RHOT1

Summary

RHOT1 (ras homolog family member T1, HGNC:21168) is a protein-coding gene on chromosome 17q11.2, encoding Mitochondrial Rho GTPase 1 (Q8IXI2). Atypical mitochondrial nucleoside-triphosphatase (NTPase) involved in mitochondrial trafficking.

Predicted to enable GTP binding activity and GTPase activity. Involved in several processes, including mitochondrial outer membrane permeabilization; mitochondrion transport along microtubule; and regulation of mitochondrion organization. Located in mitochondrial outer membrane.

Source: NCBI Gene 55288 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 78 total
• MANE Select transcript: NM_001033566

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21168
Approved symbol	RHOT1
Name	ras homolog family member T1
Location	17q11.2
Locus type	gene with protein product
Status	Approved
Aliases	MIRO-1, FLJ11040, MIRO1
Ensembl gene	ENSG00000126858
Ensembl biotype	protein_coding
OMIM	613888
Entrez	55288

Gene structure

Transcript identifiers

Ensembl transcripts: 38 — 30 protein_coding, 5 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000333942, ENST00000354266, ENST00000358365, ENST00000394692, ENST00000545287, ENST00000578205, ENST00000580392, ENST00000580976, ENST00000581031, ENST00000581094, ENST00000581148, ENST00000581567, ENST00000582586, ENST00000582602, ENST00000583994, ENST00000584692, ENST00000584852, ENST00000646284, ENST00000652713, ENST00000903812, ENST00000903813, ENST00000903814, ENST00000903815, ENST00000903816, ENST00000903817, ENST00000903818, ENST00000903819, ENST00000903820, ENST00000903821, ENST00000903822, ENST00000903823, ENST00000928287, ENST00000959386, ENST00000959387, ENST00000959388, ENST00000959389, ENST00000959390, ENST00000959391

RefSeq mRNA: 7 — MANE Select: NM_001033566 NM_001033566, NM_001033567, NM_001033568, NM_001288754, NM_001288755, NM_001288758, NM_018307

CCDS: CCDS32610, CCDS32611, CCDS32612, CCDS74030, CCDS74031

Canonical transcript exons

ENST00000545287 — 20 exons

Exon	Start	End
ENSE00001162160	32211116	32211238
ENSE00002688228	32142502	32142729
ENSE00003459923	32173831	32173912
ENSE00003462298	32193136	32193244
ENSE00003510819	32206910	32207029
ENSE00003519666	32208107	32208309
ENSE00003519842	32175962	32176015
ENSE00003533427	32176161	32176213
ENSE00003552273	32175319	32175362
ENSE00003556564	32199405	32199550
ENSE00003577453	32198947	32199031
ENSE00003577792	32202770	32202900
ENSE00003579738	32203890	32203973
ENSE00003606611	32200956	32201056
ENSE00003628950	32183171	32183272
ENSE00003632954	32193987	32194107
ENSE00003637192	32182757	32182865
ENSE00003643753	32192201	32192299
ENSE00003717450	32224616	32225727
ENSE00003742271	32171043	32171101

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 98.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.1675 / max 580.1176, expressed in 1754 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
160224	9.3546	1734
160225	1.6187	914
208126	0.1942	54

Top tissues by expression

288 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	98.97	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.44	gold quality
secondary oocyte	CL:0000655	97.37	gold quality
visceral pleura	UBERON:0002401	97.36	gold quality
primary visual cortex	UBERON:0002436	97.12	gold quality
oocyte	CL:0000023	97.09	gold quality
palpebral conjunctiva	UBERON:0001812	96.93	gold quality
upper leg skin	UBERON:0004262	96.81	gold quality
gingival epithelium	UBERON:0001949	96.64	gold quality
pleura	UBERON:0000977	96.46	gold quality
cervix squamous epithelium	UBERON:0006922	96.43	gold quality
parietal pleura	UBERON:0002400	96.36	gold quality
occipital lobe	UBERON:0002021	96.28	gold quality
cortical plate	UBERON:0005343	96.24	gold quality
sperm	CL:0000019	96.21	gold quality
choroid plexus epithelium	UBERON:0003911	96.20	gold quality
germinal epithelium of ovary	UBERON:0001304	96.16	gold quality
ventricular zone	UBERON:0003053	96.15	gold quality
skin of hip	UBERON:0001554	95.97	gold quality
squamous epithelium	UBERON:0006914	95.74	gold quality
middle temporal gyrus	UBERON:0002771	95.67	gold quality
seminal vesicle	UBERON:0000998	95.64	gold quality
male germ cell	CL:0000015	95.47	gold quality
gingiva	UBERON:0001828	95.45	gold quality
amniotic fluid	UBERON:0000173	95.34	gold quality
esophagus squamous epithelium	UBERON:0006920	95.27	gold quality
tibia	UBERON:0000979	95.22	gold quality
lateral nuclear group of thalamus	UBERON:0002736	95.10	gold quality
blood vessel layer	UBERON:0004797	95.07	gold quality
ganglionic eminence	UBERON:0004023	95.06	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

141 targeting RHOT1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4682	100.00	68.89	1258
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515

Literature-anchored findings (GeneRIF, showing 33)

• Moreover, we show that Miro interacts with the Kinesin-binding proteins, GRIF-1 and OIP106, suggesting that the Miro GTPases form a link between the mitochondria and the trafficking apparatus of the microtubules. (PMID:16630562)
• Miro1,2 proteins serve as a Ca(2+)-sensitive switch and bifunctional regulator for both the motility and fusion-fission dynamics of the mitochondria. (PMID:19098100)
• These data suggest that Miro1 and the kinesin adaptor Grif-1 play an important role in regulating mitochondrial transport in neurons. (PMID:19103291)
• Study shows that both PINK1 and Parkin halt mitochondrial movement; PINK1 phosphorylates Miro (1 and 2) and thereby initiates the rapid degradation of Miro through a Parkin- and proteasome-dependent pathway. (PMID:22078885)
• results indicated that the low-expression levels of RhoT1 and Smad4 were significantly associated with LNM and shorter survival. RhoT1 may be considered as a potential novel marker for predicting the outcome in patients with pancreatic cancer (PMID:22860091)
• Details of a robust association of DISC1 with mitochondrial transport complexes containing TRAK1 and Miro1. (PMID:24092329)
• The Miro1-mediated mitochondrial transport in neurons and recently highlighted involvement of Miro1 proteins in mitochondrial turnover, emerging as a key process affected in neurodegeneration. (PMID:24256248)
• CXCL12-dependent cell polarization and migration are reduced in Miro-1-silenced cells (PMID:24492963)
• Data indicate that outer mitochondrial membrane protein Miro1 can stabilize phospho-mutant versions of PARK2 gene (encoding Parkin) on the outer mitochondrial membrane (OMM). (PMID:24671417)
• Miro and Cenp-F promote anterograde mitochondrial movement and proper mitochondrial distribution in daughter cells. (PMID:26259702)
• Full-length APC promotes assembly of the Miro-1/Milton-2 complex. (PMID:26658612)
• Show that the C-terminal GTPase of the Parkin primary substrates Miro1 and Miro2 are necessary and sufficient for efficient ubiquitination. We present several new X-ray crystal structures of both Miro1 and Miro2 that reveal substrate recognition and ubiquitin transfer to be specific to particular protein domains and lysine residues. (PMID:27605430)
• prolonged retention of Miro, and the downstream consequences that ensue, may constitute a central component of Parkinson’s disease pathogenesis. (PMID:27618216)
• Results provide evidence that ALS mutant SOD1 inhibits axonal transport of mitochondria by inducing PINK1/Parkin-dependent Miro1 degradation. (PMID:28973175)
• The findings identify for the first time peroxisome-localized Miro1 variants as adapter proteins that link peroxisomes to the microtubule-dependent transport complexes including TRAK2 in the intracellular translocation of peroxisomes in mammalian cells. (PMID:29222186)
• a key role of Miro1, which promotes the mitochondrial transfer from multipotent mesenchymal stem cells, is reported. (PMID:29562677)
• LPS mediates intercellular tight junction destruction among TECs and RhoT1/SMAD-4/JAM-3 is a pivotal pathway to mediate the phenomenon. (PMID:29725250)
• Miro1 binds directly to a C-terminal fragment of the Myo19 tail region and that Miro1/2 recruit the Myo19 tail. (PMID:30111583)
• circRHOT1 was overexpressed in pancreatic cancer and that this circRHOT1 was predominantly located in the cytoplasm. Reducing the circRHOT1 expression inhibited pancreatic cancer cell proliferation, invasion and migration. CircRHOT1 may play important roles in pancreatic cancer through sponging tumor-associated miRNAs (PMID:30444423)
• Results find that Miro1 is not only a substrate for PINK1/ Parkin-dependent degradation but might also function as a calcium-dependent docking site and safety switch for Parkin recruitment in mitochondria. (PMID:30504269)
• the data presented here indicate novel catalytic functions of human Miro atypical GTPases through altered catalytic mechanisms. (PMID:30513825)
• The ROTH1 is a genetic risk factor for Parkinson’s disease, further implicating Miro1 in calcium homeostasis and mitochondrial quality control. (PMID:31303019)
• circRHOT1 inhibits HCC development and progression via recruiting TIP60 to initiate NR2F6 expression, indicating that circRHOT1 and NR2F6 may be potential biomarkers for HCC prognosis. (PMID:31324186)
• Miro: A molecular switch at the center of mitochondrial regulation. (PMID:32056317)
• Impaired mitochondrial-endoplasmic reticulum interaction and mitophagy in Miro1-mutant neurons in Parkinson’s disease. (PMID:32280985)
• The role of RHOT1 and RHOT2 genetic variation on Parkinson disease risk and onset. (PMID:32948353)
• Insight into human Miro1/2 domain organization based on the structure of its N-terminal GTPase. (PMID:33132189)
• Circular RNA RHOT1 promotes progression and inhibits ferroptosis via mir-106a-5p/STAT3 axis in breast cancer. (PMID:33686957)
• Circular RNA circRHOT1 contributes to pathogenesis of non-small cell lung cancer by epigenetically enhancing C-MYC expression through recruiting KAT5. (PMID:34406978)
• Miro1 functions as an inhibitory regulator of MFN at elevated mitochondrial Ca(2+) levels. (PMID:34431132)
• Hsa_circ_0005230 is up-regulated and promotes gastric cancer cell invasion and migration via regulating the miR-1299/RHOT1 axis. (PMID:35170374)
• Interaction between the mitochondrial adaptor MIRO and the motor adaptor TRAK. (PMID:37949220)
• HMGB1 promotes mitochondrial transfer between hepatocellular carcinoma cells through RHOT1 and RAC1 under hypoxia. (PMID:38378644)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	rhot1a	ENSDARG00000099996
danio_rerio	rhot1b	ENSDARG00000103313
mus_musculus	Rhot1	ENSMUSG00000017686
rattus_norvegicus	Rnf135	ENSRNOG00000004093

Paralogs (22): RHOBTB2 (ENSG00000008853), RHOA (ENSG00000067560), CDC42 (ENSG00000070831), RHOBTB1 (ENSG00000072422), RHOV (ENSG00000104140), RND2 (ENSG00000108830), RND3 (ENSG00000115963), RHOU (ENSG00000116574), RHOQ (ENSG00000119729), RHOJ (ENSG00000126785), RAC2 (ENSG00000128340), RAC1 (ENSG00000136238), RHOF (ENSG00000139725), RHOT2 (ENSG00000140983), RHOB (ENSG00000143878), RHOC (ENSG00000155366), RHOBTB3 (ENSG00000164292), RHOH (ENSG00000168421), RAC3 (ENSG00000169750), RND1 (ENSG00000172602), RHOD (ENSG00000173156), RHOG (ENSG00000177105)

Protein

Protein identifiers

Mitochondrial Rho GTPase 1 — Q8IXI2 (reviewed: Q8IXI2)

Alternative names: Rac-GTP-binding protein-like protein, Ras homolog gene family member T1

All UniProt accessions (10): Q8IXI2, A0A2R8Y4I2, A0A494C061, H7BXZ6, J3KRG7, J3KSR5, J3QLG2, J3QSG2, K7EIQ7, K7EP86

UniProt curated annotations — full annotation on UniProt →

Function. Atypical mitochondrial nucleoside-triphosphatase (NTPase) involved in mitochondrial trafficking. Probably involved in control of anterograde transport of mitochondria and their subcellular distribution. Promotes mitochondrial fission during high calcium conditions. Can hydrolyze GTP, ATP and UTP.

Subunit / interactions. Homodimer. Interacts with the kinesin-binding proteins TRAK1/OIP106 and TRAK2/GRIF1, forming a link between mitochondria and the trafficking apparatus of the microtubules. Interacts with RAP1GDS1. Interacts with ARMCX1. Found in a complex with KIF5B, OGT, RHOT2 and TRAK1.

Subcellular location. Mitochondrion outer membrane.

Tissue specificity. Ubiquitously expressed. Expressed at high level in heart and skeletal muscle.

Post-translational modifications. Ubiquitinated by PRKN during mitophagy, leading to its degradation and enhancement of mitophagy. Deubiquitinated by USP30. Acetylation on Lys-92 decreases sensitivity of mitochondrial transport to elevated Ca(2+) levels, increases mitochondrial transport and promotes axon growth. Deacetylated by HDAC6 which blocks mitochondrial transport and mediates axon growth inhibition.

Domain organisation. The Miro 2 domain is necessary for efficient ubiquitination by PRKN.

Similarity. Belongs to the mitochondrial Rho GTPase family.

Isoforms (7)

UniProt ID	Names	Canonical?
Q8IXI2-1	1	yes
Q8IXI2-2	2
Q8IXI2-3	3
Q8IXI2-4	4
Q8IXI2-5	5
Q8IXI2-6	6
Q8IXI2-7	7

RefSeq proteins (7): NP_001028738, NP_001028739, NP_001028740, NP_001275683, NP_001275684, NP_001275687, NP_060777 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001806	Small_GTPase	Family
IPR002048	EF_hand_dom	Domain
IPR005225	Small_GTP-bd	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR013566	EF_hand_assoc_1	Domain
IPR013567	EF_hand_assoc_2	Domain
IPR018247	EF_Hand_1_Ca_BS	Binding_site
IPR020860	MIRO_dom	Domain
IPR021181	Miro	Family
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR052266	Miro-EF-hand_domain	Family

Pfam: PF00071, PF08355, PF08356

Catalyzed reactions (Rhea), 3 shown:

• ATP + H2O = ADP + phosphate + H(+) (RHEA:13065)
• GTP + H2O = GDP + phosphate + H(+) (RHEA:19669)
• UTP + H2O = UDP + phosphate + H(+) (RHEA:64900)

UniProt features (138 total): binding site 51, helix 30, strand 23, splice variant 7, mutagenesis site 7, turn 4, domain 4, sequence conflict 4, cross-link 3, topological domain 2, chain 1, transmembrane region 1, modified residue 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
6D71	X-RAY DIFFRACTION	1.72
5KSP	X-RAY DIFFRACTION	2.16
5KSO	X-RAY DIFFRACTION	2.25
5KSY	X-RAY DIFFRACTION	2.48
5KSZ	X-RAY DIFFRACTION	2.5
5KU1	X-RAY DIFFRACTION	2.5
5KTY	X-RAY DIFFRACTION	2.52
9E2P	ELECTRON MICROSCOPY	3.57

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IXI2-F1	92.43	0.84

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (51): 17; 18; 18; 19; 35; 57; 59; 118; 119; 121; 149; 150 …

Post-translational modifications (4): 92, 153, 235, 572

Mutagenesis-validated functional residues (7):

Position	Phenotype
13	causes constitutive activation inducing an aggregation of the mitochondrial network.
18	causes constitutive inactivation.
156	no effect on pink1-prkn-mediated degradation.
208	abolishes the formation of thread-like mitochondria.
328	abolishes the formation of thread-like mitochondria.
427	no effect.
432	no effect.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-5689880	Ub-specific processing proteases
R-HSA-9013425	RHOT1 GTPase cycle
R-HSA-162582	Signal Transduction
R-HSA-392499	Metabolism of proteins
R-HSA-5688426	Deubiquitination
R-HSA-597592	Post-translational protein modification
R-HSA-9715370	Miro GTPase Cycle
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 196 (showing top): GCACCTT_MIR18A_MIR18B, TGGTGCT_MIR29A_MIR29B_MIR29C, ATACCTC_MIR202, TGACCTY_ERR1_Q2, GOBP_ORGANELLE_TRANSPORT_ALONG_MICROTUBULE, ACTGCAG_MIR173P, chr17q11, GOBP_MITOCHONDRIAL_TRANSPORT, GOBP_REGULATION_OF_MITOCHONDRION_ORGANIZATION, ONKEN_UVEAL_MELANOMA_UP, GOBP_APOPTOTIC_SIGNALING_PATHWAY, AAAGACA_MIR511, GOCC_MITOCHONDRIAL_ENVELOPE, AAAGGGA_MIR204_MIR211, DODD_NASOPHARYNGEAL_CARCINOMA_UP

GO Biological Process (6): mitochondrion organization (GO:0007005), regulation of mitochondrion organization (GO:0010821), cellular homeostasis (GO:0019725), mitochondrion transport along microtubule (GO:0047497), mitochondrial outer membrane permeabilization (GO:0097345), small GTPase-mediated signal transduction (GO:0007264)

GO Molecular Function (10): magnesium ion binding (GO:0000287), GTPase activity (GO:0003924), calcium ion binding (GO:0005509), GTP binding (GO:0005525), ATP hydrolysis activity (GO:0016887), GDP binding (GO:0019003), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (3): mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Deubiquitination	1
Miro GTPase Cycle	1
Post-translational protein modification	1
Metabolism of proteins	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
metal ion binding	2
ribonucleoside triphosphate phosphatase activity	2
guanyl ribonucleotide binding	2
organelle organization	1
mitochondrion organization	1
regulation of organelle organization	1
homeostatic process	1
establishment of mitochondrion localization, microtubule-mediated	1
organelle transport along microtubule	1
apoptotic signaling pathway	1
positive regulation of mitochondrial membrane permeability involved in apoptotic process	1
intracellular signaling cassette	1
purine ribonucleoside triphosphate binding	1
ATP-dependent activity	1
anion binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
cation binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrial membrane	1
organelle outer membrane	1
cellular anatomical structure	1

Protein interactions and networks

STRING

3191 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RHOT1	TRAK1	Q9UPV9	998
RHOT1	TRAK2	O60296	995
RHOT1	MFN2	O95140	964
RHOT1	MFN1	Q8IWA4	961
RHOT1	PINK1	Q9BXM7	907
RHOT1	DISC1	Q9NRI5	867
RHOT1	PRKN	O60260	795
RHOT1	MYO19	Q96H55	786
RHOT1	LRRK2	Q5S007	781
RHOT1	KIF5B	P33176	763
RHOT1	SNPH	O15079	728
RHOT1	FIS1	Q9Y3D6	698
RHOT1	MCU	Q8NE86	683
RHOT1	SYBU	Q9NX95	682
RHOT1	TOMM20	Q15388	655

IntAct

89 interactions, top by confidence:

A	B	Type	Score
RHOT1	TRAK1	psi-mi:“MI:0915”(physical association)	0.820
RHOT1	TRAK1	psi-mi:“MI:0403”(colocalization)	0.820
TRAK1	RHOT1	psi-mi:“MI:0914”(association)	0.820
TRDN	TMEM223	psi-mi:“MI:0914”(association)	0.640
Kif5c	RHOT1	psi-mi:“MI:0914”(association)	0.580
Kif5c	RHOT1	psi-mi:“MI:0403”(colocalization)	0.580
RHOT1	Kif5c	psi-mi:“MI:0915”(physical association)	0.580
RHOT1	Kif5c	psi-mi:“MI:0403”(colocalization)	0.580
APOOL	MTX2	psi-mi:“MI:0914”(association)	0.530
TRAK2	OGT	psi-mi:“MI:0914”(association)	0.530
PEX19	FAM20B	psi-mi:“MI:0914”(association)	0.530
RHOT2	UBC	psi-mi:“MI:0914”(association)	0.530
IPO5	SLC27A2	psi-mi:“MI:0914”(association)	0.530
TRAK1	MTX2	psi-mi:“MI:0914”(association)	0.530
PEX19	MYO1D	psi-mi:“MI:0914”(association)	0.530
ILK	ILVBL	psi-mi:“MI:0914”(association)	0.530
TRAK1	KIF5B	psi-mi:“MI:0914”(association)	0.530
RHOT1	KIF5C	psi-mi:“MI:0915”(physical association)	0.520
KIF5C	RHOT1	psi-mi:“MI:0915”(physical association)	0.520
RHOT1	PINK1	psi-mi:“MI:0915”(physical association)	0.520
PRKN	RHOT1	psi-mi:“MI:0915”(physical association)	0.520
RHOT1	PRKN	psi-mi:“MI:0915”(physical association)	0.520
PINK1	RHOT1	psi-mi:“MI:0915”(physical association)	0.520
Trak2	RHOT1	psi-mi:“MI:0915”(physical association)	0.460
Trak2	RHOT1	psi-mi:“MI:0403”(colocalization)	0.460

BioGRID (119): RHOT1 (Affinity Capture-MS), RHOT1 (Affinity Capture-MS), RHOT1 (Affinity Capture-RNA), RHOT1 (Affinity Capture-MS), RHOT1 (Affinity Capture-MS), RHOT1 (Affinity Capture-MS), RHOT1 (Biochemical Activity), RHOT1 (Biochemical Activity), RHOT1 (Biochemical Activity), RHOT1 (Affinity Capture-MS), RHOT1 (Affinity Capture-MS), RHOT1 (Affinity Capture-MS), RHOT1 (Affinity Capture-MS), RHOT1 (Affinity Capture-MS), RHOT1 (Affinity Capture-MS)

ESM2 similar proteins: A0A286ZK88, A1L1L6, A7MB28, A8WGF4, B8BJ39, D0G6S1, O00399, O54956, P11029, P11497, Q13085, Q148G7, Q28007, Q28943, Q28DR7, Q2HJF8, Q2RAK2, Q4R4U1, Q502J7, Q5FVD6, Q5R559, Q5R5F8, Q5R7D8, Q5R8Q7, Q5SWU9, Q5ZIT8, Q5ZM73, Q6AYR2, Q6NVC5, Q6NWV3, Q6P1X5, Q6PC62, Q7TPD1, Q7TSL3, Q86XK2, Q8BG51, Q8BH44, Q8C176, Q8CHR6, Q8IWZ6

Diamond homologs: A1L1L6, F4J0W4, O59781, P0CO78, P0CO79, P31021, P34148, P34150, P39722, P55040, P55041, Q298L5, Q2HJF8, Q2UM43, Q32LU1, Q4I2W2, Q4PB75, Q4WN24, Q55G45, Q5ABR2, Q5B5L3, Q5E9M9, Q5R541, Q5ZM73, Q5ZM83, Q623S8, Q6C2J1, Q6CY37, Q6DIS1, Q6FIR8, Q6NVC5, Q758X6, Q7RZA2, Q7TSA0, Q864R5, Q8BG51, Q8IMX7, Q8IXI1, Q8IXI2, Q8JZN7

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
PINK1	“down-regulates quantity by destabilization”	RHOT1	phosphorylation
PRKN	“down-regulates quantity by destabilization”	RHOT1	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 90 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
PINK1-PRKN Mediated Mitophagy	5	28.8×	3e-04
Mitochondrial protein import	5	13.5×	5e-03

GO biological processes:

GO term	Partners	Fold	FDR
mitochondrion organization	5	10.0×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

78 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	53
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3892 predictions. Top by Δscore:

Variant	Effect	Δscore
17:32142726:GAAC:G	donor_gain	1.0000
17:32142730:G:GG	donor_gain	1.0000
17:32171039:A:AG	acceptor_gain	1.0000
17:32171040:C:G	acceptor_gain	1.0000
17:32171041:A:AC	acceptor_loss	1.0000
17:32171041:A:AG	acceptor_gain	1.0000
17:32171042:G:GC	acceptor_gain	1.0000
17:32171042:GCT:G	acceptor_gain	1.0000
17:32171042:GCTA:G	acceptor_gain	1.0000
17:32171098:AGAGG:A	donor_loss	1.0000
17:32171099:GAG:G	donor_gain	1.0000
17:32171099:GAGGT:G	donor_loss	1.0000
17:32171100:AGG:A	donor_loss	1.0000
17:32171101:GGTAA:G	donor_loss	1.0000
17:32171102:G:GA	donor_loss	1.0000
17:32171103:T:G	donor_loss	1.0000
17:32173076:G:GT	donor_gain	1.0000
17:32173811:A:AG	acceptor_gain	1.0000
17:32173812:T:G	acceptor_gain	1.0000
17:32173813:A:AG	acceptor_gain	1.0000
17:32173813:ATTT:A	acceptor_gain	1.0000
17:32173814:T:G	acceptor_gain	1.0000
17:32173816:T:A	acceptor_gain	1.0000
17:32173820:T:TA	acceptor_gain	1.0000
17:32173823:A:AG	acceptor_gain	1.0000
17:32173823:AAAT:A	acceptor_gain	1.0000
17:32173824:A:G	acceptor_gain	1.0000
17:32173827:GAA:G	acceptor_loss	1.0000
17:32173829:AGGT:A	acceptor_loss	1.0000
17:32174436:G:T	donor_gain	1.0000

AlphaMissense

4366 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:32142715:T:C	L8P	1.000
17:32142718:T:C	L9P	1.000
17:32142723:G:A	G11R	1.000
17:32142723:G:C	G11R	1.000
17:32142724:G:A	G11E	1.000
17:32142724:G:T	G11V	1.000
17:32171051:G:A	G16R	1.000
17:32171051:G:C	G16R	1.000
17:32171051:G:T	G16W	1.000
17:32171052:G:A	G16E	1.000
17:32171052:G:T	G16V	1.000
17:32171058:C:T	T18I	1.000
17:32171064:T:A	L20Q	1.000
17:32171064:T:C	L20P	1.000
17:32171076:T:A	L24Q	1.000
17:32171076:T:C	L24P	1.000
17:32171090:T:C	F29L	1.000
17:32171092:T:A	F29L	1.000
17:32171092:T:G	F29L	1.000
17:32173853:T:A	I40N	1.000
17:32173853:T:C	I40T	1.000
17:32173853:T:G	I40S	1.000
17:32173859:T:A	I42N	1.000
17:32173859:T:C	I42T	1.000
17:32173859:T:G	I42S	1.000
17:32173862:C:A	P43Q	1.000
17:32173886:T:A	V51D	1.000
17:32173898:T:A	I55N	1.000
17:32173898:T:G	I55S	1.000
17:32173903:G:C	D57H	1.000

dbSNP variants (sampled 300 via entrez): RS1000152836 (17:32212360 C>T), RS1000222667 (17:32186322 T>G), RS1000233655 (17:32219325 G>A), RS1000236706 (17:32212276 T>C), RS1000297013 (17:32140773 G>A), RS1000379787 (17:32205297 G>A), RS1000431240 (17:32163116 G>A), RS1000458936 (17:32205066 G>A), RS1000483786 (17:32198421 A>G), RS1000560621 (17:32140667 G>A), RS1000562691 (17:32141063 C>A,T), RS1000599055 (17:32205990 G>A), RS1000645417 (17:32147745 A>C), RS1000663070 (17:32219330 G>A), RS1000672091 (17:32211939 T>G)

Disease associations

OMIM: gene MIM:613888 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001762_280	Obesity-related traits	6.000000e-06
GCST008949_2	High chromosomal aberration frequency (chromosome type) in genotoxic compound exposure	8.000000e-06
GCST008954_2	High chromosomal aberration frequency (chromosome type)	5.000000e-06
GCST90014268_35	Cataracts	7.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005119	antioxidant measurement
EFO:0009861	chromosome-type aberration frequency

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

37 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects methylation, decreases methylation, increases expression, affects cotreatment	2
Acetaminophen	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
uranyl acetate	affects expression	1
beta-lapachone	decreases expression	1
afimoxifene	decreases reaction, decreases expression	1
sodium arsenite	decreases expression, increases abundance	1
cobaltous chloride	increases expression	1
butyraldehyde	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
beta-methylcholine	affects expression	1
abrine	decreases expression	1
jinfukang	decreases expression	1
bisphenol AF	increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases expression	1
Fulvestrant	affects cotreatment, affects methylation	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	decreases expression	1
Coumestrol	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Estrogens	decreases expression, decreases reaction	1
Formaldehyde	decreases expression	1
Ivermectin	decreases expression	1
Phthalic Acids	increases methylation	1
Quercetin	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Uranium	affects expression	1

Cellosaurus cell lines

16 cell lines: 12 induced pluripotent stem cell, 3 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A0ZL	HIHTFi001-A	Induced pluripotent stem cell	Female
CVCL_A0ZM	HIHTFi001-B	Induced pluripotent stem cell	Female
CVCL_A0ZN	HIHTFi001-C	Induced pluripotent stem cell	Female
CVCL_B2DQ	Abcam HeLa RHOT1 KO	Cancer cell line	Female
CVCL_C8G3	LCSBi009-A	Induced pluripotent stem cell	Female
CVCL_C8G4	LCSBi009-A-1	Induced pluripotent stem cell	Female
CVCL_C8G5	LCSBi010-A	Induced pluripotent stem cell	Female
CVCL_C8G6	LCSBi010-A-1	Induced pluripotent stem cell	Female
CVCL_C8G7	LCSBi010-A-2	Induced pluripotent stem cell	Female
CVCL_D0HH	LCSBi011-A	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.