Details for: INTS15

Gene ID: 79034

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: INTS15

Ensembl ID: ENSG00000146576

Description: integrator complex subunit 15

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • double negative thymocyte CL0002489
    CSI 4.03
    rCSI 2.8%
    PRS 95.73
  • CD4-positive, alpha-beta memory T cell CL0000897
    CSI 3.43
    rCSI 2.46%
    PRS 96.28
  • group 3 innate lymphoid cell CL0001071
    CSI 3.34
    rCSI 2.51%
    PRS 91.4
  • interneuron CL0000099
    CSI 3.26
    rCSI 6.55%
    PRS 80.19
  • precursor B cell CL0000817
    CSI 3.19
    rCSI 2.79%
    PRS 92.24
  • vascular associated smooth muscle cell CL0000359
    CSI 3.13
    rCSI 10.14%
    PRS 85.52
  • central memory CD8-positive, alpha-beta T cell CL0000907
    CSI 3.01
    rCSI 2.03%
    PRS 96.34
  • ionocyte CL0005006
    CSI 2.9
    rCSI 3.1%
    PRS 89.25
  • mesodermal cell CL0000222
    CSI 2.85
    rCSI 3.42%
    PRS 86.02
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 2.72
    rCSI 2.1%
    PRS 90.56
  • central memory CD4-positive, alpha-beta T cell CL0000904
    CSI 2.72
    rCSI 1.6%
    PRS 97.5
  • bronchus fibroblast of lung CL2000093
    CSI 2.71
    rCSI 2.2%
    PRS 86.92
  • pro-B cell CL0000826
    CSI 2.48
    rCSI 2.05%
    PRS 89.29
  • epithelial cell of lung CL0000082
    CSI 2.37
    rCSI 1.96%
    PRS 88.55
  • myeloid leukocyte CL0000766
    CSI 2.27
    rCSI 2.1%
    PRS 88.54
  • transit amplifying cell of colon CL0009011
    CSI 2.26
    rCSI 2.65%
    PRS 88.12
  • ciliated epithelial cell CL0000067
    CSI 2.13
    rCSI 1.88%
    PRS 78.18
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.11
    rCSI 2.62%
    PRS 70.29
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 2.07
    rCSI 3.65%
    PRS 71.97
  • CD4-positive, alpha-beta cytotoxic T cell CL0000934
    CSI 1.92
    rCSI 2.63%
    PRS 96.79
  • peripheral nervous system neuron CL2000032
    CSI 1.77
    rCSI 2.42%
    PRS 80.55
  • astrocyte of the cerebral cortex CL0002605
    CSI 1.68
    rCSI 3.76%
    PRS 73.22
  • mesenchymal cell CL0008019
    CSI 1.32
    rCSI 3.36%
    PRS 81.85

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)

Loading network (please wait)...

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 [INTS15](/details-gene/79034) (Integrator Complex Subunit 15) is a protein-coding gene located on chromosome 7p22.1. It encodes a component of the Integrator complex, a multi-subunit machinery involved in the processing of small nuclear RNAs (snRNAs) and the regulation of gene expression. **Overall**, expression data suggests that [INTS15](/details-gene/79034) is broadly expressed but shows particular significance in various immune cell populations, including developing and memory lymphocytes, as well as in specific non-hematopoietic cells such as [interneurons](/details-cell/CL0000099) and [vascular associated smooth muscle cells](/details-cell/CL0000359), pointing to a fundamental role in cellular function across diverse tissues. ## Cellular Roles and Expression Landscape The expression profile of [INTS15](/details-gene/79034) highlights its significant role across multiple lineages of the hematopoietic system. The gene exhibits its highest significance in developing lymphocytes, such as [double negative thymocytes](/details-cell/CL0002489) (CSI: 4.03) and [precursor B cells](/details-cell/CL0000817) (CSI: 3.19), suggesting a crucial function during the early stages of T and B cell maturation. Furthermore, its notable expression in memory T cell subsets, including [CD4-positive, alpha-beta memory T cells](/details-cell/CL0000897) (CSI: 3.43) and [central memory CD8-positive, alpha-beta T cells](/details-cell/CL0000907) (CSI: 3.01), is consistent with a role in maintaining the transcriptional state of long-lived immune cells. Beyond the adaptive immune system, [INTS15](/details-gene/79034) is also significant in [group 3 innate lymphoid cells](/details-cell/CL0001071) (CSI: 3.34) and [myeloid leukocytes](/details-cell/CL0000766) (CSI: 2.27), indicating its importance extends to the innate immune compartment. Interestingly, the expression of [INTS15](/details-gene/79034) is not restricted to immune cells. It shows high significance in [interneurons](/details-cell/CL0000099) (CSI: 3.26), [vascular associated smooth muscle cells](/details-cell/CL0000359) (CSI: 3.13), and various lung cells, including [bronchus fibroblasts](/details-cell/CL2000093) (CSI: 2.71) and [epithelial cells](/details-cell/CL0000082) (CSI: 2.37). This broad but varied expression pattern suggests that [INTS15](/details-gene/79034) is part of a fundamental cellular machinery required by many cell types, although its functional importance may be particularly pronounced in contexts requiring dynamic gene regulation, such as lymphocyte development and neuronal function. ## Pathways and Molecular Function Functionally, [INTS15](/details-gene/79034) is annotated as a core component of the [Integrator complex](/details-go/GO:0032039). The Integrator complex is a large, multi-protein assembly primarily known for its role in the 3'-end processing of U1 and U2 snRNAs, which are essential components of the spliceosome. However, recent studies have expanded its role to include transcription termination and the regulation of messenger RNA (mRNA) expression for a subset of protein-coding genes. Its identification within global analyses of human multiprotein assemblies confirms its role as part of a stable complex ([Link](https://doi.org/10.15252/msb.202010016)). The widespread cellular significance of [INTS15](/details-gene/79034), particularly in developing and highly active cells, is consistent with its involvement in such a fundamental process of gene expression control. ## Research Directions The expression pattern of [INTS15](/details-gene/79034) suggests it plays a key housekeeping role, but with heightened importance in specific cellular contexts. This warrants further investigation into its precise regulatory functions. ### Proposed Hypotheses 1. **[INTS15](/details-gene/79034) is essential for the proper transcriptional programming and differentiation of early T and B lymphocytes.** Its high significance in [double negative thymocytes](/details-cell/CL0002489) and [precursor B cells](/details-cell/CL0000817) suggests that its disruption could lead to a block in lymphocyte development. 2. **In memory T cells, [INTS15](/details-gene/79034) is required to maintain the specific gene expression profile associated with long-term survival and recall potential.** Its function may be critical for silencing inappropriate gene expression while keeping memory-specific genes poised for rapid reactivation. 3. **The high significance of [INTS15](/details-gene/79034) in [interneurons](/details-cell/CL0000099) points to a specialized role in regulating the expression of genes critical for neuronal identity or function, potentially related to neurotransmitter synthesis or synaptic plasticity.** ### Key Experimental Approach To test the hypothesis that [INTS15](/details-gene/79034) is critical for lymphocyte development, a conditional knockout mouse model could be generated. Deletion of *Ints15* using a *Vav1-Cre* driver would ablate the gene specifically in the hematopoietic system. Subsequent analysis of lymphoid organs (thymus, bone marrow, spleen) via flow cytometry would reveal potential blocks at specific stages of T and B cell maturation. Furthermore, RNA-sequencing of sorted progenitor populations (e.g., double negative thymocytes) from both knockout and control mice would identify the downstream transcriptional targets regulated by the INTS15-containing Integrator complex in this context. ### Therapeutic Potential As a component of a core transcriptional regulatory complex, [INTS15](/details-gene/79034) presents a challenging therapeutic target. Its broad expression pattern across many healthy cell types suggests that systemic inhibition would likely result in significant toxicity. Therefore, its therapeutic potential is likely limited. However, if specific cancers (e.g., leukemias or lymphomas originating from cell types with high [INTS15](/details-gene/79034) expression) are found to have a particular dependency on the Integrator complex, targeted degradation or inhibition of [INTS15](/details-gene/79034) could be a viable strategy in those specific contexts. Such a strategy would require a deep understanding of the gene's disease-specific roles.

Genular Protein ID: 1699142775

Symbol: INT15_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q96N11 Q9BQ43

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 EMBL 3 EMDB 8 Ensembl 2 ExpressionAtlas 1 GO 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 1 KEGG 1 MANE-Select 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 8 PDBsum 8 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 RefSeq 2 SMR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

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: 33973408

Title: hu.MAP 2.0: integration of over 15,000 proteomic experiments builds a global compendium of human multiprotein assemblies.

PubMed ID: 33973408

DOI: 10.15252/msb.202010016

Sequence Information:

  • Length: 449
  • Mass: 50047
  • Checksum: CECD14EB3E97A6BA
  • Sequence:
    • MSDIRHSLLR RDALSAAKEV LYHLDIYFSS QLQSAPLPIV DKGPVELLEE FVFQVPKERS 
AQPKRLNSLQ ELQLLEIMCN YFQEQTKDSV RQIIFSSLFS PQGNKADDSR MSLLGKLVSM 
AVAVCRIPVL ECAASWLQRT PVVYCVRLAK ALVDDYCCLV PGSIQTLKQI FSASPRFCCQ 
FITSVTALYD LSSDDLIPPM DLLEMIVTWI FEDPRLILIT FLNTPIAANL PIGFLELTPL 
VGLIRWCVKA PLAYKRKKKP PLSNGHVSNK VTKDPGVGMD RDSHLLYSKL HLSVLQVLMT 
LQLHLTEKNL YGRLGLILFD HMVPLVEEIN RLADELNPLN ASQEIELSLD RLAQALQVAM 
ASGALLCTRD DLRTLCSRLP HNNLLQLVIS GPVQQSPHAA LPPGFYPHIH TPPLGYGAVP 
AHPAAHPALP THPGHTFISG VTFPFRPIR