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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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GAB3
GRB2 associated binding protein 3
Chromosome X · Xq28
NCBI Gene: 139716Ensembl: ENSG00000160219.13HGNC: HGNC:17515UniProt: Q8WWW8
22PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingsignaling adaptor activitysignal transductioncytoplasmtype 1 diabetes mellitusgliomaimmunodeficiency 18agammaglobulinemia 7, autosomal recessive
✦AI Summary

GAB3 (GRB2-associated binding protein 3) is a scaffolding/docking adaptor protein that functions as a signal transduction molecule downstream of receptor tyrosine kinases and non-RTK receptors 1. In cancer contexts, GAB3 mediates cell proliferation through activation of the Akt and Erk signaling pathways. GAB3 is significantly overexpressed in glioma tissues and colorectal cancer cells compared to normal tissues 23. In glioma, GAB3 promotes Akt activation and tumor cell proliferation; GAB3 knockdown suppresses both Akt signaling and cell growth, while overexpression enhances proliferation in vitro and tumor growth in vivo 2. Similarly, in colorectal cancer, GAB3 co-precipitates with p85 and SHP2 to activate both Akt and Erk pathways, driving cell proliferation 3. However, in lung adenocarcinoma and melanoma, GAB3 expression is downregulated and functions as a tumor suppressor; low GAB3 expression correlates with poor prognosis and immune evasion, while high expression predicts better clinical outcomes and enhanced anti-tumor immune responses 456. Additionally, GAB3 genetic variants may contribute to hypertension susceptibility in some populations 7, and GAB3 loci are associated with circulating metabolite regulation 8.

Sources cited
1
GAB3 is a scaffolding/docking adaptor protein involved in signaling pathways mediated by receptor tyrosine kinases and non-RTK receptors
PMID: 11943184
2
GAB3 is overexpressed in glioma and promotes Akt activation and tumor cell proliferation; knockdown inhibits these processes in vitro and in vivo
PMID: 28291820
3
GAB3 is expressed in colorectal cancer cells and required for proliferation through Akt and Erk activation via interaction with p85 and SHP2
PMID: 28115166
4
GAB3 is downregulated in lung adenocarcinoma and correlates with better prognosis and immune responses; associated with T cell activation and immune checkpoint genes
PMID: 35822560
5
High GAB3 expression in melanoma predicts better prognosis and correlates with enhanced macrophage and natural killer cell infiltration
PMID: 36545920
6
GAB3 acts as a tumor suppressor in lung adenocarcinoma; overexpression inhibits cancer cell proliferation and migration, while knockdown promotes these processes
PMID: 41360937
7
GAB3 genetic polymorphisms may be associated with hypertension susceptibility in specific populations
PMID: 40140746
8
GAB3 loci on the X chromosome are associated with circulating metabolite regulation
PMID: 40972578
Disease Associationsⓘ20
type 1 diabetes mellitusOpen Targets
0.10Suggestive
gliomaOpen Targets
0.07Suggestive
immunodeficiency 18Open Targets
0.06Suggestive
agammaglobulinemia 7, autosomal recessiveOpen Targets
0.05Suggestive
combined immunodeficiency due to CTPS1 deficiencyOpen Targets
0.05Suggestive
immunodeficiency 105Open Targets
0.05Suggestive
reticular dysgenesisOpen Targets
0.05Suggestive
T-B+ severe combined immunodeficiency due to JAK3 deficiencyOpen Targets
0.05Suggestive
severe combined immunodeficiency due to IKK2 deficiencyOpen Targets
0.05Suggestive
combined immunodeficiency with skin granulomasOpen Targets
0.05Suggestive
X-Linked Combined Immunodeficiency DiseasesOpen Targets
0.05Suggestive
immunodeficiency 81Open Targets
0.05Suggestive
Wiskott-Aldrich syndromeOpen Targets
0.05Suggestive
immunodeficiency 112Open Targets
0.05Suggestive
severe combined immunodeficiency due to LAT deficiencyOpen Targets
0.04Suggestive
severe combined immunodeficiency due to CD70 deficiencyOpen Targets
0.04Suggestive
autosomal recessive primary immunodeficiency with defective spontaneous natural killer cell cytotoxicityOpen Targets
0.04Suggestive
short-limb skeletal dysplasia with severe combined immunodeficiencyOpen Targets
0.04Suggestive
severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positiveOpen Targets
0.04Suggestive
immunodeficiency 67Open Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
GRB2Protein interaction99%PTPN11Protein interaction94%SRCProtein interaction83%A1BGProtein interaction82%CSF1Protein interaction77%LYNProtein interaction72%
Tissue Expression6 tissues
Bone Marrow
100%
Heart
97%
Lung
87%
Liver
16%
Ovary
9%
Brain
7%
Gene Interaction Network
Click a node to explore
GAB3GRB2PTPN11SRCA1BGCSF1LYN
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q8WWW8
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.48Moderately Constrained
pLIⓘ
0.99Intolerant
Observed/Expected LoF0.30 [0.19–0.48]
RankingsWhere GAB3 stands among ~20K protein-coding genes
  • #13,666of 20,598
    Most Researched22
  • #2,819of 17,882
    Most Constrained (LOEUF)0.48 · top quartile
Genes detectedGAB3
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Gab3 overexpression in human glioma mediates Akt activation and tumor cell proliferation.
PMID: 28291820
PLoS One · 2017
1.00
2
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
0.90
3
The gift of Gab.
PMID: 11943184
FEBS Lett · 2002
0.80
4
Gab3 is required for human colorectal cancer cell proliferation.
PMID: 28115166
Biochem Biophys Res Commun · 2017
0.70
5
Identification of Grb2-associated binding protein 3 expression to predict clinical outcomes and immunotherapeutic responses in lung adenocarcinoma.
PMID: 35822560
J Biochem Mol Toxicol · 2022
0.60