Details for: KIR3DL1

Gene ID: 3811

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: KIR3DL1

Ensembl ID: ENSG00000167633

Description: killer cell immunoglobulin like receptor, three Ig domains and long cytoplasmic tail 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • activated type II NK T cell CL0000931
    CSI 31.66
    rCSI 35.63%
    PRS 99.89
  • CD16-positive, CD56-dim natural killer cell, human CL0000939
    CSI 14.21
    rCSI 9.47%
    PRS 99.81
  • effector memory CD8-positive, alpha-beta T cell, terminally differentiated CL0001062
    CSI 1.78
    rCSI 8.94%
    PRS 99.83

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [KIR3DL1](/details-gene/3811) (Killer Cell Immunoglobulin Like Receptor, Three Ig Domains and Long Cytoplasmic Tail 1) is a protein-coding gene located on chromosome 19. It encodes a transmembrane inhibitory receptor that is a member of the killer cell immunoglobulin-like receptor (KIR) family. [KIR3DL1](/details-gene/3811) is predominantly expressed on the surface of cytotoxic lymphocytes, particularly natural killer (NK) cells and subsets of T cells. Its primary function is to regulate the cytotoxic activity of these cells by recognizing and binding to specific human leukocyte antigen (HLA) class I molecules, primarily HLA-B alleles carrying the Bw4 motif. This interaction transmits an inhibitory signal, preventing the lysis of healthy, self-MHC-expressing cells and playing a crucial role in immune tolerance and the surveillance of diseased or virally infected cells. ## Cellular Roles and Expression Landscape The expression profile of [KIR3DL1](/details-gene/3811) underscores its specialized role within the innate and adaptive immune systems. **Overall**, the gene shows exceptionally high and specific significance in cytotoxic lymphocyte populations. Its highest Cell Significance Index (CSI) is observed in [activated type II NK T cell](/details-cell/CL0000931) (CSI: 31.66), indicating it is a defining marker for this rare cell type. It is also a highly significant marker for the major circulating NK cell population, the [CD16-positive, CD56-dim natural killer cell, human](/details-cell/CL0000939) (CSI: 14.21). Furthermore, [KIR3DL1](/details-gene/3811) is expressed in a subset of highly differentiated T cells, as evidenced by its significance in [effector memory CD8-positive, alpha-beta T cell, terminally differentiated](/details-cell/CL0001062) (CSI: 1.78). This expression pattern suggests that [KIR3DL1](/details-gene/3811) contributes to the regulation of immune responses mediated by both NK cells and long-lived, antigen-experienced T cells. The highly restricted expression to these specific lymphocyte subsets implies a tightly controlled function in mediating immune surveillance and preventing autoimmunity. ## Pathways and Molecular Function Functionally, [KIR3DL1](/details-gene/3811) is integral to the regulation of the immune system. Its localization to the [plasma membrane](/details-cell/GO:0005886) is consistent with its role as a cell surface receptor. The molecular function is defined by its [Hla-b specific inhibitory mhc class i receptor activity](/details-cell/GO:0030109), which involves the direct recognition of specific HLA-B allotypes ([Link](https://doi.org/10.1038/nature10517)). This binding initiates an [immune response-regulating signaling pathway](/details-cell/GO:0002764) within the NK cell or T cell, ultimately leading to the inhibition of [natural killer cell mediated cytotoxicity](/details-cell/GO:0042267). This mechanism is a cornerstone of the "missing-self" hypothesis, where NK cells are licensed to kill target cells that have downregulated or lost MHC class I expression, a common feature of viral infections and tumors. The Reactome pathway annotations further place [KIR3DL1](/details-gene/3811) within the broader contexts of the [immune system](/details-cell/R-HSA-168256) and specifically within [immunoregulatory interactions between a lymphoid and a non-lymphoid cell](/details-cell/R-HSA-198933). Notably, an annotation for [amyloid-beta binding](/details-cell/GO:0001540) suggests a potential, though less characterized, role for this receptor outside of classical immunology, possibly in neuro-inflammatory contexts. ## Research Directions The specific expression and inhibitory function of [KIR3DL1](/details-gene/3811) present several avenues for future research, particularly in immunology, oncology, and potentially neurobiology. **Proposed Hypotheses:** 1. The extensive allelic polymorphism of [KIR3DL1](/details-gene/3811) directly dictates the functional responsiveness and cytotoxic potential of NK cell repertoires against specific viral infections (e.g., HIV, CMV) or malignancies that express the cognate HLA-Bw4 ligand. Individuals with high-affinity [KIR3DL1](/details-gene/3811)/HLA-Bw4 combinations may exhibit stronger NK cell inhibition and potentially altered disease susceptibility. 2. Based on its annotated ability to bind amyloid-beta, [KIR3DL1](/details-gene/3811)-expressing NK cells or T cells may infiltrate the central nervous system during neuroinflammation and modulate the progression of Alzheimer's disease by interacting with amyloid plaques, either promoting clearance or contributing to pathology. **Experimental Approach:** To test the first hypothesis regarding the impact of [KIR3DL1](/details-gene/3811) polymorphism on NK cell function, a high-throughput functional genomics approach could be employed. Primary [CD16-positive, CD56-dim natural killer cell, human](/details-cell/CL0000939) could be isolated from a cohort of healthy donors who have been genotyped for both KIR and HLA alleles. These NK cells would then be co-cultured with a panel of tumor cell lines engineered to express specific HLA-Bw4 alleles. NK cell activation could be quantified by measuring degranulation (CD107a surface expression) and cytokine production (IFN-γ) using flow cytometry. This would allow for a direct correlation between specific [KIR3DL1](/details-gene/3811) allotypes and the degree of inhibition conferred by their cognate HLA ligands, providing a functional map of this crucial immunoregulatory axis. **Therapeutic Potential:** [KIR3DL1](/details-gene/3811) is a highly attractive target for cancer immunotherapy. As an inhibitory receptor, its engagement by HLA ligands on tumor cells represents a key mechanism of immune evasion. Therefore, blockade of the [KIR3DL1](/details-gene/3811) receptor, likely via a monoclonal antibody, is a promising therapeutic strategy. Such an agent would function as an immune checkpoint inhibitor, preventing the "off" signal and "releasing the brakes" on NK cells, thereby enhancing their ability to recognize and kill tumor cells. This approach would be a form of **inhibition**-based therapy. The success of such a therapy would likely depend on patient stratification based on both their tumor's HLA expression profile and their germline KIR genotype, representing a personalized medicine approach to harnessing NK cell anti-tumor activity.

Genular Protein ID: 377094829

Symbol: KI3L1_HUMAN

Name: CD158 antigen-like family member E

UniProtKB Accession Codes:

P43629 O43473 Q14946 Q16541

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 DMDM 1 DNASU 1 DisGeNET 1 DisProt 1 EMBL 9 Ensembl 9 EvolutionaryTrace 1 ExpressionAtlas 1 GO 6 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 KEGG 1 MANE-Select 1 MIM 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 9 PDBsum 9 PIR 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 Reactome 1 RefSeq 2 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 7716543

Title: Cloning of immunoglobulin-superfamily members associated with HLA-C and HLA-B recognition by human natural killer cells.

PubMed ID: 7716543

DOI: 10.1126/science.7716543

PubMed ID: 8777725

Title: Killer cell inhibitory receptors specific for HLA-C and HLA-B identified by direct binding and by functional transfer.

PubMed ID: 8777725

DOI: 10.1016/1074-7613(95)90069-1

PubMed ID: 8760804

Title: The natural killer cell receptor specific for HLA-A allotypes: a novel member of the p58/p70 family of inhibitory receptors that is characterized by three immunoglobulin-like domains and is expressed as a 140-kD disulphide-linked dimer.

PubMed ID: 8760804

DOI: 10.1084/jem.184.2.505

PubMed ID: 7650366

Title: Molecular cloning of NKB1. A natural killer cell receptor for HLA-B allotypes.

PubMed ID: 7650366

PubMed ID: 9430221

Title: Human diversity in killer cell inhibitory receptor genes.

PubMed ID: 9430221

DOI: 10.1016/s1074-7613(00)80394-5

PubMed ID: 8662091

Title: Alternatively spliced forms of human killer inhibitory receptors.

PubMed ID: 8662091

DOI: 10.1007/bf02602590

PubMed ID: 15057824

Title: The DNA sequence and biology of human chromosome 19.

PubMed ID: 15057824

DOI: 10.1038/nature02399

PubMed ID: 22020283

Title: Killer cell immunoglobulin-like receptor 3DL1-mediated recognition of human leukocyte antigen B.

PubMed ID: 22020283

DOI: 10.1038/nature10517

Sequence Information:

  • Length: 444
  • Mass: 49098
  • Checksum: 47DEA12BBAFDEC53
  • Sequence:
    • MSLMVVSMAC VGLFLVQRAG PHMGGQDKPF LSAWPSAVVP RGGHVTLRCH YRHRFNNFML 
YKEDRIHIPI FHGRIFQESF NMSPVTTAHA GNYTCRGSHP HSPTGWSAPS NPVVIMVTGN 
HRKPSLLAHP GPLVKSGERV ILQCWSDIMF EHFFLHKEGI SKDPSRLVGQ IHDGVSKANF 
SIGPMMLALA GTYRCYGSVT HTPYQLSAPS DPLDIVVTGP YEKPSLSAQP GPKVQAGESV 
TLSCSSRSSY DMYHLSREGG AHERRLPAVR KVNRTFQADF PLGPATHGGT YRCFGSFRHS 
PYEWSDPSDP LLVSVTGNPS SSWPSPTEPS SKSGNPRHLH ILIGTSVVII LFILLLFFLL 
HLWCSNKKNA AVMDQEPAGN RTANSEDSDE QDPEEVTYAQ LDHCVFTQRK ITRPSQRPKT 
PPTDTILYTE LPNAKPRSKV VSCP

Genular Protein ID: 3177857429

Symbol: Q8N6C9_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q8N6C9

Database IDs:

ARBA 2 AlphaFoldDB 1 BioGRID-ORCS 1 CDD 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 14 GO 1 Gene3D 1 InterPro 5 KEGG 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PeptideAtlas 1 Pfam 1 PharmGKB 1 RefSeq 2 SAM 3 SMART 2 SUPFAM 1

Citations:

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 19411600

Title: Meiotic recombination generates rich diversity in NK cell receptor genes, alleles, and haplotypes.

PubMed ID: 19411600

DOI: 10.1101/gr.085738.108

Sequence Information:

  • Length: 444
  • Mass: 49086
  • Checksum: DD465C0E774AA6D4
  • Sequence:
    • MSLMVVSMAC VGLFLVQRAG PHMGGQDKPF LSAWPSAVVP RGGHVTLRCH YRHRFNNFML 
YKEDRIHVPI FHGRIFQEGF NMSPVTTAHA GNYTCRGSHP HSPTGWSAPS NPMVIMVTGN 
HRKPSLLAHP GPLVKSGERV ILQCWSDIMF EHFFLHKEGI SKDPSRLVGQ IHDGVSKANF 
SIGPMMLALA GTYRCYGSVT HTPYQLSAPS DPLDIVVTGP YEKPSLSAQP GPKVQAGESV 
TLSCSSRSSY DMYHLSREGG AHERRLPAVR KVNRTFQADF PLGPATHGGT YRCFGSFRHS 
PYEWSDPSDP LLVSVTGNPS SSWPSPTEPS SKSGNPRHLH ILIGTSVVII LFILLLFFLL 
HLWCSNKKNA AVMDQEPAGN RTANSEDSDE QDPEEVTYAQ LDHCVFTQRK ITRPSQRPKT 
PPTDTILYTE LPNAKPRSKV VSCP

Genular Protein ID: 2988955348

Symbol: Q6H2G3_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q6H2G3

Database IDs:

ARBA 2 BioGRID-ORCS 1 CDD 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 30 Ensembl 5 GO 1 Gene3D 1 HGNC 1 InterPro 5 KEGG 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PeptideAtlas 1 Pfam 1 Proteomes 2 ProteomicsDB 1 RefSeq 1 SAM 3 SMART 2 SUPFAM 1 UCSC 1

Citations:

PubMed ID: 14607943

Title: Activation of a subset of human NK cells upon contact with Plasmodium falciparum-infected erythrocytes.

PubMed ID: 14607943

PubMed ID: 19411600

Title: Meiotic recombination generates rich diversity in NK cell receptor genes, alleles, and haplotypes.

PubMed ID: 19411600

DOI: 10.1101/gr.085738.108

Sequence Information:

  • Length: 444
  • Mass: 49112
  • Checksum: C535D7963242A5CE
  • Sequence:
    • MLLMVVSMAC VGFFLVQRAG PHVGGQDKPF LSAWPSAVVP RGGHVTLRCH YRHRFNNFML 
YKEDRIHVPI FHGRLFQESF NMSPVTTAHA GNYTCRGSHP HSPTGWSAPS NPVVIMVTGN 
HRKPSLLAHP GPLVKSGERV ILQCWSDIMF EHFFLHKEGI SKDPSRLVGQ IHDGVSKANF 
SIGPMMLALA GTYRCYGSVT HTPYQLSAPS DPLDIVVTGP YEKPSLSAQP GPKVQAGESV 
TLSCSSRSSY DMYHLSREGG AHERRLPAVR KVNRTFQADF PLGPATHGGT YRCFGSFRHS 
PYEWSDPSDP LLVSVTGNPS SSWPSPTEPS SKSGNPRHLH ILIGTSVVII LFILLLFFLL 
HLWCSNKKNA AVMDQEPAGN RTANSEDSDE QDPEEVTYAQ LDHCVFTQRK ITRPSQRPKT 
PPTDTILYTE LPNAKPRSKV VSCP