Details for: ITGAX

Gene ID: 3687

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: ITGAX

Ensembl ID: ENSG00000140678

Description: integrin subunit alpha X

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 46.93
    rCSI 36.15%
    PRS 77.1
  • elicited macrophage CL0000861
    CSI 18.39
    rCSI 16.89%
    PRS 83.32
  • myeloid leukocyte CL0000766
    CSI 16.92
    rCSI 15.61%
    PRS 76.44
  • intermediate monocyte CL0002393
    CSI 5.62
    rCSI 8.48%
    PRS 80.14
  • granulocyte CL0000094
    CSI 5.42
    rCSI 8.28%
    PRS 83.06
  • myeloid dendritic cell CL0000782
    CSI 5.31
    rCSI 7.69%
    PRS 88.18
  • non-classical monocyte CL0000875
    CSI 4.93
    rCSI 7.91%
    PRS 88.5
  • CD16-negative, CD56-bright natural killer cell, human CL0000938
    CSI 4.25
    rCSI 3.19%
    PRS 93.65
  • Kupffer cell CL0000091
    CSI 4.08
    rCSI 9.34%
    PRS 75.49
  • inflammatory macrophage CL0000863
    CSI 3.94
    rCSI 6.74%
    PRS 91.73
  • dendritic cell, human CL0001056
    CSI 3.48
    rCSI 5.35%
    PRS 83.91
  • alternatively activated macrophage CL0000890
    CSI 2.78
    rCSI 3.5%
    PRS 84.97
  • lung interstitial macrophage CL4033043
    CSI 2.68
    rCSI 6.01%
    PRS 88.3
  • group 3 innate lymphoid cell CL0001071
    CSI 2.59
    rCSI 1.95%
    PRS 80.9
  • mature B cell CL0000785
    CSI 2.55
    rCSI 2.22%
    PRS 84.75
  • conventional dendritic cell CL0000990
    CSI 2.54
    rCSI 2.12%
    PRS 78.3
  • lung macrophage CL1001603
    CSI 2.53
    rCSI 5.65%
    PRS 82.51
  • CD14-positive monocyte CL0001054
    CSI 2.47
    rCSI 3.08%
    PRS 84.57
  • promonocyte CL0000559
    CSI 2.44
    rCSI 4.19%
    PRS 82.07
  • CD14-positive, CD16-positive monocyte CL0002397
    CSI 2.42
    rCSI 3.17%
    PRS 86.57
  • neutrophil CL0000775
    CSI 2.42
    rCSI 13.52%
    PRS 77.54
  • mature microglial cell CL0002629
    CSI 2.36
    rCSI 9.82%
    PRS 75.18
  • colon macrophage CL0009038
    CSI 2.35
    rCSI 10.84%
    PRS 88.57
  • central nervous system macrophage CL0000878
    CSI 2.13
    rCSI 7.07%
    PRS 79.77
  • CD1c-positive myeloid dendritic cell CL0002399
    CSI 2.05
    rCSI 2.48%
    PRS 83.14
  • dendritic cell CL0000451
    CSI 2.04
    rCSI 2.51%
    PRS 81.52
  • mononuclear phagocyte CL0000113
    CSI 2.01
    rCSI 4.43%
    PRS 78.92
  • CD14-positive, CD16-negative classical monocyte CL0002057
    CSI 1.98
    rCSI 11.96%
    PRS 87.99
  • Langerhans cell CL0000453
    CSI 1.76
    rCSI 2.69%
    PRS 87.46
  • monocyte CL0000576
    CSI 1.57
    rCSI 2.84%
    PRS 82.45
  • basophil CL0000767
    CSI 1.28
    rCSI 2.72%
    PRS 87.6
  • kidney interstitial alternatively activated macrophage CL1000695
    CSI 1.23
    rCSI 3.19%
    PRS 75.26
  • alveolar macrophage CL0000583
    CSI 1.15
    rCSI 1.89%
    PRS 79.51
  • Hofbauer cell CL3000001
    CSI 0.94
    rCSI 1.78%
    PRS 83.84
  • myeloid dendritic cell, human CL0001057
    CSI 0.78
    rCSI 4.4%
    PRS 90.67
  • tissue-resident macrophage CL0000864
    CSI 0.76
    rCSI 3.54%
    PRS 87.09
  • decidual natural killer cell, human CL0002343
    CSI 0.56
    rCSI 5.71%
    PRS 91.17
  • metallothionein-positive alveolar macrophage CL4033042
    CSI 0.55
    rCSI 5.96%
    PRS 87.38
  • effector memory CD8-positive, alpha-beta T cell, terminally differentiated CL0001062
    CSI 0.4
    rCSI 2.01%
    PRS 86.89

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 [ITGAX](/details-gene/3687), or Integrin Subunit Alpha X, encodes the protein commonly known as CD11c. This protein is a crucial alpha subunit that dimerizes with the beta-2 subunit (ITGB2) to form the integrin complex leukocyte-specific p150,95, also referred to as complement receptor 4 (CR4). As a cell surface adhesion molecule, [ITGAX](/details-gene/3687) plays a fundamental role in mediating cell-cell and cell-extracellular matrix interactions, which are critical for immune cell trafficking, localization, and effector functions. Its expression is highly specific to the hematopoietic system, with particularly high significance in cells of the myeloid lineage, including monocytes, macrophages, and dendritic cells, where it functions in phagocytosis, cellular activation, and antigen presentation. A clinical association has been noted for this gene ([151510](https://omim.org/entry/151510)). ## Cellular Roles and Expression Landscape The expression profile of [ITGAX](/details-gene/3687) unequivocally establishes it as a key marker for the myeloid compartment of the innate immune system. **Overall**, the gene exhibits its highest significance in phagocytic and antigen-presenting cells. It is an exceptionally strong marker for [CD14-low, CD16-positive monocytes](/details-cell/CL0002396) (CSI: 46.93), a subset involved in inflammatory responses. High significance is also observed across a spectrum of related cell types, including [elicited macrophages](/details-cell/CL0000861), general [myeloid leukocytes](/details-cell/CL0000766), [intermediate monocytes](/details-cell/CL0002393), and [myeloid dendritic cells](/details-cell/CL0000782). This pattern highlights its central role in the life cycle and function of professional phagocytes. The high significance in various macrophage populations, such as [Kupffer cells](/details-cell/CL0000091), [inflammatory macrophages](/details-cell/CL0000863), and [alternatively activated macrophages](/details-cell/CL0000890), suggests a conserved function in tissue-resident and recruited macrophages. While its primary role is in the myeloid lineage, its notable significance in certain lymphoid populations, including [group 3 innate lymphoid cells](/details-cell/CL0001071) and [mature B cells](/details-cell/CL0000785), indicates a broader, albeit more modest, role in the wider immune system. The specific expression within these immune cell types underscores its specialized function in host defense. ## Pathways and Molecular Function The molecular functions of [ITGAX](/details-gene/3687) are tightly linked to its role as a cell surface receptor in the immune system. Its participation in the [Integrin complex](https://www.ebi.ac.uk/QuickGO/term/GO:0008305), specifically the [Integrin alphax-beta2 complex](https://www.ebi.ac.uk/QuickGO/term/GO:0034689), is central to its function. This is reflected in its involvement in biological processes such as [Cell adhesion](https://www.ebi.ac.uk/QuickGO/term/GO:0007155) and the [Integrin-mediated signaling pathway](https://www.ebi.ac.uk/QuickGO/term/GO:0007229). These functions are critical for immune cell trafficking and positioning, as detailed in the [Integrin cell surface interactions](https://reactome.org/content/detail/R-HSA-216083) and [Cell surface interactions at the vascular wall](https://reactome.org/content/detail/R-HSA-202733) pathways. Consistent with its high expression in myeloid cells, [ITGAX](/details-gene/3687) is a key player in the [Innate immune system](https://reactome.org/content/detail/R-HSA-168249). Its function as a complement receptor facilitates the clearance of pathogens and cellular debris, a role supported by its involvement in the [Defense response to virus](https://www.ebi.ac.uk/QuickGO/term/GO:0051607). Furthermore, its expression on [granulocytes](/details-cell/CL0000094) aligns with its role in [Neutrophil degranulation](https://reactome.org/content/detail/R-HSA-6798695). The gene's connection to broader immune signaling is evident through its participation in [Cytokine signaling in immune system](https://reactome.org/content/detail/R-HSA-1280215), suggesting that it not only mediates physical adhesion but also contributes to the complex communication network that governs immune responses. ## Research Directions Given the established role of [ITGAX](/details-gene/3687) (CD11c) as a canonical marker for dendritic cells and its broad expression across macrophage subtypes, future research should focus on dissecting its context-specific signaling functions beyond simple adhesion. ### Proposed Hypotheses: 1. **ITGAX signaling differentially regulates macrophage polarization.** The high significance of [ITGAX](/details-gene/3687) across functionally distinct macrophage subsets ([inflammatory](/details-cell/CL0000863) vs. [alternatively activated](/details-cell/CL0000890)) suggests that ligation of the ITGAX/ITGB2 receptor by different extracellular matrix or soluble ligands may actively drive macrophage polarization toward either pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes. 2. **ITGAX is a primary receptor for non-opsonized pathogen recognition.** While its role as a complement receptor is well-known, its high expression on [myeloid dendritic cells](/details-cell/CL0000782) suggests it may also function as a pattern recognition receptor (PRR) that directly binds to conserved microbial structures, such as fungal beta-glucans or specific viral glycoproteins, initiating downstream signaling for antigen presentation independent of the complement system. ### Suggested Experimental Approach: To test the second hypothesis regarding its role as a direct pathogen receptor, a series of binding and functional assays could be conducted. Primary human [myeloid dendritic cells](/details-cell/CL0000782) could be isolated and incubated with a panel of fluorescently labeled, non-opsonized pathogens (e.g., *Candida albicans*, influenza virus). The binding specificity could be confirmed by pre-incubating the cells with a blocking antibody against [ITGAX](/details-gene/3687) (CD11c) and quantifying the reduction in pathogen binding via flow cytometry. To assess functional consequences, [ITGAX](/details-gene/3687)-knockout dendritic cells (via CRISPR-Cas9) could be challenged with these pathogens, followed by measurement of phagocytosis rates, pro-inflammatory cytokine production (e.g., IL-12, TNF-alpha) by ELISA, and the capacity to stimulate antigen-specific T-cell proliferation in a co-culture system. ### Therapeutic Potential: As a highly specific cell surface protein on myeloid antigen-presenting cells, [ITGAX](/details-gene/3687) represents an excellent target for therapeutic intervention. Its specificity allows for the targeted delivery of payloads to dendritic cells and macrophages. For cancer immunotherapy or vaccines, antibodies against [ITGAX](/details-gene/3687) could be conjugated to antigens or adjuvants to enhance their uptake and presentation, thereby boosting adaptive immune responses. Conversely, in autoimmune diseases like lupus or multiple sclerosis, where dendritic cells are implicated in pathology, targeting [ITGAX](/details-gene/3687) with depleting antibodies or immunomodulatory drugs could selectively suppress the pathogenic immune response while minimizing systemic side effects. This makes it a versatile target for therapies requiring either immune activation or inhibition.

Genular Protein ID: 376676123

Symbol: ITAX_HUMAN

Name: Integrin alpha-X

UniProtKB Accession Codes:

P20702 Q8IVA6

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BMRB 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CPTC 1 CTD 1 ChEBI 15 ChiTaRS 1 ComplexPortal 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 1 EMBL 9 Ensembl 1 EvolutionaryTrace 1 ExpressionAtlas 1 GO 27 Gene3D 5 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyConnect 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 11 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 8 PDBsum 8 PIR 1 PRINTS 2 PRO 1 PROSITE 3 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 6 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 5 RefSeq 2 SIGNOR 1 SMART 2 SMR 1 STRING 1 SUPFAM 3 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 3327687

Title: cDNA cloning and complete primary structure of the alpha subunit of a leukocyte adhesion glycoprotein, p150,95.

PubMed ID: 3327687

DOI: 10.1002/j.1460-2075.1987.tb02746.x

PubMed ID: 2303426

Title: Genomic structure of an integrin alpha subunit, the leukocyte p150,95 molecule.

PubMed ID: 2303426

DOI: 10.1016/s0021-9258(19)39870-9

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: 3549901

Title: Purification and alpha subunit N-terminal sequences of human Mac-1 and p150,95 leukocyte adhesion proteins.

PubMed ID: 3549901

PubMed ID: 19159218

Title: Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry.

PubMed ID: 19159218

DOI: 10.1021/pr8008012

PubMed ID: 20033057

Title: Structure of an integrin with an alphaI domain, complement receptor type 4.

PubMed ID: 20033057

DOI: 10.1038/emboj.2009.367

PubMed ID: 22844534

Title: Structure and binding interface of the cytosolic tails of alphaXbeta2 integrin.

PubMed ID: 22844534

DOI: 10.1371/journal.pone.0041924

PubMed ID: 21763482

Title: VPS35 mutations in Parkinson disease.

PubMed ID: 21763482

DOI: 10.1016/j.ajhg.2011.06.001

Sequence Information:

  • Length: 1163
  • Mass: 127829
  • Checksum: 8947288C43E76BE2
  • Sequence:
    • MTRTRAALLL FTALATSLGF NLDTEELTAF RVDSAGFGDS VVQYANSWVV VGAPQKITAA 
NQTGGLYQCG YSTGACEPIG LQVPPEAVNM SLGLSLASTT SPSQLLACGP TVHHECGRNM 
YLTGLCFLLG PTQLTQRLPV SRQECPRQEQ DIVFLIDGSG SISSRNFATM MNFVRAVISQ 
FQRPSTQFSL MQFSNKFQTH FTFEEFRRSS NPLSLLASVH QLQGFTYTAT AIQNVVHRLF 
HASYGARRDA AKILIVITDG KKEGDSLDYK DVIPMADAAG IIRYAIGVGL AFQNRNSWKE 
LNDIASKPSQ EHIFKVEDFD ALKDIQNQLK EKIFAIEGTE TTSSSSFELE MAQEGFSAVF 
TPDGPVLGAV GSFTWSGGAF LYPPNMSPTF INMSQENVDM RDSYLGYSTE LALWKGVQSL 
VLGAPRYQHT GKAVIFTQVS RQWRMKAEVT GTQIGSYFGA SLCSVDVDSD GSTDLVLIGA 
PHYYEQTRGG QVSVCPLPRG WRRWWCDAVL YGEQGHPWGR FGAALTVLGD VNGDKLTDVV 
IGAPGEEENR GAVYLFHGVL GPSISPSHSQ RIAGSQLSSR LQYFGQALSG GQDLTQDGLV 
DLAVGARGQV LLLRTRPVLW VGVSMQFIPA EIPRSAFECR EQVVSEQTLV QSNICLYIDK 
RSKNLLGSRD LQSSVTLDLA LDPGRLSPRA TFQETKNRSL SRVRVLGLKA HCENFNLLLP 
SCVEDSVTPI TLRLNFTLVG KPLLAFRNLR PMLAADAQRY FTASLPFEKN CGADHICQDN 
LGISFSFPGL KSLLVGSNLE LNAEVMVWND GEDSYGTTIT FSHPAGLSYR YVAEGQKQGQ 
LRSLHLTCDS APVGSQGTWS TSCRINHLIF RGGAQITFLA TFDVSPKAVL GDRLLLTANV 
SSENNTPRTS KTTFQLELPV KYAVYTVVSS HEQFTKYLNF SESEEKESHV AMHRYQVNNL 
GQRDLPVSIN FWVPVELNQE AVWMDVEVSH PQNPSLRCSS EKIAPPASDF LAHIQKNPVL 
DCSIAGCLRF RCDVPSFSVQ EELDFTLKGN LSFGWVRQIL QKKVSVVSVA EITFDTSVYS 
QLPGQEAFMR AQTTTVLEKY KVHNPTPLIV GSSIGGLLLL ALITAVLYKV GFFKRQYKEM 
MEEANGQIAP ENGTQTPSPP SEK

Genular Protein ID: 2292553503

Symbol: H3BN02_HUMAN

Name: N/A

UniProtKB Accession Codes:

H3BN02

Database IDs:

ARBA 15 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 CDD 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 1 Ensembl 2 ExpressionAtlas 1 GO 4 Gene3D 5 GeneTree 1 HGNC 1 InterPro 11 MassIVE 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PRINTS 2 PROSITE 4 PROSITE-ProRule 1 PeptideAtlas 2 Pfam 6 PhylomeDB 1 Proteomes 2 ProteomicsDB 2 RefSeq 1 RuleBase 1 SAM 1 SMART 2 SMR 1 SUPFAM 3 UCSC 1 VEuPathDB 1

Citations:

PubMed ID: 11237011

Title: Initial sequencing and analysis of the human genome.

PubMed ID: 11237011

DOI: 10.1038/35057062

PubMed ID: 15496913

Title: Finishing the euchromatic sequence of the human genome.

PubMed ID: 15496913

DOI: 10.1038/nature03001

PubMed ID: 15616553

Title: The sequence and analysis of duplication-rich human chromosome 16.

PubMed ID: 15616553

DOI: 10.1038/nature03187

Sequence Information:

  • Length: 1169
  • Mass: 128537
  • Checksum: 0E4C64E082AADB8B
  • Sequence:
    • MTRTRAALLL FTALATSLGF NLDTEELTAF RVDSAGFGDS VVQYANSWVV VGAPQKITAA 
NQTGGLYQCG YSTGACEPIG LQVPPEAVNM SLGLSLASTT SPSQLLACGP TVHHECGRNM 
YLTGLCFLLG PTQLTQRLPV SRQECPRQEQ DIVFLIDGSG SISSRNFATM MNFVRAVISQ 
FQRPSTQFSL MQFSNKFQTH FTFEEFRRSS NPLSLLASVH QLQGFTYTAT AIQNVVHRLF 
HASYGARRDA AKILIVITDG KKEGDSLDYK DVIPMADAAG IIRYAIGVGL AFQNRNSWKE 
LNDIASKPSQ EHIFKVEDFD ALKDIQNQLK EKIFAIEGTE TTSSSSFELE MAQEGFSAVF 
TPDGPVLGAV GSFTWSGGAF LYPPNMSPTF INMSQENVDM RDSYLGYSTE LALWKGVQSL 
VLGAPRYQHT GKAVIFTQVS RQWRMKAEVT GTQIGSYFGA SLCSVDVDSD GSTDLVLIGA 
PHYYEQTRGG QVSVCPLPRG WRRWWCDAVL YGEQGHPWGR FGAALTVLGD VNGDKLTDVV 
IGAPGEEENR GAVYLFHGVL GPSISPSHSQ RIAGSQLSSR LQYFGQALSG GQDLTQDGLV 
DLAVGARGQV LLLRTRPVLW VGVSMQFIPA EIPRSAFECR EQVVSEQTLV QSNICLYIDK 
RSKNLLGSRD LQSSVTLDLA LDPGRLSPRA TFQETKNRSL SRVRVLGLKA HCENFNLLLP 
SCVEDSVTPI TLRLNFTLVG KPLLAFRNLR PMLAADAQRY FTASLPFEKN CGADHICQDN 
LGISFSFPGL KSLLVGSNLE LNAEVMVWND GEDSYGTTIT FSHPAGLSYR YVAEGQKQGQ 
LRSLHLTCDS APVGSQGTWS TSCRINHLIF RGGAQITFLA TFDVSPKAVL GDRLLLTANV 
SSENNTPRTS KTTFQLELPV KYAVYTVVSS HEQFTKYLNF SESEEKESHV AMHRYQVNNL 
GQRDLPVSIN FWVPVELNQE AVWMDVEVSH PQNPSLRCSS EKIAPPASDF LAHIQKNPVL 
DCSIAGCLRF RCDVPSFSVQ EELDFTLKGN LSFGWVRQIL QKKVSVVSVA EITFDTSVYS 
QLPGQEAFMR AQTTTVLEKY KVHNPTPLIV GSSIGGLLLL ALITAVLYKV GFFKRQYKEM 
MEEANGQIAP ENGTQTPSPP TPHYPQDNV