PRPF4

Chr 9AD

pre-mRNA splicing tri-snRNP complex factor PRPF4

Also known as: HPRP4, HPRP4P, PRP4, Prp4p, RP70, SNRNP60

NCBI Gene: 9128ENSG00000136875UniProt: O43172OMIM: 607795

The protein is a component of the U4/U6-U5 tri-snRNP complex essential for pre-mRNA splicing and spliceosome assembly. Mutations cause retinitis pigmentosa 70, an inherited retinal dystrophy affecting the visual system. The condition follows autosomal dominant inheritance.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.231 OMIM phenotype
Clinical Summary— PRPF4
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Gene-Disease Validity (ClinGen)
inherited retinal dystrophy · ADModerate

Moderate evidence — consider for supplementary testing

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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
29 unique Pathogenic / Likely Pathogenic· 209 VUS of 426 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.23LOEUF
pLI 0.999
Z-score 4.94
OE 0.09 (0.04–0.23)
Highly constrained

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

Missense Constraint
1.99Z-score
OE missense 0.68 (0.61–0.76)
210 obs / 308.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.09 (0.04–0.23)
0≤0.351.4
Missense OE0.68 (0.61–0.76)
0≤0.61.4
Synonymous OE0.96
0≤1.21.6
LoF obs/exp: 3 / 34.2Missense obs/exp: 210 / 308.5Syn Z: 0.33
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitivePRPF4-related retinitis pigmentosaLOFAD
DN
0.3793th %ile
GOF
0.3491th %ile
LOF
0.71top 10%

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

LOFprediction above median · 1 literature citation · LOEUF 0.23
DN1 literature citation

Literature Evidence

DNWe conclude that mutations of PRPF4 cause RP via haploinsufficiency and dominant-negative effects, and establish PRPF4 as a new U4/U6-U5 snRNP component associated with adRP.PMID:24419317
LOFIdentification of a PRPF4 loss-of-function variant that abrogates U4/U6.U5 tri-snRNP integration and is associated with retinitis pigmentosaPMID:25383878

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

426 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic25
Likely Pathogenic4
VUS209
Likely Benign152
Benign18
Conflicting3
25
Pathogenic
4
Likely Pathogenic
209
VUS
152
Likely Benign
18
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
25
0
25
Likely Pathogenic
0
1
3
0
4
VUS
6
165
36
2
209
Likely Benign
0
4
71
77
152
Benign
0
1
10
7
18
Conflicting
—3
Total617114586411

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

View in ClinVar →

Protein Context — Lollipop Plot

PRPF4 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
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
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