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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 11-Apr-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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Location:
19q13.42
Exon count:
8
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (54803610..54814517)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (57897871..57908821)
105.20220307 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

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. Clinical significance and immune landscape of KIR2DL4 and the senescence-based signature in cutaneous melanoma. Mao R, et al. Cancer Sci, 2022 Nov. PMID 35848898, Free PMC Article
  2. KIR2DL4 promotes the proliferation of RCC cell associated with PI3K/Akt signaling activation. Ding XF, et al. Life Sci, 2022 Mar 15. PMID 35063466
  3. Killer Immunoglobulin-Like Receptor 2DL4 (CD158d) Regulates Human Mast Cells both Positively and Negatively: Possible Roles in Pregnancy and Cancer Metastasis. Kataoka TR, et al. Int J Mol Sci, 2020 Jan 31. PMID 32023940, Free PMC Article
  4. KIR2DL4-HLAG interaction at human NK cell-oligodendrocyte interfaces regulates IFN-Îł-mediated effects. Banerjee PP, et al. Mol Immunol, 2019 Nov. PMID 30482463, Free PMC Article
  5. [Association of polymorphisms of KIR2DL4 gene with leukemia among ethnic Hans from southern China]. Chen R, et al. Zhonghua Yi Xue Yi Chuan Xue Za Zhi, 2018 Feb 10. PMID 29419875

See all (150) 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)

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

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_2023_10

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

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