Details for: PRPF4

Gene ID: 9128

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: PRPF4

Ensembl ID: ENSG00000136875

Description: pre-mRNA splicing tri-snRNP complex factor PRPF4

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • CD14-low, CD16-positive monocyte CL0002396
    CSI 9.05
    rCSI 6.97%
    PRS 89.66
  • lung neuroendocrine cell CL1000223
    CSI 7.34
    rCSI 10.85%
    PRS 89
  • dendritic cell, human CL0001056
    CSI 6.14
    rCSI 9.44%
    PRS 92.9
  • interneuron CL0000099
    CSI 3.55
    rCSI 7.12%
    PRS 79
  • naive T cell CL0000898
    CSI 3.48
    rCSI 2.42%
    PRS 96.35
  • neural crest cell CL0011012
    CSI 3.36
    rCSI 2.66%
    PRS 77.76
  • CD4-positive helper T cell CL0000492
    CSI 3.16
    rCSI 2.39%
    PRS 95.38
  • ON-bipolar cell CL0000749
    CSI 3.1
    rCSI 4.61%
    PRS 86.07
  • perivascular cell CL4033054
    CSI 3.04
    rCSI 4.16%
    PRS 90.29
  • plasmacytoid dendritic cell, human CL0001058
    CSI 2.98
    rCSI 2.08%
    PRS 89.92
  • epithelial cell CL0000066
    CSI 2.97
    rCSI 4.57%
    PRS 75.15
  • multi-ciliated epithelial cell CL0005012
    CSI 2.87
    rCSI 2.86%
    PRS 80.88
  • pro-B cell CL0000826
    CSI 2.84
    rCSI 2.35%
    PRS 88.49
  • myeloid leukocyte CL0000766
    CSI 2.82
    rCSI 2.6%
    PRS 87.62
  • retinal cone cell CL0000573
    CSI 2.76
    rCSI 4.44%
    PRS 77.97
  • granulocyte CL0000094
    CSI 2.65
    rCSI 4.05%
    PRS 91.86
  • mesenchymal cell CL0008019
    CSI 2.61
    rCSI 6.63%
    PRS 80.6
  • granulocyte monocyte progenitor cell CL0000557
    CSI 2.55
    rCSI 2.21%
    PRS 89.47
  • mesodermal cell CL0000222
    CSI 2.53
    rCSI 3.04%
    PRS 84.94
  • respiratory suprabasal cell CL4033048
    CSI 2.52
    rCSI 3.23%
    PRS 88.8
  • CD8-positive, alpha-beta memory T cell CL0000909
    CSI 2.5
    rCSI 2.61%
    PRS 94.7
  • stem cell CL0000034
    CSI 2.44
    rCSI 2.35%
    PRS 81.63
  • cerebral cortex GABAergic interneuron CL0010011
    CSI 2.36
    rCSI 6.95%
    PRS 87.14
  • activated type II NK T cell CL0000931
    CSI 2.3
    rCSI 2.59%
    PRS 95.43
  • hematopoietic stem cell CL0000037
    CSI 2.3
    rCSI 1.53%
    PRS 88.44
  • retina horizontal cell CL0000745
    CSI 2.27
    rCSI 3.47%
    PRS 83.65
  • VIP GABAergic cortical interneuron CL4023016
    CSI 2.22
    rCSI 2.65%
    PRS 71.34
  • respiratory basal cell CL0002633
    CSI 2.21
    rCSI 2.29%
    PRS 89.1
  • conjunctival epithelial cell CL1000432
    CSI 2.17
    rCSI 3.32%
    PRS 86.37
  • ciliated epithelial cell CL0000067
    CSI 2.17
    rCSI 1.91%
    PRS 77.18
  • enteric smooth muscle cell CL0002504
    CSI 2.16
    rCSI 3.08%
    PRS 87.04
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 2.08
    rCSI 1.88%
    PRS 85.2
  • club cell CL0000158
    CSI 1.94
    rCSI 2.85%
    PRS 81.6
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 1.88
    rCSI 2.17%
    PRS 79.13
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 1.83
    rCSI 2.35%
    PRS 83.04
  • placental villous trophoblast CL2000060
    CSI 1.82
    rCSI 2.82%
    PRS 85.27
  • common myeloid progenitor CL0000049
    CSI 1.75
    rCSI 1.41%
    PRS 88.3
  • radial glial cell CL0000681
    CSI 1.74
    rCSI 2.42%
    PRS 84.99
  • fallopian tube secretory epithelial cell CL4030006
    CSI 1.73
    rCSI 1.66%
    PRS 85.66
  • glioblast CL0000030
    CSI 1.67
    rCSI 2.66%
    PRS 78.68
  • retinal bipolar neuron CL0000748
    CSI 1.62
    rCSI 3.03%
    PRS 76.8
  • type B pancreatic cell CL0000169
    CSI 1.56
    rCSI 3.46%
    PRS 86.53
  • promonocyte CL0000559
    CSI 1.2
    rCSI 2.05%
    PRS 90.1
  • peripheral nervous system neuron CL2000032
    CSI 1.17
    rCSI 1.6%
    PRS 79.36
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.72
    rCSI 2.26%
    PRS 72.6
  • erythroid progenitor cell CL0000038
    CSI 0.5
    rCSI 2.89%
    PRS 89.72

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [PRPF4](/details-gene/9128) (pre-mRNA splicing tri-snRNP complex factor PRPF4) is a protein-coding gene located on chromosome 9q32. It encodes a core component of the spliceosome, specifically the U4/U6.U5 tri-snRNP complex, which is essential for the processing of pre-mRNA. Functional annotations confirm its role in [mRNA splicing, via spliceosome](/details-go/GO:0000398) and its localization to nuclear structures like the [spliceosomal complex](/details-go/GO:0005681) and [nuclear speck](/details-go/GO:0016607). **Overall**, [PRPF4](/details-gene/9128) shows significant expression across a wide range of cell types, with particularly high relevance in immune cells such as [CD14-low, CD16-positive monocyte](/details-cell/CL0002396)s and [dendritic cell, human](/details-cell/CL0001056)s, suggesting a critical housekeeping role with heightened importance in immunologically active cells. Mutations in [PRPF4](/details-gene/9128) have been identified as a cause of autosomal dominant retinitis pigmentosa, highlighting its essential function in specialized cell types like photoreceptors ([Link](https://doi.org/10.1093/hmg/ddu005)). ## Cellular Roles and Expression Landscape The expression profile of [PRPF4](/details-gene/9128) underscores its fundamental role in RNA processing across diverse cellular lineages, with a notable prominence in the immune system. **Overall**, the gene exhibits its highest significance in myeloid lineage cells, including [CD14-low, CD16-positive monocyte](/details-cell/CL0002396) (CSI: 9.05) and [dendritic cell, human](/details-cell/CL0001056) (CSI: 6.14). Its importance extends to the lymphoid lineage, with significant expression in [naive T cell](/details-cell/CL0000898)s and [CD4-positive helper T cell](/details-cell/CL0000492)s. This widespread high expression in immune cells suggests that the precise regulation of mRNA splicing by [PRPF4](/details-gene/9128) is crucial for immune cell development, differentiation, and function. Beyond the immune system, [PRPF4](/details-gene/9128) is also highly significant in specialized secretory and neuronal cells, such as [lung neuroendocrine cell](/details-cell/CL1000223) (CSI: 7.34) and various neural cells including [interneuron](/details-cell/CL0000099), [ON-bipolar cell](/details-cell/CL0000749), and [retinal cone cell](/details-cell/CL0000573). Its expression in [epithelial cell](/details-cell/CL0000066)s and [perivascular cell](/details-cell/CL4033054)s further indicates its broad requirement as a core component of the cellular machinery in nearly all tissues. The data collectively portrays [PRPF4](/details-gene/9128) not as a cell-specific marker, but as an essential "workhorse" gene whose activity levels are particularly elevated in cells with high metabolic or transcriptional demands. ## Pathways and Molecular Function [PRPF4](/details-gene/9128) is an integral component of the machinery that governs mRNA processing. Its function is primarily associated with the spliceosome, the large ribonucleoprotein complex responsible for removing introns from pre-mRNA. **Biological Process:** [PRPF4](/details-gene/9128) is a key player in [Mrna splicing, via spliceosome](/details-go/GO:0000398), a fundamental step in eukaryotic gene expression. This is further specified by its involvement in [Rna splicing, via transesterification reactions](/details-go/GO:0000375). **Molecular Function:** At the molecular level, its primary function is [protein binding](/details-go/GO:0005515) within the spliceosome. It specifically engages in [U4 snrna binding](/details-go/GO:0030621) and [U6 snrna binding](/details-go/GO:0017070), which are critical for the dynamic conformational changes required for splicing catalysis. **Cellular Component:** Consistent with its function, [PRPF4](/details-gene/9128) is localized to the [nucleus](/details-go/GO:0005634), specifically within the [nucleoplasm](/details-go/GO:0005654) and subnuclear bodies like [nuclear speck](/details-go/GO:0016607)s and the [Cajal body](/details-go/GO:0015030), which are sites of snRNP biogenesis and storage. It is a stable component of the [U4/u6 x u5 tri-snrnp complex](/details-go/GO:0046540), a core sub-complex of the spliceosome, as confirmed by multiple proteomic and structural studies ([Link](https://doi.org/10.1261/rna.55406), [Link](https://doi.org/10.1126/science.aad2085)). **Reactome Pathways:** The gene's involvement is annotated in the overarching [Metabolism of rna](/details-pathway/R-HSA-8953854) pathway, with specific roles in [Mrna splicing](/details-pathway/R-HSA-72172) and the [Processing of capped intron-containing pre-mrna](/details-pathway/R-HSA-72203). This confirms its central role in the major pathway of pre-mRNA maturation. ## Research Directions The established role of [PRPF4](/details-gene/9128) in splicing and its links to human disease provide clear avenues for future investigation. **Testable Hypotheses:** 1. Given its high significance in diverse immune cell types ([CD14-low, CD16-positive monocyte](/details-cell/CL0002396), [dendritic cell, human](/details-cell/CL0001056)), it is hypothesized that [PRPF4](/details-gene/9128) regulates the alternative splicing of key immune transcripts (e.g., cytokines, receptors, transcription factors) that are essential for orchestrating innate and adaptive immune responses. Haploinsufficiency or altered expression could therefore lead to subtle immunodeficiencies. 2. Based on its causal link to retinitis pigmentosa ([Link](https://doi.org/10.1093/hmg/ddu005)), a second hypothesis is that pathogenic mutations in [PRPF4](/details-gene/9128) result in the mis-splicing of a specific subset of transcripts that are uniquely critical for the long-term survival and function of photoreceptor cells, such as those involved in phototransduction, ciliary transport, or metabolic homeostasis. **Proposed Experiment:** To test the second hypothesis regarding retinitis pigmentosa, a powerful experimental approach would be to use patient-derived induced pluripotent stem cells (iPSCs) harboring known [PRPF4](/details-gene/9128) mutations. These iPSCs, alongside isogenic controls corrected by CRISPR-Cas9, could be differentiated into retinal organoids. A combination of single-cell and bulk RNA sequencing on these organoids at different developmental stages would allow for the identification of mutation-dependent splicing defects specifically within photoreceptor precursor cells and mature [retinal cone cell](/details-cell/CL0000573)s. Subsequent functional validation of candidate mis-spliced targets could elucidate the precise molecular cascade leading to photoreceptor degeneration. **Therapeutic Potential:** As a core, ubiquitously expressed component of the spliceosome, [PRPF4](/details-gene/9128) itself is a poor candidate for systemic inhibition, as this would likely cause widespread cellular toxicity. However, for diseases like retinitis pigmentosa caused by loss-of-function mutations, AAV-mediated gene replacement therapy aimed at restoring functional [PRPF4](/details-gene/9128) expression in the retina represents a promising therapeutic strategy. Alternatively, if specific pathogenic splicing events are identified, developing antisense oligonucleotides to correct the mis-splicing of a single critical downstream transcript could offer a more targeted and safer approach than modulating [PRPF4](/details-gene/9128) directly.

Genular Protein ID: 1954649525

Symbol: PRP4_HUMAN

Name: U4/U6 small nuclear ribonucleoprotein Prp4

UniProtKB Accession Codes:

O43172 O43445 O43864 Q5T1M8 Q96DG2 Q96IK4

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 1 CORUM 1 CTD 1 ComplexPortal 1 DNASU 1 DisGeNET 1 DisProt 1 DrugCentral 1 EMBL 7 EMDB 23 Ensembl 2 EvolutionaryTrace 1 ExpressionAtlas 1 GO 15 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 7 KEGG 1 MANE-Select 1 MIM 3 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PDB 10 PDBsum 10 PRINTS 1 PRO 1 PROSITE 3 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 Reactome 1 RefSeq 2 SIGNOR 1 SMART 2 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9257651

Title: The human U4/U6 snRNP contains 60 and 90kD proteins that are structurally homologous to the yeast splicing factors Prp4p and Prp3p.

PubMed ID: 9257651

PubMed ID: 9404889

Title: A new cyclophilin and the human homologues of yeast Prp3 and Prp4 form a complex associated with U4/U6 snRNPs.

PubMed ID: 9404889

PubMed ID: 9328476

Title: Identification and characterization of human genes encoding Hprp3p and Hprp4p, interacting components of the spliceosome.

PubMed ID: 9328476

DOI: 10.1093/hmg/6.12.2117

PubMed ID: 15164053

Title: DNA sequence and analysis of human chromosome 9.

PubMed ID: 15164053

DOI: 10.1038/nature02465

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 9000057

Title: A human protein required for the second step of pre-mRNA splicing is functionally related to a yeast splicing factor.

PubMed ID: 9000057

DOI: 10.1101/gad.11.1.139

PubMed ID: 16723661

Title: The network of protein-protein interactions within the human U4/U6.U5 tri-snRNP.

PubMed ID: 16723661

DOI: 10.1261/rna.55406

PubMed ID: 19608861

Title: Lysine acetylation targets protein complexes and co-regulates major cellular functions.

PubMed ID: 19608861

DOI: 10.1126/science.1175371

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 26030138

Title: Identification of Novel Proteins Co-Purifying with Cockayne Syndrome Group B (CSB) Reveals Potential Roles for CSB in RNA Metabolism and Chromatin Dynamics.

PubMed ID: 26030138

DOI: 10.1371/journal.pone.0128558

PubMed ID: 12875835

Title: Crystal structure of a complex between human spliceosomal cyclophilin H and a U4/U6 snRNP-60K peptide.

PubMed ID: 12875835

DOI: 10.1016/s0022-2836(03)00684-3

PubMed ID: 26912367

Title: Molecular architecture of the human U4/U6.U5 tri-snRNP.

PubMed ID: 26912367

DOI: 10.1126/science.aad2085

PubMed ID: 28781166

Title: Cryo-EM Structure of a Pre-catalytic Human Spliceosome Primed for Activation.

PubMed ID: 28781166

DOI: 10.1016/j.cell.2017.07.011

PubMed ID: 24419317

Title: PRPF4 mutations cause autosomal dominant retinitis pigmentosa.

PubMed ID: 24419317

DOI: 10.1093/hmg/ddu005

PubMed ID: 25383878

Title: Identification of a PRPF4 loss-of-function variant that abrogates U4/U6.U5 tri-snRNP integration and is associated with retinitis pigmentosa.

PubMed ID: 25383878

DOI: 10.1371/journal.pone.0111754

Sequence Information:

  • Length: 522
  • Mass: 58449
  • Checksum: 08975A26D0B21857
  • Sequence:
    • MASSRASSTQ ATKTKAPDDL VAPVVKKPHI YYGSLEEKER ERLAKGESGI LGKDGLKAGI 
EAGNINITSG EVFEIEEHIS ERQAEVLAEF ERRKRARQIN VSTDDSEVKA CLRALGEPIT 
LFGEGPAERR ERLRNILSVV GTDALKKTKK DDEKSKKSKE EYQQTWYHEG PNSLKVARLW 
IANYSLPRAM KRLEEARLHK EIPETTRTSQ MQELHKSLRS LNNFCSQIGD DRPISYCHFS 
PNSKMLATAC WSGLCKLWSV PDCNLLHTLR GHNTNVGAIV FHPKSTVSLD PKDVNLASCA 
ADGSVKLWSL DSDEPVADIE GHTVRVARVM WHPSGRFLGT TCYDRSWRLW DLEAQEEILH 
QEGHSMGVYD IAFHQDGSLA GTGGLDAFGR VWDLRTGRCI MFLEGHLKEI YGINFSPNGY 
HIATGSGDNT CKVWDLRQRR CVYTIPAHQN LVTGVKFEPI HGNFLLTGAY DNTAKIWTHP 
GWSPLKTLAG HEGKVMGLDI SSDGQLIATC SYDRTFKLWM AE

Genular Protein ID: 2582083854

Symbol: Q5T1M7_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q5T1M7

Database IDs:

ARBA 2 AlphaFoldDB 1 Antibodypedia 1 BioGRID-ORCS 1 CDD 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 4 ExpressionAtlas 1 GO 5 Gene3D 2 HOGENOM 1 InterPro 7 NCBI Taxonomy 1 OMA 1 OrthoDB 1 PANTHER 2 PRINTS 1 PROSITE 3 PROSITE-ProRule 1 Pfam 2 RefSeq 1 SMART 3 SMR 1 SUPFAM 2 UCSC 1 VEuPathDB 1

Citations:

PubMed ID: 11181995

Title: The sequence of the human genome.

PubMed ID: 11181995

DOI: 10.1126/science.1058040

PubMed ID: 16723661

Title: The network of protein-protein interactions within the human U4/U6.U5 tri-snRNP.

PubMed ID: 16723661

DOI: 10.1261/rna.55406

Sequence Information:

  • Length: 521
  • Mass: 58321
  • Checksum: B4EF92D9E12C9188
  • Sequence:
    • MASSRASSTA TKTKAPDDLV APVVKKPHIY YGSLEEKERE RLAKGESGIL GKDGLKAGIE 
AGNINITSGE VFEIEEHISE RQAEVLAEFE RRKRARQINV STDDSEVKAC LRALGEPITL 
FGEGPAERRE RLRNILSVVG TDALKKTKKD DEKSKKSKEE YQQTWYHEGP NSLKVARLWI 
ANYSLPRAMK RLEEARLHKE IPETTRTSQM QELHKSLRSL NNFCSQIGDD RPISYCHFSP 
NSKMLATACW SGLCKLWSVP DCNLLHTLRG HNTNVGAIVF HPKSTVSLDP KDVNLASCAA 
DGSVKLWSLD SDEPVADIEG HTVRVARVMW HPSGRFLGTT CYDRSWRLWD LEAQEEILHQ 
EGHSMGVYDI AFHQDGSLAG TGGLDAFGRV WDLRTGRCIM FLEGHLKEIY GINFSPNGYH 
IATGSGDNTC KVWDLRQRRC VYTIPAHQNL VTGVKFEPIH GNFLLTGAYD NTAKIWTHPG 
WSPLKTLAGH EGKVMGLDIS SDGQLIATCS YDRTFKLWMA E