GAB1: GRB2-Associated Binding Protein 1
A key scaffolding adaptor in receptor tyrosine kinase and cytokine receptor signaling pathways
Gene Information Card
| Symbol | GAB1 |
|---|---|
| Full Name | GRB2-associated binding protein 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 4q31.21 |
| NCBI Gene ID | 2549 ncbi.nlm.nih.gov/gene/2549 |
| Ensembl ID | ENSG00000109458 |
| UniProt ID | Q13480 |
| OMIM ID | 604439 |
| HGNC ID | 4066 |
| Aliases | GRB2-associated binder 1, Gab1, GRB2-associated binding protein 1 |
Description
GAB1 (GRB2-associated binding protein 1) encodes a scaffolding adaptor protein that mediates signals from receptor tyrosine kinases (e.g., EGFR, MET) and cytokine receptors. It contains a pleckstrin homology (PH) domain and multiple tyrosine phosphorylation sites that recruit SH2 domain-containing proteins such as PI3K, SHP2, and GRB2. GAB1 is critical for cell growth, migration, and survival, and its dysregulation is implicated in cancer and developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Noonan syndrome | Gain-of-function mutations in GAB1 enhance RAS-MAPK signaling, leading to developmental abnormalities. | ClinVar, OMIM |
| Lung cancer | GAB1 overexpression and amplification activate PI3K-Akt and MAPK pathways, promoting tumor growth and metastasis. | COSMIC, NCBI PubMed |
| Gastric cancer | GAB1 amplification and increased expression correlate with MET-driven oncogenic signaling. | COSMIC, NCBI PubMed |
| Hepatocellular carcinoma | GAB1 upregulation contributes to HGF/MET-mediated invasion and poor prognosis. | NCBI PubMed |
| Breast cancer | GAB1 overexpression associated with HER2/EGFR signaling and resistance to targeted therapy. | COSMIC, NCBI PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 18.5 | High |
| Kidney | 15.2 | High |
| Lung | 12.8 | Medium |
| Brain | 8.3 | Medium |
| Heart | 6.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 22.4 | Embryonic kidney cells; high endogenous expression |
| A549 | 14.7 | Lung adenocarcinoma cell line |
| MCF7 | 11.2 | Breast cancer cell line |
| HepG2 | 19.1 | Hepatocellular carcinoma cell line |
| K562 | 9.8 | Chronic myeloid leukemia cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412Cys) | Missense | <0.1% | Gain-of-function; enhances MAPK signaling; associated with Noonan syndrome |
| c.1567G>A (p.Glu523Lys) | Missense | <0.1% | Gain-of-function; increased SHP2 binding; Noonan syndrome |
| c.2101_2102insA (p.Thr701Asnfs*3) | Frameshift | <0.1% | Loss-of-function; truncation; rare in cancer |
| Amplification | Copy number gain | 1-5% in lung/gastric cancer | Overexpression; activates PI3K-Akt pathway |
Mutation functional classification
Loss of Function (LOF)
Frameshift or nonsense mutations that truncate the protein, reducing scaffolding function and downstream signaling.
Gain of Function (GOF)
Missense mutations (e.g., p.Arg412Cys, p.Glu523Lys) that enhance binding to SHP2 or GRB2, leading to hyperactivation of RAS-MAPK and PI3K-Akt pathways.
Dominant Negative (DN)
Not well characterized; some truncating variants may interfere with wild-type GAB1 function in heterozygotes.
View complete mutation data：
Gene Ontology (GO)
Pathways
• PI3K-Akt signaling pathway (KEGG: hsa04151)
• RAS-MAPK signaling pathway (KEGG: hsa04010)
• EGFR tyrosine kinase inhibitor resistance (KEGG: hsa01521)
• MET signaling pathway (Reactome: R-HSA-8875878)
• Cytokine-cytokine receptor interaction (KEGG: hsa04060)
Protein Summary
GAB1 is a 694-amino-acid scaffolding protein with an N-terminal PH domain that binds phosphatidylinositol lipids for membrane recruitment, and multiple tyrosine motifs that serve as docking sites for SH2 domain-containing effectors. It is phosphorylated by receptor and non-receptor tyrosine kinases, enabling recruitment of PI3K, SHP2, and GRB2. GAB1 integrates signals from growth factors (e.g., EGF, HGF), cytokines, and hormones, regulating cell proliferation, migration, and survival. Aberrant GAB1 activity contributes to oncogenesis and developmental syndromes.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GAB1 Knockout HEK293 Cell Line | EDJ-KQ1204 | Human | 2549 | Details Get a Quote |
| GAB1 Knockout A-549 Cell Line | EDJ-KQ20518 | Human | 2549 | Details Get a Quote |
| GAB1 Knockout HCT 116 Cell Line | EDJ-KQ20519 | Human | 2549 | Details Get a Quote |
| GAB1 Knockout HeLa Cell Line | EDJ-KQ20520 | Human | 2549 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
