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    KIR2DS4 killer cell immunoglobulin like receptor, two Ig domains and short cytoplasmic tail 4 (gene/pseudogene) [ Homo sapiens (human) ]

    Gene ID: 3809, updated on 28-Oct-2024

    Summary

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    Official Symbol
    KIR2DS4provided by HGNC
    Official Full Name
    killer cell immunoglobulin like receptor, two Ig domains and short cytoplasmic tail 4 (gene/pseudogene)provided by HGNC
    Primary source
    HGNC:HGNC:6336
    See related
    Ensembl:ENSG00000221957 MIM:604955; AllianceGenome:HGNC:6336
    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
    KKA3; KIR1D; NKAT8; CD158I; KIR412; NKAT-8; KIR-2DS4
    Summary
    Killer cell immunoglobulin-like receptors (KIRs) are transmembrane glycoproteins expressed by natural killer cells and subsets of T cells. The KIR genes are polymorphic and highly homologous and they are found in a cluster on chromosome 19q13.4 within the 1 Mb leukocyte receptor complex (LRC). The gene content of the KIR gene cluster varies among haplotypes, although several "framework" genes are found in all haplotypes (KIR3DL3, KIR3DP1, KIR3DL4, KIR3DL2). The KIR proteins are classified by the number of extracellular immunoglobulin domains (2D or 3D) and by whether they have a long (L) or short (S) cytoplasmic domain. KIR proteins with the long cytoplasmic domain transduce inhibitory signals upon ligand binding via an immune tyrosine-based inhibitory motif (ITIM), while KIR proteins with the short cytoplasmic domain lack the ITIM motif and instead associate with the TYRO protein tyrosine kinase binding protein to transduce activating signals. The ligands for several KIR proteins are subsets of HLA class I molecules; thus, KIR proteins are thought to play an important role in regulation of the immune response. [provided by RefSeq, Jul 2008]
    Expression
    Low expression observed in reference dataset See more
    Orthologs
    all
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    Genomic context

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    See KIR2DS4 in Genome Data Viewer
    Location:
    19q13.42
    Exon count:
    8
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (54832707..54848575)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (57927015..57942905)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (55344162..55360030)

    Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene killer cell immunoglobulin like receptor, two Ig domains and long cytoplasmic tail 4 Neighboring gene killer cell immunoglobulin like receptor, three Ig domains and long cytoplasmic tail 1 Neighboring gene killer cell immunoglobulin like receptor, three Ig domains and long cytoplasmic tail 2 Neighboring gene RNA, U6 small nuclear 222, pseudogene

    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 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. Killer cell immunoglobulin-like receptor gene's repertoire in rheumatoid arthritis. Yen JH, et al. Scand J Rheumatol, 2006 Mar-Apr. PMID 16641046
    2. The early onset of type 1 autoimmune hepatitis has a strong genetic influence: role of HLA and KIR genes. Podhorzer A, et al. Genes Immun, 2016 Apr. PMID 26890333
    3. KIR2DS4 and Its Variant KIR1D Are Associated with Acute Graft-versus-Host Disease, Cytomegalovirus, and Overall Survival after Sibling-Related HLA-Matched Transplantation in Patients with Donors with KIR Gene Haplotype A. Wu X, et al. Biol Blood Marrow Transplant, 2016 Feb. PMID 26476204
    4. The number of activating KIR genes inversely correlates with the rate of CMV infection/reactivation in kidney transplant recipients. Stern M, et al. Am J Transplant, 2008 Jun. PMID 18444913
    5. Presence of the full-length KIR2DS4 gene reduces the chance of rheumatoid arthritis patients to respond to methotrexate treatment. Majorczyk E, et al. BMC Musculoskelet Disord, 2014 Jul 28. PMID 25069714, Free PMC Article

    See all (140) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Evaluation of the genetic diversity of KIR genes in patients with endometrial cancer.
      Title: Evaluation of the genetic diversity of KIR genes in patients with endometrial cancer.
    2. KIR2DS4 and Its Variant KIR1D in KIR-AA Genotype Donors Showed Differential Survival Impact in Patients with Lymphoid Disease after HLA-Matched Unrelated Hematopoietic Stem Cell Transplantation.
      Title: KIR2DS4 and Its Variant KIR1D in KIR-AA Genotype Donors Showed Differential Survival Impact in Patients with Lymphoid Disease after HLA-Matched Unrelated Hematopoietic Stem Cell Transplantation.
    3. Association of KIR gene polymorphisms with COVID-19 disease.
      Title: Association of KIR gene polymorphisms with COVID-19 disease.
    4. The impact of donor full-length KIR2DS4 in the development of acute and chronic GVHD after unrelated allogeneic HSCT.
      Title: The impact of donor full-length KIR2DS4 in the development of acute and chronic GVHD after unrelated allogeneic HSCT.
    5. Positive association of Bx genotype, KIR2L5, KIR2DS5 and full-length KIR2DS4 with the risk of meningioma.
      Title: Positive association of Bx genotype, KIR2L5, KIR2DS5 and full-length KIR2DS4 with the risk of meningioma.
    6. Natural killer cell receptor variants and chronic hepatitis B virus infection in the Vietnamese population.
      Title: Natural killer cell receptor variants and chronic hepatitis B virus infection in the Vietnamese population.
    7. In head and neck squamous cell carcinoma (HNSCC), KIR2DL2 is positively while KIR2DS4 is negatively associated with advanced stage. The higher proportion of LNM in carriers of KIR2DL2 and carriers of 5 iKIRs, suggested that inhibitory KIRs are associated with metastatic risk
      Title: KIR2DS4, KIR2DL2, and KIR2DS4del are linked with basaloid tumors, lymph node metastasis, advanced stage and metastatic risk in head and neck squamous cell carcinoma.
    8. KIR2DS4 has a strong preference for rare peptides carrying a Trp at position 8 (p8) of 9-mer peptides bound to HLA-C*05:01. The complex of a peptide bound to HLA-C*05:01 with a Trp at p8 was sufficient for activation of primary KIR2DS4+ NK cells, independent of activation by other receptors and of prior NK cell licensing. Study predicts that over 1,000 bacterial species could activate NK cells through KIR2DS4.
      Title: Human NK cell receptor KIR2DS4 detects a conserved bacterial epitope presented by HLA-C.
    9. The higher frequencies of KIR3DS1-Bw4 and homozygotic KIR2DS4- in patients compared with controls suggest they confer susceptibility to polycystic ovary syndrome. A lower frequency of KIR2DS4-full was observed in patients.
      Title: Killer-cell immunoglobulin-like receptors associated with polycystic ovary syndrome.
    10. Promoter methylation decreased and gene expression increased for KIR2DS4 after acute exercise. Chronic exercise resulted in a minor decrease of DNA methylation and did not alter gene expression.
      Title: Acute Exercise Increases the Expression of KIR2DS4 by Promoter Demethylation in NK Cells.
    Submit: New GeneRIF Correction See all GeneRIFs (47)

    Phenotypes

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    Review eQTL and phenotype association data in this region using PheGenI

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    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

    Clone Names

    • MGC120019, MGC125315, MGC125317

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables MHC class Ib protein binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in immune response-regulating signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    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
    killer cell immunoglobulin-like receptor 2DS4
    Names
    CD158 antigen-like family member I
    KIR antigen 2DS4
    P58 natural killer cell receptor clones CL-39/CL-17
    killer cell immunoglobulin-like receptor, two domains, short cytoplasmic tail, 4
    killer inhibitory receptor 4-1-2
    natural killer-associated transcript 8
    p50 killer cell activating receptor KAR-K1d
    p58 NK receptor CL-39/CL-17

    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.

    mRNA and Protein(s)

    1. NM_001281971.2 → NP_001268900.1  killer cell immunoglobulin-like receptor 2DS4 isoform 2 precursor

      See identical proteins and their annotated locations for NP_001268900.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) represents the 22nt deletion allele KIR2DS4*003 which results in a frameshift and loss of the C-terminal membrane binding domain. The resulting protein (isoform 2) has a distinct C-teminus and is likely secreted.
      Source sequence(s)
      AC245128
      UniProtKB/TrEMBL
      A0A0C4ZN11, A0A0C4ZN30
      Related
      ENSP00000340011.8, ENST00000339924.12
      Conserved Domains (3) summary
      cl28612
      Location:96 → 236
      PHA03128; dUTPase; Provisional
      cd00096
      Location:29 → 33
      Ig; Ig strand A [structural motif]
      cl11960
      Location:28 → 122
      Ig; Immunoglobulin domain

    2. NM_001281972.2 → NP_001268901.1  killer cell immunoglobulin-like receptor 2DS4 isoform 3 precursor

      See identical proteins and their annotated locations for NP_001268901.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) represents a 22nt deletion allele which also lacks a coding exon. The resulting protein (isoform 3) is frameshifted and lacks the C-terminal membrane binding domain found in the functional allele (KRI2DS4*001).
      Source sequence(s)
      AC245128
      UniProtKB/TrEMBL
      A0A1W2PR63, A0A5F9ZHK4, Q86VI6
      Related
      ENSP00000375609.1, ENST00000391729.1
      Conserved Domains (2) summary
      cd05711
      Location:28 → 122
      Ig_FcalphaRI; Immunoglobulin (IG)-like domain of of FcalphaRI
      cl11960
      Location:128 → 151
      Ig; Immunoglobulin domain

    3. NM_012314.6 → NP_036446.3  killer cell immunoglobulin-like receptor 2DS4 isoform 1 precursor

      See identical proteins and their annotated locations for NP_036446.3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the functional allele (KIR2DS4*001) and encodes a functional, membrane-bound, activating receptor (isoform 1).
      Source sequence(s)
      GU182342
      UniProtKB/Swiss-Prot
      P43632, Q6H2G7
      UniProtKB/TrEMBL
      A0A0C4ZN05, A0A0C5CF12, A0A5J6VNI0, A0A7D5BS96, Q4KN55
      Conserved Domains (3) summary
      cd00096
      Location:129 → 133
      Ig; Ig strand A [structural motif]
      cd05711
      Location:28 → 122
      IgC2_D2_LILR_KIR_like; Second immunoglobulin (Ig)-like domain found in Leukocyte Ig-like receptors, Natural killer inhibitory receptors (KIRs) and similar domains; member of Immunoglobulin Constant-2 set of IgSF domains
      cl11960
      Location:128 → 216
      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
      54832707..54848575
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 PATCHES

    Genomic

    1. NW_016107300.1 Reference GRCh38.p14 PATCHES

      Range
      134363..150018
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      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 PATCHES

    Genomic

    1. NW_016107301.1 Reference GRCh38.p14 PATCHES

      Range
      134350..150218
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 PATCHES

    Genomic

    1. NW_016107302.1 Reference GRCh38.p14 PATCHES

      Range
      134345..150212
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 PATCHES

    Genomic

    1. NW_016107305.1 Reference GRCh38.p14 PATCHES

      Range
      134336..150226
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      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 PATCHES

    Genomic

    1. NW_016107306.1 Reference GRCh38.p14 PATCHES

      Range
      134160..149171
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 PATCHES

    Genomic

    1. NW_016107307.1 Reference GRCh38.p14 PATCHES

      Range
      134307..150174
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      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 PATCHES

    Genomic

    1. NW_016107309.1 Reference GRCh38.p14 PATCHES

      Range
      134345..150212
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 PATCHES

    Genomic

    1. NW_016107313.1 Reference GRCh38.p14 PATCHES

      Range
      134312..150202
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      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 PATCHES

    Genomic

    1. NW_016107314.1 Reference GRCh38.p14 PATCHES

      Range
      120697..136565
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      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 ALT_REF_LOCI_3

    Genomic

    1. NW_003571056.2 Reference GRCh38.p14 ALT_REF_LOCI_3

      Range
      812586..828454
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      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 ALT_REF_LOCI_5

    Genomic

    1. NW_003571058.2 Reference GRCh38.p14 ALT_REF_LOCI_5

      Range
      819633..830497
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      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 ALT_REF_LOCI_7

    Genomic

    1. NW_003571060.1 Reference GRCh38.p14 ALT_REF_LOCI_7

      Range
      737076..752966
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 ALT_REF_LOCI_9

    Genomic

    1. NT_187693.1 Reference GRCh38.p14 ALT_REF_LOCI_9

      Range
      815276..831144
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 ALT_REF_LOCI_11

    Genomic

    1. NT_187637.1 Reference GRCh38.p14 ALT_REF_LOCI_11

      Range
      20234..36101 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 ALT_REF_LOCI_12

    Genomic

    1. NT_187638.1 Reference GRCh38.p14 ALT_REF_LOCI_12

      Range
      20630..36302 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 ALT_REF_LOCI_13

    Genomic

    1. NT_187639.1 Reference GRCh38.p14 ALT_REF_LOCI_13

      Range
      20776..36666 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 ALT_REF_LOCI_14

    Genomic

    1. NT_187640.1 Reference GRCh38.p14 ALT_REF_LOCI_14

      Range
      10257..25493 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 ALT_REF_LOCI_16

    Genomic

    1. NT_187642.1 Reference GRCh38.p14 ALT_REF_LOCI_16

      Range
      20341..34795 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 ALT_REF_LOCI_17

    Genomic

    1. NT_187643.1 Reference GRCh38.p14 ALT_REF_LOCI_17

      Range
      20467..36357 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 ALT_REF_LOCI_19

    Genomic

    1. NT_187645.1 Reference GRCh38.p14 ALT_REF_LOCI_19

      Range
      20481..36372 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 ALT_REF_LOCI_20

    Genomic

    1. NT_187668.1 Reference GRCh38.p14 ALT_REF_LOCI_20

      Range
      10396..26263 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 ALT_REF_LOCI_21

    Genomic

    1. NT_187669.1 Reference GRCh38.p14 ALT_REF_LOCI_21

      Range
      20467..36357 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 ALT_REF_LOCI_23

    Genomic

    1. NT_187671.1 Reference GRCh38.p14 ALT_REF_LOCI_23

      Range
      111653..127543
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 ALT_REF_LOCI_25

    Genomic

    1. NT_187673.1 Reference GRCh38.p14 ALT_REF_LOCI_25

      Range
      20503..36371 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 ALT_REF_LOCI_26

    Genomic

    1. NT_187674.1 Reference GRCh38.p14 ALT_REF_LOCI_26

      Range
      119582..134593
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 ALT_REF_LOCI_28

    Genomic

    1. NT_187676.1 Reference GRCh38.p14 ALT_REF_LOCI_28

      Range
      108653..124518
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 ALT_REF_LOCI_29

    Genomic

    1. NT_187677.1 Reference GRCh38.p14 ALT_REF_LOCI_29

      Range
      110073..125941
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 ALT_REF_LOCI_30

    Genomic

    1. NT_187683.1 Reference GRCh38.p14 ALT_REF_LOCI_30

      Range
      106919..122809
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 ALT_REF_LOCI_31

    Genomic

    1. NT_187684.1 Reference GRCh38.p14 ALT_REF_LOCI_31

      Range
      20485..36159 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 ALT_REF_LOCI_32

    Genomic

    1. NT_187685.1 Reference GRCh38.p14 ALT_REF_LOCI_32

      Range
      20840..35851 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 ALT_REF_LOCI_33

    Genomic

    1. NT_187686.1 Reference GRCh38.p14 ALT_REF_LOCI_33

      Range
      20835..36702 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 ALT_REF_LOCI_34

    Genomic

    1. NT_187687.1 Reference GRCh38.p14 ALT_REF_LOCI_34

      Range
      20482..36177 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060943.1 Alternate T2T-CHM13v2.0

      Range
      57927015..57942905
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P43632.2 GenPept UniProtKB/Swiss-Prot:P43632

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