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28 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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GAB2
GRB2 associated binding protein 2
Chromosome 11 · 11q14.1
NCBI Gene: 9846Ensembl: ENSG00000033327.13HGNC: HGNC:14458UniProt: Q9UQC2
179PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
transmembrane receptor protein tyrosine kinase adaptor activityprotein bindingpositive regulation of cell population proliferationosteoclast differentiationcancerchronic myelogenous leukemiahair colorAbnormality of the skeletal system
✦AI Summary

GAB2 is a cytoplasmic adapter protein that functions as a molecular scaffold linking membrane receptors to intracellular signaling pathways 1. Lacking intrinsic catalytic activity, GAB2 becomes phosphorylated by protein-tyrosine kinases and recruits SH2 domain-containing proteins including SHP2, PI3K p85, PLCγ, and Crk 1. This scaffolding facilitates downstream signaling cascades including PI3K/AKT and ERK/MAPK pathways that regulate cell growth, differentiation, migration, and apoptosis 2. GAB2 mediates osteoclast differentiation through RANK signaling and regulates mast cell degranulation in allergic responses 1. Clinically, GAB2 dysregulation associates with multiple malignancies. GAB2 is recurrently amplified in lung adenocarcinoma and ovarian cancer, with overexpression capable of transforming immortalized cell lines 3. Recent evidence indicates GAB2 overexpression accelerates acute myeloid leukemia progression by facilitating survival of transformed cells, potentially preceding signaling mutations 4. GAB2 genetic variants (rs2373115) associate with Alzheimer's disease susceptibility, particularly in white populations 5, 6. These findings identify GAB2 as both an oncogene and disease-associated locus with therapeutic potential through disruption of its scaffolding function or upstream signaling interactions.

Sources cited
1
GAB2 structure, phosphorylation-dependent recruitment of SH2 proteins, and downstream signaling through PI3K/AKT and MAPK pathways
PMID: 26095858
2
GAB2 scaffolding function in cancer, role in PI3K-AKT and ERK pathways, and cancer relevance
PMID: 22871571
3
GAB2 recurrent amplification in lung adenocarcinoma and ovarian cancer, ability to transform cell lines
PMID: 26554907
4
GAB2 overexpression accelerates AML progression and supports survival of transformed cells
PMID: 40773291
5
GAB2 rs2373115 genetic association with Alzheimer's disease risk in white populations
PMID: 33331110
6
GAB2 protein structure, function as scaffolding molecule, and involvement in Alzheimer's disease pathogenesis
PMID: 20502503
Disease Associationsⓘ20
cancerOpen Targets
0.61Moderate
chronic myelogenous leukemiaOpen Targets
0.54Moderate
hair colorOpen Targets
0.48Moderate
Abnormality of the skeletal systemOpen Targets
0.42Moderate
smoking initiationOpen Targets
0.36Weak
viral eye infectionOpen Targets
0.32Weak
kidney failureOpen Targets
0.31Weak
Alzheimer diseaseOpen Targets
0.30Weak
scoliosisOpen Targets
0.30Weak
multinodular goiterOpen Targets
0.29Weak
squamous cell carcinomaOpen Targets
0.23Weak
acute myeloid leukemiaOpen Targets
0.22Weak
Testicular Germ Cell TumorOpen Targets
0.19Weak
response to statinOpen Targets
0.18Weak
color vision disorderOpen Targets
0.16Weak
benign prostatic hyperplasiaOpen Targets
0.15Weak
Abnormality of the gastrointestinal tractOpen Targets
0.14Weak
chronic obstructive pulmonary diseaseOpen Targets
0.13Weak
ovarian cancerOpen Targets
0.10Weak
colorectal carcinomaOpen Targets
0.10Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
PIK3R3Protein interaction100%PIK3CDProtein interaction100%EGFRProtein interaction100%TRAF6Protein interaction100%GAB1Protein interaction99%GRB2Protein interaction99%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
69%
Lung
40%
Ovary
37%
Heart
37%
Liver
6%
Gene Interaction Network
Click a node to explore
GAB2PIK3R3PIK3CDEGFRTRAF6GAB1GRB2
PROTEIN STRUCTURE
Preparing viewer…
PDB6Y3R · 1.50 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.56Moderately Constrained
pLIⓘ
0.68Intermediate
Observed/Expected LoF0.38 [0.27–0.56]
RankingsWhere GAB2 stands among ~20K protein-coding genes
  • #2,433of 20,598
    Most Researched179 · top quartile
  • #3,617of 17,882
    Most Constrained (LOEUF)0.56 · top quartile
Genes detectedGAB2
Sources retrieved28 papers
Response time—
📄 Sources
28▼
1
Structure and function of Gab2 and its role in cancer (Review).
PMID: 26095858
Mol Med Rep · 2015
1.00
2
Expression characteristics of lipid metabolism-related genes and correlative immune infiltration landscape in acute myocardial infarction.
PMID: 38890389
Sci Rep · 2024
0.92
3
Endothelial cell-mediated venous thrombosis.
PMID: 36173663
Blood · 2022
0.90
4
Genetic susceptibility to essential hypertension in the Chinese han population: a study on GAB1, GAB2, and GAB3 gene polymorphisms.
PMID: 40140746
BMC Cardiovasc Disord · 2025
0.80
5
Tyrosine phosphatase SHP2 inhibitors in tumor-targeted therapies.
PMID: 33532178
Acta Pharm Sin B · 2021
0.80