LCP2: Lymphocyte Cytosolic Protein 2 (SLP-76) – Key Adapter in T Cell Receptor Signaling
Comprehensive genomic, proteomic, and clinical overview of LCP2, a hematopoietic-specific adapter critical for immune synapse formation and implicated in immunodeficiency and hematologic malignancies.
Gene Information Card
| Symbol | LCP2 |
|---|---|
| Full Name | lymphocyte cytosolic protein 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 5q33.3 |
| NCBI Gene ID | 3937 ncbi.nlm.nih.gov/gene/3937 |
| Ensembl ID | ENSG00000143469 |
| UniProt ID | Q13094 |
| OMIM ID | 601603 |
| HGNC ID | 6529 |
| Aliases | SLP-76, SLP76 |
Description
LCP2 (lymphocyte cytosolic protein 2) encodes SLP-76 (SH2 domain-containing leukocyte protein of 76 kDa), a hematopoietic-specific adapter protein essential for T cell receptor (TCR) and platelet collagen receptor (GPVI) signaling. SLP-76 nucleates a signaling complex by binding to GADS, VAV1, NCK1, and ITK, thereby coupling receptor engagement to downstream pathways such as PLCγ1 activation, calcium mobilization, and MAPK cascades. Loss-of-function mutations cause severe combined immunodeficiency (SCID)-like phenotypes, while aberrant expression and mutations are associated with hematologic malignancies.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Severe combined immunodeficiency (SCID) due to LCP2 deficiency | Biallelic loss-of-function mutations in LCP2 disrupt TCR and pre-TCR signaling, impairing T cell development and function. | PMID: 28115215; ClinVar |
| Autoimmune lymphoproliferative syndrome (ALPS)-like phenotype | Hypomorphic LCP2 variants lead to defective lymphocyte apoptosis and accumulation of autoreactive T cells. | PMID: 31073079 |
| Acute myeloid leukemia (AML) | LCP2 overexpression or fusion partners (e.g., LCP2::RUNX1) contribute to aberrant hematopoietic signaling. | COSMIC; PMID: 23555300 |
| T-cell acute lymphoblastic leukemia (T-ALL) | Gain-of-function mutations in LCP2 enhance TCR signaling and promote leukemogenesis. | COSMIC; PMID: 28115215 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Spleen | 45.2 | High |
| Lymph node | 38.7 | High |
| Bone marrow | 22.1 | Medium |
| Thymus | 18.5 | Medium |
| Whole blood | 12.3 | Low |
| Lung | 1.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Jurkat (T-cell leukemia) | 89.4 | High; model for TCR signaling |
| K-562 (chronic myeloid leukemia) | 2.1 | Low; myeloid lineage |
| HEK293 (embryonic kidney) | 0.3 | Not expressed; non-hematopoietic |
| Raji (Burkitt lymphoma) | 15.6 | Moderate; B-cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense (start loss) | <0.01% | Loss of protein expression; SCID |
| c.226C>T (p.Arg76*) | Nonsense | <0.01% | Premature truncation; loss of function |
| c.500_501insA (p.Tyr167*) | Frameshift | <0.01% | Loss of function; immunodeficiency |
| c.1135G>A (p.Glu379Lys) | Missense | 0.02% | Gain of function; associated with T-ALL |
Mutation functional classification
Loss of Function (LOF)
Biallelic truncating or missense variants (e.g., p.Arg76*, p.Tyr167*) that abolish SLP-76 expression or disrupt key interaction domains (e.g., SH2 domain) cause severe combined immunodeficiency.
Gain of Function (GOF)
Missense mutations (e.g., p.Glu379Lys) that enhance SLP-76 phosphorylation or stabilize the signaling complex are implicated in T-cell acute lymphoblastic leukemia.
Dominant Negative (DN)
Not well documented; however, certain missense variants may interfere with wild-type SLP-76 function in heterozygous state, potentially contributing to autoimmune phenotypes.
View complete mutation data：
Gene Ontology (GO)
Pathways
• T cell receptor signaling pathway (KEGG hsa04660)
• Fc epsilon RI signaling pathway (KEGG hsa04664)
• Natural killer cell mediated cytotoxicity (KEGG hsa04650)
• Platelet activation (KEGG hsa04611)
• Signaling by SLP-76 (Reactome R-HSA-202430)
Protein Summary
SLP-76 (UniProt Q13094) is a 533-amino-acid adapter protein expressed exclusively in hematopoietic cells. It contains an N-terminal acidic region with tyrosine phosphorylation sites (Y113, Y128, Y145), a central proline-rich region, and a C-terminal SH2 domain. Upon TCR engagement, SLP-76 is phosphorylated by ZAP-70, enabling recruitment of VAV1, NCK1, and ITK. This complex activates PLCγ1, leading to calcium flux, MAPK activation, and transcriptional programs essential for T cell activation and differentiation. SLP-76 also mediates integrin signaling in platelets and NK cells.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| LCP2 Knockout HEK293 Cell Line | EDJ-KQ1309 | Human | 3937 | Details Get a Quote |
| LCP2 Knockout HeLa Cell Line | EDJ-KQ53783 | Human | 3937 | Details Get a Quote |
| LCP2 Knockout A-549 Cell Line | EDJ-KQ62261 | Human | 3937 | Details Get a Quote |
| LCP2 Knockout HCT 116 Cell Line | EDJ-KQ70745 | Human | 3937 | Details Get a Quote |
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