RHOT2

Summary

RHOT2 (ras homolog family member T2, HGNC:21169) is a protein-coding gene on chromosome 16p13.3, encoding Mitochondrial Rho GTPase 2 (Q8IXI1). Atypical mitochondrial nucleoside-triphosphatase (NTPase) involved in mitochondrial trafficking.

This gene encodes a member of the Rho family of GTPases. The encoded protein is localized to the outer mitochondrial membrane and plays a role in mitochondrial trafficking and fusion-fission dynamics.

Source: NCBI Gene 89941 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 174 total
• Druggable target: yes
• MANE Select transcript: NM_138769

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21169
Approved symbol	RHOT2
Name	ras homolog family member T2
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	MIRO-2, MIRO2
Ensembl gene	ENSG00000140983
Ensembl biotype	protein_coding
OMIM	613889
Entrez	89941

Gene structure

Transcript identifiers

Ensembl transcripts: 36 — 17 retained_intron, 13 protein_coding, 5 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000315082, ENST00000561711, ENST00000561929, ENST00000561983, ENST00000562333, ENST00000562598, ENST00000562708, ENST00000562957, ENST00000563134, ENST00000563637, ENST00000563776, ENST00000564659, ENST00000565004, ENST00000566214, ENST00000566965, ENST00000567017, ENST00000567589, ENST00000568636, ENST00000568950, ENST00000569197, ENST00000569358, ENST00000569675, ENST00000569706, ENST00000569943, ENST00000570092, ENST00000570280, ENST00000602564, ENST00000697194, ENST00000858879, ENST00000858880, ENST00000858881, ENST00000927720, ENST00000927721, ENST00000927722, ENST00000958324, ENST00000958325

RefSeq mRNA: 21 — MANE Select: NM_138769 NM_001352275, NM_001352276, NM_001352277, NM_001352278, NM_001352279, NM_001352280, NM_001352281, NM_001352282, NM_001352283, NM_001352284, NM_001352285, NM_001352286, NM_001352287, NM_001352288, NM_001352289, NM_001352290, NM_001352291, NM_001352292, NM_001352293, NM_001352294, NM_138769

CCDS: CCDS10417, CCDS92073

Canonical transcript exons

ENST00000315082 — 19 exons

Exon	Start	End
ENSE00003465954	668656	668699
ENSE00003475238	670123	670175
ENSE00003476152	669553	669606
ENSE00003479544	670456	670557
ENSE00003489394	670675	670773
ENSE00003513357	671083	671203
ENSE00003516002	672254	672384
ENSE00003521296	672084	672181
ENSE00003597784	672928	673130
ENSE00003608959	672489	672566
ENSE00003611261	668488	668569
ENSE00003621431	671860	672002
ENSE00003624813	670249	670357
ENSE00003631466	672703	672825
ENSE00003660815	671697	671781
ENSE00003674332	668353	668411
ENSE00003969898	668132	668236
ENSE00003969899	673480	674171
ENSE00003969900	670892	671000

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 98.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.8144 / max 206.2583, expressed in 1814 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
151963	17.5937	1807
151964	5.2207	1657

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	98.88	gold quality
cerebellar hemisphere	UBERON:0002245	98.66	gold quality
cerebellar cortex	UBERON:0002129	98.60	gold quality
apex of heart	UBERON:0002098	98.49	gold quality
adenohypophysis	UBERON:0002196	98.33	gold quality
right lobe of thyroid gland	UBERON:0001119	98.23	gold quality
granulocyte	CL:0000094	98.21	gold quality
right uterine tube	UBERON:0001302	98.20	gold quality
metanephros cortex	UBERON:0010533	98.19	gold quality
left lobe of thyroid gland	UBERON:0001120	98.07	gold quality
mucosa of transverse colon	UBERON:0004991	98.00	gold quality
mucosa of stomach	UBERON:0001199	97.96	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.96	gold quality
transverse colon	UBERON:0001157	97.83	gold quality
body of stomach	UBERON:0001161	97.79	gold quality
left uterine tube	UBERON:0001303	97.76	gold quality
right frontal lobe	UBERON:0002810	97.65	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.64	gold quality
endocervix	UBERON:0000458	97.56	gold quality
left adrenal gland cortex	UBERON:0035825	97.56	gold quality
right ovary	UBERON:0002118	97.55	gold quality
left ovary	UBERON:0002119	97.47	gold quality
body of uterus	UBERON:0009853	97.47	gold quality
right atrium auricular region	UBERON:0006631	97.46	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.46	gold quality
minor salivary gland	UBERON:0001830	97.43	gold quality
nerve	UBERON:0001021	97.42	gold quality
tibial nerve	UBERON:0001323	97.42	gold quality
lower esophagus mucosa	UBERON:0035834	97.39	gold quality
pituitary gland	UBERON:0000007	97.38	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.64

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

9 targeting RHOT2, 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-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-330-3P	99.41	69.95	2521
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-4324	99.04	70.14	1569

Literature-anchored findings (GeneRIF, showing 13)

• 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)
• Miro proteins serve as a Ca(2+)-sensitive switch and bifunctional regulator for both the motility and fusion-fission dynamics of the mitochondria. (PMID:19098100)
• 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)
• The Miro2-mediated mitochondrial transport in neurons and recently highlighted involvement of Miro2 proteins in mitochondrial turnover, emerging as a key process affected in neurodegeneration. (PMID:24256248)
• Miro and Cenp-F promote anterograde mitochondrial movement and proper mitochondrial distribution in daughter cells. (PMID:26259702)
• 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)
• Miro1 binds directly to a C-terminal fragment of the Myo19 tail region and that Miro1/2 recruit the Myo19 tail. (PMID:30111583)
• MIRO2 regulate the spatial organization of mitochondria in a microtubule-dependent manner.GBF1 and Arf1 interact with Miro2. (PMID:30459446)
• the data presented here indicate novel catalytic functions of human Miro atypical GTPases through altered catalytic mechanisms. (PMID:30513825)
• This study showed that RAB32 and RHOT2 were associated with aging, and that individuals exhibiting methylation levels of the RAB32 CpG site higher than 10% were observed more prone to disability than people with lower levels. (PMID:30787202)
• 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)
• MIRO2 Regulates Prostate Cancer Cell Growth via GCN1-Dependent Stress Signaling. (PMID:34992146)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rhot2	ENSDARG00000056328
mus_musculus	Rhot2	ENSMUSG00000025733
rattus_norvegicus	Rhot2	ENSRNOG00000019930

Paralogs (22): RHOBTB2 (ENSG00000008853), RHOA (ENSG00000067560), CDC42 (ENSG00000070831), RHOBTB1 (ENSG00000072422), RHOV (ENSG00000104140), RND2 (ENSG00000108830), RND3 (ENSG00000115963), RHOU (ENSG00000116574), RHOQ (ENSG00000119729), RHOJ (ENSG00000126785), RHOT1 (ENSG00000126858), RAC2 (ENSG00000128340), RAC1 (ENSG00000136238), RHOF (ENSG00000139725), RHOB (ENSG00000143878), RHOC (ENSG00000155366), RHOBTB3 (ENSG00000164292), RHOH (ENSG00000168421), RAC3 (ENSG00000169750), RND1 (ENSG00000172602), RHOD (ENSG00000173156), RHOG (ENSG00000177105)

Protein

Protein identifiers

Mitochondrial Rho GTPase 2 — Q8IXI1 (reviewed: Q8IXI1)

Alternative names: Ras homolog gene family member T2

All UniProt accessions (9): Q8IXI1, A0A8V8TM48, H3BMP9, H3BP40, H3BST5, H3BU27, H3BUX4, H3BVI5, I3L2C6

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. Can hydrolyze GTP. Can hydrolyze 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 ARMCX3. Found in a complex with KIF5B, OGT, RHOT1 and TRAK1.

Subcellular location. Mitochondrion outer membrane.

Tissue specificity. Ubiquitously expressed. Highly expressed in heart, liver, skeletal muscle, kidney and pancreas.

Post-translational modifications. Ubiquitinated by PRKN in a PINK1-dependent manner, leading to its degradation.

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

Similarity. Belongs to the mitochondrial Rho GTPase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8IXI1-1	1	yes
Q8IXI1-2	2

RefSeq proteins (21): NP_001339204, NP_001339205, NP_001339206, NP_001339207, NP_001339208, NP_001339209, NP_001339210, NP_001339211, NP_001339212, NP_001339213, NP_001339214, NP_001339215, NP_001339216, NP_001339217, NP_001339218, NP_001339219, NP_001339220, NP_001339221, NP_001339222, NP_001339223, NP_620124* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001806	Small_GTPase	Family
IPR002048	EF_hand_dom	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 (73 total): binding site 39, strand 8, helix 6, domain 4, cross-link 3, splice variant 3, topological domain 2, sequence variant 2, mutagenesis site 2, chain 1, transmembrane region 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
5KUT	X-RAY DIFFRACTION	1.69

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IXI1-F1	89.10	0.76

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 (39): 18; 18; 19; 35; 57; 59; 118; 119; 121; 149; 150; 197 …

Post-translational modifications (3): 96, 119, 164

Mutagenesis-validated functional residues (2):

Position	Phenotype
13	causes constitutive activation inducing an aggregation of the mitochondrial network.
18	induces an aggregation of the mitochondrial network.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-9013419	RHOT2 GTPase cycle
R-HSA-162582	Signal Transduction
R-HSA-9715370	Miro GTPase Cycle
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 0 (showing top):

GO Biological Process (5): mitochondrion organization (GO:0007005), 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-3 pathways:

Category	Pathways
Miro GTPase Cycle	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
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

3156 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RHOT2	TRAK1	Q9UPV9	995
RHOT2	TRAK2	O60296	988
RHOT2	MFN2	O95140	953
RHOT2	MFN1	Q8IWA4	923
RHOT2	MYO19	Q96H55	755
RHOT2	PINK1	Q9BXM7	627
RHOT2	SNPH	O15079	625
RHOT2	FIS1	Q9Y3D6	608
RHOT2	MYO10	Q9HD67	547
RHOT2	TOMM20	Q15388	519
RHOT2	RHOT1	Q8IXI2	519
RHOT2	PRKN	O60260	518
RHOT2	RANBP2	P49792	515
RHOT2	DNM1L	O00429	508
RHOT2	SYBU	Q9NX95	507

IntAct

115 interactions, top by confidence:

A	B	Type	Score
DDX19B	MIF4GD	psi-mi:“MI:0914”(association)	0.870
TRAK1	RHOT2	psi-mi:“MI:0915”(physical association)	0.710
RHOT2	TRAK1	psi-mi:“MI:0403”(colocalization)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
RHOT2	TRAK1	psi-mi:“MI:0915”(physical association)	0.710
RHOT2	TMEM86B	psi-mi:“MI:0915”(physical association)	0.560
RHOT2	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
RHOT2	SAR1A	psi-mi:“MI:0915”(physical association)	0.560
APOOL	MTX2	psi-mi:“MI:0914”(association)	0.530
MYO19	MYL12B	psi-mi:“MI:0914”(association)	0.530
RHOT2	UBC	psi-mi:“MI:0914”(association)	0.530
APLNR	SLC33A1	psi-mi:“MI:0914”(association)	0.530
IPO5	SLC27A2	psi-mi:“MI:0914”(association)	0.530
TRAK2	OGT	psi-mi:“MI:0914”(association)	0.530
TRAK1	MTX2	psi-mi:“MI:0914”(association)	0.530
ILK	ILVBL	psi-mi:“MI:0914”(association)	0.530
RHOT2	Trak2	psi-mi:“MI:0915”(physical association)	0.460
RHOT2	Trak2	psi-mi:“MI:0403”(colocalization)	0.460
AIFM1	HAX1	psi-mi:“MI:0914”(association)	0.420
GPC1	SNAP23	psi-mi:“MI:0915”(physical association)	0.400
GPC1	GANAB	psi-mi:“MI:0915”(physical association)	0.400
RHOT2	ZFYVE9	psi-mi:“MI:0915”(physical association)	0.370
MYO19	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
	VWA8	psi-mi:“MI:0914”(association)	0.350
RIPK4	VWA8	psi-mi:“MI:0914”(association)	0.350

BioGRID (413): RHOT2 (Affinity Capture-MS), RHOT2 (Affinity Capture-Western), PINK1 (Affinity Capture-Western), RHOT2 (Affinity Capture-MS), RHOT2 (Affinity Capture-MS), RHOT2 (Affinity Capture-MS), RHOT2 (Affinity Capture-MS), UBC (Affinity Capture-MS), MRPL20 (Affinity Capture-MS), RHOT1 (Affinity Capture-MS), SARM1 (Affinity Capture-MS), XPR1 (Affinity Capture-MS), FKRP (Affinity Capture-MS), RHOT2 (Affinity Capture-MS), MYO19 (Affinity Capture-MS)

ESM2 similar proteins: A0A1D5PJB7, A1A4Q9, A5YM72, A6NLP5, D3KCC4, I3L5V6, O43292, P10938, Q00973, Q05B52, Q09200, Q10468, Q14623, Q148G5, Q16586, Q2V8X7, Q3SZV0, Q561R2, Q5E9M9, Q5M868, Q5ZL13, Q66H45, Q69ZF3, Q6P3D0, Q6P7A1, Q6P9Z4, Q6SZW1, Q6TEC1, Q6ZPS2, Q7TMC8, Q864R5, Q86TX2, Q8IXI1, Q8N0W3, Q8N3Y3, Q8N6R0, Q8NF37, Q8NI29, Q8TCD5, Q8VBW8

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

2 interactions.

A	Effect	B	Mechanism
PRKN	“down-regulates quantity by destabilization”	RHOT2	polyubiquitination
PINK1	“down-regulates quantity by destabilization”	RHOT2	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 135 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	18.8×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
obsolete protein targeting to mitochondrion	6	28.8×	2e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	124
Likely benign	20
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

2699 predictions. Top by Δscore:

Variant	Effect	Δscore
16:668408:GGAG:G	donor_gain	1.0000
16:668409:G:GT	donor_gain	1.0000
16:668412:GT:G	donor_loss	1.0000
16:668696:CAAG:C	donor_loss	1.0000
16:668697:AAG:A	donor_loss	1.0000
16:668698:AG:A	donor_loss	1.0000
16:668699:GG:G	donor_loss	1.0000
16:668700:GT:G	donor_loss	1.0000
16:670247:A:AG	acceptor_gain	1.0000
16:670247:AG:A	acceptor_gain	1.0000
16:670248:G:GG	acceptor_gain	1.0000
16:670248:GG:G	acceptor_gain	1.0000
16:670355:GAG:G	donor_gain	1.0000
16:670358:G:GA	donor_loss	1.0000
16:670358:G:GG	donor_gain	1.0000
16:670362:G:GG	donor_gain	1.0000
16:670451:CCCA:C	acceptor_loss	1.0000
16:670452:CCAGT:C	acceptor_loss	1.0000
16:670453:CA:C	acceptor_loss	1.0000
16:670454:A:AG	acceptor_gain	1.0000
16:670454:AGT:A	acceptor_gain	1.0000
16:670455:G:GA	acceptor_gain	1.0000
16:670455:GT:G	acceptor_gain	1.0000
16:670455:GTG:G	acceptor_gain	1.0000
16:670455:GTGT:G	acceptor_gain	1.0000
16:670455:GTGTT:G	acceptor_gain	1.0000
16:670456:T:TA	acceptor_gain	1.0000
16:670554:GCAG:G	donor_gain	1.0000
16:670556:AGGT:A	donor_loss	1.0000
16:670557:GGTG:G	donor_loss	1.0000

AlphaMissense

3986 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:668516:T:C	I42T	0.999
16:668555:T:A	I55N	0.999
16:670502:C:A	A162D	0.999
16:668516:T:A	I42N	0.998
16:668560:G:C	D57H	0.998
16:670135:T:A	W97R	0.998
16:670135:T:C	W97R	0.998
16:670463:C:A	A149D	0.998
16:670510:G:C	A165P	0.998
16:671136:T:A	W268R	0.998
16:671136:T:C	W268R	0.998
16:668374:T:C	L20P	0.997
16:668386:T:C	L24P	0.997
16:668516:T:G	I42S	0.997
16:668555:T:G	I55S	0.997
16:669565:T:C	C79R	0.997
16:670506:G:C	Q163H	0.997
16:670506:G:T	Q163H	0.997
16:668510:T:G	I40S	0.996
16:668562:C:A	D57E	0.996
16:668562:C:G	D57E	0.996
16:670535:T:A	L173H	0.996
16:670901:T:C	F217L	0.996
16:670903:T:A	F217L	0.996
16:670903:T:G	F217L	0.996
16:671085:T:C	F251L	0.996
16:671087:C:A	F251L	0.996
16:671087:C:G	F251L	0.996
16:671106:T:C	F258L	0.996
16:671108:C:A	F258L	0.996

dbSNP variants (sampled 300 via entrez): RS1000432796 (16:669065 G>C), RS1000866824 (16:669129 T>TCA), RS1000888363 (16:668923 T>C), RS1001681087 (16:668443 C>A,G,T), RS1001778598 (16:670189 G>A), RS1001989805 (16:666805 G>C), RS1002235239 (16:671640 C>A,T), RS1002496699 (16:674496 C>G,T), RS1003122039 (16:674601 G>A), RS1003190776 (16:671108 C>G), RS1003608515 (16:673469 C>A,T), RS1004119187 (16:668153 A>C,G,T), RS1004141524 (16:667179 C>T), RS1004170281 (16:674127 T>C), RS1004239802 (16:670241 C>T)

Disease associations

OMIM: gene MIM:613889 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST001873_8	Red blood cell traits	4.000000e-22
GCST005951_12	Body mass index	5.000000e-11
GCST010796_5294	Electrocardiogram morphology (amplitude at temporal datapoints)	9.000000e-09
GCST010796_5295	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-08
GCST010796_5296	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-08
GCST010796_5297	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST012227_355	Hip circumference adjusted for BMI	4.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004327	electrocardiography
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066267 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.94	Kd	1136	nM	CHEMBL3752910
5.94	ED50	1136	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 4 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149225: Binding affinity to human RHOT2 incubated for 45 mins by Kinobead based pull down assay	kd	1.1364	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, affects cotreatment, decreases expression	5
Air Pollutants	affects cotreatment, increases abundance, increases expression, affects expression	3
bisphenol A	decreases methylation, increases expression	2
Ozone	affects cotreatment, increases expression, increases abundance, affects expression	2
Smoke	increases abundance, increases expression, decreases expression	2
triphenyl phosphate	affects expression	1
alpha-pinene	increases abundance, affects cotreatment, increases expression	1
nobiletin	decreases expression, decreases reaction	1
sodium arsenate	decreases expression, decreases reaction	1
beta-lapachone	increases expression	1
ochratoxin A	affects binding	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
K 7174	decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
bisphenol S	affects expression	1
MT19c compound	decreases expression	1
Bortezomib	decreases expression	1
Temozolomide	increases expression	1
Acrolein	affects cotreatment, increases expression, increases abundance	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Cannabidiol	increases expression	1
Carbamazepine	affects expression	1
Catechin	affects cotreatment, decreases expression	1
Diclofenac	affects expression	1
Hydrogen Peroxide	affects cotreatment, decreases expression	1
Ivermectin	decreases expression	1
Lead	affects expression	1
Theophylline	affects cotreatment, decreases expression	1
Thiram	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652267	Binding	Binding affinity to human RHOT2 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2DR	Abcam HeLa RHOT2 KO	Cancer cell line	Female
CVCL_E0MQ	Ubigene HeLa RHOT2 KO	Cancer cell line	Female
CVCL_E2JA	HAP1 RHOT2 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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