GGA3: Golgi-associated, gamma adaptin ear containing, ARF binding protein 3
A key regulator of intracellular trafficking and signaling, implicated in cancer and neurodegenerative disorders.
Gene Information Card
| Symbol | GGA3 |
|---|---|
| Full Name | Golgi associated, gamma adaptin ear containing, ARF binding protein 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 17q25.1 |
| NCBI Gene ID | 23163 ncbi.nlm.nih.gov/gene/23163 |
| Ensembl ID | ENSG00000125447 |
| UniProt ID | Q9NZ52 |
| OMIM ID | 608152 |
| HGNC ID | 17070 |
| Aliases | GGA3, KIAA0154, MGC138207 |
Description
GGA3 encodes a member of the Golgi-localized, gamma-adaptin ear domain homology, ARF-binding (GGA) protein family. This protein functions as an adaptor in clathrin-mediated trafficking between the trans-Golgi network and endosomes, regulating the sorting of cargo proteins such as BACE1 and Notch. GGA3 is also involved in cell signaling and has been linked to cancer progression and Alzheimer disease.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Alzheimer disease | GGA3 regulates BACE1 trafficking and lysosomal degradation; reduced GGA3 levels increase BACE1 stability and amyloid-beta production. | PMID: 22948142; PMID: 25639757 |
| Breast cancer | GGA3 overexpression correlates with poor prognosis; promotes cell proliferation and migration via EGFR recycling. | PMID: 29367600; PMID: 31073084 |
| Glioblastoma | GGA3 depletion impairs Notch signaling and reduces tumor growth in preclinical models. | PMID: 25639757 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Breast | 8.3 | Low |
| Lung | 15.1 | Medium |
| Liver | 6.2 | Low |
| Kidney | 9.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 14.2 | Embryonic kidney; high expression |
| MCF7 | 11.5 | Breast cancer; moderate expression |
| U87MG | 9.8 | Glioblastoma; moderate expression |
| HepG2 | 7.1 | Hepatocellular carcinoma; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1123C>T (p.Arg375Trp) | Missense | <0.01% | Unknown; predicted damaging by SIFT |
| c.1456G>A (p.Glu486Lys) | Missense | <0.01% | Unknown; predicted benign |
| c.1789_1790insA (p.Thr597Asnfs*2) | Frameshift | <0.01% | Loss of function; truncation |
Mutation functional classification
Loss of Function (LOF)
Frameshift mutations (e.g., p.Thr597Asnfs*2) lead to premature termination and loss of clathrin/ARF binding domains.
Gain of Function (GOF)
Not well documented; some missense variants may alter cargo specificity but evidence is limited.
Dominant Negative (DN)
No confirmed dominant-negative mutations reported in literature.
View complete mutation data：ClinVar: https://www.clinvar.com/gene/23163 COSMIC: https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=GGA3
Gene Ontology (GO)
| • GO:0006886 - intracellular protein transport | • GO:0016192 - vesicle-mediated transport |
| • GO:0030131 - clathrin adaptor complex | • GO:0031410 - cytoplasmic vesicle |
| • GO:0005794 - Golgi apparatus | • GO:0005515 - protein binding |
Pathways
• Clathrin-mediated endocytosis (Reactome: R-HSA-8856828)
• Trans-Golgi network vesicle budding (Reactome: R-HSA-421837)
• Notch signaling (Reactome: R-HSA-157118)
Protein Summary
GGA3 is a 723-amino acid protein containing a VHS domain, a GAT domain, and a gamma-adaptin ear domain. It binds ARF-GTP and clathrin, facilitating the sorting of transmembrane receptors at the trans-Golgi network. The protein is ubiquitously expressed with highest levels in brain and lung. Post-translational modifications include phosphorylation and ubiquitination, which regulate its stability and function.
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GGA3 Knockout HEK293 Cell Line | EDJ-KQ13587 | Human | 23163 | Details Get a Quote |
| GGA3 Knockout HeLa Cell Line | EDJ-KQ18094 | Human | 23163 | Details Get a Quote |
| GGA3 Knockout A-549 Cell Line | EDJ-KQ43248 | Human | 23163 | Details Get a Quote |
| GGA3 Knockout HCT 116 Cell Line | EDJ-KQ43249 | Human | 23163 | Details Get a Quote |
| Gga3 Knockout PC12 Cell Line | EDJ-KZ260 | Rat | Details Get a Quote |
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