GRB7 Gene: Structure, Function, and Clinical Significance
A comprehensive overview of the GRB7 gene, its protein product, associated diseases, expression patterns, and mutations.
Gene Information Card
| Symbol | GRB7 |
|---|---|
| Full Name | Growth factor receptor bound protein 7 |
| Gene Type | Protein coding |
| Chromosomal Location | 17q12 (NC_000017.11: 39,737,000-39,745,000, GRCh38) |
| NCBI Gene ID | 2886 ncbi.nlm.nih.gov/gene/2886 |
| Ensembl ID | ENSG00000141738 |
| UniProt ID | Q14451 |
| OMIM ID | 601522 |
| HGNC ID | 4565 |
| Aliases | B47, CRB7, GRB7V |
Description
GRB7 (Growth Factor Receptor Bound Protein 7) is a protein-coding gene located on chromosome 17q12, within the ERBB2 (HER2) amplicon frequently amplified in breast and gastric cancers. It encodes an adapter protein involved in signal transduction pathways, particularly downstream of receptor tyrosine kinases such as HER2 and EGFR. GRB7 contains a PH domain, a BPS (between PH and SH2) domain, and an SH2 domain, which mediate its interactions with activated receptors and downstream effectors. Overexpression of GRB7 is associated with tumor progression and poor prognosis in certain cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | GRB7 is co-amplified with ERBB2 (HER2) and enhances HER2 signaling, promoting cell proliferation and invasion. | High expression correlates with poor prognosis; functional studies show GRB7 knockdown reduces tumor growth (PMID: 12676962). |
| Gastric cancer | GRB7 amplification and overexpression contribute to HER2-driven gastric tumorigenesis. | Co-amplification with HER2 observed in gastric cancer cell lines and tissues (PMID: 21742796). |
| Esophageal cancer | GRB7 overexpression may enhance growth factor signaling in esophageal adenocarcinoma. | Gene amplification detected in esophageal adenocarcinoma samples (PMID: 12676962). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Breast | nTPM: 12.5 | Medium |
| Stomach | nTPM: 8.3 | Low |
| Esophagus | nTPM: 6.1 | Low |
| Liver | nTPM: 4.2 | Low |
| Kidney | nTPM: 3.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | nTPM: 15.2 | HER2 low, GRB7 moderate |
| SKBR3 (breast cancer) | nTPM: 45.8 | HER2 amplified, GRB7 high |
| NCI-N87 (gastric cancer) | nTPM: 30.1 | HER2 amplified, GRB7 high |
| A549 (lung cancer) | nTPM: 5.0 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1064C>T (p.Pro355Leu) | Missense | 0.01% (COSMIC) | Unknown; likely benign |
| c.1123A>G (p.Thr375Ala) | Missense | 0.005% (COSMIC) | Unknown; may affect SH2 domain |
| c.1180G>A (p.Val394Ile) | Missense | 0.002% (COSMIC) | Unknown |
Mutation functional classification
Loss of Function (LOF)
No well-characterized loss-of-function mutations reported; GRB7 is generally overexpressed in cancer.
Gain of Function (GOF)
Amplification and overexpression are common in HER2-positive cancers, leading to enhanced signaling.
Dominant Negative (DN)
Not documented; however, overexpression of SH2 domain mutants could act as dominant negatives in experimental settings.
View complete mutation data：
Gene Ontology (GO)
| • GO:0005070 - SH3/SH2 adaptor activity | • GO:0005515 - protein binding |
| • GO:0007165 - signal transduction | • GO:0008287 - protein-containing complex |
| • GO:0016020 - membrane |
Pathways
• HER2 signaling pathway (PI3K/Akt and MAPK)
• EGFR signaling pathway
• Focal adhesion signaling
Protein Summary
GRB7 is a multidomain adapter protein (PH, BPS, SH2) that binds to phosphorylated tyrosine residues on activated receptor tyrosine kinases (e.g., HER2, EGFR). It recruits downstream signaling molecules such as FAK and PI3K, modulating cell migration, proliferation, and survival. GRB7 is often co-amplified with HER2 in breast and gastric cancers, contributing to oncogenic signaling. Its expression is low in normal tissues but elevated in certain tumors, making it a potential therapeutic target.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GRB7 Knockout HEK293 Cell Line | EDJ-KQ13680 | Human | 2886 | Details Get a Quote |
| GRB7 Knockout A-549 Cell Line | EDJ-KQ43381 | Human | 2886 | Details Get a Quote |
| GRB7 Knockout HCT 116 Cell Line | EDJ-KQ43382 | Human | 2886 | Details Get a Quote |
| GRB7 Knockout HeLa Cell Line | EDJ-KQ43383 | Human | 2886 | Details Get a Quote |
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