Details for: KLRB1

Gene ID: 3820

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: KLRB1

Ensembl ID: ENSG00000111796

Description: killer cell lectin like receptor B1

Cell Significance Landscape

Associated with

Significant Cells

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

  • T-helper 17 cell CL0000899
    CSI 79.46
    rCSI 63.09%
    PRS 99.94
  • CD16-positive, CD56-dim natural killer cell, human CL0000939
    CSI 75.32
    rCSI 50.19%
    PRS 99.91
  • group 3 innate lymphoid cell CL0001071
    CSI 72.9
    rCSI 54.77%
    PRS 99.68
  • mucosal invariant T cell CL0000940
    CSI 69.74
    rCSI 56.35%
    PRS 99.91
  • CD4-positive, alpha-beta memory T cell CL0000897
    CSI 61.98
    rCSI 44.49%
    PRS 99.91
  • CD16-negative, CD56-bright natural killer cell, human CL0000938
    CSI 61.76
    rCSI 46.31%
    PRS 99.95
  • CD4-positive helper T cell CL0000492
    CSI 57.87
    rCSI 43.78%
    PRS 99.98
  • activated type II NK T cell CL0000931
    CSI 56.02
    rCSI 63.05%
    PRS 99.94
  • mature T cell CL0002419
    CSI 46.92
    rCSI 36.5%
    PRS 99.98
  • conventional dendritic cell CL0000990
    CSI 36.51
    rCSI 30.48%
    PRS 97.23
  • effector CD8-positive, alpha-beta T cell CL0001050
    CSI 34.57
    rCSI 26.3%
    PRS 99.93
  • central memory CD8-positive, alpha-beta T cell CL0000907
    CSI 32.63
    rCSI 21.98%
    PRS 99.96
  • T-helper 1 cell CL0000545
    CSI 31.91
    rCSI 57.61%
    PRS 99.95
  • alpha-beta T cell CL0000789
    CSI 29.13
    rCSI 34.13%
    PRS 99.89
  • central memory CD4-positive, alpha-beta T cell CL0000904
    CSI 27.14
    rCSI 16.03%
    PRS 100
  • natural T-regulatory cell CL0000903
    CSI 26.65
    rCSI 50.49%
    PRS 99.9
  • activated CD4-positive, alpha-beta T cell CL0000896
    CSI 24.83
    rCSI 22.95%
    PRS 99.82
  • gamma-delta T cell CL0000798
    CSI 23.93
    rCSI 28.1%
    PRS 100
  • effector memory CD4-positive, alpha-beta T cell CL0000905
    CSI 23.44
    rCSI 31.92%
    PRS 99.96
  • CD8-positive, alpha-beta cytotoxic T cell CL0000794
    CSI 23.01
    rCSI 27.47%
    PRS 99.77
  • naive T cell CL0000898
    CSI 21.42
    rCSI 14.9%
    PRS 99.98
  • CD8-positive, alpha-beta memory T cell CL0000909
    CSI 19.93
    rCSI 20.81%
    PRS 99.79
  • T follicular helper cell CL0002038
    CSI 18.88
    rCSI 14.13%
    PRS 99.62
  • activated CD8-positive, alpha-beta T cell CL0000906
    CSI 17.89
    rCSI 17.59%
    PRS 99.85
  • mononuclear phagocyte CL0000113
    CSI 17.71
    rCSI 38.99%
    PRS 99.84
  • mature NK T cell CL0000814
    CSI 17.29
    rCSI 22.12%
    PRS 100
  • intraepithelial lymphocyte CL0002496
    CSI 17.03
    rCSI 46.34%
    PRS 100
  • erythrocyte CL0000232
    CSI 16.87
    rCSI 38.27%
    PRS 99.21
  • early lymphoid progenitor CL0000936
    CSI 15.55
    rCSI 13.66%
    PRS 99.8
  • effector CD4-positive, alpha-beta T cell CL0001044
    CSI 15.46
    rCSI 44.35%
    PRS 99.98
  • effector memory CD8-positive, alpha-beta T cell CL0000913
    CSI 15.32
    rCSI 13.95%
    PRS 99.9
  • activated CD4-positive, alpha-beta T cell, human CL0001043
    CSI 14.86
    rCSI 35.75%
    PRS 99.87
  • innate lymphoid cell CL0001065
    CSI 14.25
    rCSI 29.42%
    PRS 97.94
  • platelet CL0000233
    CSI 13.78
    rCSI 57.18%
    PRS 98.28
  • CD8-positive, alpha-beta thymocyte CL0000811
    CSI 12.85
    rCSI 20.03%
    PRS 98.91
  • CD4-positive, alpha-beta thymocyte CL0000810
    CSI 12.82
    rCSI 10.27%
    PRS 97.11
  • CD4-positive, CD25-positive, alpha-beta regulatory T cell CL0000792
    CSI 12.38
    rCSI 12.16%
    PRS 99.97
  • CD4-positive, alpha-beta cytotoxic T cell CL0000934
    CSI 12.35
    rCSI 16.97%
    PRS 99.96
  • group 2 innate lymphoid cell CL0001069
    CSI 11.57
    rCSI 62.57%
    PRS 99.71
  • natural killer cell CL0000623
    CSI 10.86
    rCSI 21.04%
    PRS 99.16
  • plasmablast CL0000980
    CSI 10
    rCSI 7.87%
    PRS 99.37
  • activated CD8-positive, alpha-beta T cell, human CL0001049
    CSI 9.62
    rCSI 16.46%
    PRS 99.79
  • basal cell of epidermis CL0002187
    CSI 8.57
    rCSI 15.19%
    PRS 92.54
  • CD8-positive, CD28-negative, alpha-beta regulatory T cell CL0000920
    CSI 7.38
    rCSI 14.7%
    PRS 99.81
  • memory T cell CL0000813
    CSI 7.26
    rCSI 13.99%
    PRS 99.89
  • double negative thymocyte CL0002489
    CSI 6.48
    rCSI 4.51%
    PRS 99.92
  • lung resident memory CD8-positive, alpha-beta T cell CL4033039
    CSI 5.79
    rCSI 14.97%
    PRS 99.88
  • mature alpha-beta T cell CL0000791
    CSI 5.11
    rCSI 18.5%
    PRS 100
  • CD34-positive, CD56-positive, CD117-positive common innate lymphoid precursor, human CL0001074
    CSI 5.1
    rCSI 59.15%
    PRS 100
  • helper T cell CL0000912
    CSI 3.56
    rCSI 5.03%
    PRS 98.03
  • effector memory CD8-positive, alpha-beta T cell, terminally differentiated CL0001062
    CSI 3.29
    rCSI 16.52%
    PRS 99.87
  • CD8-alpha-alpha-positive, alpha-beta intraepithelial T cell CL0000915
    CSI 3.2
    rCSI 14.54%
    PRS 99.94
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 2.55
    rCSI 3.08%
    PRS 94.46
  • lung resident memory CD4-positive, alpha-beta T cell CL4033038
    CSI 2.51
    rCSI 24.7%
    PRS 99.77
  • NKp44-negative group 3 innate lymphoid cell, human CL0001080
    CSI 2.12
    rCSI 65.98%
    PRS 100
  • hepatic pit cell CL2000054
    CSI 1.85
    rCSI 25.37%
    PRS 100
  • decidual natural killer cell, human CL0002343
    CSI 1.82
    rCSI 18.46%
    PRS 99.84
  • cytotoxic T cell CL0000910
    CSI 1.41
    rCSI 8.07%
    PRS 98.25
  • group 3 innate lymphoid cell, human CL0001078
    CSI 1.08
    rCSI 22.89%
    PRS 100

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.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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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 [KLRB1](/details-gene/3820), or Killer Cell Lectin Like Receptor B1, encodes a C-type lectin-like receptor also known as CD161 or NKR-P1A. It is a transmembrane protein that functions as a homodimer and is predominantly expressed on subsets of natural killer (NK) cells and T lymphocytes, as described in early characterization studies ([Link](https://pubmed.ncbi.nlm.nih.gov/8077657/)). The expression data highlights its particular significance in [T-helper 17 cell](/details-cell/CL0000899), various [natural killer cell](/details-cell/CL0000623) subtypes, and [group 3 innate lymphoid cell](/details-cell/CL0001071). Functionally, [KLRB1](/details-gene/3820) is involved in immunoregulatory signaling, including the [regulation of natural killer cell mediated cytotoxicity](/details-gene/GO:0042269), and recognizes the ligand LLT1 ([Link](https://doi.org/10.4049/jimmunol.175.12.7791), [Link](https://doi.org/10.4049/jimmunol.175.12.7796)). A clinical association has been noted for this gene ([153245](https://omim.org/entry/602890)). ## Cellular Roles and Expression Landscape The expression profile of [KLRB1](/details-gene/3820) firmly establishes it as a key molecule within specific lymphocyte populations at the intersection of innate and adaptive immunity. **Overall**, its highest significance is observed in cell types crucial for mucosal immunity and rapid cytotoxic responses. The most significant expression is found in [T-helper 17 cell](/details-cell/CL0000899) (CSI: 79.46), a subset of T cells critical for defense against extracellular pathogens at mucosal surfaces. This is complemented by high significance in [group 3 innate lymphoid cell](/details-cell/CL0001071) (CSI: 72.90), the innate counterpart to Th17 cells, and [mucosal invariant T cell](/details-cell/CL0000940) (CSI: 69.74), which are also abundant at barrier tissues. This is consistent with reports identifying [KLRB1](/details-gene/3820)-positive T cells in the human intestinal epithelium and liver ([Link](https://doi.org/10.1046/j.1365-2249.2002.01886.x)). Concurrently, [KLRB1](/details-gene/3820) is a defining marker for [natural killer cell](/details-cell/CL0000623) populations, including both [CD16-positive, CD56-dim natural killer cell, human](/details-cell/CL0000939) (CSI: 75.32) and [CD16-negative, CD56-bright natural killer cell, human](/details-cell/CL0000938) (CSI: 61.76). Its expression extends across a broad range of T cell subsets, including multiple memory populations like [CD4-positive, alpha-beta memory T cell](/details-cell/CL0000897) and effector cells such as [effector CD8-positive, alpha-beta T cell](/details-cell/CL0001050), indicating a widespread role in T cell biology beyond a single lineage. ## Pathways and Molecular Function [KLRB1](/details-gene/3820) functions as a [signaling receptor](/details-gene/GO:0038023) on the [cell surface](/details-gene/GO:0009986), consistent with its role in the [plasma membrane](/details-gene/GO:0005886). Its involvement in the [cell surface receptor signaling pathway](/details-gene/GO:0007166) is central to its function. As a C-type lectin, its [carbohydrate binding](/details-gene/GO:0030246) capacity is crucial for ligand recognition ([Link](https://doi.org/10.1111/j.1399-3089.2006.00332.x)). The primary biological process associated with [KLRB1](/details-gene/3820) is the [regulation of natural killer cell mediated cytotoxicity](/details-gene/GO:0042269). Studies suggest that signaling through [KLRB1](/details-gene/3820) can be both activating and inhibitory, depending on the context, and can involve the activation of acid sphingomyelinase ([Link](https://doi.org/10.4049/jimmunol.176.4.2397)). For instance, IL-12 can upregulate [KLRB1](/details-gene/3820) expression, which in turn can down-regulate NK cell activation, suggesting a negative feedback loop ([Link](https://doi.org/10.1002/(sici)1521-4141(199805)28:05<1611::aid-immu1611>3.0.co;2-6)). Its role is contextualized within the broader [Immune system](/details-gene/R-HSA-168256) and [Adaptive immune system](/details-gene/R-HSA-1280218) pathways, specifically in [Immunoregulatory interactions between a lymphoid and a non-lymphoid cell](/details-gene/R-HSA-198933), highlighting its function in mediating cellular cross-talk. ## Research Directions The expression pattern and known functions of [KLRB1](/details-gene/3820) suggest it plays a critical immunomodulatory role. Future research could focus on its context-dependent signaling in immunity and disease. **Proposed Hypotheses:** 1. Given its high expression on both [T-helper 17 cell](/details-cell/CL0000899) and [group 3 innate lymphoid cell](/details-cell/CL0001071), [KLRB1](/details-gene/3820) signaling may be a key regulator of type 3 immunity at mucosal barriers. Its engagement by the ligand LLT1, which can be expressed on epithelial or antigen-presenting cells, could modulate cytokine production (e.g., IL-17, IL-22) and influence the pathogenesis of inflammatory conditions like inflammatory bowel disease (IBD). 2. The expression of [KLRB1](/details-gene/3820) on cytotoxic lymphocytes, including NK cells and effector CD8+ T cells, alongside its known inhibitory potential, suggests that its pathway could be exploited by tumors for immune evasion. Upregulation of its ligand, LLT1, on cancer cells may serve as a mechanism to suppress the anti-tumor activity of these key immune effectors. **Experimental Approach:** To test the second hypothesis, one could employ a functional immunology approach. A co-culture system could be established using human NK cells and CD8+ T cells isolated from healthy donors. These effector cells would be co-cultured with a tumor cell line (e.g., a melanoma or colon cancer line) that has been engineered using CRISPR-Cas9 to either knock out or overexpress the [KLRB1](/details-gene/3820) ligand, LLT1. The primary readouts would be effector cell degranulation (CD107a expression), cytokine production (IFN-γ), and target cell lysis, measured by flow cytometry or a luminescence-based cytotoxicity assay. The addition of a [KLRB1](/details-gene/3820) blocking antibody would be expected to restore cytotoxicity against LLT1-overexpressing tumor cells, confirming the pathway's role in immune suppression. **Therapeutic Potential:** Based on its role as a potentially inhibitory receptor on cytotoxic immune cells, [KLRB1](/details-gene/3820) represents an attractive candidate for therapeutic intervention, particularly in oncology. Inhibition of the KLRB1-LLT1 axis could enhance the anti-tumor activity of both NK and T cells. Therefore, a monoclonal antibody that blocks the [KLRB1](/details-gene/3820) receptor could function as a novel immune checkpoint inhibitor. Such a therapy would aim to "release the brakes" on the immune system, potentially synergizing with existing checkpoint inhibitors that target the PD-1/PD-L1 or CTLA-4 pathways.

Genular Protein ID: 2712804400

Symbol: KLRB1_HUMAN

Name: Killer cell lectin-like receptor subfamily B member 1

UniProtKB Accession Codes:

Q12918 Q24K24

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 EMBL 3 Ensembl 1 GO 7 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 3 PDBsum 3 PIR 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 1 RefSeq 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 UniLectin 1 VEuPathDB 1 eggNOG 1 neXtProt 1

Citations:

PubMed ID: 8077657

Title: Human NKR-P1A: a disulfide-linked homodimer of the C-type lectin superfamily expressed by a subset of NK and T lymphocytes.

PubMed ID: 8077657

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: 9603467

Title: IL-12-induced up-regulation of NKRP1A expression in human NK cells and consequent NKRP1A-mediated down-regulation of NK cell activation.

PubMed ID: 9603467

DOI: 10.1002/(sici)1521-4141(199805)28:05&lt;1611::aid-immu1611&gt;3.0.co;2-6

PubMed ID: 12100027

Title: CD161+ T (NT) cells exist predominantly in human intestinal epithelium as well as in liver.

PubMed ID: 12100027

DOI: 10.1046/j.1365-2249.2002.01886.x

PubMed ID: 16339512

Title: Lectin-like transcript 1 is a ligand for the CD161 receptor.

PubMed ID: 16339512

DOI: 10.4049/jimmunol.175.12.7791

PubMed ID: 16339513

Title: Lectin-like transcript-1 is a ligand for the inhibitory human NKR-P1A receptor.

PubMed ID: 16339513

DOI: 10.4049/jimmunol.175.12.7796

PubMed ID: 16455998

Title: CD161 (human NKR-P1A) signaling in NK cells involves the activation of acid sphingomyelinase.

PubMed ID: 16455998

DOI: 10.4049/jimmunol.176.4.2397

PubMed ID: 16925668

Title: Recognition of a carbohydrate xenoepitope by human NKRP1A (CD161).

PubMed ID: 16925668

DOI: 10.1111/j.1399-3089.2006.00332.x

PubMed ID: 20843815

Title: Characterization of alternatively spliced transcript variants of CLEC2D gene.

PubMed ID: 20843815

DOI: 10.1074/jbc.m110.179622

Sequence Information:

  • Length: 225
  • Mass: 25415
  • Checksum: 01BFA925445B83B0
  • Sequence:
    • MDQQAIYAEL NLPTDSGPES SSPSSLPRDV CQGSPWHQFA LKLSCAGIIL LVLVVTGLSV 
SVTSLIQKSS IEKCSVDIQQ SRNKTTERPG LLNCPIYWQQ LREKCLLFSH TVNPWNNSLA 
DCSTKESSLL LIRDKDELIH TQNLIRDKAI LFWIGLNFSL SEKNWKWING SFLNSNDLEI 
RGDAKENSCI SISQTSVYSE YCSTEIRWIC QKELTPVRNK VYPDS