GDI1: Rab GDP Dissociation Inhibitor 1
Key regulator of Rab GTPase recycling and vesicle trafficking; implicated in X-linked intellectual disability and cancer
Gene Information Card
| Symbol | GDI1 |
|---|---|
| Full Name | GDP dissociation inhibitor 1 |
| Gene Type | Protein coding |
| Chromosomal Location | Xq28 |
| NCBI Gene ID | 2664 ncbi.nlm.nih.gov/gene/2664 |
| Ensembl ID | ENSG00000102081 |
| UniProt ID | P31150 |
| OMIM ID | 300104 |
| HGNC ID | 4226 |
| Aliases | GDIL, RABGDIA, XAP-4, MRX41, MRX48 |
Description
GDI1 encodes Rab GDP dissociation inhibitor alpha, a protein that regulates the GDP/GTP exchange reaction of most Rab GTPases by inhibiting the dissociation of GDP from them and preventing the exchange of GDP for GTP. This protein is essential for proper vesicle trafficking, membrane transport, and neurotransmitter release. Mutations in GDI1 cause X-linked intellectual disability (MRX41, MRX48) and have been associated with cancer progression.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| X-linked intellectual disability (MRX41, MRX48) | Loss-of-function mutations impair Rab recycling, disrupting synaptic vesicle trafficking and neuronal signaling | ClinVar, OMIM |
| Epilepsy | GDI1 variants linked to altered GABAergic transmission and seizure susceptibility | ClinVar |
| Breast cancer | GDI1 overexpression promotes Rab GTPase cycling and tumor cell migration | COSMIC |
| Lung cancer | GDI1 amplification associated with poor prognosis and metastatic potential | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 32.5 | High |
| Testis | 18.2 | Medium |
| Lung | 12.1 | Medium |
| Breast | 9.8 | Low |
| Liver | 6.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 28.3 | Neuronal model |
| MCF7 (breast cancer) | 15.7 | Overexpressed in cancer |
| A549 (lung cancer) | 14.2 | Amplified in lung tumors |
| HEK293 (embryonic kidney) | 11.5 | Baseline expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.221G>A (p.Arg74Gln) | Missense | Rare | Loss of Rab binding; intellectual disability |
| c.364C>T (p.Arg122*) | Nonsense | Rare | Premature truncation; loss of function |
| c.479_480del (p.Leu160fs) | Frameshift | Rare | Disrupted GDI domain; X-linked MR |
| Amplification (Xq28) | Copy number gain | ~5% in breast cancer | Increased GDI1 expression; tumor progression |
Mutation functional classification
Loss of Function (LOF)
Missense, nonsense, and frameshift mutations (e.g., p.Arg74Gln, p.Arg122*, p.Leu160fs) impair Rab GDP dissociation activity, leading to defective vesicle trafficking and neuronal dysfunction.
Gain of Function (GOF)
Gene amplification and overexpression in cancers (breast, lung) enhance Rab GTPase cycling, promoting cell migration and metastasis.
Dominant Negative (DN)
Not reported for GDI1; all known pathogenic mutations are loss-of-function or copy number gains.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Rab GTPase cycle (Reactome R-HSA-9007101)
• Vesicle-mediated transport (Reactome R-HSA-5653656)
• Neurotransmitter release cycle (Reactome R-HSA-112310)
Protein Summary
GDI1 (Rab GDP dissociation inhibitor 1) is a 447-amino acid protein that binds prenylated Rab GTPases and extracts them from membranes, recycling them for subsequent rounds of vesicle transport. It is highly expressed in brain and testis. Loss-of-function mutations cause X-linked intellectual disability, while overexpression in cancers promotes metastasis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GDI1 Knockout HEK293 Cell Line | EDJ-KQ3928 | Human | 2664 | Details Get a Quote |
| GDI1 Knockout A-549 Cell Line | EDJ-KQ27403 | Human | 2664 | Details Get a Quote |
| GDI1 Knockout HCT 116 Cell Line | EDJ-KQ27404 | Human | 2664 | Details Get a Quote |
| GDI1 Knockout HeLa Cell Line | EDJ-KQ27405 | Human | 2664 | Details Get a Quote |
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