CD244: Natural Killer Cell Receptor 2B4
A key immune checkpoint receptor regulating NK and T cell activation
Gene Information Card
| Symbol | CD244 |
|---|---|
| Full Name | CD244 molecule, natural killer cell receptor 2B4 |
| Gene Type | protein-coding |
| Chromosomal Location | 1q23.3 |
| NCBI Gene ID | 51744 ncbi.nlm.nih.gov/gene/51744 |
| Ensembl ID | ENSG00000122223 |
| UniProt ID | Q9BZW8 |
| OMIM ID | 605554 |
| HGNC ID | 18171 |
| Aliases | 2B4, NAIL, NKR2B4, SLAMF4 |
Description
CD244 (2B4) is a member of the signaling lymphocyte activation molecule (SLAM) family of immunoreceptors. It is expressed on natural killer (NK) cells, a subset of T cells, and some myeloid cells. CD244 binds CD48 and can either activate or inhibit immune cell function depending on the cellular context and adaptor protein availability. It plays a critical role in NK cell cytotoxicity, cytokine production, and immune surveillance against tumors and viruses.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| X-linked lymphoproliferative disease (XLP) | CD244 signaling is impaired due to SAP (SH2D1A) deficiency, leading to defective NK cell cytotoxicity and uncontrolled lymphocyte proliferation in response to Epstein-Barr virus infection. | OMIM #308240; Tangye et al., Nat Rev Immunol 2013 |
| Systemic lupus erythematosus (SLE) | Polymorphisms in CD244 are associated with increased risk of SLE; altered CD244 expression on NK cells correlates with disease activity. | OMIM #605554; Suzuki et al., J Immunol 2008 |
| Chronic lymphocytic leukemia (CLL) | CD244 overexpression on CLL cells contributes to immune evasion by inhibiting NK cell-mediated killing. | Gattazzo et al., Blood 2014 |
| Melanoma | CD244 expression on tumor-infiltrating lymphocytes is associated with exhausted phenotype and poor prognosis. | Messal et al., Cancer Res 2011 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Spleen | 12.3 | Medium |
| Lung | 8.7 | Medium |
| Whole blood | 6.5 | Low |
| Lymph node | 15.1 | Medium |
| Bone marrow | 4.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| NK-92 | 45.2 | High expression |
| Jurkat (T cell) | 2.1 | Low expression |
| K562 | 0.8 | Not detected |
| Raji (B cell) | 1.3 | Low expression |
| THP-1 (monocyte) | 3.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | missense | <0.01% | Loss of start codon; likely loss of function |
| c.497C>T (p.Thr166Ile) | missense | 0.02% | Reduced CD48 binding affinity |
| c.862G>A (p.Gly288Arg) | missense | 0.01% | Altered signaling; associated with SLE |
| c.1045_1047del (p.Lys349del) | in-frame deletion | <0.01% | Impaired adaptor recruitment |
Mutation functional classification
Loss of Function (LOF)
Mutations that disrupt the start codon or critical residues in the Ig-like domain (e.g., p.Met1?, p.Thr166Ile) reduce CD48 binding and downstream signaling, leading to impaired NK cell activation.
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported in CD244.
Dominant Negative (DN)
Truncating mutations in the cytoplasmic tail (e.g., p.Lys349del) may interfere with SAP binding and exert dominant-negative effects on SLAM family signaling.
View complete mutation data：
Gene Ontology (GO)
Pathways
• SLAM family signaling pathway (Reactome: R-HSA-2424491)
• Natural killer cell mediated cytotoxicity (KEGG: hsa04650)
• Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (Reactome: R-HSA-198933)
Protein Summary
CD244 (2B4) is a 367-amino acid transmembrane glycoprotein belonging to the SLAM family (SLAMF4). It contains an extracellular Ig-like V-type domain that binds CD48, and a cytoplasmic tail with immunoreceptor tyrosine-based switch motifs (ITSMs). Upon ligand binding, CD244 recruits the adaptor SAP (SH2D1A) or EAT-2, leading to activation of NK cell cytotoxicity and cytokine secretion. In the absence of SAP, CD244 can deliver inhibitory signals. The protein is a target for cancer immunotherapy and a biomarker for immune exhaustion.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CD244 Knockout HEK293 Cell Line | EDJ-KQ11213 | Human | 51744 | Details Get a Quote |
| CD244 Knockout HeLa Cell Line | EDJ-KQ56356 | Human | 51744 | Details Get a Quote |
| CD244 Knockout A-549 Cell Line | EDJ-KQ64846 | Human | 51744 | Details Get a Quote |
| CD244 Knockout HCT 116 Cell Line | EDJ-KQ73290 | Human | 51744 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
