PTPN22
Protein Tyrosine Phosphatase Non-Receptor Type 22
Gene Information Card
| Symbol | PTPN22 |
|---|---|
| Full Name | Protein Tyrosine Phosphatase Non-Receptor Type 22 |
| Gene Type | Protein coding |
| Chromosomal Location | 1p13.2 |
| NCBI Gene ID | 26191 ncbi.nlm.nih.gov/gene/26191 |
| Ensembl ID | ENSG00000134242 |
| UniProt ID | Q9Y2R2 |
| OMIM ID | 600716 |
| HGNC ID | 9652 |
| Aliases | Lyp, PTPN8, PTPN22.1, PTPN22.2 |
Description
PTPN22 encodes lymphoid tyrosine phosphatase (Lyp), a protein tyrosine phosphatase expressed primarily in hematopoietic cells. Lyp negatively regulates T cell receptor (TCR) signaling by dephosphorylating and inactivating key signaling molecules such as Lck, ZAP70, and CD3ζ. A common missense variant (R620W, rs2476601) is associated with increased risk for several autoimmune diseases, including type 1 diabetes, rheumatoid arthritis, and systemic lupus erythematosus.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Type 1 Diabetes | R620W variant reduces Lyp activity, leading to enhanced TCR signaling and autoimmunity | Multiple genome-wide association studies (GWAS) and meta-analyses |
| Rheumatoid Arthritis | R620W variant impairs negative regulation of T cells, promoting autoreactive responses | GWAS and case-control studies |
| Systemic Lupus Erythematosus | R620W variant alters B cell and T cell tolerance mechanisms | Association studies and functional assays |
| Graves' Disease | R620W variant linked to increased thyroid autoantibody production | Candidate gene studies |
| Myasthenia Gravis | R620W variant associated with early-onset disease | Case-control studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Spleen | 42.3 | High |
| Lymph node | 38.1 | High |
| Bone marrow | 25.7 | Medium |
| Whole blood | 18.9 | Medium |
| Thymus | 15.2 | Medium |
| Lung | 1.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Jurkat (T cell leukemia) | 58.4 | High expression; model for TCR signaling |
| Raji (B cell lymphoma) | 22.1 | Moderate expression |
| K562 (myelogenous leukemia) | 3.5 | Low expression |
| HEK293 (embryonic kidney) | 0.8 | Very low; not hematopoietic |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| R620W (rs2476601) | Missense | ~10-15% in European populations | Reduces phosphatase activity; impairs interaction with CSK; increases autoimmune risk |
| L387F (rs33996649) | Missense | <1% | Unknown functional effect; rare |
| R263Q (rs3765598) | Missense | <1% | Potential loss-of-function; limited data |
Mutation functional classification
Loss of Function (LOF)
R620W variant reduces catalytic activity and disrupts binding to CSK, leading to diminished negative regulation of TCR signaling.
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported in PTPN22.
Dominant Negative (DN)
R620W may act in a dominant-negative manner by sequestering CSK away from the TCR complex.
View complete mutation data：
Gene Ontology (GO)
| • protein tyrosine phosphatase activity | • protein binding |
| • T cell receptor signaling pathway | • negative regulation of T cell activation |
| • dephosphorylation | • cytoplasm |
| • nucleus |
Pathways
• T cell receptor signaling pathway (KEGG: hsa04660)
• PD-1 signaling
• CSK-mediated inhibition of TCR signaling
Protein Summary
Lymphoid tyrosine phosphatase (Lyp) is a 105 kDa protein encoded by PTPN22. It contains an N-terminal catalytic phosphatase domain and a C-terminal proline-rich region that mediates interaction with the SH3 domain of CSK. Lyp is predominantly expressed in immune cells and functions as a key negative regulator of TCR signaling. The R620W variant (rs2476601) is one of the most replicated genetic risk factors for autoimmune diseases, affecting approximately 10-15% of individuals of European descent.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PTPN22 Knockout HEK293 Cell Line | EDJ-KQ3809 | Human | 26191 | Details Get a Quote |
| PTPN22 Knockout HeLa Cell Line | EDJ-KQ55894 | Human | 26191 | Details Get a Quote |
| PTPN22 Knockout A-549 Cell Line | EDJ-KQ64384 | Human | 26191 | Details Get a Quote |
| PTPN22 Knockout HCT 116 Cell Line | EDJ-KQ72835 | Human | 26191 | Details Get a Quote |
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