GAB2 (GRB2 Associated Binding Protein 2)
A scaffold protein in signal transduction pathways, implicated in cancer and immune disorders.
Gene Information Card
| Symbol | GAB2 |
|---|---|
| Full Name | GRB2 Associated Binding Protein 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 11q14.1 |
| NCBI Gene ID | 9846 ncbi.nlm.nih.gov/gene/9846 |
| Ensembl ID | ENSG00000133313 |
| UniProt ID | Q9UQC2 |
| OMIM ID | 606203 |
| HGNC ID | 4894 |
| Aliases | p85, GRB2-associated binding protein 2, KIAA0571 |
Description
GAB2 (GRB2 Associated Binding Protein 2) is a scaffold protein that mediates signal transduction downstream of various receptor tyrosine kinases and cytokine receptors. It plays a critical role in the PI3K-Akt and MAPK signaling pathways, influencing cell growth, differentiation, and survival. GAB2 is implicated in several cancers, including breast cancer, melanoma, and leukemia, as well as in immune system disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | GAB2 amplification and overexpression enhance PI3K-Akt signaling, promoting cell proliferation and survival. | NCBI Gene, COSMIC |
| Melanoma | GAB2 overexpression activates MAPK/ERK pathway, contributing to tumor progression and metastasis. | COSMIC, PubMed (PMID: 20010872) |
| Acute myeloid leukemia (AML) | GAB2 mutations and fusions (e.g., with TEL) lead to constitutive activation of downstream signaling. | COSMIC, ClinVar |
| Noonan syndrome-like disorder | Gain-of-function mutations in GAB2 disrupt RAS-MAPK signaling, causing developmental abnormalities. | OMIM (606203) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Breast | 8.3 | Low |
| Lung | 15.2 | Medium |
| Ovary | 20.1 | High |
| Testis | 18.7 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | 22.4 | High expression |
| A549 (lung cancer) | 14.1 | Medium expression |
| HEK293 (embryonic kidney) | 9.8 | Low expression |
| K562 (leukemia) | 30.2 | Very high expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1118A>G (p.Asn373Ser) | Missense | <0.1% | Altered protein interaction; potential gain-of-function |
| c.1456C>T (p.Arg486Trp) | Missense | <0.1% | Impaired binding to SH2 domain; loss-of-function |
| Amplification | Copy number gain | 5-10% in breast cancer | Increased GAB2 expression; oncogenic |
| TEL-GAB2 fusion | Gene fusion | Rare | Constitutive activation of signaling; leukemogenic |
Mutation functional classification
Loss of Function (LOF)
Mutations such as p.Arg486Trp reduce binding to downstream effectors, impairing signal transduction.
Gain of Function (GOF)
Amplification and missense mutations like p.Asn373Ser enhance PI3K-Akt and MAPK signaling, promoting oncogenesis.
Dominant Negative (DN)
Not well characterized; some truncating mutations may interfere with wild-type GAB2 function.
View complete mutation data：
Gene Ontology (GO)
| • SH3/SH2 adaptor activity (GO:0005070) | • signal transduction (GO:0007165) |
| • positive regulation of GTPase activity (GO:0043547) | • insulin receptor signaling pathway (GO:0008286) |
| • intracellular signal transduction (GO:0035556) |
Pathways
• PI3K-Akt signaling pathway (KEGG: hsa04151)
• MAPK signaling pathway (KEGG: hsa04010)
• ErbB signaling pathway (KEGG: hsa04012)
• Fc epsilon RI signaling pathway (KEGG: hsa04664)
Protein Summary
GAB2 is a 676-amino acid scaffold protein containing an N-terminal PH domain, multiple proline-rich regions, and several tyrosine phosphorylation sites. It binds to GRB2, SHC, and p85 (PI3K regulatory subunit), facilitating the assembly of signaling complexes. GAB2 is essential for normal immune cell function and is frequently dysregulated in cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GAB2 Knockout HEK293 Cell Line | EDJ-KQ1205 | Human | 9846 | Details Get a Quote |
| GAB2 Knockout A-549 Cell Line | EDJ-KQ20521 | Human | 9846 | Details Get a Quote |
| GAB2 Knockout HCT 116 Cell Line | EDJ-KQ20522 | Human | 9846 | Details Get a Quote |
| GAB2 Knockout HeLa Cell Line | EDJ-KQ20523 | Human | 9846 | Details Get a Quote |
