Details for: INTS6L

Gene ID: 203522

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: INTS6L

Ensembl ID: ENSG00000165359

Description: integrator complex subunit 6 like

Cell Significance Landscape

Associated with

Significant Cells

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

  • naive thymus-derived CD8-positive, alpha-beta T cell CL0000900
    CSI 4.71
    rCSI 3.31%
    PRS 96.96
  • mesothelial cell CL0000077
    CSI 4.69
    rCSI 18.35%
    PRS 77.31
  • myeloid leukocyte CL0000766
    CSI 4.39
    rCSI 4.05%
    PRS 92.94
  • Schwann cell CL0002573
    CSI 3.91
    rCSI 11.13%
    PRS 88.75
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 3.75
    rCSI 22.11%
    PRS 80.75
  • CD4-positive, alpha-beta memory T cell CL0000897
    CSI 3.72
    rCSI 2.67%
    PRS 98.15
  • mucosal invariant T cell CL0000940
    CSI 3.66
    rCSI 2.96%
    PRS 95.87
  • cerebellar granule cell CL0001031
    CSI 3.55
    rCSI 5.21%
    PRS 87.51
  • precursor B cell CL0000817
    CSI 3.49
    rCSI 3.06%
    PRS 95.02
  • parietal epithelial cell CL1000452
    CSI 3.43
    rCSI 9.17%
    PRS 87.44
  • chondrocyte CL0000138
    CSI 3.35
    rCSI 5.34%
    PRS 87.85
  • naive B cell CL0000788
    CSI 3.17
    rCSI 2.72%
    PRS 94.83
  • melanocyte CL0000148
    CSI 3.01
    rCSI 2.23%
    PRS 88.8
  • vascular leptomeningeal cell CL4023051
    CSI 2.86
    rCSI 5.01%
    PRS 88.88
  • retina horizontal cell CL0000745
    CSI 2.73
    rCSI 4.16%
    PRS 88.9
  • hepatic stellate cell CL0000632
    CSI 2.68
    rCSI 10.04%
    PRS 88.21
  • alpha-beta T cell CL0000789
    CSI 2.61
    rCSI 3.06%
    PRS 97.62
  • lung neuroendocrine cell CL1000223
    CSI 2.59
    rCSI 3.84%
    PRS 93.1
  • interneuron CL0000099
    CSI 2.58
    rCSI 5.18%
    PRS 86.56
  • double-positive, alpha-beta thymocyte CL0000809
    CSI 2.49
    rCSI 2.53%
    PRS 95.88
  • cerebral cortex endothelial cell CL1001602
    CSI 2.49
    rCSI 4.3%
    PRS 87.14
  • Mueller cell CL0000636
    CSI 2.46
    rCSI 5.62%
    PRS 86.23
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.45
    rCSI 3.04%
    PRS 78.12
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 2.39
    rCSI 1.84%
    PRS 94.54
  • retinal bipolar neuron CL0000748
    CSI 2.28
    rCSI 4.26%
    PRS 84.46
  • effector memory CD8-positive, alpha-beta T cell CL0000913
    CSI 2.19
    rCSI 1.99%
    PRS 97.64
  • lung secretory cell CL1000272
    CSI 2.18
    rCSI 5.39%
    PRS 92.7
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 2.09
    rCSI 7.9%
    PRS 80.5
  • CD14-positive monocyte CL0001054
    CSI 2.06
    rCSI 2.57%
    PRS 96.49
  • ciliated epithelial cell CL0000067
    CSI 2.01
    rCSI 1.77%
    PRS 83.9
  • conjunctival epithelial cell CL1000432
    CSI 1.94
    rCSI 2.96%
    PRS 90.87
  • sst GABAergic cortical interneuron CL4023017
    CSI 1.94
    rCSI 2.5%
    PRS 81.42
  • VIP GABAergic cortical interneuron CL4023016
    CSI 1.93
    rCSI 2.31%
    PRS 80.35
  • basal cell CL0000646
    CSI 1.88
    rCSI 2.51%
    PRS 89.49
  • astrocyte of the cerebral cortex CL0002605
    CSI 1.82
    rCSI 4.08%
    PRS 80.62
  • BEST4+ enteroycte CL4030026
    CSI 1.76
    rCSI 2.18%
    PRS 91.5
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.61
    rCSI 2.71%
    PRS 80.3
  • cardiac muscle cell CL0000746
    CSI 1.55
    rCSI 2.23%
    PRS 84.67
  • sncg GABAergic cortical interneuron CL4023015
    CSI 1.38
    rCSI 2.22%
    PRS 81.35
  • kidney connecting tubule epithelial cell CL1000768
    CSI 1.38
    rCSI 3.49%
    PRS 86.7
  • retinal ganglion cell CL0000740
    CSI 1.37
    rCSI 3.02%
    PRS 82.62
  • L4 intratelencephalic projecting glutamatergic neuron CL4030063
    CSI 1.33
    rCSI 3.17%
    PRS 82.6
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.16
    rCSI 2.04%
    PRS 79.76
  • regular atrial cardiac myocyte CL0002129
    CSI 1.11
    rCSI 3.56%
    PRS 88.7
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 1.09
    rCSI 2.64%
    PRS 78.16
  • suprabasal keratinocyte CL4033013
    CSI 1.08
    rCSI 1.77%
    PRS 64.64
  • GABAergic neuron CL0000617
    CSI 0.92
    rCSI 3.08%
    PRS 79.73
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.9
    rCSI 2.82%
    PRS 81.59
  • L5/6 near-projecting glutamatergic neuron CL4030067
    CSI 0.87
    rCSI 2.87%
    PRS 81.46
  • dopaminergic neuron CL0000700
    CSI 0.83
    rCSI 4.68%
    PRS 82.08
  • enteroglial cell CL4040002
    CSI 0.8
    rCSI 4.19%
    PRS 91.66
  • enterocyte of epithelium of large intestine CL0002071
    CSI 0.66
    rCSI 3.47%
    PRS 93.35
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.66
    rCSI 2.38%
    PRS 78.41
  • H2 horizontal cell CL0004218
    CSI 0.63
    rCSI 3.16%
    PRS 87.04
  • blood vessel smooth muscle cell CL0019018
    CSI 0.4
    rCSI 3.29%
    PRS 89.94
  • direct pathway medium spiny neuron CL4023026
    CSI 0.25
    rCSI 6%
    PRS 78.12
  • indirect pathway medium spiny neuron CL4023029
    CSI 0.24
    rCSI 5.71%
    PRS 78.26

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 [INTS6L](/details-gene/203522) (Integrator Complex Subunit 6 Like) is a protein-coding gene located on the X chromosome. As its name suggests, it is a component of the Integrator complex, a multi-subunit protein assembly essential for the 3'-end processing of small nuclear RNAs (snRNAs), particularly those involved in splicing ([Link](https://doi.org/10.1038/nature03440)). The expression profile of [INTS6L](/details-gene/203522) is notably broad, with high significance scores observed across a diverse range of cell types. **Overall**, it is a key marker in immune cells such as [naive thymus-derived CD8-positive, alpha-beta T cells](/details-cell/CL0000900) and [myeloid leukocytes](/details-cell/CL0000766), as well as non-immune cells including [mesothelial cells](/details-cell/CL0000077) and various neuronal subtypes. This widespread expression underscores its likely role in a fundamental cellular process required by many different cell lineages. ## Cellular Roles and Expression Landscape The expression pattern of [INTS6L](/details-gene/203522) indicates a ubiquitous and vital role in cellular function rather than a lineage-defining one. **Overall**, the gene shows high significance across several distinct biological systems: * **Immune System:** [INTS6L](/details-gene/203522) is highly significant in multiple lymphocyte populations, including [naive thymus-derived CD8-positive, alpha-beta T cell](/details-cell/CL0000900) (CSI: 4.71), [CD4-positive, alpha-beta memory T cell](/details-cell/CL0000897) (CSI: 3.72), [mucosal invariant T cell](/details-cell/CL0000940) (CSI: 3.66), [precursor B cell](/details-cell/CL0000817) (CSI: 3.49), and [naive B cell](/details-cell/CL0000788) (CSI: 3.17). Its presence in [myeloid leukocytes](/details-cell/CL0000766) (CSI: 4.39) further supports a broad role in both the adaptive and innate immune systems. * **Nervous System:** The gene is also a prominent marker in various neural cell types, including peripheral [Schwann cells](/details-cell/CL0002573) (CSI: 3.91) and central nervous system cells like [corticothalamic-projecting glutamatergic cortical neurons](/details-cell/CL4023013) (CSI: 3.75) and [cerebellar granule cells](/details-cell/CL0001031) (CSI: 3.55). This suggests it is important for the maintenance and function of both neurons and their supporting glial cells. * **Structural and Epithelial Tissues:** High significance in [mesothelial cells](/details-cell/CL0000077) (CSI: 4.69), [parietal epithelial cells](/details-cell/CL1000452) (CSI: 3.43), and [chondrocytes](/details-cell/CL0000138) (CSI: 3.35) highlights its importance in tissues that provide structural support and line body cavities. The widespread expression across such functionally disparate cell types is consistent with the gene's role in a core molecular process essential for proper gene regulation in eukaryotic cells. ## Pathways and Molecular Function Functionally, [INTS6L](/details-gene/203522) is annotated as a core component of the **[Integrator complex](/details-cell/GO:0032039)**. This complex is primarily responsible for **[snRNA 3'-end processing](/details-cell/GO:0034472)**, a critical step in the maturation of U1, U2, U4, and U5 snRNAs, which form the spliceosome. By ensuring the proper formation of these snRNAs, the Integrator complex, and by extension [INTS6L](/details-gene/203522), plays an indirect but essential role in pre-mRNA splicing. This fundamental function in gene expression regulation explains its high significance in a wide array of metabolically active and highly differentiated cells, from immune cells undergoing activation to neurons maintaining complex signaling networks. ## Research Directions The ubiquitous expression of [INTS6L](/details-gene/203522) suggests its function is critical for general cell viability, but its varying levels of significance across cell types imply that certain lineages may be more dependent on its activity. ### Proposed Hypotheses: 1. **Hypothesis 1:** Given the high significance of [INTS6L](/details-gene/203522) in multiple lymphocyte subsets, its function in snRNA processing may be critically required during specific stages of lymphocyte development and activation. A reduction in its activity could lead to splicing defects in key immune-related transcripts, thereby compromising adaptive immune responses. 2. **Hypothesis 2:** The high significance of [INTS6L](/details-gene/203522) in diverse neuronal and glial cell types suggests that the nervous system is particularly sensitive to the fidelity of snRNA processing. Suboptimal function of the Integrator complex due to mutations or altered expression of [INTS6L](/details-gene/203522) could contribute to neurodevelopmental disorders or neurodegeneration, a concept broadly supported by studies linking exome variants to severe intellectual disability ([Link](https://doi.org/10.1056/nejmoa1206524)). ### Experimental Approach: To test the role of [INTS6L](/details-gene/203522) in the immune system (Hypothesis 1), a conditional knockout mouse model could be generated. By crossing a mouse with a floxed *Ints6l* allele to a CD4-Cre driver, the gene could be specifically deleted in the T cell lineage. The resulting phenotype could be assessed by: * **Immunophenotyping:** Using flow cytometry to analyze the development and frequencies of T cell populations in the thymus, spleen, and lymph nodes. * **Functional Assays:** Challenging the knockout mice with a pathogen (e.g., LCMV) to evaluate their capacity to mount an effective primary and memory T cell response. * **Molecular Analysis:** Performing RNA-sequencing on sorted T cells from control and knockout mice to identify specific splicing defects and dysregulated gene expression profiles resulting from the loss of [INTS6L](/details-gene/203522). ### Therapeutic Potential: As a core component of a fundamental cellular machine, [INTS6L](/details-gene/203522) is likely a poor therapeutic target for systemic inhibition. Its knockout would be expected to be detrimental to most healthy tissues, leading to high toxicity. Therefore, targeting [INTS6L](/details-gene/203522) would only be plausible in specific contexts, such as cancers that exhibit a unique dependency on the Integrator complex (a concept known as non-oncogene addiction) or via highly localized delivery systems to minimize off-target effects. Activation of the gene is not a clear therapeutic strategy without evidence of its role as a haploinsufficient tumor suppressor.

Genular Protein ID: 838084124

Symbol: INT6L_HUMAN

Name: Integrator complex subunit 6-like

UniProtKB Accession Codes:

Q5JSJ4 Q5CZA2 Q6IPS3 Q6ZTU5 Q6ZWE4

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 4 Ensembl 1 ExpressionAtlas 1 GO 2 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MassIVE 1 NCBI Taxonomy 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 RefSeq 1 SMR 1 STRING 1 SUPFAM 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: 17974005

Title: The full-ORF clone resource of the German cDNA consortium.

PubMed ID: 17974005

DOI: 10.1186/1471-2164-8-399

PubMed ID: 15772651

Title: The DNA sequence of the human X chromosome.

PubMed ID: 15772651

DOI: 10.1038/nature03440

PubMed ID: 21406692

Title: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.

PubMed ID: 21406692

DOI: 10.1126/scisignal.2001570

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 23033978

Title: Diagnostic exome sequencing in persons with severe intellectual disability.

PubMed ID: 23033978

DOI: 10.1056/nejmoa1206524

Sequence Information:

  • Length: 861
  • Mass: 96673
  • Checksum: 46CE8A7FB8A377C5
  • Sequence:
    • MPILLFLIDT SASMNQRTDL GTSYLDIAKG AVELFLKLRA RDPASRGDRY MLVTYDEPPY 
CIKAGWKENH ATFMSELKNL QASGLTTLGQ ALRSSFDLLN LNRLISGIDN YGQGRNPFFL 
EPSILITITD GNKLTSTAGV QEELHLPLNS PLPGSELTKE PFRWDQRLFA LVLRLPGVAS 
TEPEQLGSVP TDESAITQMC EVTGGRSYCV RTQRMLNQCL ESLVQKVQSG VVINFEKTGP 
DPLPIGEDGL MDSSRPSNSF AAQPWHSCHK LIYVRPNSKT GVPVGHWPIP ESFWPDQNLP 
SLPPRTSHPV VRFSCVDCEP MVIDKLPFDK YELEPSPLTQ YILERKSPHT CWQVFVTSSG 
KYNELGYPFG YLKASTTLTC VNLFVMPYNY PVLLPLLDDL FKVHKLKPNL KWRQAFDSYL 
KTLPPYYLLT KLESERILAS VGKKPPQEIG IKVKNHSGGG MSLTHNKNFR KLLKEITGET 
ALRLTELNTK EFAGFQIGLL NKDLKPQTYR NAYDIPRRGL LDQLTRMRSN LLKTHKFIVG 
QDEDSLHSVP VAQMGNYQEY LKTLASPLRE IDPDQPKRLH TFGNPFKQDK KGMMIDEADE 
FVAGPQNKVK RPGEPNSPMS SKRRRSMSLL LRKPQTPPTV TNHVGGKGPP SASWFPSYPN 
LIKPTLVHTD ATIIHDGHEE KMENGQITPD GFLSKSAPSE LINMTGDLMP PNQVDSLSDD 
FTSLSKDGLI QKPGSNAFVG GAKNCSLSVD DQKDPVASTL GAMPNTLQIT PAMAQGINAD 
IKHQLMKEVR KFGRKYERIF ILLEEVQGPL EMKKQFVEFT IKEAARFKRR VLIQYLEKVL 
EKINSHHLHN NISHINSRSS C