KLRC4-KLRK1 readthrough (NKG2-D) gene
A readthrough transcript encoding a natural killer cell receptor involved in immune surveillance and cancer immunotherapy
Gene Information Card
| Symbol | KLRC4-KLRK1 |
|---|---|
| Full Name | KLRC4-KLRK1 readthrough (NKG2-D) |
| Gene Type | readthrough transcript (protein-coding) |
| Chromosomal Location | 12p13.2 |
| NCBI Gene ID | 100528032 ncbi.nlm.nih.gov/gene/100528032 |
| Ensembl ID | ENSG00000273489 |
| UniProt ID | P26718 |
| OMIM ID | 611817 |
| HGNC ID | 43947 |
| Aliases | NKG2-D, NKG2D, CD314, KLRK1, KLRC4 |
Description
KLRC4-KLRK1 is a readthrough transcript that spans the adjacent KLRC4 and KLRK1 genes on chromosome 12. It encodes the NKG2-D (NKG2D) receptor, a type II transmembrane protein expressed on natural killer (NK) cells, CD8+ T cells, and subsets of NKT cells. NKG2D recognizes stress-induced ligands such as MICA, MICB, and ULBP proteins, playing a critical role in immune surveillance against tumors and infected cells. The readthrough transcript produces a functional protein identical to the canonical KLRK1 product.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various) | NKG2D-mediated recognition of stress ligands on tumor cells; loss of ligand expression or receptor shedding leads to immune evasion | ClinVar, COSMIC, literature |
| Rheumatoid arthritis | Dysregulated NKG2D signaling contributes to autoimmune inflammation | ClinVar, literature |
| Celiac disease | NKG2D+ intraepithelial lymphocytes recognize MIC-expressing enterocytes | ClinVar, literature |
| Inflammatory bowel disease | Altered NKG2D expression on mucosal T cells | ClinVar, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Spleen | 12.5 | Medium |
| Lung | 8.3 | Medium |
| Blood | 15.1 | High |
| Bone marrow | 10.2 | Medium |
| Small intestine | 6.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| NK-92 (NK cell line) | 45.2 | High expression |
| Jurkat (T cell line) | 3.1 | Low expression |
| K562 (erythroleukemia) | 0.8 | No significant expression |
| HEK293 (embryonic kidney) | 0.2 | No significant expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1Val) | Missense | <0.01% | Potential loss of start codon; functional impact unknown |
| c.503C>T (p.Thr168Ile) | Missense | 0.02% | Reduced ligand binding affinity |
| c.790G>A (p.Gly264Arg) | Missense | <0.01% | Impaired receptor dimerization |
Mutation functional classification
Loss of Function (LOF)
Mutations affecting start codon or dimerization interface reduce NKG2D surface expression and signaling.
Gain of Function (GOF)
Not well documented; no common gain-of-function variants reported.
Dominant Negative (DN)
No dominant-negative mutations described in literature.
View complete mutation data：
Gene Ontology (GO)
Pathways
• NK cell mediated cytotoxicity (KEGG hsa04650)
• Natural killer cell signaling (Reactome R-HSA-168256)
• Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (Reactome R-HSA-198933)
Protein Summary
The NKG2-D protein (also known as NKG2D, CD314) is a 216-amino-acid type II transmembrane receptor with an extracellular C-type lectin-like domain. It forms homodimers and associates with DAP10 (HCST) adaptor protein to transduce activating signals. NKG2D binds stress-induced ligands MICA, MICB, and ULBP1-6, triggering cytotoxicity and cytokine production in NK cells and co-stimulation in T cells. The protein is encoded by the KLRK1 gene and also by the KLRC4-KLRK1 readthrough transcript.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KLRC4-KLRK1 Knockout HEK293 Cell Line | EDJ-KQ52488 | Human | 100528032 | Details Get a Quote |
| KLRC4-KLRK1 Knockout HeLa Cell Line | EDJ-KQ60951 | Human | 100528032 | Details Get a Quote |
| KLRC4-KLRK1 Knockout A-549 Cell Line | EDJ-KQ69426 | Human | 100528032 | Details Get a Quote |
| KLRC4-KLRK1 Knockout HCT 116 Cell Line | EDJ-KQ77777 | Human | 100528032 | Details Get a Quote |
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