pathogenic5
VUS115
Likely Benign45
Benign11
Conflicting2
21
Pathogenic
5
Likely Pathogenic
115
VUS
45
Likely Benign
11
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
21
0
21
Likely Pathogenic
1
0
4
0
5
VUS
8
84
21
2
115
Likely Benign
1
0
23
21
45
Benign
0
5
4
2
11
Conflicting
—2
Total10897325199

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

View 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.

Gene2Phenotype Curations

RP9-related retinitis pigmentosa

strong
ADUndeterminedAltered Gene Product Structure
Eye
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

2 OMIM entries

OMIM

?Retinitis pigmentosa 9

MIM #180104

Molecular basis of disorder known

Autosomal dominant

?Retinitis pigmentosa 9

MIM #180104

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — RP9
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
ADH1C maintains the homeostasis of metabolic microenvironment to inhibit steatotic hepatocellular carcinoma.
Xu K et al.·Metabolism
2025
Mutations in spliceosomal proteins and retina degeneration.
Růžičková Š et al.·RNA Biol
2017Review
Mutations in a protein target of the Pim-1 kinase associated with the RP9 form of autosomal dominant retinitis pigmentosa.
Keen TJ et al.·Eur J Hum Genet
2002
RP9 revisited; RP9 p.(H137L) remains a likely cause of dominant splicing factor-Retinitis Pigmentosa.
Chang L et al.·Eur J Hum Genet
2026
Modeling retinal degeneration using patient-specific induced pluripotent stem cells.
Jin ZB et al.·PLoS One
2011Functional
Prevalence of disease-causing mutations in families with autosomal dominant retinitis pigmentosa: a screen of known genes in 200 families.
Sullivan LS et al.·Invest Ophthalmol Vis Sci
2006
Cationic Antimicrobial Peptides Derived from Crocodylus siamensis Leukocyte Extract, Revealing Anticancer Activity and Apoptotic Induction on Human Cervical Cancer Cells.
Theansungnoen T et al.·Protein J
2016
Systematic mapping of registered interventional studies addressing the top 10 research priorities in Barrett's oesophagus and gastro-oesophageal reflux disease.
Gamakaranage C et al.·BMJ Open Gastroenterol
2025
Evidence for a major retinitis pigmentosa locus on 19q13.4 (RP11) and association with a unique bimodal expressivity phenotype.
Al-Maghtheh M et al.·Am J Hum Genet
1996
A Japanese encephalitis virus vaccine candidate strain is attenuated by decreasing its interferon antagonistic ability.
Liang JJ et al.·Vaccine
2009
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools