GBF1: Golgi-specific Brefeldin A Resistance Factor 1
A key ARF guanine nucleotide exchange factor regulating Golgi trafficking and vesicular transport
Gene Information Card
| Symbol | GBF1 |
|---|---|
| Full Name | Golgi-specific Brefeldin A Resistance Factor 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 10q24.32 |
| NCBI Gene ID | 8729 ncbi.nlm.nih.gov/gene/8729 |
| Ensembl ID | ENSG00000107862 |
| UniProt ID | Q92538 |
| OMIM ID | 603698 |
| HGNC ID | 4181 |
| Aliases | ARFGEF1, BIG1, KIAA0248 |
Description
GBF1 encodes a guanine nucleotide exchange factor (GEF) that activates ADP-ribosylation factor (ARF) family members, particularly ARF1 and ARF5. It localizes to the Golgi apparatus and is essential for maintaining Golgi structure, regulating vesicular transport between the endoplasmic reticulum and Golgi, and facilitating protein secretion. GBF1 is the target of the fungal metabolite brefeldin A (BFA), which inhibits its GEF activity, leading to Golgi disassembly.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neurodevelopmental disorder with hypotonia and brain abnormalities | Impaired Golgi trafficking due to GBF1 loss-of-function variants | ClinVar, OMIM |
| Intellectual disability | Disrupted ARF1/ARF5 activation affecting neuronal vesicle transport | ClinVar |
| Cancer (various) | GBF1 overexpression or mutation may alter secretory pathway and cell proliferation | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Lung | 10.2 | Medium |
| Liver | 8.9 | Medium |
| Kidney | 9.1 | Medium |
| Testis | 15.3 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 14.0 | High expression |
| HEK293 | 11.5 | Medium expression |
| A549 | 10.8 | Medium expression |
| K562 | 8.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2032C>T (p.Arg678Cys) | Missense | Rare | Loss of GEF activity; associated with neurodevelopmental disorder |
| c.2875G>A (p.Gly959Arg) | Missense | Rare | Impaired Golgi localization; reported in ClinVar |
| c.1234_1236del (p.Lys412del) | In-frame deletion | Rare | Reduced ARF1 activation; functional impact uncertain |
Mutation functional classification
Loss of Function (LOF)
Missense variants (e.g., p.Arg678Cys) reduce or abolish GEF activity, impairing ARF1/ARF5 activation and Golgi trafficking.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in GBF1.
Dominant Negative (DN)
Some missense variants may exert dominant-negative effects by sequestering ARF substrates or disrupting Golgi dynamics.
View complete mutation data：
Gene Ontology (GO)
| • Golgi apparatus | • ARF guanyl-nucleotide exchange factor activity |
| • vesicle-mediated transport | • intracellular protein transport |
| • Golgi organization | • activation of ARF GTPase activity |
Pathways
• ARF1-mediated vesicular transport
• Golgi-to-ER retrograde transport
• Brefeldin A sensitivity pathway
Protein Summary
GBF1 is a large, multi-domain protein (approximately 206 kDa) containing a Sec7 domain responsible for catalyzing nucleotide exchange on ARF GTPases. It also possesses DCB (dimerization and cyclophilin binding) and HUS (homology upstream of Sec7) domains that regulate its localization and activity. GBF1 is primarily cytosolic but cycles onto Golgi membranes, where it activates ARF1 to recruit coat proteins (e.g., COPI) for vesicle budding. Its activity is essential for maintaining Golgi ribbon integrity and efficient protein secretion.
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