RHOT1

Chr 17

ras homolog family member T1

Also known as: ARHT1, MIRO-1, MIRO1

NCBI Gene: 55288ENSG00000126858UniProt: Q8IXI2

The RHOT1 protein is an atypical mitochondrial nucleoside-triphosphatase that hydrolyzes GTP, ATP and UTP to control anterograde transport of mitochondria, regulate their subcellular distribution, and promote mitochondrial fission during high calcium conditions. The gene has a low LOEUF score of 0.35 and high pLI of 0.80, indicating strong intolerance to loss-of-function variants, but specific disease associations and inheritance patterns have not been established from the provided data.

Summary from RefSeq, UniProt
0
Active trials
9
Pubs (1 yr)
10
P/LP submissions
0%
P/LP missense
0.35
LOEUF
GOF
Mechanism· predicted
Clinical Summary— RHOT1
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.80) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
10 unique Pathogenic / Likely Pathogenic· 60 VUS of 95 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.35LOEUF
pLI 0.799
Z-score 4.97
OE 0.20 (0.12–0.35)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.47Z-score
OE missense 0.63 (0.57–0.71)
230 obs / 362.3 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.20 (0.12–0.35)
0≤0.351.4
Missense OE0.63 (0.57–0.71)
0≤0.61.4
Synonymous OE0.81
0≤1.21.6
LoF obs/exp: 9 / 44.9Missense obs/exp: 230 / 362.3Syn Z: 1.62
DN
0.5082th %ile
GOF
0.6932th %ile
LOF
0.48top 25%

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

95 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9
Likely Pathogenic1
VUS60
Likely Benign2
9
Pathogenic
1
Likely Pathogenic
60
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
9
0
9
Likely Pathogenic
0
0
1
0
1
VUS
0
54
6
0
60
Likely Benign
0
2
0
0
2
Benign
0
0
0
0
0
Total05616072

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

RHOT1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients