Details for: UTP4

Gene ID: 84916

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: UTP4

Ensembl ID: ENSG00000141076

Description: UTP4 small subunit processome component

Cell Significance Landscape

Associated with

Significant Cells

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

  • epithelial cell of proximal tubule CL0002306
    CSI 3.81
    rCSI 9.31%
    PRS 89.91
  • melanocyte CL0000148
    CSI 3.47
    rCSI 2.57%
    PRS 92.42
  • neural crest cell CL0011012
    CSI 3.03
    rCSI 2.39%
    PRS 90.2
  • fibroblast of lung CL0002553
    CSI 2.91
    rCSI 2.7%
    PRS 95.69
  • central memory CD8-positive, alpha-beta T cell CL0000907
    CSI 2.84
    rCSI 1.92%
    PRS 99.02
  • stem cell CL0000034
    CSI 2.81
    rCSI 2.71%
    PRS 92.15
  • hepatic stellate cell CL0000632
    CSI 2.73
    rCSI 10.22%
    PRS 92.22
  • respiratory suprabasal cell CL4033048
    CSI 2.69
    rCSI 3.45%
    PRS 95.6
  • keratinocyte CL0000312
    CSI 2.65
    rCSI 2.22%
    PRS 94.3
  • basal cell CL0000646
    CSI 2.6
    rCSI 3.48%
    PRS 92.44
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 2.23
    rCSI 3.93%
    PRS 85.45
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.07
    rCSI 2.58%
    PRS 83.93
  • sst GABAergic cortical interneuron CL4023017
    CSI 2.04
    rCSI 2.62%
    PRS 86.97
  • multi-ciliated epithelial cell CL0005012
    CSI 2.02
    rCSI 2.02%
    PRS 90.21
  • mesenchymal cell CL0008019
    CSI 1.8
    rCSI 4.58%
    PRS 91.59
  • renal interstitial pericyte CL1001318
    CSI 1.52
    rCSI 4.19%
    PRS 93.4
  • kidney connecting tubule epithelial cell CL1000768
    CSI 1.45
    rCSI 3.68%
    PRS 91.02
  • primitive red blood cell CL0002355
    CSI 0.84
    rCSI 4.54%
    PRS 94.99
  • direct pathway medium spiny neuron CL4023026
    CSI 0.32
    rCSI 7.73%
    PRS 83.86

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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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 [UTP4](/details-gene/84916), also known as UTP4 small subunit processome component, is a protein-coding gene located on chromosome 16q22.1. It is a core component of the small-subunit (SSU) processome, a large ribonucleoprotein complex essential for the biogenesis of the ribosomal small subunit. Functionally, [UTP4](/details-gene/84916) is primarily localized to the [nucleolus](/details-go/GO:0005730) where it plays a critical role in the processing and maturation of 18S ribosomal RNA ([rRNA](/details-reactome/R-HSA-72312)), a foundational step in ribosome production [Link](https://pubmed.ncbi.nlm.nih.gov/12429849/). Its expression profile suggests a ubiquitous and vital role in maintaining cellular function, with particularly high significance in metabolically active or highly proliferative cells, such as [epithelial cell of proximal tubule](/details-cell/CL0002306), [melanocyte](/details-cell/CL0000148), and [stem cell](/details-cell/CL0000034). ## Cellular Roles and Expression Landscape The expression pattern of [UTP4](/details-gene/84916) underscores its fundamental importance in protein synthesis across a wide array of cell types. **Overall**, the gene shows the highest significance in cells characterized by high metabolic activity and/or a high capacity for proliferation, which places a heavy demand on ribosome production. Key cell types with high [UTP4](/details-gene/84916) significance include: * **Metabolically Active Cells:** The highest significance is observed in [epithelial cell of proximal tubule](/details-cell/CL0002306) (CSI: 3.81), which are responsible for massive reabsorption and secretion in the kidney and thus require a high rate of protein synthesis. * **Proliferative and Differentiating Cells:** High significance in [melanocyte](/details-cell/CL0000148) (CSI: 3.47), [stem cell](/details-cell/CL0000034) (CSI: 2.81), [keratinocyte](/details-cell/CL0000312) (CSI: 2.65), and [basal cell](/details-cell/CL0000646) (CSI: 2.60) is consistent with the need for rapid cell division and differentiation, processes that are critically dependent on ribosome biogenesis. * **Developmental and Immune Cells:** Notable expression in [neural crest cell](/details-cell/CL0011012) (CSI: 3.03) and [central memory CD8-positive, alpha-beta T cell](/details-cell/CL0000907) (CSI: 2.84) suggests a vital role during embryonic development and in maintaining the protein synthesis machinery required for immune cell memory and activation. * **Structural and Neuronal Cells:** The gene is also significantly expressed in [fibroblast of lung](/details-cell/CL0002553) (CSI: 2.91) and various GABAergic cortical interneurons, highlighting its housekeeping function in both structural and post-mitotic, but metabolically active, cell types. Collectively, this expression landscape paints a picture of [UTP4](/details-gene/84916) as a crucial "workhorse" gene whose activity is a prerequisite for the high-level protein production necessary for specialized cellular functions and proliferation. ## Pathways and Molecular Function The functional annotations for [UTP4](/details-gene/84916) confirm its central role in ribosome synthesis. It is an integral component of the [Small-subunit processome](/details-go/GO:0032040), also known as the 90S preribosome, and specifically participates in the t-UTP sub-complex [Link](https://pubmed.ncbi.nlm.nih.gov/24219289/). This complex is one of the earliest to assemble on pre-rRNA transcripts. * **Biological Process:** The gene is most prominently associated with [Maturation of ssu-rrna](/details-go/GO:0030490) and [Ribosomal small subunit biogenesis](/details-go/GO:0042274). These processes are fundamental for producing the 40S ribosomal subunit. * **Molecular Function:** Its functions as an [Rna binding](/details-go/GO:0003723) and [Protein binding](/details-go/GO:0005515) molecule are essential for its role within the SSU processome, where it mediates the complex interactions required to correctly fold and process pre-rRNA. * **Cellular Location:** [UTP4](/details-gene/84916) is localized to the [nucleolus](/details-go/GO:0005730), the primary site of ribosome synthesis, and specifically within the [fibrillar center](/details-go/GO:0001650), where rRNA transcription begins [Link](https://pubmed.ncbi.nlm.nih.gov/12429849/). * **Reactome Pathways:** Its involvement is explicitly detailed in pathways such as [Major pathway of rrna processing in the nucleolus and cytosol](/details-reactome/R-HSA-6791226) and [Rrna processing](/details-reactome/R-HSA-72312), which encompasses the entire series of cleavage and modification events that convert the initial 47S pre-rRNA transcript into mature rRNAs. Research has also implicated its interacting partner, cirhin, in North American Indian childhood cirrhosis, a disease linked to defective ribosome biogenesis [Link](https://pubmed.ncbi.nlm.nih.gov/12417987/), suggesting that the pathway [UTP4](/details-gene/84916) participates in is clinically relevant. ## Research Directions The fundamental role of [UTP4](/details-gene/84916) in ribosome biogenesis makes it a critical gene for cellular health, and its dysfunction is a plausible contributor to human disease, particularly ribosomopathies. The established interaction between [UTP4](/details-gene/84916) (also known as CIRH1A) and cirhin, the protein mutated in North American Indian childhood cirrhosis (NAICC), provides a direct link to a human pathology associated with impaired ribosome synthesis [Link](https://pubmed.ncbi.nlm.nih.gov/16225863/). Based on this, several testable hypotheses can be proposed: 1. **Hypothesis on Disease Causation:** Given its critical function and interaction with a known disease-related protein, it is hypothesized that rare, biallelic loss-of-function mutations in [UTP4](/details-gene/84916) could be a cause of an undiagnosed human ribosomopathy, presenting with features similar to NAICC or other syndromes like Treacher Collins syndrome, which are also caused by defects in ribosome biogenesis. 2. **Hypothesis on Cellular Vulnerability:** The exceptionally high significance of [UTP4](/details-gene/84916) in specific cell types, like the [epithelial cell of proximal tubule](/details-cell/CL0002306), suggests these cells may be uniquely vulnerable to even subtle reductions in [UTP4](/details-gene/84916) expression or function. It is hypothesized that haploinsufficiency of [UTP4](/details-gene/84916) could predispose individuals to kidney dysfunction under metabolic stress. **Experimental Approach to Test Hypothesis 1:** To investigate the pathogenic potential of [UTP4](/details-gene/84916) mutations, a cellular model could be developed. CRISPR-Cas9 could be used to introduce patient-derived or engineered loss-of-function mutations into a human cell line relevant to NAICC, such as the hepatocyte cell line HepG2. The functional consequences would be assessed by: * **rRNA Processing Analysis:** Northern blotting with probes specific to pre-rRNA intermediates to detect defects in 18S rRNA maturation. * **Ribosome Profiling:** Sucrose gradient polysome profiling to determine if the mutations lead to deficits in 40S subunit assembly and overall translation. * **Cellular Stress Response:** Western blotting for key markers of the ribosomopathy-associated stress response, such as p53 stabilization and activation. **Therapeutic Potential:** As a core, ubiquitously expressed component of the ribosome biogenesis machinery, [UTP4](/details-gene/84916) is a challenging therapeutic target. Systemic inhibition would likely result in severe, on-target toxicity to all healthy, proliferating tissues. However, in the context of cancer, which is often characterized by an addiction to elevated ribosome production, targeting the SSU processome is a valid anti-neoplastic strategy. Therefore, developing small molecules that disrupt the function or protein-protein interactions of [UTP4](/details-gene/84916) could have potential as a cancer therapeutic, though achieving a suitable therapeutic window would be difficult. For potential monogenic diseases caused by [UTP4](/details-gene/84916) deficiency, therapeutic strategies would more likely focus on gene replacement therapy or approaches to stabilize a partially functional mutant protein.

Genular Protein ID: 3517862987

Symbol: UTP4_HUMAN

Name: U3 small nucleolar RNA-associated protein 4 homolog

UniProtKB Accession Codes:

Q969X6 Q8NCD9 Q8TF14 Q96SP0 Q96SR9 Q96SZ9 Q96T13 Q9BWK6

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChiTaRS 1 ComplexPortal 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 9 EMDB 3 Ensembl 4 ExpressionAtlas 1 GO 12 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PDB 3 PDBsum 3 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 3 Pumba 1 RNAct 1 Reactome 2 RefSeq 1 SMART 1 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: 11853319

Title: Prediction of the coding sequences of unidentified human genes. XXII. The complete sequences of 50 new cDNA clones which code for large proteins.

PubMed ID: 11853319

DOI: 10.1093/dnares/8.6.319

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

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: 12429849

Title: Functional proteomic analysis of human nucleolus.

PubMed ID: 12429849

DOI: 10.1091/mbc.e02-05-0271

PubMed ID: 16225863

Title: Nucleolar localization of cirhin, the protein mutated in North American Indian childhood cirrhosis.

PubMed ID: 16225863

DOI: 10.1016/j.yexcr.2005.08.012

PubMed ID: 17699751

Title: Recruitment of factors linking transcription and processing of pre-rRNA to NOR chromatin is UBF-dependent and occurs independent of transcription in human cells.

PubMed ID: 17699751

DOI: 10.1101/gad.436707

PubMed ID: 19732766

Title: Cirhin up-regulates a canonical NF-kappaB element through strong interaction with Cirip/HIVEP1.

PubMed ID: 19732766

DOI: 10.1016/j.yexcr.2009.08.017

PubMed ID: 20813266

Title: The protein composition of mitotic chromosomes determined using multiclassifier combinatorial proteomics.

PubMed ID: 20813266

DOI: 10.1016/j.cell.2010.07.047

PubMed ID: 22916032

Title: NOL11, implicated in the pathogenesis of North American Indian childhood cirrhosis, is required for pre-rRNA transcription and processing.

PubMed ID: 22916032

DOI: 10.1371/journal.pgen.1002892

PubMed ID: 24219289

Title: Interaction, mobility, and phosphorylation of human orthologues of WD repeat-containing components of the yeast SSU processome t-UTP sub-complex.

PubMed ID: 24219289

DOI: 10.1139/bcb-2013-0062

PubMed ID: 28112733

Title: Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation.

PubMed ID: 28112733

DOI: 10.1038/nsmb.3366

PubMed ID: 34516797

Title: Nucleolar maturation of the human small subunit processome.

PubMed ID: 34516797

DOI: 10.1126/science.abj5338

PubMed ID: 12417987

Title: A missense mutation (R565W) in cirhin (FLJ14728) in North American Indian childhood cirrhosis.

PubMed ID: 12417987

DOI: 10.1086/344580

PubMed ID: 27535533

Title: Analysis of protein-coding genetic variation in 60,706 humans.

PubMed ID: 27535533

DOI: 10.1038/nature19057

Sequence Information:

  • Length: 686
  • Mass: 76890
  • Checksum: 595D8B2F47C03299
  • Sequence:
    • MGEFKVHRVR FFNYVPSGIR CVAYNNQSNR LAVSRTDGTV EIYNLSANYF QEKFFPGHES 
RATEALCWAE GQRLFSAGLN GEIMEYDLQA LNIKYAMDAF GGPIWSMAAS PSGSQLLVGC 
EDGSVKLFQI TPDKIQFERN FDRQKSRILS LSWHPSGTHI AAGSIDYISV FDVKSGSAVH 
KMIVDRQYMG VSKRKCIVWG VAFLSDGTII SVDSAGKVQF WDSATGTLVK SHLIANADVQ 
SIAVADQEDS FVVGTAEGTV FHFQLVPVTS NSSEKQWVRT KPFQHHTHDV RTVAHSPTAL 
ISGGTDTHLV FRPLMEKVEV KNYDAALRKI TFPHRCLISC SKKRQLLLFQ FAHHLELWRL 
GSTVATGKNG DTLPLSKNAD HLLHLKTKGP ENIICSCISP CGSWIAYSTV SRFFLYRLNY 
EHDNISLKRV SKMPAFLRSA LQILFSEDST KLFVASNQGA LHIVQLSGGS FKHLHAFQPQ 
SGTVEAMCLL AVSPDGNWLA ASGTSAGVHV YNVKQLKLHC TVPAYNFPVT AMAIAPNTNN 
LVIAHSDQQV FEYSIPDKQY TDWSRTVQKQ GFHHLWLQRD TPITHISFHP KRPMHILLHD 
AYMFCIIDKS LPLPNDKTLL YNPFPPTNES DVIRRRTAHA FKISKIYKPL LFMDLLDERT 
LVAVERPLDD IIAQLPPPIK KKKFGT