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    KIR2DL4 killer cell immunoglobulin like receptor, two Ig domains and long cytoplasmic tail 4 [ Homo sapiens (human) ]

    Gene ID: 3805, updated on 10-Dec-2024

    Summary

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    Official Symbol
    KIR2DL4provided by HGNC
    Official Full Name
    killer cell immunoglobulin like receptor, two Ig domains and long cytoplasmic tail 4provided by HGNC
    Primary source
    HGNC:HGNC:6332
    See related
    Ensembl:ENSG00000189013 MIM:604945; AllianceGenome:HGNC:6332
    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
    G9P; CD158D; KIR103; KIR-2DL4; KIR103AS; KIR-103AS
    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. This gene is one of the "framework" loci that is present on all haplotypes. Alternate alleles of this gene are represented on multiple alternate reference loci (ALT_REF_LOCs). Alternative splicing results in multiple transcript variants, some of which may not be annotated on the primary reference assembly. [provided by RefSeq, Jul 2016]
    Expression
    Biased expression in spleen (RPKM 1.3), endometrium (RPKM 0.5) and 12 other tissues See more
    Orthologs
    all
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    Genomic context

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    See KIR2DL4 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 (54803610..54814517)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (57897871..57908821)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (55315065..55325972)

    Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC101928804 Neighboring gene killer cell immunoglobulin like receptor, two Ig domains and long cytoplasmic tail 1 Neighboring gene killer cell immunoglobulin like receptor, three Ig domains pseudogene 1 Neighboring gene killer cell immunoglobulin like receptor, three Ig domains and long cytoplasmic tail 1 Neighboring gene killer cell immunoglobulin like receptor, two Ig domains and short cytoplasmic tail 4 (gene/pseudogene)

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: Tissue-specific circular RNA induction during human fetal development
    • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
    • BioProject: PRJNA270632
    • Publication: PMID 26076956
    • Analysis date: Mon Apr 2 22:54:59 2018

    Bibliography

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    Related articles in PubMed

    1. The elucidation of KIR2DL4 gene polymorphism. Schellekens J, et al. Mol Immunol, 2008 Apr. PMID 18082267
    2. KIR2DL4 expression rather than its single nucleotide polymorphisms correlates with pre-eclampsia. Wang D, et al. Int J Clin Exp Pathol, 2015. PMID 26823774, Free PMC Article
    3. Maternal KIR repertoire is not associated with recurrent spontaneous abortion. Witt CS, et al. Hum Reprod, 2004 Nov. PMID 15333596
    4. The structure of the atypical killer cell immunoglobulin-like receptor, KIR2DL4. Moradi S, et al. J Biol Chem, 2015 Apr 17. PMID 25759384, Free PMC Article
    5. The Killer Cell Ig-like Receptor 2DL4 Expression in Human Mast Cells and Its Potential Role in Breast Cancer Invasion. Ueshima C, et al. Cancer Immunol Res, 2015 Aug. PMID 25735953

    See all (151) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Underrepresentation of activating KIR gene expression in single-cell RNA-seq data is due to KIR gene misassignment.
      Title: Underrepresentation of activating KIR gene expression in single-cell RNA-seq data is due to KIR gene misassignment.
    2. KIR2DL4/HLA-G polymorphisms were associated with HCV infection susceptibility among Chinese high-risk population.
      Title: KIR2DL4/HLA-G polymorphisms were associated with HCV infection susceptibility among Chinese high-risk population.
    3. Clinical significance and immune landscape of KIR2DL4 and the senescence-based signature in cutaneous melanoma.
      Title: Clinical significance and immune landscape of KIR2DL4 and the senescence-based signature in cutaneous melanoma.
    4. Roles of HLA-G/KIR2DL4 in Breast Cancer Immune Microenvironment.
      Title: Roles of HLA-G/KIR2DL4 in Breast Cancer Immune Microenvironment.
    5. Interaction between HLA-G and NK cell receptor KIR2DL4 orchestrates HER2-positive breast cancer resistance to trastuzumab.
      Title: Interaction between HLA-G and NK cell receptor KIR2DL4 orchestrates HER2-positive breast cancer resistance to trastuzumab.
    6. KIR2DL4 promotes the proliferation of RCC cell associated with PI3K/Akt signaling activation.
      Title: KIR2DL4 promotes the proliferation of RCC cell associated with PI3K/Akt signaling activation.
    7. Expression of HLA-G and KIR2DL4 receptor in chorionic villous in missed abortion.
      Title: Expression of HLA-G and KIR2DL4 receptor in chorionic villous in missed abortion.
    8. Possible roles of HLA-G regulating immune cells in pregnancy and endometrial diseases via KIR2DL4.
      Title: Possible roles of HLA-G regulating immune cells in pregnancy and endometrial diseases via KIR2DL4.
    9. Family-based exome sequencing identifies rare coding variants in age-related macular degeneration.
      Title: Family-based exome sequencing identifies rare coding variants in age-related macular degeneration.
    10. Altered oxidative stress markers in relation to T cells, NK cells & killer immunoglobulin receptors that are associated with disease activity in SLE patients.
      Title: Altered oxidative stress markers in relation to T cells, NK cells & killer immunoglobulin receptors that are associated with disease activity in SLE patients.
    Submit: New GeneRIF Correction See all GeneRIFs (74)

    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

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables MHC class Ib receptor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables transmembrane signaling receptor activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in cellular defense response TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in immune response-regulating signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in negative regulation of natural killer cell mediated cytotoxicity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of cellular senescence IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of natural killer cell cytokine production IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in signal transduction TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in early endosome membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in membrane HDA 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
    killer cell immunoglobulin-like receptor 2DL4
    Names
    CD158 antigen-like family member D
    KIR2DL4 Killer-cell Immunoglobulin-like Receptor
    KIR2DL4*00102
    KIR2DL4*00103
    KIR2DL4*00501
    KIR2DL4*00801
    KIR2DL4*00802
    KIR2DL4*01101
    KIR2DL4*021
    KIR2DL4*022
    KIR2DL4_00201
    KIR2DL4_00201 protein
    MHC class I NK cell receptor KIR103AS
    killer cell immunoglobulin-like receptor, two domains, long cytoplasmic tail, 4
    killer cell inhibitory receptor 103AS

    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_005994.1 

      Range
      124068..134982
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001080770.2 → NP_001074239.1  killer cell immunoglobulin-like receptor 2DL4 isoform c precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks an internal exon in the coding region, compared to variant 1. It encodes isoform c, which is shorter than isoform a.
      Source sequence(s)
      AC245128, BC028137, BC041611
      Consensus CDS
      CCDS42619.1
      UniProtKB/TrEMBL
      A0A0G2JNE8, A0A0G2JPE3, A0A376A929
      Related
      ENSP00000339634.5, ENST00000345540.10
      Conserved Domains (1) summary
      cl11960
      Location:30 → 119
      Ig; Immunoglobulin domain

    2. NM_001080772.2 → NP_001074241.1  killer cell immunoglobulin-like receptor 2DL4 isoform b precursor

      See identical proteins and their annotated locations for NP_001074241.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) is one nt shorter than variant 1. It encodes isoform b, which is shorter and has a distinct C-terminus, compared to isoform a.
      Source sequence(s)
      AC245128, BC028137, BC041611
      Consensus CDS
      CCDS42620.1
      UniProtKB/TrEMBL
      A0A0B4J1S6, A0A1W2PQ98, A0A7D5C391, K7RE46
      Related
      ENSP00000351988.4, ENST00000359085.8
      Conserved Domains (2) summary
      cd00096
      Location:31 → 35
      Ig; Ig strand A [structural motif]
      cl11960
      Location:30 → 119
      Ig; Immunoglobulin domain

    3. NM_002255.6 → NP_002246.5  killer cell immunoglobulin-like receptor 2DL4 isoform a precursor

      See identical proteins and their annotated locations for NP_002246.5

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
      Source sequence(s)
      AC245128, BC028137, BC041611
      UniProtKB/Swiss-Prot
      A8W795, O14621, O14622, O14623, O14624, O43534, P78400, P78401, Q8N738, Q99559, Q99560, Q99561, Q99562, Q99706, Q9UQJ7
      UniProtKB/TrEMBL
      A0A0C4ZR19, A0A6G6CZ72, K7QUS9, K7QUT1
      Conserved Domains (2) summary
      smart00410
      Location:37 → 98
      IG_like; Immunoglobulin like
      cl11960
      Location:30 → 119
      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
      54803610..54814517
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 PATCHES

    Genomic

    1. NW_016107300.1 Reference GRCh38.p14 PATCHES

      Range
      105242..116152
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 PATCHES

    Genomic

    1. NW_016107301.1 Reference GRCh38.p14 PATCHES

      Range
      105253..116160
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 PATCHES

    Genomic

    1. NW_016107302.1 Reference GRCh38.p14 PATCHES

      Range
      105206..116154
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 PATCHES

    Genomic

    1. NW_016107304.1 Reference GRCh38.p14 PATCHES

      Range
      105227..116143
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 PATCHES

    Genomic

    1. NW_016107305.1 Reference GRCh38.p14 PATCHES

      Range
      105193..116143
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 PATCHES

    Genomic

    1. NW_016107306.1 Reference GRCh38.p14 PATCHES

      Range
      105016..115966
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 PATCHES

    Genomic

    1. NW_016107307.1 Reference GRCh38.p14 PATCHES

      Range
      105168..116116
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 PATCHES

    Genomic

    1. NW_016107309.1 Reference GRCh38.p14 PATCHES

      Range
      105206..116154
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 PATCHES

    Genomic

    1. NW_016107310.1 Reference GRCh38.p14 PATCHES

      Range
      135594..146510
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 PATCHES

    Genomic

    1. NW_016107313.1 Reference GRCh38.p14 PATCHES

      Range
      105168..116118
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 PATCHES

    Genomic

    1. NW_016107314.1 Reference GRCh38.p14 PATCHES

      Range
      91600..102507
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 ALT_REF_LOCI_2

    Genomic

    1. NW_003571055.2 Reference GRCh38.p14 ALT_REF_LOCI_2

      Range
      421466..432382
      Download
      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
      707932..718882
      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
      786179..797086
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 ALT_REF_LOCI_10

    Genomic

    1. NT_187636.1 Reference GRCh38.p14 ALT_REF_LOCI_10

      Range
      88224..99140 complement
      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
      54292..65240 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
      54497..65407 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
      54860..65810 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
      43688..54598 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 ALT_REF_LOCI_15

    Genomic

    1. NT_187641.1 Reference GRCh38.p14 ALT_REF_LOCI_15

      Range
      93900..104816 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
      52989..63939 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
      54551..65501 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 ALT_REF_LOCI_18

    Genomic

    1. NT_187644.1 Reference GRCh38.p14 ALT_REF_LOCI_18

      Range
      81938..92854 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
      54566..65516 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
      44454..55402 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
      54551..65501 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 ALT_REF_LOCI_22

    Genomic

    1. NT_187670.1 Reference GRCh38.p14 ALT_REF_LOCI_22

      Range
      82011..92927 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
      82509..93459
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 ALT_REF_LOCI_24

    Genomic

    1. NT_187672.1 Reference GRCh38.p14 ALT_REF_LOCI_24

      Range
      105164..116149
      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
      54561..65468 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
      90438..101388
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 ALT_REF_LOCI_27

    Genomic

    1. NT_187675.1 Reference GRCh38.p14 ALT_REF_LOCI_27

      Range
      146611..157527
      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
      79509..90459
      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
      80976..91883
      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
      77774..88724
      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
      54367..65276 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
      54043..64993 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
      54893..65841 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
      54387..65295 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 ALT_REF_LOCI_35

    Genomic

    1. NT_113949.2 Reference GRCh38.p14 ALT_REF_LOCI_35

      Range
      74867..85783 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060943.1 Alternate T2T-CHM13v2.0

      Range
      57897871..57908821
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_001258383.1: Suppressed sequence

      Description
      NM_001258383.1: This RefSeq was permanently suppressed 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
    Q99706.3 GenPept UniProtKB/Swiss-Prot:Q99706

    Gene LinkOut

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

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