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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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NCR2
natural cytotoxicity triggering receptor 2
Chromosome 6 · 6p21.1
NCBI Gene: 9436Ensembl: ENSG00000096264.14HGNC: HGNC:6732UniProt: O95944
53PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Receptor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingsignaling receptor activitycell surfaceplasma membraneliver diseasecardiac transplantrheumatoid arthritisneoplasm
✦AI Summary

NCR2 (natural cytotoxicity triggering receptor 2), also known as NKp44, is an activating immunoreceptor expressed on natural killer (NK) cells and innate lymphoid cells that mediates cytotoxic and immunoregulatory functions 1. Primary function: NCR2 serves as a cytotoxicity-activating receptor that enhances NK cell-mediated tumor cell lysis 2. Mechanism: NCR2 recognizes diverse ligands including platelet-derived growth factor (PDGF)-DD on tumor cells and HLA-DP on activated CD8+ T cells 23. Upon ligand engagement, NCR2 triggers NK cell secretion of interferon-gamma and tumor necrosis factor-alpha, inducing tumor cell growth arrest 2. NCR2 also participates in immune regulation by mediating HLA-DP-dependent editing of CD8+ effector T cell populations, preventing hyper-expanded T cell clones 3. Disease relevance: Higher NCR2 expression correlates with improved survival in glioblastoma, and NCR2+ NK cells more effectively control dissemination of PDGF-DD-expressing tumors 2. Additionally, NCR2+ innate lymphoid cells in the female genital tract display rapid antiviral responses to HIV stimulation 4. Clinical significance: NCR2 expression represents a potential biomarker for tumor prognosis and immunotherapy response, with therapeutic potential for enhancing NK cell-mediated tumor surveillance 1.

Sources cited
1
NCR2/NKp44 recognizes PDGF-DD on tumors and triggers NK cell IFN-γ and TNF-α secretion that induces tumor cell growth arrest; NCR2 expression correlates with survival in glioblastoma
PMID: 29275861
2
NKp44/NCR2 recognizes HLA-DP ligands on CD8+ T cells and mediates immune regulation by preventing hyper-expanded T cell clones
PMID: 38615318
3
NCR2/NKp44 is an activating NK cell receptor with diverse ligands; NCR2 biology is being harnessed for novel therapeutic interventions for enhanced tumor surveillance
PMID: 31134055
4
NCR2/NKp44+ innate lymphoid cells are present in the female genital tract and display rapid antiviral responses to HIV stimulation
PMID: 40983704
5
NCR2/NKp44 is expressed on decidual NK cells involved in NK cell residence during pregnancy
PMID: 33030400
6
NKp44/NCR2 expression is upregulated on NK cells upon stimulation with IL-2 or IL-15
PMID: 35154097
Disease Associationsⓘ20
liver diseaseOpen Targets
0.12Weak
cardiac transplantOpen Targets
0.12Weak
rheumatoid arthritisOpen Targets
0.08Suggestive
neoplasmOpen Targets
0.08Suggestive
hypertensionOpen Targets
0.06Suggestive
acute myeloid leukemiaOpen Targets
0.06Suggestive
Abnormality of the breastOpen Targets
0.05Suggestive
hemolytic anemiaOpen Targets
0.05Suggestive
pleural empyemaOpen Targets
0.05Suggestive
synovial sarcomaOpen Targets
0.05Suggestive
lung diseaseOpen Targets
0.04Suggestive
pneumothoraxOpen Targets
0.04Suggestive
lymphomaOpen Targets
0.04Suggestive
viral diseaseOpen Targets
0.04Suggestive
androgenetic alopeciaOpen Targets
0.04Suggestive
telomere syndromeOpen Targets
0.03Suggestive
cancerOpen Targets
0.03Suggestive
ulcerative colitisOpen Targets
0.03Suggestive
salivary gland diseaseOpen Targets
0.03Suggestive
infectionOpen Targets
0.03Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
LSP1Shared pathway100%IFNGProtein interaction99%KMT2EProtein interaction98%CD247Protein interaction96%HLA-EProtein interaction96%KIR2DL1Protein interaction96%
Tissue Expression6 tissues
Lung
0%
Bone Marrow
0%
Heart
0%
Ovary
0%
Liver
0%
Brain
0%
Gene Interaction Network
Click a node to explore
NCR2LSP1IFNGKMT2ECD247HLA-EKIR2DL1
PROTEIN STRUCTURE
Preparing viewer…
PDB1HKF · 2.20 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.47LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.09 [0.82–1.47]
RankingsWhere NCR2 stands among ~20K protein-coding genes
  • #8,463of 20,598
    Most Researched53
  • #15,004of 17,882
    Most Constrained (LOEUF)1.47
Genes detectedNCR2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Rapamycin prevents spontaneous abortion by triggering decidual stromal cell autophagy-mediated NK cell residence.
PMID: 33030400
Autophagy · 2021
1.00
2
A genetic association study of circulating coagulation factor VIII and von Willebrand factor levels.
PMID: 38320121
Blood · 2024
0.90
3
NKp44/HLA-DP-dependent regulation of CD8 effector T cells by NK cells.
PMID: 38615318
Cell Rep · 2024
0.80
4
Natural Killer Cell Receptor Genes in Camels: Another Mammalian Model.
PMID: 31312212
Front Genet · 2019
0.70
5
Spatial and functional diversity of innate lymphoid cells in the human female genital tract may contribute to antiviral responses to HIV.
PMID: 40983704
Nat Immunol · 2025
0.60