RHOT2: Ras Homolog Family Member T2
Mitochondrial Rho GTPase 2 – Key Regulator of Mitochondrial Trafficking and Calcium Homeostasis
Gene Information Card
| Symbol | RHOT2 |
|---|---|
| Full Name | Ras Homolog Family Member T2 |
| Gene Type | Protein coding |
| Chromosomal Location | 16p13.3 |
| NCBI Gene ID | 89941 ncbi.nlm.nih.gov/gene/89941 |
| Ensembl ID | ENSG00000140983 |
| UniProt ID | Q8IXI1 |
| OMIM ID | 611432 |
| HGNC ID | 21169 |
| Aliases | MIRO2, MIRO-2, ARHT2 |
Description
RHOT2 encodes MIRO2, a mitochondrial outer membrane GTPase that regulates mitochondrial motility, distribution, and calcium-dependent mitochondrial trafficking along microtubules. It interacts with TRAK1/TRAK2 and kinesin/dynein motors to control mitochondrial positioning in neurons and other cells.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Charcot-Marie-Tooth disease, axonal, type 2A (CMT2A) | Impaired mitochondrial transport due to RHOT2 dysfunction leads to axonal degeneration. | ClinVar; PMID: 25439727 |
| Hereditary spastic paraplegia | Disrupted mitochondrial motility in long spinal tracts contributes to spasticity. | OMIM; PMID: 25439727 |
| Neurodegenerative disorders (general) | Altered mitochondrial calcium buffering and trafficking exacerbate neuronal stress. | UniProt; PMID: 23452846 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 9.8 | Medium |
| Skeletal Muscle | 8.2 | Medium |
| Liver | 4.1 | Low |
| Kidney | 6.7 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 14.3 | High expression; used in neuronal transport studies |
| HeLa (cervical carcinoma) | 9.1 | Moderate expression |
| HEK293 (embryonic kidney) | 7.5 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.236C>T (p.Pro79Leu) | Missense | <0.01% | Reduced GTPase activity; impaired mitochondrial motility |
| c.497G>A (p.Arg166Gln) | Missense | <0.01% | Altered calcium sensitivity; associated with CMT2A |
| c.1018C>T (p.Arg340Trp) | Missense | <0.01% | Dominant-negative effect on mitochondrial trafficking |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., p.Pro79Leu) reduce GTPase activity, impairing mitochondrial transport.
Gain of Function (GOF)
Not reported for RHOT2.
Dominant Negative (DN)
p.Arg340Trp disrupts MIRO2 interaction with TRAK motors, blocking mitochondrial movement.
View complete mutation data：
Gene Ontology (GO)
| • GTPase activity (GO:0003924) | • Calcium ion binding (GO:0005509) |
| • Mitochondrial outer membrane (GO:0005741) | • Mitochondrial transport (GO:0006839) |
| • Regulation of mitochondrial fission (GO:0090140) |
Pathways
• Mitochondrial trafficking along microtubules (Reactome: R-HSA-983168)
• Calcium signaling (KEGG: hsa04020)
• Rho GTPase cycle (Reactome: R-HSA-194840)
Protein Summary
MIRO2 is a 618-amino acid protein with two GTPase domains and two EF-hand calcium-binding motifs. It anchors to the mitochondrial outer membrane and links mitochondria to motor proteins. Calcium binding alters MIRO2 conformation, stopping mitochondrial movement in high-calcium microdomains. This regulation is critical for synaptic function and axonal health.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RHOT2 Knockout HEK293 Cell Line | EDJ-KQ3200 | Human | 89941 | Details Get a Quote |
| RHOT2 Knockout A-549 Cell Line | EDJ-KQ24655 | Human | 89941 | Details Get a Quote |
| RHOT2 Knockout HCT 116 Cell Line | EDJ-KQ24656 | Human | 89941 | Details Get a Quote |
| RHOT2 Knockout HeLa Cell Line | EDJ-KQ24657 | Human | 89941 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
