PTPN6
Protein Tyrosine Phosphatase Non-Receptor Type 6 (SHP-1)
Gene Information Card
| Symbol | PTPN6 |
|---|---|
| Full Name | Protein Tyrosine Phosphatase Non-Receptor Type 6 |
| Gene Type | protein-coding |
| Chromosomal Location | 12p13.31 |
| NCBI Gene ID | 5777 ncbi.nlm.nih.gov/gene/5777 |
| Ensembl ID | ENSG00000111679 |
| UniProt ID | P29350 |
| OMIM ID | 176883 |
| HGNC ID | 9658 |
| Aliases | SHP-1, HCP, PTP1C, SHP1, SH-PTP1 |
Description
PTPN6 encodes a member of the protein tyrosine phosphatase (PTP) family, known as SHP-1. This cytoplasmic phosphatase contains two SH2 domains and is predominantly expressed in hematopoietic cells. SHP-1 negatively regulates multiple signaling pathways by dephosphorylating key tyrosine kinases and receptors, thereby modulating immune cell activation, proliferation, and differentiation. Loss-of-function mutations in PTPN6 are associated with immune dysregulation and hematologic malignancies.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neutropenia, severe congenital, 7 (SCN7) | Biallelic loss-of-function mutations impair SHP-1 activity, leading to defective myeloid differentiation and increased apoptosis of neutrophil progenitors. | ClinVar, OMIM #617014 |
| Myelodysplastic syndrome (MDS) | Somatic mutations or reduced expression of PTPN6 contribute to aberrant hematopoietic signaling and clonal expansion. | COSMIC, PubMed studies |
| Lymphoma, various subtypes | Epigenetic silencing or mutation of PTPN6 disrupts negative regulation of JAK/STAT and BCR signaling, promoting lymphomagenesis. | COSMIC, PubMed studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone marrow | 38.5 | High |
| Spleen | 32.1 | High |
| Lymph node | 28.7 | High |
| Whole blood | 25.3 | High |
| Lung | 6.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (leukemia) | 42.1 | High expression; used in functional studies |
| HL-60 (promyelocytic) | 38.9 | High expression; model for myeloid differentiation |
| Jurkat (T-cell) | 35.4 | High expression; T-cell signaling model |
| HeLa (cervical) | 4.8 | Low expression; non-hematopoietic |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.139G>A (p.Gly47Arg) | Missense | <0.01% | Loss of SH2 domain function; associated with SCN7 |
| c.550C>T (p.Arg184*) | Nonsense | <0.01% | Truncation; loss of phosphatase activity; SCN7 |
| c.1123A>G (p.Asn375Asp) | Missense | <0.01% | Reduced catalytic activity; reported in MDS |
Mutation functional classification
Loss of Function (LOF)
Most reported pathogenic mutations (missense, nonsense, frameshift) lead to reduced or absent phosphatase activity, impairing negative regulation of hematopoietic signaling.
Gain of Function (GOF)
Not well documented; no recurrent gain-of-function mutations described in major databases.
Dominant Negative (DN)
Some missense mutations in the SH2 domains may exert dominant-negative effects by competing with wild-type SHP-1 for binding partners, though evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • protein tyrosine phosphatase activity | • SH2 domain binding |
| • negative regulation of cell population proliferation | • negative regulation of signal transduction |
| • hematopoietic progenitor cell differentiation | • immune system process |
Pathways
• JAK-STAT signaling pathway (negative regulation)
• B cell receptor signaling pathway (negative regulation)
• T cell receptor signaling pathway (negative regulation)
• ErbB signaling pathway (negative regulation)
Protein Summary
SHP-1 (PTPN6) is a 68 kDa cytoplasmic protein tyrosine phosphatase with two N-terminal SH2 domains and a C-terminal catalytic domain. It is expressed primarily in hematopoietic cells and functions as a key negative regulator of immune receptor signaling. SHP-1 dephosphorylates activated tyrosine kinases (e.g., JAK, SYK, LYN) and receptor subunits, thereby attenuating proliferative and inflammatory signals. Loss of SHP-1 function leads to hyperresponsive immune cells and contributes to autoimmunity, immunodeficiency, and hematologic cancers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PTPN6 Knockout HEK293 Cell Line | EDJ-KQ525 | Human | 5777 | Details Get a Quote |
| PTPN6 Knockout HeLa Cell Line | EDJ-KQ18017 | Human | 5777 | Details Get a Quote |
| PTPN6 Knockout A-549 Cell Line | EDJ-KQ18863 | Human | 5777 | Details Get a Quote |
| PTPN6 Knockout HCT 116 Cell Line | EDJ-KQ18864 | Human | 5777 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
