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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 10-Dec-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
  • 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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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

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)

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
    Download
    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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