Details for: IGSF6

Gene ID: 10261

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: IGSF6

Ensembl ID: ENSG00000140749

Description: immunoglobulin superfamily member 6

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • CD14-low, CD16-positive monocyte CL0002396
    CSI 85.88
    rCSI 66.16%
    PRS 99.16
  • conventional dendritic cell CL0000990
    CSI 38.73
    rCSI 32.33%
    PRS 93.33
  • kidney interstitial alternatively activated macrophage CL1000695
    CSI 29.78
    rCSI 77.62%
    PRS 98.92
  • Langerhans cell CL0000453
    CSI 28.75
    rCSI 43.91%
    PRS 99.48
  • melanocyte of skin CL1000458
    CSI 28.39
    rCSI 38.69%
    PRS 82.29
  • Hofbauer cell CL3000001
    CSI 28
    rCSI 52.86%
    PRS 99.21
  • mononuclear phagocyte CL0000113
    CSI 26.25
    rCSI 57.79%
    PRS 98.88
  • mature NK T cell CL0000814
    CSI 24.48
    rCSI 31.32%
    PRS 98.53
  • alveolar macrophage CL0000583
    CSI 21.72
    rCSI 35.77%
    PRS 98.44
  • suprabasal keratinocyte CL4033013
    CSI 20.9
    rCSI 34.12%
    PRS 83.15
  • basal cell of epidermis CL0002187
    CSI 19.57
    rCSI 34.68%
    PRS 81.32
  • promonocyte CL0000559
    CSI 19.07
    rCSI 32.66%
    PRS 98.83
  • Kupffer cell CL0000091
    CSI 17.57
    rCSI 40.18%
    PRS 98.38
  • dendritic cell CL0000451
    CSI 17.21
    rCSI 21.21%
    PRS 97.14
  • myeloid dendritic cell CL0000782
    CSI 16.9
    rCSI 24.48%
    PRS 99.73
  • myeloid leukocyte CL0000766
    CSI 16.61
    rCSI 15.32%
    PRS 98.78
  • glutamatergic neuron CL0000679
    CSI 16.46
    rCSI 33.82%
    PRS 91.87
  • CD14-positive, CD16-positive monocyte CL0002397
    CSI 16.28
    rCSI 21.33%
    PRS 99.56
  • non-classical monocyte CL0000875
    CSI 15.84
    rCSI 25.39%
    PRS 98.51
  • melanocyte CL0000148
    CSI 15.39
    rCSI 11.4%
    PRS 96.94
  • inflammatory macrophage CL0000863
    CSI 15.17
    rCSI 25.93%
    PRS 99.86
  • classical monocyte CL0000860
    CSI 14.9
    rCSI 22.1%
    PRS 98.36
  • CD14-positive monocyte CL0001054
    CSI 14.37
    rCSI 17.9%
    PRS 99.66
  • colon macrophage CL0009038
    CSI 13.36
    rCSI 61.72%
    PRS 99.61
  • microglial cell CL0000129
    CSI 12.99
    rCSI 52.31%
    PRS 96.6
  • chondrocyte CL0000138
    CSI 12.81
    rCSI 20.38%
    PRS 96.44
  • lung interstitial macrophage CL4033043
    CSI 12.68
    rCSI 28.45%
    PRS 99.69
  • dendritic cell, human CL0001056
    CSI 12.07
    rCSI 18.53%
    PRS 99.39
  • macrophage CL0000235
    CSI 11.35
    rCSI 20.65%
    PRS 97.74
  • GABAergic neuron CL0000617
    CSI 11
    rCSI 36.86%
    PRS 91.57
  • monocyte CL0000576
    CSI 10.27
    rCSI 18.57%
    PRS 98.53
  • CD14-positive, CD16-negative classical monocyte CL0002057
    CSI 10.16
    rCSI 61.44%
    PRS 99.41
  • pericyte CL0000669
    CSI 9.8
    rCSI 26.09%
    PRS 84.57
  • alternatively activated macrophage CL0000890
    CSI 9.78
    rCSI 12.3%
    PRS 99.59
  • innate lymphoid cell CL0001065
    CSI 9.36
    rCSI 19.32%
    PRS 93.69
  • ependymal cell CL0000065
    CSI 9.33
    rCSI 18.93%
    PRS 90.55
  • CD1c-positive myeloid dendritic cell CL0002399
    CSI 9.03
    rCSI 10.9%
    PRS 99.24
  • plasmacytoid dendritic cell, human CL0001058
    CSI 8.53
    rCSI 5.96%
    PRS 99.08
  • intermediate monocyte CL0002393
    CSI 8.21
    rCSI 12.38%
    PRS 99.33
  • professional antigen presenting cell CL0000145
    CSI 5.61
    rCSI 19.32%
    PRS 97.1
  • neutrophil CL0000775
    CSI 5.13
    rCSI 28.69%
    PRS 96.04
  • lung macrophage CL1001603
    CSI 4.52
    rCSI 10.11%
    PRS 99.46
  • myeloid dendritic cell, human CL0001057
    CSI 4.27
    rCSI 24.05%
    PRS 99.48
  • common dendritic progenitor CL0001029
    CSI 3.76
    rCSI 4.72%
    PRS 99.33
  • promyelocyte CL0000836
    CSI 3.67
    rCSI 5.3%
    PRS 98.44
  • granulocyte CL0000094
    CSI 2.95
    rCSI 4.5%
    PRS 98.9
  • metallothionein-positive alveolar macrophage CL4033042
    CSI 2.48
    rCSI 26.93%
    PRS 99.56
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 2.43
    rCSI 2.95%
    PRS 86.51
  • tissue-resident macrophage CL0000864
    CSI 1.64
    rCSI 7.7%
    PRS 99.44
  • helper T cell CL0000912
    CSI 1.2
    rCSI 1.7%
    PRS 94.31
  • pre-conventional dendritic cell CL0002010
    CSI 0.56
    rCSI 7.37%
    PRS 99.64

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 [IGSF6](/details-gene/10261) (Immunoglobulin Superfamily Member 6) is a protein-coding gene located on chromosome 16p12.2. As its name suggests, it is a member of the immunoglobulin superfamily and functions as a transmembrane signaling receptor integral to the [plasma membrane](/details-go/GO:0005886). Gene Ontology annotations indicate its involvement in the [immune response](/details-go/GO:0006955) and [cell surface receptor signaling pathway](/details-go/GO:0007166). Expression data reveals that **Overall**, [IGSF6](/details-gene/10261) is a highly specific marker for cells of the myeloid lineage, with exceptionally high significance in [CD14-low, CD16-positive monocyte](/details-cell/CL0002396)s, as well as various populations of dendritic cells and macrophages. Research suggests it may play a regulatory role, as its expression is reportedly downregulated upon dendritic cell activation [Link](https://doi.org/10.1016/s0161-5890(98)00045-5). ## Cellular Roles and Expression Landscape The expression pattern of [IGSF6](/details-gene/10261) firmly establishes its role within the mononuclear phagocyte system. **Overall**, its most significant expression is observed in [CD14-low, CD16-positive monocyte](/details-cell/CL0002396) (CSI: 85.88), a subset of monocytes known for their "patrolling" behavior along the endothelium. The gene is also a prominent marker across multiple professional antigen-presenting cells. It shows high significance in [conventional dendritic cell](/details-cell/CL0000990)s (CSI: 38.73) and skin-resident [Langerhans cell](/details-cell/CL0000453)s (CSI: 28.75). This broad expression in dendritic cell subtypes suggests a fundamental role in the initiation of adaptive immunity. Consistent with this, early research identified this gene (also known as DORA) and demonstrated its expression is down-regulated in dendritic cells following activation by CD40L [Link](https://doi.org/10.1016/s0161-5890(98)00045-5). This finding indicates that [IGSF6](/details-gene/10261) may not simply be a lineage marker but rather a marker of a resting or immature state in these key immune sentinels. Furthermore, [IGSF6](/details-gene/10261) is significantly expressed in a variety of tissue-resident macrophage populations, including [kidney interstitial alternatively activated macrophage](/details-cell/CL1000695)s, placental [Hofbauer cell](/details-cell/CL3000001)s, [alveolar macrophage](/details-cell/CL0000583)s, and liver [Kupffer cell](/details-cell/CL0000091)s. This widespread expression across diverse macrophage types points to a conserved function in tissue homeostasis and immune surveillance. Notably, significant expression is also seen in non-immune cells of the skin, including [melanocyte of skin](/details-cell/CL1000458) and keratinocytes ([suprabasal keratinocyte](/details-cell/CL4033013) and [basal cell of epidermis](/details-cell/CL0002187)), suggesting potential functions beyond the immune system. ## Pathways and Molecular Function Functionally, [IGSF6](/details-gene/10261) is annotated as a protein with [transmembrane signaling receptor activity](/details-go/GO:0004888). Its localization to the [plasma membrane](/details-go/GO:0005886) is consistent with this role, placing it in an ideal position to mediate cell-cell communication or receive extracellular signals. The gene's involvement in the broader [immune response](/details-go/GO:0006955) biological process aligns perfectly with its observed expression profile in monocytes, macrophages, and dendritic cells. While the precise downstream signaling pathways initiated by [IGSF6](/details-gene/10261) remain to be fully elucidated, its structure as an immunoglobulin superfamily member suggests a role in cell adhesion or receptor-ligand interactions that modulate myeloid cell function. Its mapping to the inflammatory bowel disease 1 (IBD1) locus has suggested a potential clinical link [Link](https://doi.org/10.1007/s002510000259), although subsequent genetic studies did not find a direct association between common variants in the gene and IBD risk [Link](https://doi.org/10.1046/j.1365-2370.2003.00387.x). ## Research Directions The specific role of [IGSF6](/details-gene/10261) in regulating myeloid cell function presents several compelling avenues for future research. Although its genetic link to IBD is contested, its high expression in immune cells central to IBD pathogenesis warrants further investigation into its functional role in the context of chronic inflammation. Based on current data, several testable hypotheses can be proposed: 1. **Hypothesis 1:** Consistent with early findings [Link](https://doi.org/10.1016/s0161-5890(98)00045-5), [IGSF6](/details-gene/10261) acts as a negative regulator of dendritic cell activation. Its downregulation is a necessary step for dendritic cell maturation, subsequent antigen presentation, and the priming of T cell responses. 2. **Hypothesis 2:** The exceptionally high expression of [IGSF6](/details-gene/10261) in "patrolling" [CD14-low, CD16-positive monocyte](/details-cell/CL0002396)s is critical for their function, potentially mediating their interaction with the endothelium or their ability to survey for pathogens and cellular damage. To test the first hypothesis, a key experiment would be to use CRISPR-Cas9 to generate an [IGSF6](/details-gene/10261) knockout in primary human monocytes and differentiate them into dendritic cells. These knockout and wild-type dendritic cells would then be stimulated with a maturation signal like LPS. The functional consequences could be assessed by measuring the upregulation of co-stimulatory molecules (e.g., CD80, CD86) by flow cytometry, profiling cytokine secretion using ELISA, and quantifying their ability to stimulate T cell proliferation in a mixed lymphocyte reaction. Given its cell surface location and specific expression on myeloid subsets, [IGSF6](/details-gene/10261) presents a promising therapeutic target. If it functions as an inhibitory receptor, an antagonist antibody that blocks [IGSF6](/details-gene/10261) signaling could be developed to enhance dendritic cell function and boost anti-tumor immunity. Conversely, if its engagement leads to a tolerogenic or anti-inflammatory state, an agonist antibody could be explored as a treatment for autoimmune or inflammatory diseases where dampening myeloid cell activity is desirable.

Genular Protein ID: 3010263130

Symbol: IGSF6_HUMAN

Name: Immunoglobulin superfamily member 6

UniProtKB Accession Codes:

O95976 Q8WWD8

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 Ensembl 3 ExpressionAtlas 1 GO 4 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 RefSeq 1 SIGNOR 1 SMART 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: 9809579

Title: CD40L activation of dendritic cells down-regulates DORA, a novel member of the immunoglobulin superfamily.

PubMed ID: 9809579

DOI: 10.1016/s0161-5890(98)00045-5

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: 11132146

Title: The mouse and human IGSF6 (DORA) genes map to the inflammatory bowel disease 1 locus and are embedded in an intron of a gene of unknown function.

PubMed ID: 11132146

DOI: 10.1007/s002510000259

PubMed ID: 12786995

Title: Genetic variation in the IGSF6 gene and lack of association with inflammatory bowel disease.

PubMed ID: 12786995

DOI: 10.1046/j.1365-2370.2003.00387.x

Sequence Information:

  • Length: 241
  • Mass: 27013
  • Checksum: 1FA0637611138193
  • Sequence:
    • MGTASRSNIA RHLQTNLILF CVGAVGACTL SVTQPWYLEV DYTHEAVTIK CTFSATGCPS 
EQPTCLWFRY GAHQPENLCL DGCKSEADKF TVREALKENQ VSLTVNRVTS NDSAIYICGI 
AFPSVPEARA KQTGGGTTLV VREIKLLSKE LRSFLTALVS LLSVYVTGVC VAFILLSKSK 
SNPLRNKEIK EDSQKKKSAR RIFQEIAQEL YHKRHVETNQ QSEKDNNTYE NRRVLSNYER 
P