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    ICAM4 intercellular adhesion molecule 4 (Landsteiner-Wiener blood group) [ Homo sapiens (human) ]

    Gene ID: 3386, updated on 10-Dec-2024

    Summary

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    Official Symbol
    ICAM4provided by HGNC
    Official Full Name
    intercellular adhesion molecule 4 (Landsteiner-Wiener blood group)provided by HGNC
    Primary source
    HGNC:HGNC:5347
    See related
    Ensembl:ENSG00000105371 MIM:614088; AllianceGenome:HGNC:5347
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    LW; CD242
    Summary
    This gene encodes the Landsteiner-Wiener (LW) blood group antigen(s) that belongs to the immunoglobulin (Ig) superfamily, and that shares similarity with the intercellular adhesion molecule (ICAM) protein family. This ICAM protein contains 2 Ig-like C2-type domains and binds to the leukocyte adhesion LFA-1 protein. The molecular basis of the LW(A)/LW(B) blood group antigens is a single aa variation at position 100; Gln-100=LW(A) and Arg-100=LW(B). Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]
    Expression
    Biased expression in lung (RPKM 3.3), bone marrow (RPKM 3.1) and 13 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See ICAM4 in Genome Data Viewer
    Location:
    19p13.2
    Exon count:
    3
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (10286955..10288520)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (10413067..10414632)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (10397631..10399196)

    Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene H3K27ac hESC enhancers GRCh37_chr19:10362245-10362818 and GRCh37_chr19:10362819-10363392 Neighboring gene mitochondrial ribosomal protein L4 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13951 Neighboring gene lncRNA inflammatory and mucous response associated, antisense to ICAM1 Neighboring gene Sharpr-MPRA regulatory region 14536 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13952 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13953 Neighboring gene intercellular adhesion molecule 1 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:10397303-10398272 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13954 Neighboring gene ICAM4 antisense RNA 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10061 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10062 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:10402483-10403475 Neighboring gene intercellular adhesion molecule 5 Neighboring gene CRISPRi-validated cis-regulatory element chr19.1775 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr19:10415538-10416737 Neighboring gene FDX2-ZGLP1 readthrough Neighboring gene zinc finger GATA like protein 1

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Red cell ICAM-4 is a novel ligand for platelet-activated alpha IIbbeta 3 integrin. Hermand P, et al. J Biol Chem, 2003 Feb 14. PMID 12477717
    2. Identification of critical amino-acid residues on the erythroid intercellular adhesion molecule-4 (ICAM-4) mediating adhesion to alpha V integrins. Mankelow TJ, et al. Blood, 2004 Feb 15. PMID 14551135
    3. Linkage of the LW blood group locus with the complement C3 and Lutheran blood group loci. Sistonen P. Ann Hum Genet, 1984 Jul. PMID 6431896
    4. Molecular basis and expression of the LWa/LWb blood group polymorphism. Hermand P, et al. Blood, 1995 Aug 15. PMID 7632968
    5. The LW blood group glycoprotein is homologous to intercellular adhesion molecules. Bailly P, et al. Proc Natl Acad Sci U S A, 1994 Jun 7. PMID 8202485, Free PMC Article

    See all (54) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. DNA methylation of ICAM4 and NOXO1 participate in the formation of uterine fibroids via regulating immune cell infiltration.
      Title: DNA methylation of ICAM4 and NOXO1 participate in the formation of uterine fibroids via regulating immune cell infiltration.
    2. Immunological Study of IFN-gamma, ICAM-4, and Vitamin D3 Markers among Gastrointestinal Tumor Patients in Babylon Province, Iraq.
      Title: Immunological Study of IFN-γ, ICAM-4, and Vitamin D3 Markers among Gastrointestinal Tumor Patients in Babylon Province, Iraq.
    3. the effect of modulation of the cAMP-PKA-dependent pathway on ICAM-4 receptor activation
      Title: Regulation of Active ICAM-4 on Normal and Sickle Cell Disease RBCs via AKAPs Is Revealed by AFM.
    4. Cytometry analysis evidenced a specific expression profile on reticulocytes of SCA infants, with notably an increased expression of the adhesion molecules Lu/BCAM, ICAM-4 and LFA-3, both in percentage of positive cells and in surface density.
      Title: Erythroid Adhesion Molecules in Sickle Cell Anaemia Infants: Insights Into Early Pathophysiology.
    5. ICAM-1 and ICAM-4 play roles in host cell invasion by M. tuberculosis and P. falciparum, respectively.
      Title: Host ICAMs play a role in cell invasion by Mycobacterium tuberculosis and Plasmodium falciparum.
    6. Seven variant ICAM4 alleles were found, distinct from the wild-type ICAM4 allele (GenBank KF712272), known as LW*05 and encoding LW(a) .
      Title: Genetic variation of the whole ICAM4 gene in Caucasians and African Americans.
    7. Data from differentiating cultured erythroid precursor cells suggest that RhAG (Rh-associated glycoprotein) knockdown abolishes Rh blood group expression (ICAM4; RhoD [ras homolog family member D]; CD47 Rh-related antigen) in erythroid cells.
      Title: In vitro generated Rh(null) red cells recapitulate the in vivo deficiency: a model for rare blood group phenotypes and erythroid membrane disorders.
    8. Erythrocyte plasma membrane-bound ERK1/2 activation promotes ICAM-4-mediated sickle red cell adhesion to endothelium.
      Title: Erythrocyte plasma membrane-bound ERK1/2 activation promotes ICAM-4-mediated sickle red cell adhesion to endothelium.
    9. In a transgenic mouse model of sickle cell disease ICAM-4 is implicated in abnormal adhesiveness of erythrocytes to endothelium.
      Title: Intercellular adhesion molecule-4 and CD36 are implicated in the abnormal adhesiveness of sickle cell SAD mouse erythrocytes to endothelium.
    10. Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
      Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
    Submit: New GeneRIF Correction See all GeneRIFs (22)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Landsteiner-Wiener phenotype
    MedGen: C3887952 OMIM: 111250 GeneReviews: Not available
    		not available

    EBI GWAS Catalog

    Description
    Genome-wide association analysis of soluble ICAM-1 concentration reveals novel associations at the NFKBIK, PNPLA3, RELA, and SH2B3 loci.
    EBI GWAS Catalog
    Large-scale genomic studies reveal central role of ABO in sP-selectin and sICAM-1 levels.
    EBI GWAS Catalog
    Novel association of ABO histo-blood group antigen with soluble ICAM-1: results of a genome-wide association study of 6,578 women.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    HIV-1 interactions

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    Replication interactions

    Interaction Pubs
    Knockdown of intercellular adhesion molecule 4 (ICAM4) by siRNA enhances the early stages of HIV-1 replication in HeLa-CD4 cells infected with viral pseudotypes HIV89.6R and HIV8.2N PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables integrin binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in cell adhesion IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in cell-cell adhesion IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in extracellular region IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in membrane TAS
    Traceable Author Statement
    more info
    		 PubMed 
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    intercellular adhesion molecule 4
    Names
    CD242 antigen
    LW antigen a
    Landsteiner-Wiener blood group antigen a
    Landsteiner-Wiener blood group glycoprotein
    bloodgroup LW protein
    intercellular adhesion molecule 4 (LW blood group)

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_007728.1 RefSeqGene

      Range
      4982..6547
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_809

    mRNA and Protein(s)

    1. NM_001039132.3 → NP_001034221.1  intercellular adhesion molecule 4 isoform 3 precursor

      See identical proteins and their annotated locations for NP_001034221.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) uses an alternate splice site, which results in a frameshift compared to variant 1. The encoded isoform (3) has the same N-terminus but a distinct C-terminus compared to isoform 1.
      Source sequence(s)
      AC011511, BC000046, BC029364, BX114065
      Consensus CDS
      CCDS32904.1
      UniProtKB/TrEMBL
      U5U3F7, U5U6J5, U5U6J9, U5U6P3, U5U6P8
      Related
      ENSP00000342114.3, ENST00000340992.4
      Conserved Domains (1) summary
      pfam03921
      Location:48 → 131
      ICAM_N; Intercellular adhesion molecule (ICAM), N-terminal domain

    2. NM_001544.5 → NP_001535.1  intercellular adhesion molecule 4 isoform 1 precursor

      See identical proteins and their annotated locations for NP_001535.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes isoform 1.
      Source sequence(s)
      AC011511, BC029364, BX114065
      Consensus CDS
      CCDS12232.1
      UniProtKB/Swiss-Prot
      A0M8X2, Q14771, Q14772, Q14773, Q16375, Q9BWR0
      Related
      ENSP00000370147.2, ENST00000380770.5
      Conserved Domains (2) summary
      pfam03921
      Location:48 → 131
      ICAM_N; Intercellular adhesion molecule (ICAM), N-terminal domain
      cl11960
      Location:132 → 217
      Ig; Immunoglobulin domain

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000019.10 Reference GRCh38.p14 Primary Assembly

      Range
      10286955..10288520
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060943.1 Alternate T2T-CHM13v2.0

      Range
      10413067..10414632
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_022377.3: Suppressed sequence

      Description
      NM_022377.3: This RefSeq was removed because currently there is insufficient support for the transcript and the protein.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q14773.1 GenPept UniProtKB/Swiss-Prot:Q14773

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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