RHOT1: Ras Homolog Family Member T1
Mitochondrial Rho GTPase 1 – Key Regulator of Mitochondrial Trafficking and Calcium Homeostasis
Gene Information Card
| Symbol | RHOT1 |
|---|---|
| Full Name | Ras homolog family member T1 |
| Gene Type | Protein coding |
| Chromosomal Location | 17q11.2 |
| NCBI Gene ID | 55288 ncbi.nlm.nih.gov/gene/55288 |
| Ensembl ID | ENSG00000126814 |
| UniProt ID | Q8IXI2 |
| OMIM ID | 613888 |
| HGNC ID | 21169 |
| Aliases | MIRO1, ARHT1, Miro-1 |
Description
RHOT1 (Ras homolog family member T1) encodes a mitochondrial Rho GTPase, also known as MIRO1. The protein localizes to the outer mitochondrial membrane and functions as a calcium-sensitive adaptor for kinesin and dynein motors, regulating mitochondrial trafficking along microtubules. It also plays a role in mitochondrial calcium uptake and cellular stress responses. RHOT1 is essential for neuronal mitochondrial distribution and synaptic function.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Charcot-Marie-Tooth disease type 2A (CMT2A) | Altered mitochondrial transport due to RHOT1 mutations leads to axonal degeneration; MFN2 is the primary gene, but RHOT1 variants may modify disease severity. | ClinVar; PMID: 24752314 |
| Hereditary spastic paraplegia (HSP) | Impaired mitochondrial motility in long spinal tracts; RHOT1 mutations disrupt mitochondrial positioning in neurons. | ClinVar; PMID: 25168382 |
| Parkinson disease | Dysregulation of mitochondrial trafficking and calcium homeostasis; RHOT1 interacts with PINK1 and Parkin to mediate mitophagy. | UniProt; PMID: 21903422 |
| Type 2 diabetes | RHOT1-mediated mitochondrial dysfunction in pancreatic beta cells may impair insulin secretion. | NCBI Gene; PMID: 23395176 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.3 | Medium |
| Heart | 9.8 | Medium |
| Skeletal Muscle | 8.5 | Medium |
| Liver | 4.2 | Low |
| Kidney | 6.1 | Low |
| Pancreas | 5.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 14.2 | High expression; used in neuronal trafficking studies |
| HeLa (cervical carcinoma) | 10.5 | Moderate expression; mitochondrial dynamics model |
| HEK293 (embryonic kidney) | 8.9 | Moderate expression; common overexpression system |
| HepG2 (hepatocellular carcinoma) | 4.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.109C>T (p.Arg37Cys) | Missense | <0.01% | Reduced calcium binding; impaired mitochondrial motility |
| c.455G>A (p.Arg152Gln) | Missense | <0.01% | Altered GTPase activity; associated with HSP |
| c.832C>T (p.Arg278Trp) | Missense | <0.01% | Disrupted MIRO1–kinesin interaction; neuronal transport defect |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., p.Arg37Cys) impair calcium sensing and reduce mitochondrial motility, leading to axonal transport deficits.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in RHOT1.
Dominant Negative (DN)
Heterozygous mutations (e.g., p.Arg152Gln) may exert dominant-negative effects by disrupting MIRO1 dimerization and motor protein recruitment.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Mitochondrial transport along microtubules (Reactome: R-HSA-983189)
• PINK1-PRKN mediated mitophagy (Reactome: R-HSA-5205685)
• Calcium signaling (Reactome: R-HSA-397014)
Protein Summary
The RHOT1 protein (MIRO1) is a 618-amino-acid mitochondrial Rho GTPase with two GTPase domains and two calcium-binding EF-hand motifs. It anchors to the outer mitochondrial membrane and links mitochondria to microtubule motors (kinesin and dynein). Calcium binding to the EF-hands inhibits motor attachment, halting mitochondrial movement in high-calcium microdomains. MIRO1 also interacts with PINK1 and Parkin to facilitate mitophagy. Mutations in RHOT1 disrupt mitochondrial positioning, particularly in neurons, contributing to neurodegenerative and neuromuscular disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RHOT1 Knockout HEK293 Cell Line | EDJ-KQ15064 | Human | 55288 | Details Get a Quote |
| RHOT1 Knockout HeLa Cell Line | EDJ-KQ44372 | Human | 55288 | Details Get a Quote |
| RHOT1 Knockout A-549 Cell Line | EDJ-KQ45616 | Human | 55288 | Details Get a Quote |
| RHOT1 Knockout HCT 116 Cell Line | EDJ-KQ45617 | Human | 55288 | Details Get a Quote |
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