| RAB4B | |
|---|---|
| Gene Symbol | RAB4B |
| Full Name | RAB4B, Member RAS Oncogene Family |
| Chromosomal Location | 15q21.2 |
| NCBI Gene ID | [51678](https://www.ncbi.nlm.nih.gov/gene/51678) |
| OMIM ID | [608759](https://www.omim.org/entry/608759) |
| Ensembl ID | ENSG00000167842 |
| UniProt ID | [Q9NPF7](https://www.uniprot.org/uniprot/Q9NPF7) |
| Encoded Protein | [Rab4B Protein](/proteins/rab4b-protein) |
| Associated Diseases | [Parkinson's Disease](/diseases/parkinsons-disease), [Alzheimer's Disease](/diseases/alzheimers-disease), [Huntington's Disease](/diseases/huntingtons-disease), [Synucleinopathies](/diseases/synucleinopathies) |
RAB4B (RAB4B, Member RAS Oncogene Family) is a member of the RAB GTPase family that plays critical roles in synaptic vesicle recycling, endocytic trafficking, and protein homeostasis in neurons. Located on chromosome 15q21.2, RAB4B encodes a 219-amino acid small GTPase that regulates rapid recycling of synaptic vesicles at the presynaptic terminal and controls endosomal sorting of neurotransmitter receptors[1][2].
RAB4B is a member of the Rab4 subfamily, which also includes RAB4A and RAB4B. These proteins are essential for coordinating the movement and sorting of vesicles between different cellular compartments. In neurons, RAB4B's function is particularly critical due to the extremely high demands of synaptic vesicle cycling during neurotransmission[3].
| Property | Value |
|---|---|
| Official Symbol | RAB4B |
| Official Full Name | RAB4B, Member RAS Oncogene Family |
| Also Known As | RAB4B, RAB4B GTPase |
| Chromosomal Location | 15q21.2 |
| NCBI Gene ID | 51678 |
| OMIM ID | 608759 |
| Ensembl ID | ENSG00000167842 |
| UniProt ID | Q9NPF7 |
| Protein Length | 219 amino acids |
| Expression | Brain (high), heart, lung, testis |
RAB4B plays a central role in the rapid recycling of synaptic vesicles, a process critical for sustained neurotransmission[4][5]:
Vesicle Lifecycle:
RAB4B-Specific Functions:
Beyond synaptic vesicles, RAB4B regulates general endocytic trafficking pathways[2:1][@steine2020]:
Endosomal Sorting:
Receptor Trafficking:
In neurons, RAB4B localizes to:
RAB4B has been strongly implicated in Parkinson's disease pathogenesis[6][7]:
Alpha-Synuclein Interplay:
Dopaminergic Neuron Vulnerability:
LRRK2 Connection:
RAB4B dysfunction contributes to AD through multiple mechanisms[8][9]:
Amyloid Metabolism:
Tau Pathology:
Synaptic Dysfunction:
RAB4B involvement in Huntington's disease:
Amyotrophic Lateral Sclerosis:
Frontotemporal Dementia:
RAB4B shows high and specific expression in the brain:
In neurons, RAB4B localizes to:
RAB4B as disease biomarker:
Strategies targeting RAB4B in neurodegeneration[10][11]:
RAB4B Modulators:
Downstream Effectors:
Gene Therapy:
Several approaches in development:
RAB4B variants in disease[12]:
RAB4B as diagnostic tool:
RAB4B interacts with several proteins:
| Partner | Interaction Type | Functional Consequence |
|---|---|---|
| RABEP1 | Effector | Endosome tethering |
| RABPHILIN | Effector | Synaptic vesicle regulation |
| RAB3IP | Effector | Rabin8 interaction |
| RABGAP | GAP | GTP hydrolysis regulation |
| RABGDI | GDI | Membrane extraction |
Synaptic Deficits[13]:
Endosomal Abnormalities:
Cellular Stress:
Knockout Models:
Conditional Knockouts:
Transgenic Models:
Gould GW, Dempsey C, Lalli G, et al. RAB GTPases in neuronal function and dysfunction. Nature Reviews Neuroscience. 2021. ↩︎
Stirzaker C, Kerman K, Lawson DJ, et al. Endocytic trafficking in neurodegeneration. Acta Neuropathologica. 2021. ↩︎ ↩︎
Ramachandran R, Mehta D, Zhang J, et al. Molecular mechanisms of synaptic vesicle recycling. Current Opinion in Neurobiology. 2021. ↩︎
Kim K, Lee J, Kim J, et al. Synaptic RAB4 regulates vesicle pool maintenance. Journal of Cell Science. 2021. ↩︎
Bittins CM, Wang Z, Zhang H, et al. RAB proteins and synaptic plasticity. Cellular and Molecular Neurobiology. 2021. ↩︎
Matthiessen HP, Schwarz T, Herrmann A, et al. RAB4B in dopaminergic neuron function and Parkinson's disease. Journal of Parkinson's Disease. 2020. ↩︎
Zhang M, Liu L, Chen Y, et al. RAB4B and alpha-synuclein interplay in Parkinson's disease. Cell Death & Disease. 2020. ↩︎
Bauer L, Battista M, van der Kant R, et al. RAB GTPases in Alzheimer's disease pathogenesis. Brain. 2022. ↩︎
Chan G, Liu T, Wang X, et al. RAB4B in amyloid-beta trafficking and clearance. Molecular Neurodegeneration. 2022. ↩︎
Ng EL, Gan BQ, Lim LH, et al. RAB GTPases as therapeutic targets in neurodegeneration. Pharmacological Research. 2021. ↩︎
Yang L, Cao L, Lin Y, et al. Modulating RAB4B activity as therapeutic strategy. Advanced Science. 2020. ↩︎
Iwai K, Saito Y, Arai N, et al. RAB4B genetic variants and neurodegenerative disease risk. Human Genetics. 2020. ↩︎
Wang Y, Cheng Q, Narayanan N, et al. RAB4B loss leads to synaptic dysfunction and behavior deficits. Synapse. 2022. ↩︎