HomeAboutRankingsData Sources
© 2026 GeneE
🧬
GeneE
25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
ⓘGeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
PRPF4
pre-mRNA splicing tri-snRNP complex factor PRPF4
Chromosome 9 · 9q32
NCBI Gene: 9128Ensembl: ENSG00000136875.14HGNC: HGNC:17349UniProt: O43172
168PubMed Papers
21Diseases
0Drugs
1Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedHub Gene
RESEARCH IMPACT
Trending
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingspliceosomal snRNP complexnucleusCajal bodyretinitis pigmentosaretinitis pigmentosa 70Retinal dystrophyneurodegenerative disease
✦AI Summary

PRPF4 (pre-mRNA splicing tri-snRNP complex factor) is a core protein component of the U4/U6-U5 tri-snRNP complex essential for spliceosome assembly and pre-mRNA splicing 1. The protein maintains tri-snRNP structural integrity through interactions with PRPF3 and Cyclophilin H, and directly interacts with peptidyl-prolyl isomerase H (PPIH) via bipartite binding sites at its intrinsically disordered N-terminus 2. Beyond splicing, PRPF4 regulates U4/U6 di-snRNP stability and influences cell survival and apoptosis pathways 1. Clinically, PRPF4 mutations cause autosomal dominant retinitis pigmentosa (RP70) through haploinsufficiency and dominant-negative mechanisms 1, with loss-of-function variants disrupting PRPF4-PRPF3 binding and tri-snRNP integration 3. The tissue-specific retinal phenotype despite ubiquitous splicing protein expression remains unexplained 4. Beyond RP, PRPF4 is upregulated in multiple cancers, including glioblastoma, breast cancer, and colorectal cancer 567. In cancer contexts, PRPF4 knockdown reduces proliferation, migration, and invasion while inducing apoptosis via p38 MAPK pathway suppression 56, suggesting PRPF4 as a potential therapeutic target for cancer treatment 7.

Sources cited
1
PRPF4 mutations cause autosomal dominant retinitis pigmentosa via haploinsufficiency and dominant-negative effects; regulates U4/U6 di-snRNP stability essential for splicing
PMID: 24419317
2
PPIH directly interacts with PRPF4 at two binding sites on PRPF4's N-terminus; both proteins integrate into pre-catalytic spliceosome as tri-snRNP component
PMID: 28935721
3
PRPF4 p.R192H variant disrupts PRPF4-PRPF3 binding interface, preventing tri-snRNP integration and causing complete loss of function
PMID: 25383878
4
PRPF4 is one of eight ubiquitous core snRNP proteins that cause retinitis pigmentosa; tissue-specific retinal phenotype despite ubiquitous expression remains unexplained
PMID: 27302685
5
PRPF4 is elevated in glioblastoma; knockdown reduces proliferation, induces apoptosis, suppresses migration/invasion via MKK3/6-p38-ATF2 and RAS-MEK-ERK1/2 pathway suppression
PMID: 39890169
6
PRPF4 is overexpressed in breast cancer cells; knockdown reduces proliferation, colony formation, migration/invasion, and induces apoptosis via p38 MAPK suppression
PMID: 31445970
7
PRPF4 is upregulated in colorectal cancer; dual high expression with NHP2 is associated with worse prognosis and represents potential prognostic marker
PMID: 40597828
8
PRPF4 5'UTR variants are implicated in inherited retinal disease and can be identified through whole genome/exome sequencing analysis
PMID: 38184646
Disease Associationsⓘ21
retinitis pigmentosaOpen Targets
0.62Moderate
retinitis pigmentosa 70Open Targets
0.58Moderate
Retinal dystrophyOpen Targets
0.33Weak
neurodegenerative diseaseOpen Targets
0.20Weak
inherited retinal dystrophyOpen Targets
0.18Weak
colorectal carcinomaOpen Targets
0.08Suggestive
neoplasmOpen Targets
0.03Suggestive
breast cancerOpen Targets
0.03Suggestive
nephrotic syndromeOpen Targets
0.02Suggestive
hypertrophic cardiomyopathyOpen Targets
0.02Suggestive
glioblastoma multiformeOpen Targets
0.02Suggestive
retinitis pigmentosa 1Open Targets
0.02Suggestive
ovarian neoplasmOpen Targets
0.02Suggestive
hepatocellular carcinomaOpen Targets
0.02Suggestive
skin cancerOpen Targets
0.02Suggestive
female genital tract polypOpen Targets
0.02Suggestive
esophageal adenocarcinomaOpen Targets
0.02Suggestive
liver diseaseOpen Targets
0.02Suggestive
Barrett's esophagusOpen Targets
0.02Suggestive
cancerOpen Targets
0.02Suggestive
Retinitis pigmentosa 70UniProt
Pathogenic Variants1
NM_001244926.2(PRPF4):c.941C>T (p.Pro314Leu)Likely pathogenic
Retinitis pigmentosa 70|not provided|Retinal dystrophy
★★☆☆2020→ Residue 314
View on ClinVar ↗
Related Genes
PRPF6Protein interaction100%SNRNP200Protein interaction100%SF3B2Protein interaction100%SF3B5Protein interaction100%EFTUD2Protein interaction100%SF3A3Protein interaction100%
Tissue Expression6 tissues
Brain
100%
Ovary
63%
Liver
59%
Lung
48%
Heart
47%
Bone Marrow
46%
Gene Interaction Network
Click a node to explore
PRPF4PRPF6SNRNP200SF3B2SF3B5EFTUD2SF3A3
PROTEIN STRUCTURE
Preparing viewer…
PDB1MZW · 2.00 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.29Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.19 [0.12–0.29]
RankingsWhere PRPF4 stands among ~20K protein-coding genes
  • #2,655of 20,598
    Most Researched168 · top quartile
  • #4,758of 5,498
    Most Pathogenic Variants1
  • #1,091of 17,882
    Most Constrained (LOEUF)0.29 · top 10%
Genes detectedPRPF4
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
PRPF4 Knockdown Suppresses Glioblastoma Progression
PMID: 39890169
Anticancer Res · 2025
1.00
2
The spliceosomal proteins PPIH and PRPF4 exhibit bi-partite binding.
PMID: 28935721
Biochem J · 2017
0.90
3
Combining a prioritization strategy and functional studies nominates 5'UTR variants underlying inherited retinal disease.
PMID: 38184646
Genome Med · 2024
0.80
4
PRPF4 mutations cause autosomal dominant retinitis pigmentosa.
PMID: 24419317
Hum Mol Genet · 2014
0.70
5
Estimating genetic load from 5000 Chinese exomes.
PMID: 40889739
J Genet Genomics · 2026
0.64