Details for: U2AF1L4

Gene ID: 199746

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: U2AF1L4

Ensembl ID: ENSG00000161265

Description: U2 small nuclear RNA auxiliary factor 1 like 4

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • IgG plasma cell CL0000985
    CSI 8.37
    rCSI 10.03%
    PRS 92.21
  • rod bipolar cell CL0000751
    CSI 7.22
    rCSI 12.97%
    PRS 79.09
  • effector memory CD4-positive, alpha-beta T cell CL0000905
    CSI 4.38
    rCSI 5.97%
    PRS 96.84
  • CD4-positive, alpha-beta memory T cell CL0000897
    CSI 4
    rCSI 2.87%
    PRS 95.08
  • double negative thymocyte CL0002489
    CSI 3.93
    rCSI 2.73%
    PRS 94.36
  • mature alpha-beta T cell CL0000791
    CSI 3.9
    rCSI 14.11%
    PRS 96.63
  • effector CD8-positive, alpha-beta T cell CL0001050
    CSI 3.83
    rCSI 2.91%
    PRS 95.1
  • central memory CD8-positive, alpha-beta T cell CL0000907
    CSI 3.68
    rCSI 2.48%
    PRS 95.22
  • immature B cell CL0000816
    CSI 3.43
    rCSI 2.55%
    PRS 93.18
  • ON-bipolar cell CL0000749
    CSI 3.27
    rCSI 4.86%
    PRS 84.58
  • plasmablast CL0000980
    CSI 3.22
    rCSI 2.54%
    PRS 88.86
  • central memory CD4-positive, alpha-beta T cell CL0000904
    CSI 3.22
    rCSI 1.9%
    PRS 96.6
  • bronchus fibroblast of lung CL2000093
    CSI 3.04
    rCSI 2.47%
    PRS 84.31
  • unswitched memory B cell CL0000970
    CSI 3
    rCSI 2.52%
    PRS 95
  • class switched memory B cell CL0000972
    CSI 2.98
    rCSI 2.23%
    PRS 94.11
  • CD1c-positive myeloid dendritic cell CL0002399
    CSI 2.88
    rCSI 3.48%
    PRS 91.37
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 2.79
    rCSI 2.15%
    PRS 88.34
  • naive T cell CL0000898
    CSI 2.76
    rCSI 1.92%
    PRS 95.65
  • T follicular helper cell CL0002038
    CSI 2.75
    rCSI 2.06%
    PRS 94.62
  • pulmonary ionocyte CL0017000
    CSI 2.6
    rCSI 3.16%
    PRS 90.16
  • granulocyte monocyte progenitor cell CL0000557
    CSI 2.56
    rCSI 2.22%
    PRS 88.29
  • group 3 innate lymphoid cell CL0001071
    CSI 2.55
    rCSI 1.92%
    PRS 89.75
  • early lymphoid progenitor CL0000936
    CSI 2.55
    rCSI 2.24%
    PRS 89.16
  • precursor B cell CL0000817
    CSI 2.54
    rCSI 2.23%
    PRS 90.68
  • double-positive, alpha-beta thymocyte CL0000809
    CSI 2.53
    rCSI 2.58%
    PRS 92.42
  • mesodermal cell CL0000222
    CSI 2.46
    rCSI 2.96%
    PRS 83.3
  • mature B cell CL0000785
    CSI 2.45
    rCSI 2.13%
    PRS 92.63
  • OFF-bipolar cell CL0000750
    CSI 2.39
    rCSI 3.26%
    PRS 85.62
  • plasmacytoid dendritic cell, human CL0001058
    CSI 2.38
    rCSI 1.66%
    PRS 88.46
  • retina horizontal cell CL0000745
    CSI 2.25
    rCSI 3.42%
    PRS 82.07
  • CD4-positive, alpha-beta cytotoxic T cell CL0000934
    CSI 2.13
    rCSI 2.93%
    PRS 96.12
  • mononuclear phagocyte CL0000113
    CSI 2.11
    rCSI 4.63%
    PRS 88.04
  • lung ciliated cell CL1000271
    CSI 2.03
    rCSI 2.35%
    PRS 78.37
  • peripheral nervous system neuron CL2000032
    CSI 1.95
    rCSI 2.66%
    PRS 77.51
  • retinal rod cell CL0000604
    CSI 1.7
    rCSI 3%
    PRS 80.64
  • club cell CL0000158
    CSI 1.66
    rCSI 2.44%
    PRS 80.03
  • Langerhans cell CL0000453
    CSI 1.64
    rCSI 2.5%
    PRS 93.41
  • common dendritic progenitor CL0001029
    CSI 1.57
    rCSI 1.97%
    PRS 91.69
  • CD8-positive, alpha-beta cytotoxic T cell CL0000794
    CSI 1.55
    rCSI 1.85%
    PRS 95.93
  • astrocyte of the cerebral cortex CL0002605
    CSI 1.53
    rCSI 3.44%
    PRS 69.83
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.47
    rCSI 2.6%
    PRS 68.44
  • effector memory CD8-positive, alpha-beta T cell, terminally differentiated CL0001062
    CSI 1.21
    rCSI 6.06%
    PRS 94.28
  • mesenchymal cell CL0008019
    CSI 1.2
    rCSI 3.05%
    PRS 78.85
  • retinal cone cell CL0000573
    CSI 1.19
    rCSI 1.91%
    PRS 76.07
  • CD8-positive, CD28-negative, alpha-beta regulatory T cell CL0000920
    CSI 1.17
    rCSI 2.34%
    PRS 93.91
  • cytotoxic T cell CL0000910
    CSI 0.23
    rCSI 1.3%
    PRS 86.6

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.

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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 [U2AF1L4](/details-gene/199746) (U2 small nuclear RNA auxiliary factor 1 like 4) is a protein-coding gene located on chromosome 19q13.12. It encodes a component of the U2AF complex, which is essential for the recognition of the 3'-splice site during the initial stages of pre-mRNA splicing ([GO:0030628](https://www.ebi.ac.uk/QuickGO/term/GO:0030628)). Functionally, [U2AF1L4](/details-gene/199746) is integral to the spliceosome, playing a critical role in [mRNA splicing, via spliceosome](/details-cell/GO:0000398). Expression data indicates its significance is particularly high in terminally differentiated and highly active cell types, most notably [IgG plasma cell](/details-cell/CL0000985) and various subsets of memory T cells, suggesting a crucial role in maintaining the complex transcriptomes required for specialized immune functions. Its association with Mendelian disease is noted in OMIM ([601080](https://omim.org/entry/601080)). ## Cellular Roles and Expression Landscape The expression profile of [U2AF1L4](/details-gene/199746) highlights its fundamental role in cells undergoing significant transcriptional activity and post-transcriptional regulation. **Overall**, the gene shows the highest significance in cells of the adaptive immune system. Its most prominent expression is in [IgG plasma cell](/details-cell/CL0000985) (CSI: 8.37), a cell type characterized by massive production and secretion of antibodies, a process that demands high-fidelity mRNA splicing. Following this, [U2AF1L4](/details-gene/199746) is also a significant marker across various T lymphocyte populations, including [effector memory CD4-positive, alpha-beta T cell](/details-cell/CL0000905), [CD4-positive, alpha-beta memory T cell](/details-cell/CL0000897), [mature alpha-beta T cell](/details-cell/CL0000791), and [central memory CD8-positive, alpha-beta T cell](/details-cell/CL0000907). This pattern suggests its involvement in maintaining the specific splicing programs necessary for T cell memory and effector functions. The gene is also important in the B cell lineage, with notable expression in [immature B cell](/details-cell/CL0000816), [plasmablast](/details-cell/CL0000980), and both [unswitched memory B cell](/details-cell/CL0000970) and [class switched memory B cell](/details-cell/CL0000972). Interestingly, outside of the immune system, [U2AF1L4](/details-gene/199746) shows high significance in specialized neuronal cells of the retina, specifically [rod bipolar cell](/details-cell/CL0000751) and [ON-bipolar cell](/details-cell/CL0000749). This suggests a conserved role in regulating complex splicing events in terminally differentiated, metabolically active cells beyond the hematopoietic lineage. ## Pathways and Molecular Function Consistent with its identity as a core spliceosomal component, the functional annotations for [U2AF1L4](/details-gene/199746) are centered on RNA processing. It is a key constituent of the [Spliceosomal complex](/details-cell/GO:0005681) and the [U2af complex](/details-cell/GO:0089701), localizing to the [Nucleoplasm](/details-cell/GO:0005654) and [Nuclear speck](/details-cell/GO:0016607) where splicing machinery is concentrated. The gene's activity is integral to multiple steps in gene expression, as detailed by Reactome pathways. It participates in the entire lifecycle of an mRNA molecule, from [Gene expression (transcription)](https://reactome.org/content/detail/R-HSA-74160) and [Rna polymerase ii transcription](https://reactome.org/content/detail/R-HSA-73857) to the specific processes of [Mrna splicing](https://reactome.org/content/detail/R-HSA-72172) and [Processing of capped intron-containing pre-mrna](https://reactome.org/content/detail/R-HSA-72203). Its function in the [Mrna splicing - major pathway](https://reactome.org/content/detail/R-HSA-72163) underscores its fundamental role, which is consistent with its high expression in cells like plasma cells that depend on the accurate and efficient processing of a large volume of transcripts. The established role of the U2AF complex in recognizing the 3'-splice site is a critical checkpoint for defining exon-intron boundaries [Link](https://pubmed.ncbi.nlm.nih.gov/15057824/). ## Research Directions The specific expression pattern of [U2AF1L4](/details-gene/199746) in highly specialized, long-lived cell types suggests that it may regulate alternative splicing events critical for maintaining cellular identity and function. Based on the available data, several testable hypotheses can be proposed: 1. The exceptionally high CSI score in [IgG plasma cell](/details-cell/CL0000985) suggests that [U2AF1L4](/details-gene/199746) is indispensable for splicing immunoglobulin heavy and light chain transcripts. Its dysregulation may be a key event in plasma cell malignancies like multiple myeloma, potentially leading to the production of aberrant antibodies or affecting cell survival pathways. 2. The shared high expression in disparate long-lived cell types, such as memory T cells and retinal bipolar cells, indicates that [U2AF1L4](/details-gene/199746) may control a common splicing program that governs cellular maintenance, stress response, or metabolic homeostasis essential for longevity in these non-proliferating cells. **Experimental Proposal:** To test the first hypothesis, one could utilize CRISPR interference (CRISPRi) to achieve a tunable knockdown of [U2AF1L4](/details-gene/199746) in an *in vitro* system that differentiates human B cells into plasma cells. Following knockdown, RNA-sequencing combined with bioinformatic analysis of differential splicing events (e.g., intron retention, exon skipping) would reveal its specific impact on the immunoglobulin transcriptome and other key plasma cell identity genes. Concurrently, secreted immunoglobulin levels could be quantified via ELISA to directly assess the functional consequence on antibody production. **Therapeutic Potential:** As a core component of the essential splicing machinery, targeting [U2AF1L4](/details-gene/199746) systemically would likely cause significant toxicity. However, its high expression in specific cell types suggests a potential therapeutic window in certain pathologies. In cancers defined by the over-proliferation of cells where [U2AF1L4](/details-gene/199746) is a top marker, such as multiple myeloma, developing inhibitors that modulate its activity could be a viable strategy. Such an approach would aim for inhibition, leveraging the principle of "transcriptional addiction" where cancer cells are exquisitely sensitive to perturbations in the splicing machinery. This strategy is being explored for other splicing factors and could be applicable to [U2AF1L4](/details-gene/199746).

Genular Protein ID: 284812157

Symbol: U2AF4_HUMAN

Name: Splicing factor U2AF 26 kDa subunit

UniProtKB Accession Codes:

Q8WU68 A6NKI8 Q56UU3

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 3 Ensembl 3 ExpressionAtlas 1 GO 8 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 6 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRINTS 1 PRO 1 PROSITE 2 PathwayCommons 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 3 Pumba 1 RNAct 1 Reactome 4 RefSeq 2 SMART 2 SMR 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 17312947

Title: Cloning and characterization of a novel splice variant of human U2AF1L3 gene.

PubMed ID: 17312947

DOI: 10.1080/10425170600807744

PubMed ID: 15057824

Title: The DNA sequence and biology of human chromosome 19.

PubMed ID: 15057824

DOI: 10.1038/nature02399

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

Sequence Information:

  • Length: 220
  • Mass: 25744
  • Checksum: 64BA09EEDE3FB093
  • Sequence:
    • MAEYLASIFG TEKDKVNCSF YFKIGVCRHG DRCSRLHNKP TFSQTIVLLN LYRNPQNTAQ 
TADGSHCHVS DVEVQEHYDS FFEEVFTELQ EKYGEIEEMN VCDNLGDHLV GNVYVKFRRE 
EDGERAVAEL SNRWFNGQAV HGELSPVTDF RESCCRQYEM GECTRGGFCN FMHLRPISQN 
LQRQLYGRGP RRRSPPRFHT GHHPRERNHR CSPDHWHGRF