RHOT1
protein-codingras homolog family member T1, the group of EF-hand domain containing|Miro like atypical Rho GTPases
Gene summary
Enables guanyl ribonucleotide binding activity; metal ion binding activity; and ribonucleoside triphosphate phosphatase activity. Involved in several processes, including mitochondrial outer membrane permeabilization; mitochondrion transport along microtubule; and regulation of mitochondrion organization. Located in mitochondrial outer membrane. [provided by Alliance of Genome Resources, Jun 2026]
- ARHT1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~110.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to RHOT1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001033566.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | ||||
| missense | 53 | 2 | 55 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 8 | 8 | ||||
| Total | 0 | 0 | 62 | 2 | 0 | 64 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001028738.1 | 20 | MANE Select | |
| Ensembl | ENSP00000439737.2 | 20 | MANE Select | |
| RefSeq | NP_001028739.2 | 13 | Standard | |
| RefSeq | NP_001028740.1 | 21 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| rhot1b | Danio rerio | Structure: whole organism Quality: decreased length abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Mitophagy - animal - Homo sapiens (human)
- Signal Transduction
- Post-translational protein modification
- Metabolism of proteins
- Rho GTPase cycle
Biological Process
- mitochondrion organization
- Rho protein signal transduction
- regulation of mitochondrion organization
- protein deubiquitination
- cellular homeostasis
Molecular Function
- molecular_function
- GTPase activity
- calcium ion binding
- protein binding
- GTP binding
Cellular Component
- mitochondrion
- mitochondrial outer membrane
- cytosol
- plasma membrane
- membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000358365
- Coding exons
- 21
- Length
- 110921
- Individuals with no LoFs
- 125727
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 21
- Defined
- 125748
- p
- 0.0000835
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.47 | 230 | 362 | 0.635 | 0.0000179 | 4569 |
| Missense (PolyPhen) | 40 | 107.97 | 0.37049 | 1376 | ||
| Synonymous | 1.62 | 101 | 124 | 0.815 | 0.00000619 | 1243 |
| Loss of Function | 4.97 | 9 | 44.9 | 0.200 | 0.00000248 | 530 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00018 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0.00020 | 0.00020 | rare |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0.000047 | 0.000046 | rare |
| European (Non-Finnish) | 0.000089 | 0.000088 | rare |
| South Asian | 0.000099 | 0.000098 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Mitochondrial GTPase involved in mitochondrial trafficking. Probably involved in control of anterograde transport of mitochondria and their subcellular distribution. {ECO:0000269|PubMed:12482879, ECO:0000269|PubMed:16630562}.;
Recessive Scores
- pRec
- 0.154
Intolerance Scores
- LoFtool
- 0.709
- RVIS EVS
- -0.43
- RVIS percentile EVS
- 25.37
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.419
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |