LCK Gene: Structure, Function, and Clinical Significance
A comprehensive overview of the LCK gene, its protein product, associated diseases, expression patterns, and mutations.
Gene Information Card
| Symbol | LCK |
|---|---|
| Full Name | LCK proto-oncogene, Src family tyrosine kinase |
| Gene Type | protein coding |
| Chromosomal Location | 1p35.2 |
| NCBI Gene ID | 3932 ncbi.nlm.nih.gov/gene/3932 |
| Ensembl ID | ENSG00000182866 |
| UniProt ID | P06239 |
| OMIM ID | 153390 |
| HGNC ID | 6524 |
| Aliases | p56lck, YT16, Hck-3, LSK |
Description
The LCK gene encodes a member of the Src family of non-receptor tyrosine kinases. LCK is primarily expressed in T cells and natural killer (NK) cells, where it plays a critical role in T cell receptor (TCR) signaling, T cell development, and activation. It phosphorylates immunoreceptor tyrosine-based activation motifs (ITAMs) on the CD3 complex and ZAP-70, initiating downstream signaling cascades. Mutations in LCK are associated with immunodeficiency and certain cancers, while aberrant expression is linked to T cell malignancies.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Severe combined immunodeficiency (SCID) | Loss-of-function mutations in LCK impair TCR signaling, leading to defective T cell development and function. | OMIM, PubMed |
| T cell acute lymphoblastic leukemia (T-ALL) | Gain-of-function mutations or overexpression of LCK can promote uncontrolled T cell proliferation. | COSMIC, PubMed |
| Non-small cell lung cancer (NSCLC) | LCK expression is elevated in some NSCLC tumors and may contribute to tumor progression. | PubMed |
| Colorectal cancer | LCK overexpression has been observed in colorectal cancer and may be associated with poor prognosis. | PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Tonsil | High | High |
| Lymph node | High | High |
| Spleen | High | High |
| Appendix | High | High |
| Bone marrow | Medium | Medium |
| Thymus | High | High |
| Lung | Low | Low |
| Colon | Low | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Jurkat (T cell leukemia) | High | T cell line, commonly used for TCR signaling studies |
| MOLT-4 (T cell leukemia) | High | T cell line |
| K-562 (CML) | Low | Myeloid line, low LCK expression |
| HeLa (cervical cancer) | Low | Non-hematopoietic line, minimal expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1024C>T (p.Arg342Ter) | Nonsense | Rare | Loss-of-function, truncates protein, causes SCID |
| c.767T>C (p.Leu256Pro) | Missense | Rare | Loss-of-function, disrupts kinase domain, impairs signaling |
| c.833G>A (p.Arg278His) | Missense | Rare | Gain-of-function, increased kinase activity, associated with T-ALL |
| c.1282A>G (p.Thr428Ala) | Missense | Rare | Gain-of-function, enhances autophosphorylation, oncogenic potential |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in LCK, such as nonsense or missense variants in the kinase domain, impair TCR signaling and T cell development, leading to immunodeficiency (e.g., SCID).
Gain of Function (GOF)
Gain-of-function mutations, often in the kinase domain or SH2 domain, increase LCK kinase activity, promoting aberrant T cell proliferation and contributing to T cell malignancies like T-ALL.
Dominant Negative (DN)
Dominant-negative mutations, though rare, can interfere with wild-type LCK function by forming inactive heterodimers, thereby suppressing TCR signaling.
View complete mutation data：
Gene Ontology (GO)
| • protein tyrosine kinase activity | • ATP binding |
| • signal transduction | • T cell receptor signaling pathway |
| • cell proliferation | • immune response |
| • protein phosphorylation | • cell surface receptor signaling pathway |
Pathways
• T cell receptor signaling pathway
• Natural killer cell mediated cytotoxicity
• PD-1 signaling
• Fc epsilon RI signaling pathway
• Neurotrophin signaling pathway
Protein Summary
The LCK protein (p56lck) is a 56 kDa Src family tyrosine kinase composed of SH3, SH2, and kinase domains. It is myristoylated at its N-terminus, anchoring to the plasma membrane. In T cells, LCK associates with the co-receptors CD4 and CD8 and phosphorylates ITAMs on the TCR/CD3 complex upon antigen recognition. This initiates a signaling cascade involving ZAP-70, LAT, and SLP-76, leading to T cell activation, proliferation, and cytokine production. LCK also plays roles in thymocyte development and apoptosis. Dysregulation of LCK is implicated in immunodeficiency and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| LCK Knockout HEK293 Cell Line | EDJ-KQ17831 | Human | 3932 | Details Get a Quote |
| LCK Knockout HeLa Cell Line | EDJ-KQ53779 | Human | 3932 | Details Get a Quote |
| LCK Knockout A-549 Cell Line | EDJ-KQ62258 | Human | 3932 | Details Get a Quote |
| LCK Knockout HCT 116 Cell Line | EDJ-KQ70743 | Human | 3932 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
