RHOV

Summary

RHOV (ras homolog family member V, HGNC:18313) is a protein-coding gene on chromosome 15q15.1, encoding Rho-related GTP-binding protein RhoV (Q96L33). Plays a role in the control of the actin cytoskeleton via activation of the JNK pathway.

Predicted to enable GTP binding activity; GTPase activity; and protein kinase binding activity. Predicted to be involved in several processes, including actin filament organization; endocytosis; and establishment of cell polarity. Predicted to be located in endosome membrane. Predicted to be active in plasma membrane.

Source: NCBI Gene 171177 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 15 total
• MANE Select transcript: NM_133639

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18313
Approved symbol	RHOV
Name	ras homolog family member V
Location	15q15.1
Locus type	gene with protein product
Status	Approved
Aliases	Chp, WRCH2
Ensembl gene	ENSG00000104140
Ensembl biotype	protein_coding
OMIM	620101
Entrez	171177

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000220507, ENST00000865319

RefSeq mRNA: 1 — MANE Select: NM_133639 NM_133639

CCDS: CCDS10068

Canonical transcript exons

ENST00000220507 — 3 exons

Exon	Start	End
ENSE00000675641	40873684	40873742
ENSE00001153781	40872214	40873501
ENSE00001643239	40873932	40874234

Expression profiles

Bgee: expression breadth ubiquitous, 183 present calls, max score 98.83.

FANTOM5 (CAGE): breadth broad, TPM avg 4.0395 / max 197.2637, expressed in 541 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
149514	3.9421	531
149513	0.0974	65

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	98.83	gold quality
pharyngeal mucosa	UBERON:0000355	97.11	gold quality
esophagus mucosa	UBERON:0002469	96.71	gold quality
skin of abdomen	UBERON:0001416	96.58	gold quality
skin of leg	UBERON:0001511	96.30	gold quality
gingival epithelium	UBERON:0001949	94.96	gold quality
zone of skin	UBERON:0000014	94.90	gold quality
upper arm skin	UBERON:0004263	94.35	gold quality
gingiva	UBERON:0001828	93.95	gold quality
nipple	UBERON:0002030	93.23	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.21	gold quality
body of tongue	UBERON:0011876	92.85	gold quality
penis	UBERON:0000989	91.63	gold quality
tongue	UBERON:0001723	90.89	gold quality
trachea	UBERON:0003126	90.76	gold quality
palpebral conjunctiva	UBERON:0001812	90.45	gold quality
mouth mucosa	UBERON:0003729	89.48	gold quality
nasal cavity epithelium	UBERON:0005384	89.45	gold quality
nasal cavity mucosa	UBERON:0001826	88.98	gold quality
vena cava	UBERON:0004087	88.93	silver quality
minor salivary gland	UBERON:0001830	88.85	gold quality
urethra	UBERON:0000057	87.89	gold quality
superior surface of tongue	UBERON:0007371	87.85	gold quality
pancreatic ductal cell	CL:0002079	87.57	silver quality
saliva-secreting gland	UBERON:0001044	87.22	gold quality
vagina	UBERON:0000996	87.20	gold quality
oral cavity	UBERON:0000167	86.89	gold quality
cerebellar vermis	UBERON:0004720	86.89	gold quality
mammalian vulva	UBERON:0000997	86.77	gold quality
tonsil	UBERON:0002372	85.09	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-CURD-114	yes	295.81
E-HCAD-1	yes	235.19
E-MTAB-8142	yes	141.09
E-GEOD-125970	yes	16.52
E-ANND-3	yes	11.27

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

37 targeting RHOV, 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-4673	100.00	66.64	1490
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-6727-3P	99.49	65.92	1333
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-519D-5P	99.41	69.30	2057
HSA-MIR-4722-3P	99.35	65.22	1099
HSA-MIR-1273H-3P	99.29	67.55	980
HSA-MIR-329-5P	99.27	68.11	1597
HSA-MIR-4667-3P	99.26	65.45	1608
HSA-MIR-4758-3P	99.12	63.96	869
HSA-MIR-4478	99.07	65.16	2320
HSA-MIR-520G-3P	98.91	67.38	1914
HSA-MIR-520H	98.91	67.38	1914
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-4725-5P	98.67	65.42	628
HSA-MIR-504-5P	98.67	65.40	631
HSA-MIR-4290	98.51	65.17	907
HSA-MIR-4726-3P	98.49	63.89	1385
HSA-MIR-6516-5P	98.42	70.19	1551
HSA-MIR-5008-5P	98.42	65.87	1019
HSA-MIR-6784-3P	98.39	64.88	662
HSA-MIR-499B-5P	98.35	68.39	988
HSA-MIR-660-3P	98.14	66.04	1434
HSA-MIR-4691-3P	98.11	66.83	1204
HSA-MIR-6862-3P	97.92	64.86	531
HSA-MIR-4660	97.79	67.44	1328
HSA-MIR-6879-5P	97.77	65.52	1521
HSA-MIR-6747-3P	97.73	64.84	1596

Literature-anchored findings (GeneRIF, showing 12)

• cloning and characterization of WRCH2 on human chromosome 15q15 (PMID:11956592)
• Data suggest that Chp is implicated in cell transformation, and the unique amino and carboxyl termini of Chp represent atypical mechanisms of regulation of Rho GTPase function. (PMID:15664990)
• Results demonstrate a novel mechanism of signal termination mediated by the Rho-family GTPases Chp and Cdc42, which results in ubiquitin-mediated degradation of one of their direct effectors, Pak1. (PMID:17355222)
• CDC42 homologous protein does not enhance the level of Ser60 phosphorylation in Pak6. (RHO V protein) (PMID:22339630)
• Authors propose that the RHOV gene could be validated as a diagnostic or prognostic marker for NSCLC, and that observed overexpression of RHOV might contribute to tumorigenesis. (PMID:24388711)
• This review addresses the developmental roles of 2 GTPases of the Rho family, RhoV/Chp and RhoU/Wrch. (PMID:26555387)
• Our results suggest that the effector domain of RhoV mediates its binding to Pak1, complementing the current view of the molecular basics of RhoV binding to effectors of the Pak family. (PMID:30113035)
• RHOV promotes lung adenocarcinoma cell growth and metastasis through JNK/c-Jun pathway. (PMID:34326698)
• A CRISPR Activation Screen Identifies an Atypical Rho GTPase That Enhances Zika Viral Entry. (PMID:34834920)
• In vivo CRISPR screens identify RhoV as a pro-metastasis factor of triple-negative breast cancer. (PMID:36898847)
• Prognostic significance of the rho GTPase RHOV and its role in tumor immune cell infiltration: a comprehensive pan-cancer analysis. (PMID:37596964)
• Regulation of RHOV signaling by interaction with SH3 domain-containing adaptor proteins and phosphorylation by PKA. (PMID:38959529)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rhov	ENSDARG00000070434
mus_musculus	Rhov	ENSMUSG00000034226
rattus_norvegicus	Rhov	ENSRNOG00000013380

Paralogs (22): RHOBTB2 (ENSG00000008853), RHOA (ENSG00000067560), CDC42 (ENSG00000070831), RHOBTB1 (ENSG00000072422), RND2 (ENSG00000108830), RND3 (ENSG00000115963), RHOU (ENSG00000116574), RHOQ (ENSG00000119729), RHOJ (ENSG00000126785), RHOT1 (ENSG00000126858), 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

Rho-related GTP-binding protein RhoV — Q96L33 (reviewed: Q96L33)

Alternative names: CDC42-like GTPase 2, GTP-binding protein-like 2, Rho GTPase-like protein ARHV, Wnt-1 responsive Cdc42 homolog 2

All UniProt accessions (1): Q96L33

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in the control of the actin cytoskeleton via activation of the JNK pathway.

Subunit / interactions. Interacts with PAK2.

Subcellular location. Cell membrane. Endosome membrane.

Tissue specificity. Highly expressed in pancreas, placenta, and fetal brain.

Similarity. Belongs to the small GTPase superfamily. Rho family.

RefSeq proteins (1): NP_598378* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001806	Small_GTPase	Family
IPR003578	Small_GTPase_Rho	Family
IPR005225	Small_GTP-bd	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily

Pfam: PF00071

UniProt features (9 total): binding site 3, chain 1, region of interest 1, compositionally biased region 1, modified residue 1, lipid moiety-binding region 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96L33-F1	85.91	0.69

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 (3): 38–45; 85–89; 143–146

Post-translational modifications (2): 25, 234

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9013424	RHOV GTPase cycle

MSigDB gene sets: 114 (showing top): GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_ESTABLISHMENT_OF_CELL_POLARITY, MARTINEZ_RB1_TARGETS_UP, RICKMAN_METASTASIS_DN, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GOBP_ACTIN_FILAMENT_ORGANIZATION, PETRETTO_BLOOD_PRESSURE_UP, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_DN, RYTTCCTG_ETS2_B, ELK1_01, P300_01, SOX5_01

GO Biological Process (7): endocytosis (GO:0006897), actin filament organization (GO:0007015), signal transduction (GO:0007165), small GTPase-mediated signal transduction (GO:0007264), regulation of cell shape (GO:0008360), establishment of cell polarity (GO:0030010), cytoskeleton organization (GO:0007010)

GO Molecular Function (6): GTPase activity (GO:0003924), GTP binding (GO:0005525), protein kinase binding (GO:0019901), metal ion binding (GO:0046872), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (4): plasma membrane (GO:0005886), endosome membrane (GO:0010008), endosome (GO:0005768), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
RHO GTPase cycle	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
vesicle budding from membrane	1
membrane invagination	1
vesicle-mediated transport	1
import into cell	1
actin cytoskeleton organization	1
supramolecular fiber organization	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
intracellular signaling cassette	1
regulation of cell morphogenesis	1
regulation of biological quality	1
establishment or maintenance of cell polarity	1
organelle organization	1
ribonucleoside triphosphate phosphatase activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
kinase binding	1
cation binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
membrane	1
cell periphery	1
endosome	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
endomembrane system	1
cytoplasmic vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

2683 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RHOV	PAK6	Q9NQU5	616
RHOV	NCK1	P16333	552
RHOV	ARHGEF7	Q14155	548
RHOV	RHOBTB3	O94955	518
RHOV	GRB2	P29354	504
RHOV	CDH17	Q12864	457
RHOV	FGF2	P09038	384
RHOV	ARHGDIA	P52565	383
RHOV	BCAR3	O75815	377
RHOV	FAT4	Q6V0I7	376
RHOV	KRTDAP	P60985	372
RHOV	FGF13	Q92913	372
RHOV	CD109	Q6YHK3	368
RHOV	CSPG4	Q6UVK1	364
RHOV	PSMG2	Q969U7	353

IntAct

8 interactions, top by confidence:

A	B	Type	Score
RHOV	PAK6	psi-mi:“MI:0915”(physical association)	0.560
RHOV	NCK2	psi-mi:“MI:0407”(direct interaction)	0.560
NCK2	RHOV	psi-mi:“MI:0407”(direct interaction)	0.560
PAK6	RHOV	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (244): RHOV (Affinity Capture-Western), PAK6 (Two-hybrid), RHOV (Affinity Capture-RNA), GIT1 (Affinity Capture-MS), GIT2 (Affinity Capture-MS), CDC42 (Affinity Capture-MS), CCP110 (Affinity Capture-MS), CEP97 (Affinity Capture-MS), NCK1 (Affinity Capture-MS), NCK2 (Affinity Capture-MS), DEPDC1B (Affinity Capture-MS), DLG5 (Affinity Capture-MS), DST (Affinity Capture-MS), SH3RF1 (Affinity Capture-MS), EPHA2 (Affinity Capture-MS)

ESM2 similar proteins: A0FGR8, A1DZY4, A5D7J5, O35141, O35929, O75628, O75808, O94103, P01114, P01115, P0C0E4, P27040, P35739, P55040, P55041, P55043, P63032, P63033, P70268, Q00993, Q06AU5, Q13637, Q17QI8, Q3UFB7, Q496Y0, Q5R541, Q63433, Q67VP4, Q6IMB1, Q6P0U3, Q6T310, Q7L0Q8, Q7YS69, Q864R5, Q8HXH0, Q8IYK8, Q8J212, Q8QFP8, Q8VDU1, Q8VEL9

Diamond homologs: A0A286QZ36, A5D7J5, C4YDI6, O04369, O76321, O82480, O88931, O96390, P01122, P08134, P0CY33, P15153, P17081, P19073, P34144, P34145, P34146, P34148, P34149, P34150, P40792, P40793, P48148, P48554, P60763, P60764, P60766, P60952, P60953, P61585, P61586, P62745, P62746, P62747, P62998, P62999, P63000, P63001, P84095, P84096

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	12
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

187 predictions. Top by Δscore:

Variant	Effect	Δscore
15:40873465:CCGGG:C	acceptor_gain	1.0000
15:40873466:CGGG:C	acceptor_gain	1.0000
15:40873741:CA:C	acceptor_gain	1.0000
15:40873743:C:CC	acceptor_gain	1.0000
15:40873927:CGTA:C	donor_gain	1.0000
15:40873930:A:AC	donor_gain	1.0000
15:40873930:A:T	donor_loss	1.0000
15:40873931:C:CA	donor_loss	1.0000
15:40873931:C:CC	donor_gain	1.0000
15:40873466:C:T	acceptor_gain	0.9900
15:40873467:G:T	acceptor_gain	0.9900
15:40873473:C:CT	acceptor_gain	0.9900
15:40873497:TCCTC:T	acceptor_gain	0.9900
15:40873498:CCTCC:C	acceptor_gain	0.9900
15:40873499:CTC:C	acceptor_gain	0.9900
15:40873499:CTCCT:C	acceptor_loss	0.9900
15:40873502:C:CC	acceptor_gain	0.9900
15:40873502:CT:C	acceptor_loss	0.9900
15:40873503:T:G	acceptor_loss	0.9900
15:40873678:TCTCA:T	donor_loss	0.9900
15:40873679:CTCAC:C	donor_loss	0.9900
15:40873680:TCACC:T	donor_loss	0.9900
15:40873681:CACCT:C	donor_loss	0.9900
15:40873682:ACCT:A	donor_loss	0.9900
15:40873683:C:CA	donor_loss	0.9900
15:40873738:TTGCA:T	acceptor_gain	0.9900
15:40873739:TGCA:T	acceptor_gain	0.9900
15:40873740:GCA:G	acceptor_gain	0.9900
15:40873741:CAC:C	acceptor_gain	0.9900
15:40873742:AC:A	acceptor_loss	0.9900

AlphaMissense

1515 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:40873167:G:T	A201D	0.999
15:40873394:C:A	W125C	0.999
15:40873394:C:G	W125C	0.999
15:40873396:A:G	W125R	0.999
15:40873396:A:T	W125R	0.999
15:40873439:G:C	F110L	0.999
15:40873439:G:T	F110L	0.999
15:40873441:A:G	F110L	0.999
15:40873442:G:C	C109W	0.999
15:40873697:T:A	D85V	0.999
15:40873697:T:G	D85A	0.999
15:40874008:C:A	K44N	0.999
15:40874008:C:G	K44N	0.999
15:40874009:T:A	K44M	0.999
15:40873164:A:T	I202N	0.998
15:40873175:A:C	F198L	0.998
15:40873175:A:T	F198L	0.998
15:40873177:A:G	F198L	0.998
15:40873210:A:G	S187P	0.998
15:40873211:G:C	C186W	0.998
15:40873329:A:G	L147P	0.998
15:40873344:C:T	G142D	0.998
15:40873440:A:G	F110S	0.998
15:40873697:T:C	D85G	0.998
15:40873698:C:G	D85H	0.998
15:40874010:T:G	K44Q	0.998
15:40874027:C:A	G38V	0.998
15:40873168:C:G	A201P	0.997
15:40873176:A:G	F198S	0.997
15:40873188:A:C	L194W	0.997

dbSNP variants (sampled 300 via entrez): RS1001097613 (15:40872788 C>A,T), RS1001304523 (15:40871792 G>A,C), RS1001354719 (15:40872125 C>T), RS1001697263 (15:40874868 C>G,T), RS1002326673 (15:40873277 G>A), RS1002338024 (15:40873565 G>A,T), RS1002966145 (15:40876178 A>C), RS1003011664 (15:40875162 T>G), RS1003329944 (15:40874677 T>A), RS1004335044 (15:40875760 C>T), RS1004344955 (15:40876041 A>G), RS1005924481 (15:40873137 C>T), RS1005949819 (15:40871732 G>A,C), RS1006875874 (15:40874267 C>A,G,T), RS1006905242 (15:40874493 G>T)

Disease associations

OMIM: gene MIM:620101 | 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
GCST001524_12	Visceral adipose tissue/subcutaneous adipose tissue ratio	3.000000e-06
GCST010725_23	Malaria	2.000000e-06
GCST010725_38	Malaria	3.000000e-06
GCST010725_80	Malaria	7.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004767	visceral:subcutaneous adipose tissue ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Particulate Matter	decreases expression, increases abundance, increases expression	4
sodium arsenite	decreases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Benzo(a)pyrene	decreases methylation, increases expression	2
Cadmium	decreases expression, increases abundance, increases expression	2
Silicon Dioxide	decreases expression	2
Cadmium Chloride	increases abundance, decreases expression	2
aristolochic acid I	increases expression	1
bisphenol A	decreases methylation	1
lead acetate	decreases expression	1
sodium arsenate	increases abundance, decreases expression	1
hydroxyhydroquinone	decreases expression	1
sulforaphane	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
tobacco tar	decreases expression, decreases reaction	1
diallyl disulfide	decreases expression, decreases reaction	1
cupric chloride	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
CGP 52608	affects binding, increases reaction	1
bisphenol S	affects cotreatment, decreases expression	1
prothioconazole	decreases expression	1
Zoledronic Acid	increases expression	1
Acetaminophen	decreases expression	1
Arsenic	decreases expression, increases abundance	1
Cannabidiol	increases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Estradiol	affects cotreatment, decreases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Lipopolysaccharides	affects response to substance, increases expression	1
Methotrexate	increases expression	1

Clinical trials (associated diseases)

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