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27 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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GAB1
GRB2 associated binding protein 1
Chromosome 4 · 4q31.21
NCBI Gene: 2549Ensembl: ENSG00000109458.10HGNC: HGNC:4066UniProt: B7Z3B9
222PubMed Papers
21Diseases
0Drugs
1Pathogenic Variants
RESEARCH IMPACT
Trending
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
angiogenesisvascular endothelial growth factor signaling pathwaypositive regulation of angiogenesiscell-cell junctioncancerbone development diseasehearing loss, autosomal recessiveAbnormality of the skeletal system
✦AI Summary

GAB1 (GRB2-associated binding protein 1) is a cytoplasmic adapter protein that mediates intracellular signaling downstream of activated receptor tyrosine kinases (RTKs), including FGFR1, EGFR, insulin receptor, and MET/HGF pathways 1. GAB1 functions by recruiting signaling molecules such as Grb2 into receptor-signaling complexes 2, where it activates key downstream cascades including PI3K/AKT, ERK/MAPK, and integrin/FAK signaling 3. The protein promotes positive regulation of angiogenesis, vascular endothelial growth factor signaling, and cell migration processes [GO annotations]. In disease contexts, GAB1 overexpression drives aggressive cellular phenotypes: it promotes oral squamous cell carcinoma proliferation and invasion via the Akt/Cdh1 pathway 4, and facilitates lung adenocarcinoma cell motility through the AXL-Gab1-PI3K axis 5. Conversely, GAB1 inhibition suppresses fibroblast fibrogenesis, migration, and proliferation in skin fibrosis 3. GAB1 variants associate with asthma severity and inhaled corticosteroid responsiveness in children, with specific SNVs affecting eosinophil levels and treatment outcomes 6. These findings establish GAB1 as a critical signaling node in both normal physiological processes and pathological conditions including cancer and fibrotic diseases.

Sources cited
1
GAB1 involvement in MET/HGF-signaling pathway and receptor tyrosine kinase signaling
PMID: 29408807
2
GAB1 recruitment into receptor-signaling complexes upon TRAP phosphorylation in hematopoietic cells
PMID: 17118694
3
GAB1 targeting by miR-3606-3p suppresses integrin/FAK and p-AKT/p-ERK signaling in skin fibrosis
PMID: 39571732
4
GAB1 overexpression promotes oral squamous cell carcinoma proliferation and invasion via Akt/Cdh1 pathway
PMID: 28893350
5
AXL-Gab1-PI3K axis mediates Rac1-dependent lung adenocarcinoma cell motility downstream of EGFR
PMID: 34731623
6
GAB1 SNVs associate with asthma severity and inhaled corticosteroid response in children via NF-κB pathway regulation
PMID: 38057792
Disease Associationsⓘ21
cancerOpen Targets
0.60Moderate
bone development diseaseOpen Targets
0.56Moderate
hearing loss, autosomal recessiveOpen Targets
0.38Weak
Abnormality of the skeletal systemOpen Targets
0.30Weak
hypothyroidismOpen Targets
0.29Weak
15q14 microdeletion syndromeOpen Targets
0.27Weak
goutOpen Targets
0.23Weak
neurodegenerative diseaseOpen Targets
0.21Weak
glioblastomaOpen Targets
0.16Weak
papillary renal cell carcinomaOpen Targets
0.11Weak
cardiovascular diseaseOpen Targets
0.10Weak
hepatocellular carcinomaOpen Targets
0.10Weak
oral squamous cell carcinomaOpen Targets
0.09Suggestive
hilar cholangiocarcinomaOpen Targets
0.08Suggestive
bronchopulmonary dysplasiaOpen Targets
0.07Suggestive
meningiomaOpen Targets
0.07Suggestive
neoplasmOpen Targets
0.07Suggestive
hypertensionOpen Targets
0.07Suggestive
asthmaOpen Targets
0.06Suggestive
colitisOpen Targets
0.06Suggestive
Deafness, autosomal recessive, 26UniProt
Pathogenic Variants1
NM_002039.4(GAB1):c.347G>A (p.Gly116Glu)Pathogenic
Autosomal recessive nonsyndromic hearing loss 26
★☆☆☆2018→ Residue 116
View on ClinVar ↗
Related Genes
GRB2Protein interaction100%PIK3R3Protein interaction100%PIK3R1Protein interaction100%PIK3CBProtein interaction100%PIK3CDProtein interaction100%GAB2Protein interaction99%
Tissue Expression6 tissues
Heart
100%
Brain
57%
Bone Marrow
51%
Ovary
31%
Lung
31%
Liver
17%
Gene Interaction Network
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GAB1GRB2PIK3R3PIK3R1PIK3CBPIK3CDGAB2
PROTEIN STRUCTURE
Preparing viewer…
PDB4QSY · 2.10 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.50Moderately Constrained
pLIⓘ
0.98Intolerant
Observed/Expected LoF0.34 [0.24–0.50]
RankingsWhere GAB1 stands among ~20K protein-coding genes
  • #1,840of 20,598
    Most Researched222 · top 10%
  • #4,714of 5,498
    Most Pathogenic Variants1
  • #3,032of 17,882
    Most Constrained (LOEUF)0.50 · top quartile
Genes detectedGAB1
Sources retrieved27 papers
Response time—
📄 Sources
27▼
1
A comprehensive review of SHP2 and its role in cancer.
PMID: 36066752
Cell Oncol (Dordr) · 2022
1.00
2
Ntal/Lab/Lat2.
PMID: 17118694
Int J Biochem Cell Biol · 2007
0.90
3
Kinase-mediated RAS signaling via membraneless cytoplasmic protein granules.
PMID: 33848463
Cell · 2021
0.80
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
0.72
5
Glucocorticoids, genes and brain function.
PMID: 29180230
Prog Neuropsychopharmacol Biol Psychiatry · 2018
0.70