RHOB

Summary

RHOB (ras homolog family member B, HGNC:668) is a protein-coding gene on chromosome 2p24.1, encoding Rho-related GTP-binding protein RhoB (P62745). Mediates apoptosis in neoplastically transformed cells after DNA damage.

Predicted to enable GTP binding activity and GTPase activity. Involved in several processes, including cellular response to hydrogen peroxide; cellular response to ionizing radiation; and regulation of cell migration. Located in cleavage furrow and endosome membrane. Biomarker of breast cancer.

Source: NCBI Gene 388 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cerebral palsy (Moderate, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 11 total
• Druggable target: yes
• MANE Select transcript: NM_004040

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:668
Approved symbol	RHOB
Name	ras homolog family member B
Location	2p24.1
Locus type	gene with protein product
Status	Approved
Aliases	RHOH6, MST081
Ensembl gene	ENSG00000143878
Ensembl biotype	protein_coding
OMIM	165370
Entrez	388

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000272233

RefSeq mRNA: 1 — MANE Select: NM_004040 NM_004040

CCDS: CCDS1699

Canonical transcript exons

ENST00000272233 — 1 exons

Exon	Start	End
ENSE00001402526	20447074	20449440

Expression profiles

Bgee: expression breadth ubiquitous, 299 present calls, max score 99.79.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 117.2731 / max 2169.8636, expressed in 1777 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
19122	115.3526	1777
19127	1.7609	774
202109	0.1596	60

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of stomach	UBERON:0001199	99.79	gold quality
saphenous vein	UBERON:0007318	99.78	gold quality
vein	UBERON:0001638	99.76	gold quality
popliteal artery	UBERON:0002250	99.76	gold quality
tibial artery	UBERON:0007610	99.76	gold quality
vena cava	UBERON:0004087	99.74	gold quality
artery	UBERON:0001637	99.71	gold quality
urethra	UBERON:0000057	99.69	gold quality
medial globus pallidus	UBERON:0002477	99.68	gold quality
nipple	UBERON:0002030	99.65	gold quality
aorta	UBERON:0000947	99.63	gold quality
left uterine tube	UBERON:0001303	99.63	gold quality
globus pallidus	UBERON:0001875	99.61	gold quality
cauda epididymis	UBERON:0004360	99.55	gold quality
ascending aorta	UBERON:0001496	99.48	gold quality
thoracic aorta	UBERON:0001515	99.47	gold quality
lower lobe of lung	UBERON:0008949	99.47	gold quality
olfactory bulb	UBERON:0002264	99.46	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.46	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.46	gold quality
lower esophagus	UBERON:0013473	99.45	gold quality
left coronary artery	UBERON:0001626	99.44	gold quality
endocervix	UBERON:0000458	99.42	gold quality
coronary artery	UBERON:0001621	99.42	gold quality
right lung	UBERON:0002167	99.42	gold quality
pericardium	UBERON:0002407	99.42	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.41	gold quality
subthalamic nucleus	UBERON:0001906	99.35	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.35	gold quality
adipose tissue of abdominal region	UBERON:0007808	99.33	gold quality

Single-cell (SCXA)

Detected in 15 experiment(s), a significant marker in 11.

Experiment	Marker?	Max mean expression
E-MTAB-10287	yes	70.46
E-GEOD-135922	yes	45.63
E-HCAD-1	yes	34.38
E-MTAB-8410	yes	27.55
E-CURD-46	yes	26.08
E-MTAB-10553	yes	25.49
E-GEOD-134144	yes	12.31
E-CURD-122	yes	10.97
E-GEOD-125970	yes	7.16
E-HCAD-25	yes	4.75
E-GEOD-110499	no	861.29
E-ENAD-20	no	410.95
E-MTAB-7303	no	123.05
E-MTAB-7249	no	85.47
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, AR, ATF2, DRAM2, FOXC1, HDAC1, HOXA1, JUN, MYC, NR3C1, PARP1, SMAD2, SMAD3

miRNA regulators (miRDB)

86 targeting RHOB, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-4648	99.91	67.00	710
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540

Literature-anchored findings (GeneRIF, showing 40)

• RhoB is essential for apoptosis and antineoplastic activity of farnesyltransferase inhibitors in a mouse model. (PMID:10913192)
• RhoB is essential for DNA damage-induced apoptosis in neoplastically transformed cells. (PMID:11353846)
• Altogether, these results identify a mechanism by which RhoB antagonizes TGF-beta action through transcriptional down-regulation of AP1 in T beta R-II promoter. (PMID:11741970)
• Consequences of mevalonate depletion. Differential transcriptional, translational, and post-translational up-regulation (PMID:11788600)
• RhoB is dispensable for normal cell physiology but it has a suppressor or negative modifier function in stress-associated processes including cancer. (PMID:11905808)
• acted on by XPLN, a guanine nucleotide exchange factor (PMID:12221096)
• Proapoptotic targets of RhoB signaling include regulators of cell cycle checkpoints, cell adhesion, vesicle trafficking, MAPK signaling, transcription, and immunity. (PMID:12878865)
• RhoGAP-Rho chimeras specifically down-regulate RhoA, RhoB and RhoC activity and demonstrated that this approach may be applied to multiple human tumor cells to reverse the growth and/or invasion phenotypes associated with a distinct subtype of Rho GTPase (PMID:12939257)
• Histone deacetylase 1 represses the small GTPase RhoB expression in human nonsmall lung carcinoma cell line. (PMID:13679859)
• RhoB expression is suppressed by EGFR, ErbB2 and Ras, but not Src. (PMID:14647415)
• RhoB has a role as a tumor suppressor in lung neoplasms (PMID:15102679)
• EGF receptor traffic is disrupted by farnesyltransferase inhibitors through modulation of the RhoB GTPase (PMID:15226397)
• RHOB activation is required for mannose receptor-mediated phagocytosis by alveolar macrophages. (PMID:15574879)
• prenylated proteins (at least RhoA, RhoB and/or RhoC) antagonize the ability of ERalpha and ERbeta to stimulate ERE-dependent transcriptional activity, potentially acting through both AF-1 and AF-2 transcriptional activities (PMID:15642170)
• both palmitoylated cysteine 192 and prenylated cysteine 193, but not palmitoylated cysteine 189, are required for RhoB tumor-suppressive and proapoptotic activities (PMID:15713677)
• Rho GTPases are crucial regulators of the actin cytoskeleton and they play a role in the control of membrane trafficking (PMID:15944396)
• RhoB is essential in regulating keratinocyte cell survival after UVB exposure through epidermal growth factor receptor signaling (PMID:16278215)
• Our approach yielded 26 candidate genes differentially expressed between patients (Osteoarthritis) and controls. The presence of allelic imbalances confirms cis-regulatory mechanisms for RHOB and TXNDC3. (PMID:16642435)
• RhoB pathway is involved in the regulation of NF-kappaB activity and is essential for Dex transcriptional repression on NF-kappaB signaling in HO-8910 cells. (PMID:17046241)
• We here define its subcellular localization and dissect the significance of its domains. By subcellular fractionation and colocalization experiments, rhophilin-2 is recruited to subcellular organelles by activated RhoB-GTP. (PMID:17054945)
• Sudy demonstrates that RhoB expression is frequently downregulated in non-small-cell lung cancer (NSCLC) by multiple mechanisms, suggesting that RhoB is a candidate tumor suppressor gene for NSCLC. (PMID:17096327)
• These studies further suggest that Rho GTPases significantly influence the activity of mDia family formins in driving cellular membrane remodeling through the regulation of actin dynamics. (PMID:17198702)
• genetic association of RHOB and TXNDC3 with osteoarthritis was detected (PMID:17304710)
• Oscillation of RhoB GTPase activity is essential for appropriate sorting decisions, and for directing CXCR2 degradation and recycling – events that are required for optimal chemotaxis. (PMID:17405813)
• ROCK I cooperates with RhoB to activate NF-kappaB, and suppression of ROCK I activity by genetic or pharmacological inhibitors blocks NF-kappaB activation. (PMID:17728102)
• We thus propose that RhoB regulation of expression occurs mainly by histone deacetylation rather than by promoter hypermethylation and that this process can be modulated by specific 5’ sequences within the promoter. (PMID:18047684)
• postulate that the RhoB and MAP1A/LC2 interactions facilitate endocytic vesicle trafficking and regulate the trafficking of signaling molecules (PMID:18056259)
• in glioblastoma, PKC iota and RhoB are mutually antagonistic, potentially creating a sensitive switch between invasive and non-invasive phenotypes (PMID:18212741)
• Both integrins, v3 and v5, are involved in the glioma cell radioresistance through the integrin-linked kinase (ILK) and the small GTPase RhoB, at least by regulating the radiation-induced mitotic cell death (rhoB GTP-Binding Protein). (PMID:18464290)
• The minor allele frequency of RHOB in East Asian individuals is much lower than that of European Caucasians; a definite association of RHOB with knee osteoarthritis in East Asian individuals is not detected. (PMID:18471322)
• in basal conditions, RhoGDIalpha is rate-limiting and the suppression of RhoA makes it available to stabilize RhoB (PMID:18524772)
• Our data provide the first demonstration of RhoB phosphorylation and indicate that this post-translational maturation would be a novel critical mechanism to control the RhoB functions. (PMID:18590726)
• Data suggest that RhoA and B small GTPases, along with ROCK, are major membrane androgen receptor effectors controlling actin reorganization and apoptosis in prostate cancer cells. (PMID:18694745)
• RhoB is a novel intermediate in critical signaling pathways and as an additional target for therapeutic intervention in anaplastic thyroid cancer growth. (PMID:19208833)
• RhoB plays a role in protecting these cells from apoptosis as inhibiting its expression strikingly increases programmed cell death. (PMID:19477269)
• RhoB promotes cell motility and invasion in a metastatic prostate cancer cell. (PMID:19782069)
• we report, for the first time, the distribution of RhoB protein in the human scalp skin and hair follicles. (PMID:19889053)
• These results suggest that JNK contributes to RhoB induction, affecting the cell death response to gamma-radiation. (PMID:19995557)
• These findings suggest the involvement of RhoB in the process of spermatogenesis in humans (PMID:19997872)
• miR-21 promotes multiple components of the metastatic phenotype in vitro by regulating several important tumor suppressors, including RHOB. (PMID:20460403)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Rhob	ENSMUSG00000054364
rattus_norvegicus	Rhob	ENSRNOG00000021403
drosophila_melanogaster	Rho1	FBGN0014020

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), RHOT2 (ENSG00000140983), RHOC (ENSG00000155366), RHOBTB3 (ENSG00000164292), RHOH (ENSG00000168421), RAC3 (ENSG00000169750), RND1 (ENSG00000172602), RHOD (ENSG00000173156), RHOG (ENSG00000177105)

Protein

Protein identifiers

Rho-related GTP-binding protein RhoB — P62745 (reviewed: P62745)

Alternative names: Rho cDNA clone 6

All UniProt accessions (1): P62745

UniProt curated annotations — full annotation on UniProt →

Function. Mediates apoptosis in neoplastically transformed cells after DNA damage. Not essential for development but affects cell adhesion and growth factor signaling in transformed cells. Plays a negative role in tumorigenesis as deletion causes tumor formation. Involved in intracellular protein trafficking of a number of proteins. Targets PKN1 to endosomes and is involved in trafficking of the EGF receptor from late endosomes to lysosomes. Also required for stability and nuclear trafficking of AKT1/AKT which promotes endothelial cell survival during vascular development. Serves as a microtubule-dependent signal that is required for the myosin contractile ring formation during cell cycle cytokinesis. Required for genotoxic stress-induced cell death in breast cancer cells.

Subunit / interactions. Binds ROCK1 and ROCK2. Also binds PKN1/PRK1. Interacts with ARGGEF3. Interacts with RTKN. Interacts with AKAP13. Interacts with RIPOR1.

Subcellular location. Late endosome membrane. Cell membrane. Nucleus. Cleavage furrow.

Post-translational modifications. Prenylation specifies the subcellular location of RHOB. The farnesylated form is localized to the plasma membrane while the geranylgeranylated form is localized to the endosome. (Microbial infection) Glycosylated at Tyr-34 by Photorhabdus asymbiotica toxin PAU_02230. Mono-O-GlcNAcylation by PAU_02230 inhibits downstream signaling by an impaired interaction with diverse regulator and effector proteins of Rho and leads to actin disassembly. (Microbial infection) Glucosylated at Thr-37 by C.difficile toxins TcdA and TcdB in the colonic epithelium. Monoglucosylation completely prevents the recognition of the downstream effector, blocking the GTPases in their inactive form, leading to actin cytoskeleton disruption.

Induction. Up-regulated by DNA damaging agents like H(2)O(2) or ionizing radiation (IR).

Miscellaneous. RHOB is one of the targets of farnesyltransferase inhibitors which are currently under investigation as cancer therapeutics. These elevate the levels of geranylgeranylated RHOB and cause mislocalization, leading to apoptosis and antineoplastic effects.

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

RefSeq proteins (1): NP_004031* (*=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

Enzyme classification (BRENDA):

• EC 3.6.5.2 — small monomeric GTPase (BRENDA: 49 organisms, 138 substrates, 55 inhibitors, 5 Km, 1 kcat entries)

Substrate kinetics (BRENDA)

1 substrates with measured Km, best-characterized 1. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
GTP	—	0

UniProt features (38 total): helix 9, mutagenesis site 6, strand 6, lipid moiety-binding region 4, binding site 3, modified residue 3, glycosylation site 2, turn 2, chain 1, propeptide 1, short sequence motif 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
6HXU	X-RAY DIFFRACTION	1.19
6SGE	X-RAY DIFFRACTION	1.5
2FV8	X-RAY DIFFRACTION	1.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P62745-F1	92.54	0.89

Antibody-complex structures (SAbDab): 1 — 6SGE

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): 12–19; 59–63; 117–120

Post-translational modifications (7): 192, 193, 193, 41, 154, 193, 189

Glycosylation sites (2): 34, 37

Mutagenesis-validated functional residues (6):

Position	Phenotype
14	no effect on internalization of egf receptor but decreases trafficking of receptor to the lysosome with associated accum
39	abolishes binding to pkn1 and trafficking of egf receptor.
189	no effect on prenylation. reduced palmitoylation. abolishes palmitoylation; when associated with s-192.
192	reduced geranylgeranylation but no effect on farnesylation. reduced palmitoylation. abolishes palmitoylation; when assoc
193	abolishes methylation, palmitoylation and prenylation.
194	no effect on palmitoylation or prenylation.

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-114604	GPVI-mediated activation cascade
R-HSA-416482	G alpha (12/13) signalling events
R-HSA-416572	Sema4D induced cell migration and growth-cone collapse
R-HSA-5625740	RHO GTPases activate PKNs
R-HSA-5625900	RHO GTPases activate CIT
R-HSA-5627117	RHO GTPases Activate ROCKs
R-HSA-5663220	RHO GTPases Activate Formins
R-HSA-5666185	RHO GTPases Activate Rhotekin and Rhophilins
R-HSA-9013026	RHOB GTPase cycle

MSigDB gene sets: 524 (showing top): GOBP_MITOTIC_CYTOKINESIS, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_6HR_DN, GOBP_RESPONSE_TO_IONIZING_RADIATION, GOBP_EPITHELIUM_DEVELOPMENT, MODY_HIPPOCAMPUS_POSTNATAL, GOBP_LYSOSOMAL_TRANSPORT, CCAWYNNGAAR_UNKNOWN, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, BROWNE_HCMV_INFECTION_8HR_UP, PEREZ_TP63_TARGETS, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, AMIT_EGF_RESPONSE_60_HELA, GOBP_ENDOSOME_TO_LYSOSOME_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_VASCULATURE_DEVELOPMENT

GO Biological Process (23): mitotic cytokinesis (GO:0000281), angiogenesis (GO:0001525), intracellular protein transport (GO:0006886), apoptotic process (GO:0006915), actin filament organization (GO:0007015), cell adhesion (GO:0007155), signal transduction (GO:0007165), Rho protein signal transduction (GO:0007266), endosome to lysosome transport (GO:0008333), positive regulation of endothelial cell migration (GO:0010595), cell differentiation (GO:0030154), regulation of cell migration (GO:0030334), negative regulation of cell migration (GO:0030336), positive regulation of apoptotic process (GO:0043065), positive regulation of angiogenesis (GO:0045766), negative regulation of cell cycle (GO:0045786), endothelial tube morphogenesis (GO:0061154), cellular response to hydrogen peroxide (GO:0070301), cellular response to ionizing radiation (GO:0071479), regulation of modification of postsynaptic structure (GO:0099159), small GTPase-mediated signal transduction (GO:0007264), protein transport (GO:0015031), positive regulation of cell migration (GO:0030335)

GO Molecular Function (5): GTPase activity (GO:0003924), GTP binding (GO:0005525), GDP binding (GO:0019003), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (14): nucleus (GO:0005634), early endosome (GO:0005769), cytosol (GO:0005829), plasma membrane (GO:0005886), focal adhesion (GO:0005925), endosome membrane (GO:0010008), late endosome membrane (GO:0031902), cleavage furrow (GO:0032154), extracellular exosome (GO:0070062), Schaffer collateral - CA1 synapse (GO:0098685), endosome (GO:0005768), late endosome (GO:0005770), membrane (GO:0016020), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
RHO GTPase Effectors	5
Platelet activation, signaling and aggregation	1
GPCR downstream signalling	1
Sema4D in semaphorin signaling	1
RHO GTPase cycle	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
endosome	3
cellular process	2
cell migration	2
guanyl ribonucleotide binding	2
cellular anatomical structure	2
mitotic cell cycle	1
cytoskeleton-dependent cytokinesis	1
mitotic cell cycle process	1
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
intracellular protein localization	1
protein transport	1
intracellular transport	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
actin cytoskeleton organization	1
supramolecular fiber organization	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
small GTPase-mediated signal transduction	1
lysosomal transport	1
intercellular transport	1
vesicle-mediated transport	1
regulation of endothelial cell migration	1
positive regulation of cell migration	1
endothelial cell migration	1
cellular developmental process	1
regulation of cell motility	1
regulation of cell migration	1
negative regulation of cell motility	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
angiogenesis	1
regulation of angiogenesis	1
positive regulation of vasculature development	1
cell cycle	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

52 interactions, top by confidence:

A	B	Type	Score
RHOA	CTSA	psi-mi:“MI:0914”(association)	0.730
SMURF1	RHOB	psi-mi:“MI:0915”(physical association)	0.600
RHOB	SMURF1	psi-mi:“MI:0407”(direct interaction)	0.600
ARHGEF1	RHOB	psi-mi:“MI:0915”(physical association)	0.550
RHOB	TNFAIP1	psi-mi:“MI:0915”(physical association)	0.540
TNFAIP1	RHOB	psi-mi:“MI:0915”(physical association)	0.540
TNFAIP1	RHOB	psi-mi:“MI:0403”(colocalization)	0.540
CD81	C2orf72	psi-mi:“MI:0914”(association)	0.530
sseJ	NPC1	psi-mi:“MI:0914”(association)	0.460
RHOB	DAAM1	psi-mi:“MI:0407”(direct interaction)	0.440
DIAPH1	RHOB	psi-mi:“MI:0407”(direct interaction)	0.440
RHOB	Fnta	psi-mi:“MI:0915”(physical association)	0.400
KCTD10	RHOB	psi-mi:“MI:0915”(physical association)	0.370
NEK2	RHOB	psi-mi:“MI:0915”(physical association)	0.370
RHOB	NME2	psi-mi:“MI:0915”(physical association)	0.370
SERTAD1	RHOB	psi-mi:“MI:0915”(physical association)	0.370
RHOB	FBN1	psi-mi:“MI:0915”(physical association)	0.370
PHGDH	RHOB	psi-mi:“MI:0915”(physical association)	0.370
RHOB	NQO2	psi-mi:“MI:0915”(physical association)	0.370
RHOB	NGEF	psi-mi:“MI:0915”(physical association)	0.370
RHOB	ARHGDIA	psi-mi:“MI:0915”(physical association)	0.370
DUT	RHOB	psi-mi:“MI:0915”(physical association)	0.370
RHOB	PPIG	psi-mi:“MI:0915”(physical association)	0.370
RHOB	EIF1B	psi-mi:“MI:0915”(physical association)	0.370
RHOB	PRAF2	psi-mi:“MI:0915”(physical association)	0.370
RHOB	FBXO42	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (1168): RAC1 (Affinity Capture-Western), RAC1 (Affinity Capture-Luminescence), RHOB (Two-hybrid), RHOB (Affinity Capture-MS), CUL2 (Affinity Capture-Western), RHOB (Affinity Capture-MS), RHOB (Affinity Capture-Western), RBX1 (Affinity Capture-Western), RHOB (Affinity Capture-Western), RHOB (Affinity Capture-Western), RHOB (Biochemical Activity), RHOB (Affinity Capture-MS), RHOB (Affinity Capture-MS), MAP1A (Two-hybrid), MAP1A (Reconstituted Complex)

ESM2 similar proteins: A0A286QZ36, C4YDI6, O04369, O42825, O88931, P0CY33, P15153, P17081, P19073, P34144, P34145, P34146, P34148, P34149, P40793, P48554, P60766, P60952, P60953, P62745, P62746, P62747, Q007T2, Q01112, Q03206, Q05062, Q05144, Q09914, Q16YG0, Q17031, Q24814, Q29HY3, Q2KJ93, Q38903, Q38912, Q38919, Q3ZBW5, Q40220, Q41253, Q41254

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

6 interactions.

A	Effect	B	Mechanism
RAP1GDS1	up-regulates	RHOB	binding
CSNK1A1	down-regulates	RHOB	phosphorylation
DRAM2	“down-regulates quantity by repression”	RHOB	“transcriptional regulation”
MIPOL1	“up-regulates activity”	RHOB	binding
CHEK1	“up-regulates activity”	RHOB	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 52 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
RHOC GTPase cycle	6	22.5×	5e-05
RHOA GTPase cycle	7	13.4×	8e-05
CDC42 GTPase cycle	5	9.3×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	10
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

39 predictions. Top by Δscore:

Variant	Effect	Δscore
2:20447719:C:A	acceptor_gain	0.6800
2:20447559:G:GC	acceptor_gain	0.4600
2:20448681:T:TA	acceptor_gain	0.4600
2:20447720:G:A	acceptor_gain	0.4400
2:20448682:G:A	acceptor_gain	0.4400
2:20447806:T:TA	acceptor_gain	0.4300
2:20447722:T:TA	acceptor_gain	0.4000
2:20447727:A:AG	acceptor_gain	0.4000
2:20447728:G:GG	acceptor_gain	0.4000
2:20447723:G:A	acceptor_gain	0.3900
2:20447727:AGCCC:A	acceptor_gain	0.3900
2:20447728:GCCCG:G	acceptor_gain	0.3900
2:20447728:GCCC:G	acceptor_gain	0.3500
2:20448594:A:AC	acceptor_gain	0.3400
2:20447773:TG:T	donor_gain	0.3100
2:20448572:C:CA	acceptor_gain	0.2800
2:20448919:C:G	acceptor_gain	0.2700
2:20447604:G:GC	acceptor_gain	0.2600
2:20447728:GCC:G	acceptor_gain	0.2600
2:20447802:ATCCT:A	acceptor_gain	0.2600
2:20447809:T:TA	acceptor_gain	0.2600
2:20447723:GGACA:G	acceptor_loss	0.2500
2:20447724:GACAG:G	acceptor_loss	0.2500
2:20447725:ACAGC:A	acceptor_loss	0.2500
2:20447726:CAG:C	acceptor_loss	0.2500
2:20447727:A:C	acceptor_loss	0.2500
2:20447728:GC:G	acceptor_gain	0.2500
2:20447774:GA:G	donor_gain	0.2300
2:20447775:AA:A	donor_gain	0.2300
2:20447792:T:TA	acceptor_gain	0.2300

AlphaMissense

1285 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:20447499:G:C	G12R	1.000
2:20447499:G:T	G12C	1.000
2:20447500:G:A	G12D	1.000
2:20447500:G:T	G12V	1.000
2:20447502:G:C	D13H	1.000
2:20447503:A:T	D13V	1.000
2:20447514:G:C	G17R	1.000
2:20447514:G:T	G17C	1.000
2:20447515:G:A	G17D	1.000
2:20447515:G:T	G17V	1.000
2:20447517:A:C	K18Q	1.000
2:20447518:A:T	K18M	1.000
2:20447519:G:C	K18N	1.000
2:20447519:G:T	K18N	1.000
2:20447521:C:T	T19M	1.000
2:20447553:T:C	F30L	1.000
2:20447555:C:A	F30L	1.000
2:20447555:C:G	F30L	1.000
2:20447575:C:T	T37I	1.000
2:20447580:T:C	F39L	1.000
2:20447582:C:A	F39L	1.000
2:20447582:C:G	F39L	1.000
2:20447629:T:C	L55P	1.000
2:20447637:T:A	W58R	1.000
2:20447637:T:C	W58R	1.000
2:20447640:G:A	D59N	1.000
2:20447640:G:C	D59H	1.000
2:20447640:G:T	D59Y	1.000
2:20447641:A:C	D59A	1.000
2:20447641:A:G	D59G	1.000

dbSNP variants (sampled 300 via entrez): RS1000033993 (2:20448668 T>A), RS1000450848 (2:20446585 T>G), RS1000590807 (2:20446653 C>G,T), RS1000634916 (2:20449701 A>G), RS1000744875 (2:20445591 C>A,G,T), RS1000865424 (2:20446786 C>G,T), RS1000985672 (2:20449539 G>A), RS1001270444 (2:20448301 C>A,T), RS1001617590 (2:20446840 C>G,T), RS1001618535 (2:20448461 G>A), RS1001969649 (2:20445984 C>T), RS1002361369 (2:20445722 A>C), RS1002630226 (2:20447593 T>A), RS1002882570 (2:20449324 T>A), RS1003028644 (2:20447359 C>T)

Disease associations

OMIM: gene MIM:165370 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
cerebral palsy	Moderate	Autosomal dominant

Mondo (1): cerebral palsy (MONDO:0006497)

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001146_6	Systemic sclerosis	3.000000e-06
GCST004068_9	Venous thromboembolism adjusted for sickle cell variant rs77121243-T	5.000000e-06

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D002547	Cerebral Palsy	C10.228.140.140.254

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1795102 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, decreases reaction, increases abundance, increases expression	6
Valproic Acid	affects cotreatment, increases expression, affects expression	6
Benzo(a)pyrene	affects methylation, decreases expression, increases expression, increases methylation	5
methylmercuric chloride	increases expression, affects cotreatment	4
trichostatin A	increases expression, increases reaction, affects cotreatment	4
Zoledronic Acid	affects cotreatment, increases expression, affects localization	3
Cadmium Chloride	decreases expression, increases expression	3
Particulate Matter	affects cotreatment, decreases expression, increases abundance, increases expression	3
bisphenol A	decreases expression, increases expression	2
mercuric bromide	increases expression, affects cotreatment	2
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	decreases reaction, increases degradation, decreases expression	2
torcetrapib	increases expression	2
belinostat	affects cotreatment, increases expression	2
(+)-JQ1 compound	decreases expression, increases expression	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Air Pollutants	affects expression, increases abundance, increases expression	2
Arsenic	decreases expression, increases abundance	2
Copper	affects binding, decreases expression, increases expression	2
Estradiol	decreases expression, increases expression	2
Formaldehyde	increases expression	2
Lovastatin	decreases prenylation, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Tretinoin	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
Glupearl 19S	increases expression	1
4-oxoretinoic acid	decreases expression	1
testosterone enanthate	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1799459	Binding	Transactivation of RhoB expressed in human HeLa cells at 5 uM by dual renilla/firefly luciferase reporter assay	Synthesis and biological evaluation of novel aliphatic amido-quaternary ammonium salts for anticancer chemotherapy: part I. — Eur J Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1YS	Abcam A-549 RHOB KO	Cancer cell line	Male
CVCL_D2CU	Abcam HCT 116 RHOB KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00154830	PHASE4	COMPLETED	Alterations of Functional Activities and Leg Stiffness After Hamstring Lengthening in Cerebral Palsy Children
NCT00432055	PHASE4	COMPLETED	Effects of Botulinum Toxin Type A in Adults With Cerebral Palsy
NCT00549471	PHASE4	TERMINATED	Improvement After Botulinum Toxin Injections to the Arms in Children With Cerebral Palsy
NCT00752934	PHASE4	TERMINATED	Does Oral Baclofen Improve Care and Comfort in Spastic Children in Nursing Homes?
NCT00964639	PHASE4	COMPLETED	Postoperative Pain in Children With Cerebral Palsy After Pelvic and Femoral Osteotomies
NCT01386255	PHASE4	WITHDRAWN	Placebo Controlled Study of Baclofen for GERD in Children With Cerebral Palsy
NCT02546999	PHASE4	COMPLETED	Does Botulinum Toxin A Make Walking Easier in Children With Cerebral Palsy?
NCT02633241	PHASE4	COMPLETED	A Pilot Study of Dexmedetomidine-Propofol in Children Undergoing Magnetic Resonance Imaging
NCT03117322	PHASE4	COMPLETED	Synbiotic, Prebiotics and Probiotics in Children With Cerebral Palsy and Constipation
NCT03648658	PHASE4	UNKNOWN	Paracetamol Study in Patients With Low Muscle Mass
NCT04074265	PHASE4	COMPLETED	Peri-operative Use of a Pain Injection in Pediatric Patients With Cerebral Palsy
NCT04273737	PHASE4	TERMINATED	Amantadine in Treating Cognitive & Motor Impairments in Adolescents and Adults With Cerebral Palsy
NCT04523935	PHASE4	COMPLETED	Excessive Crying in Children With Cerebral Palsy and Communication Deficits
NCT05887765	PHASE4	COMPLETED	Effect of Systematic Dexamethasone on the Duration of Popliteal Nerve Block for Anesthesia After Pediatric Ankle Surgery
NCT06176430	PHASE4	UNKNOWN	Comparison of Twice Weekly Versus Daily Iron Therapy in Treating Anemia in Children With Cerebral Palsy
NCT06189781	PHASE4	RECRUITING	Pain Injection Versus Epidural Anesthesia for Hip Surgery in Pediatric Patients With Cerebral Palsy
NCT00014989	PHASE3	COMPLETED	Beneficial Effects of Antenatal Magnesium Sulfate (BEAM Trial)
NCT00065949	PHASE3	UNKNOWN	Magnesium Sulfate to Prevent Brain Injury in Premature Infants
NCT00367068	PHASE3	COMPLETED	Dutch National ITB Study in Children With Cerebral Palsy
NCT00491894	PHASE3	COMPLETED	Safety and Efficacy Study of Oral Glycopyrrolate Liquid for the Treatment of Pathologic (Chronic Moderate to Severe) Drooling in Pediatric Patients 3 to 18 Years of Age With Cerebral Palsy or Other Neurologic Conditions
NCT00632528	PHASE3	COMPLETED	MEOPA to Improve Physical Therapy Results After Multilevel Surgery
NCT00822029	PHASE3	TERMINATED	Use of Oral Bisphosphonates in the Treatment of Osteoporosis of Non-walking Children With Cerebral Palsy
NCT00922077	PHASE3	COMPLETED	Individualized Neurodevelopmental Treatment
NCT01249417	PHASE3	COMPLETED	Dysport® Pediatric Lower Limb Spasticity Study
NCT01251380	PHASE3	COMPLETED	Dysport® Pediatric Lower Limb Spasticity Follow-on Study
NCT01437644	PHASE3	COMPLETED	The Post-Operative Pain in Cerebral Palsy (POPPIES) Trial
NCT01492608	PHASE3	COMPLETED	Magnesium Sulphate for Preterm Birth (MASP Study)
NCT01603602	PHASE3	COMPLETED	BOTOX® Treatment in Pediatric Upper Limb Spasticity
NCT01603615	PHASE3	COMPLETED	BOTOX® Open-Label Treatment in Pediatric Upper Limb Spasticity
NCT01603628	PHASE3	COMPLETED	BOTOX® Treatment in Pediatric Lower Limb Spasticity
NCT01603641	PHASE3	COMPLETED	BOTOX® Open-Label Treatment in Pediatric Lower Limb Spasticity
NCT01633736	PHASE3	UNKNOWN	Targeted Hip Strength Training in Children With Cerebral Palsy (CP)
NCT01898520	PHASE3	COMPLETED	A Safety, Efficacy and Tolerability Study of Sativex for the Treatment of Spasticity in Children Aged 8 to 18 Years
NCT01929434	PHASE3	COMPLETED	Efficacy of Stem Cell Transplantation Compared to Rehabilitation Treatment of Patients With Cerebral Paralysis
NCT02002884	PHASE3	COMPLETED	Dose-response Study of Efficacy and Safety of Botulinum Toxin Type A to Treat Spasticity of the Arm(s) or of Arm(s) and Leg(s) in Cerebral Palsy
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02839785	PHASE3	TERMINATED	Analgesia and Physiotherapy in Children With Cerebral Palsy (ANTALKINECP)
NCT03110341	PHASE3	UNKNOWN	Effect of Erythropoietin in Premature Infants on White Matter Lesions and Neurodevelopmental Outcome
NCT03302871	PHASE3	COMPLETED	Integrated Management Enhances Functional Gains in Children With Cerebral Palsy Treated by BoNT-A
NCT03306212	PHASE3	COMPLETED	Efficacy of Intermittent Serial Casting on Spastic Wrist Flexion Deformity