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25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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PRPF6
pre-mRNA processing factor 6
Chromosome 20 · 20q13.33
NCBI Gene: 24148Ensembl: ENSG00000101161.9HGNC: HGNC:15860UniProt: O94906
226PubMed Papers
21Diseases
0Drugs
2Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
RNA localizationpositive regulation of transcription by RNA polymerase IIRNA bindingprotein bindingretinitis pigmentosaneurodegenerative diseaseRetinal dystrophydengue disease
✦AI Summary

PRPF6 (pre-mRNA processing factor 6) is a core component of the U4/U6-U5 tri-snRNP complex within the spliceosome, functioning as an essential regulator of pre-mRNA splicing 1. Beyond its canonical splicing role, PRPF6 localizes to the connecting cilium and is critical for primary cilium biogenesis 2. The protein also enhances androgen receptor and glucocorticoid receptor transactivation, indicating roles in nuclear hormone signaling. Germline mutations in PRPF6 cause autosomal dominant retinitis pigmentosa (RP60), a progressive inherited retinal disease characterized by vision loss and night blindness 3. The tissue-restricted phenotype despite PRPF6's ubiquitous expression remains mechanistically unclear 4. Additionally, PRPF6 mutations associate with periventricular heterotopia, where defective PRPF6 causes missplicing of microtubule-associated kinases essential for proper brain development 5. Beyond germline disease, PRPF6 is upregulated in cancer contexts. In ovarian cancer, PRPF6 promotes metastasis and paclitaxel resistance through alternative splicing regulation of SNHG16 lncRNA 6. In hepatocellular carcinoma, USP13-mediated stabilization of PRPF6 enhances proliferation via AKT-mTOR pathway activation 7. These findings reveal PRPF6 as a multifunctional protein relevant to splicing, ciliogenesis, and cancer biology.

Sources cited
1
PRPF6 is a component of the U4/U6-U5 tri-snRNP complex involved in pre-mRNA splicing
PMID: 20118938
2
PRPF6 localizes to the connecting cilium and is involved in primary cilium biogenesis; mutations are associated with retinitis pigmentosa
PMID: 26167768
3
PRPF6 mutations cause retinitis pigmentosa; mutations in spliceosomal proteins cause tissue-specific retinal degeneration
PMID: 27302685
4
PRPF6 variants cause retinitis pigmentosa; U5 snRNP proteins have tissue-restricted disease phenotypes despite ubiquitous expression
PMID: 33584830
5
PRPF6 mutations cause periventricular heterotopia through altered splicing of microtubule-associated kinases
PMID: 35709258
6
PRPF6 promotes ovarian cancer metastasis and paclitaxel resistance via SNHG16 alternative splicing regulation
PMID: 37303939
7
USP13 stabilizes PRPF6, promoting hepatocellular carcinoma proliferation through AKT-mTOR pathway activation
PMID: 40208227
8
YTHDF1 regulates PRPF6 translation in an m6A-dependent manner relevant to breast cancer proliferation
PMID: 40827557
Disease Associationsⓘ21
retinitis pigmentosaOpen Targets
0.65Moderate
neurodegenerative diseaseOpen Targets
0.51Moderate
Retinal dystrophyOpen Targets
0.37Weak
dengue diseaseOpen Targets
0.37Weak
Abnormality of the skeletal systemOpen Targets
0.35Weak
autosomal dominant retinitis pigmentosaOpen Targets
0.15Weak
neoplasmOpen Targets
0.10Weak
facioscapulohumeral muscular dystrophyOpen Targets
0.08Suggestive
Parkinson diseaseOpen Targets
0.08Suggestive
hepatocellular carcinomaOpen Targets
0.08Suggestive
hypertensionOpen Targets
0.08Suggestive
prostate cancerOpen Targets
0.07Suggestive
cancerOpen Targets
0.07Suggestive
kidney diseaseOpen Targets
0.05Suggestive
Facioscapulohumeral dystrophyOpen Targets
0.05Suggestive
hemoglobin D diseaseOpen Targets
0.04Suggestive
lung cancerOpen Targets
0.03Suggestive
hemoglobin E diseaseOpen Targets
0.03Suggestive
bipolar disorderOpen Targets
0.03Suggestive
cardiomyopathyOpen Targets
0.02Suggestive
Retinitis pigmentosa 60UniProt
Pathogenic Variants2
NM_012469.4(PRPF6):c.1629G>A (p.Trp543Ter)Likely pathogenic
Retinal dystrophy
★☆☆☆2023→ Residue 543
NM_012469.4(PRPF6):c.550G>C (p.Asp184His)Likely pathogenic
Retinitis pigmentosa
☆☆☆☆→ Residue 184
View on ClinVar ↗
Related Genes
PRPF4Protein interaction100%IKProtein interaction100%MFAP1Protein interaction100%SNRPAProtein interaction100%SNRPCProtein interaction100%SNRPNProtein interaction100%
Tissue Expression6 tissues
Brain
100%
Ovary
71%
Heart
61%
Lung
53%
Bone Marrow
50%
Liver
43%
Gene Interaction Network
Click a node to explore
PRPF6PRPF4IKMFAP1SNRPASNRPCSNRPN
PROTEIN STRUCTURE
Preparing viewer…
PDB8H6L · 2.60 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.45Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.34 [0.27–0.45]
RankingsWhere PRPF6 stands among ~20K protein-coding genes
  • #1,797of 20,598
    Most Researched226 · top 10%
  • #4,234of 5,498
    Most Pathogenic Variants2
  • #2,455of 17,882
    Most Constrained (LOEUF)0.45 · top quartile
Genes detectedPRPF6
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
PMID: 20301590
1.00
2
An siRNA-based functional genomics screen for the identification of regulators of ciliogenesis and ciliopathy genes.
PMID: 26167768
Nat Cell Biol · 2015
0.90
3
Generation of a gene-corrected human iPSC line (CSUASOi004-A-1) from a retinitis pigmentosa patient with heterozygous c.2699 G>A mutation in the PRPF6 gene.
PMID: 36103774
Stem Cell Res · 2022
0.80
4
Pathogenic Variants in
PMID: 38139438
Int J Mol Sci · 2023
0.72
5
Spatial centrosome proteome of human neural cells uncovers disease-relevant heterogeneity.
PMID: 35709258
Science · 2022
0.70