RHOG

Summary

RHOG (ras homolog family member G, HGNC:672) is a protein-coding gene on chromosome 11p15.4, encoding Rho-related GTP-binding protein RhoG (P84095). Plays a role in immunological synaptic F-actin density and architecture organization.

This gene encodes a member of the Rho family of small GTPases, which cycle between inactive GDP-bound and active GTP-bound states and function as molecular switches in signal transduction cascades. Rho proteins promote reorganization of the actin cytoskeleton and regulate cell shape, attachment, and motility. The encoded protein facilitates translocation of a functional guanine nucleotide exchange factor (GEF) complex from the cytoplasm to the plasma membrane where ras-related C3 botulinum toxin substrate 1 is activated to promote lamellipodium formation and cell migration. Two related pseudogene have been identified on chromosomes 20 and X.

Source: NCBI Gene 391 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hemophagocytic lymphohistiocytosis due to RhoG deficiency (Moderate, ClinGen) — +1 more curated relationship
• GWAS associations: 6
• Clinical variants (ClinVar): 18 total
• MANE Select transcript: NM_001665

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:672
Approved symbol	RHOG
Name	ras homolog family member G
Location	11p15.4
Locus type	gene with protein product
Status	Approved
Aliases	MGC125835, MGC125836
Ensembl gene	ENSG00000177105
Ensembl biotype	protein_coding
OMIM	179505
Entrez	391

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 11 protein_coding

ENST00000351018, ENST00000396978, ENST00000396979, ENST00000533217, ENST00000881794, ENST00000881795, ENST00000930896, ENST00000943876, ENST00000943877, ENST00000943878, ENST00000943879

RefSeq mRNA: 1 — MANE Select: NM_001665 NM_001665

CCDS: CCDS7748

Canonical transcript exons

ENST00000351018 — 2 exons

Exon	Start	End
ENSE00001214727	3840894	3840959
ENSE00001393048	3826978	3828206

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 98.96.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 123.6159 / max 2485.2962, expressed in 1826 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
118325	108.1553	1826
118326	7.2376	1781
118324	4.6520	1274
118320	1.4122	781
118327	1.0283	511
118319	0.3595	154
118321	0.2989	131
118323	0.2917	145
118322	0.1805	84

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	98.96	gold quality
blood	UBERON:0000178	98.33	gold quality
leukocyte	CL:0000738	98.32	gold quality
monocyte	CL:0000576	98.30	gold quality
mononuclear cell	CL:0000842	98.26	gold quality
spleen	UBERON:0002106	97.71	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.46	gold quality
lower esophagus mucosa	UBERON:0035834	96.87	gold quality
spinal cord	UBERON:0002240	96.80	gold quality
bone marrow	UBERON:0002371	96.79	gold quality
lymph node	UBERON:0000029	96.21	gold quality
olfactory bulb	UBERON:0002264	96.06	gold quality
bone marrow cell	CL:0002092	96.03	gold quality
right lung	UBERON:0002167	96.01	gold quality
upper lobe of left lung	UBERON:0008952	95.94	gold quality
mucosa of transverse colon	UBERON:0004991	95.65	gold quality
inferior vagus X ganglion	UBERON:0005363	95.63	gold quality
upper lobe of lung	UBERON:0008948	95.60	gold quality
esophagus mucosa	UBERON:0002469	95.34	gold quality
vermiform appendix	UBERON:0001154	95.25	gold quality
right coronary artery	UBERON:0001625	95.00	gold quality
ileal mucosa	UBERON:0000331	94.98	gold quality
thoracic aorta	UBERON:0001515	94.76	gold quality
ascending aorta	UBERON:0001496	94.70	gold quality
small intestine Peyer’s patch	UBERON:0003454	94.65	gold quality
left coronary artery	UBERON:0001626	94.62	gold quality
apex of heart	UBERON:0002098	94.60	gold quality
descending thoracic aorta	UBERON:0002345	94.51	gold quality
esophagus	UBERON:0001043	94.48	gold quality
coronary artery	UBERON:0001621	94.48	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-HCAD-1	yes	50.92
E-CURD-122	yes	36.09
E-HCAD-10	yes	27.32
E-CURD-112	yes	22.68
E-MTAB-6701	yes	21.43
E-MTAB-8410	yes	14.45
E-CURD-88	yes	12.14
E-CURD-120	no	35.06
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

miRNA regulators (miRDB)

67 targeting RHOG, 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-8075	99.97	67.20	962
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-9851-3P	99.63	69.68	1110
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-6751-5P	99.56	64.99	1145
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-12131	99.48	68.72	1673
HSA-MIR-4728-3P	99.47	68.94	981
HSA-MIR-3911	99.38	66.95	1087
HSA-MIR-593-5P	99.34	69.50	965
HSA-MIR-5582-5P	99.27	71.42	1879
HSA-MIR-329-5P	99.27	68.11	1597
HSA-MIR-3978	99.24	68.39	2201

Literature-anchored findings (GeneRIF, showing 27)

• RhoG function is mediated by signals independent of Rac1 and Cdc42 activation and instead by direct utilization of a subset of common effectors (PMID:12376551)
• we show a novel function for the small GTPase RhoG on the regulation of the interferon-gamma promoter and nuclear factor of activated T cells (NFAT) gene. RhoG also promotes T-cell spreading on fibronectin (PMID:12545154)
• C-terminal basic tail of RhoG specifically assists the recruitment of the TrioN-PH domain to specific membrane-bound phospholipids (PMID:15199069)
• Results suggest that RhoG contributes to the regulation of Rac1 activity in migrating cells. (PMID:16339170)
• RhoG is involved in caveolar trafficking. Such translocation is associated with changes in RhoG GDP/GTP levels and is highly dependent on lipid raft integrity and on the function of the GTPase dynamin2. (PMID:16568096)
• define RhoG as a critical component of G protein-coupled receptor-stimulated signaling cascades in murine neutrophils (PMID:16621998)
• Taken together, these results suggest that Dock4 plays an important role in the regulation of cell migration through activation of Rac1, and that RhoG is a key upstream regulator for Dock4. (PMID:17027967)
• RhoG protects cells from apoptosis caused by the loss of anchorage through a PI3K-dependent mechanism, independent of its activation of Rac1. (PMID:17570359)
• These results identify a new signaling pathway involving RhoG and its exchange factor SGEF downstream from ICAM1 that is critical for leukocyte trans-endothelial migration. (PMID:17875742)
• Results suggest that RhoG is a central target of the Yersinia stratagem and a major upstream regulator of Rac1 during different phases of the Yersinia infection cycle. (PMID:19208761)
• The activation of RhoG recruits its effector ELMO2 and a Rac GEF Dock4 to form a complex with EphA2 at the tips of cortactin-rich protrusions in migrating breast cancer cells. (PMID:20679435)
• The authors show that enteropathogenic Escherichia coli translocates EspH, which inactivates mammalian RhoGEFs and triggers cytotoxicity. (PMID:22251971)
• The invasive capacity of HPV transformed cells requires the hDlg-dependent enhancement of SGEF/RhoG activity. (PMID:22383878)
• several Rho family small GTPases activate PI3K by an indirect cooperative positive feedback that required a combination of Rac, CDC42, and RhoG small GTPase activities (PMID:22683270)
• RhoG is expressed and activated in platelets, plays an important role in GPVI-Fc receptor gamma-chain complex-mediated platelet activation, and is critical for thrombus formation in vivo. (PMID:24106269)
• This study describes the regulation of EMT in RPE cells by TGF-beta1/miR-124/RHOG signaling and suggests that the supplement of miR-124 exogenously would be a valuable therapeutic approach for the prevention or treatment of proliferative vitreoretinopathy. (PMID:26746014)
• yrosine phosphorylation of SGEF suppresses its interaction with RhoG, the elevation of RhoG activity, and SGEF-mediated promotion of cell migration. We identified tyrosine 530 (Y530), which is located within the Dbl homology domain, as a major phosphorylation site of SGEF by Src, and Y530F mutation blocked the inhibitory effect of Src on SGEF (PMID:27437949)
• These data suggest a novel link between Tiam1 and RhoG/ILK /ELMO2 pathway as upstream effectors of the Rac1-mediated phagocytic process in trabecular meshwork cells. (PMID:27539661)
• These results suggest that the levels of RhoG and RhoB GTPases and their negative regulator RhoGDI3 might be linked to the aggressiveness of the pancreatic cancerous cell lines. It is possible that RhoGDI3 could induce the downregulation of RhoG and RhoB. (PMID:27832197)
• RhoG and SGEF modulate the phosphorylation of paxillin, which plays a key role during invadopodia disassembly. (PMID:28202690)
• High RHOG expression is associated with lung adenocarcinoma. (PMID:29454349)
• siRNA-mediated depletion of RHOG strongly inhibits tube formation in vascular endothelial cells (ECV cells), an effect reversed by transfecting dominant active constructs of CDC42 or RAC1 in the RHOG-depleted cells. (PMID:30781697)
• The small GTPase RhoG regulates microtubule-mediated focal adhesion disassembly. (PMID:30914742)
• RhoG/Rac1 signaling pathway was involved in salivary adenoid cystic carcinoma (SACC) cell migration and invasion. RhoG/Rac1 at least partially mediated epiregulin/Src/AKT/ERK1/2 signaling to promote SACC cell migration and invasion. (PMID:31793126)
• Regulation of Ras homolog family member G by microRNA-124 regulates proliferation and migration of human retinal pigment epithelial cells. (PMID:32963317)
• RhoG deficiency abrogates cytotoxicity of human lymphocytes and causes hemophagocytic lymphohistiocytosis. (PMID:33513601)
• RhoG facilitates a conformational transition in the guanine nucleotide exchange factor complex DOCK5/ELMO1 to an open state. (PMID:38857861)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	rhogb	ENSDARG00000004301
danio_rerio	rhoga	ENSDARG00000068653
mus_musculus	Rhog	ENSMUSG00000073982
rattus_norvegicus	Rhog	ENSRNOG00000020393
rattus_norvegicus		ENSRNOG00000063236
caenorhabditis_elegans		WBGENE00003239

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), RHOB (ENSG00000143878), RHOC (ENSG00000155366), RHOBTB3 (ENSG00000164292), RHOH (ENSG00000168421), RAC3 (ENSG00000169750), RND1 (ENSG00000172602), RHOD (ENSG00000173156)

Protein

Protein identifiers

Rho-related GTP-binding protein RhoG — P84095 (reviewed: P84095)

All UniProt accessions (2): P84095, Q6ICQ8

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in immunological synaptic F-actin density and architecture organization. Regulates actin reorganization in lymphocytes, possibly through the modulation of Rac1 activity. Required for the formation of membrane ruffles during macropinocytosis. Plays a role in cell migration and is required for the formation of cup-like structures during trans-endothelial migration of leukocytes. Binds phospholipids in an activation-dependent manner; thereby acting as an anchor for other proteins to the plasma membrane (PM). Plays a role in exocytosis of cytotoxic granules (CG) by lymphocytes/Component of the exocytosis machinery in natural killer (NK) and CD8+ T cells. Promotes the docking of cytotoxic granules (CG) to the plasma membrane through the interaction with UNC13D. Involved in the cytotoxic activity of lymphocytes/primary CD8+ T cells. (Microbial infection) In case of Salmonella enterica infection, activated by SopB and ARHGEF26/SGEF, which induces cytoskeleton rearrangements and promotes bacterial entry.

Subunit / interactions. Interacts with ARHGEF26. Interacts with ARHGEF16. Interacts with UNC13D; the interaction increases RhoG affinity to the membrane lipids, targets UNC13D to membrane lipids and facilitates cytotoxic granule (CG) docking to the plasma membrane.

Subcellular location. Cell membrane.

Post-translational modifications. (Microbial infection) Glucosylated at Thr-35 by C.difficile toxin TcdB. (Microbial infection) Glycosylated (O-GlcNAcylated) at Thr-35 by C.novyi toxin TcdA. O-GlcNAcylation completely prevents the recognition of the downstream effector, blocking the GTPases in their inactive form, leading to actin cytoskeleton disruption.

Disease relevance. Defects in RHOG may be the cause of a severe hemophagocytic lymphohistiocytosis (HLH). The affected patient shows characteristic HLH features, such as hemophagocytosis, hepatosplenomegaly, fever, cytopenias, low hemoglobin, hypertriglyceridemia, and elevated ferritin and soluble interleukin-2 receptor.

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

RefSeq proteins (1): NP_001656* (*=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
IPR042734	RhoG	Family

Pfam: PF00071

UniProt features (33 total): helix 9, strand 6, modified residue 4, binding site 4, glycosylation site 2, sequence conflict 2, chain 1, propeptide 1, lipid moiety-binding region 1, sequence variant 1, short sequence motif 1, turn 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
7Y4A	X-RAY DIFFRACTION	1.6
6UKA	X-RAY DIFFRACTION	2.4
8ZJ2	ELECTRON MICROSCOPY	4.66
8XM7	ELECTRON MICROSCOPY	4.91
9LX0	ELECTRON MICROSCOPY	6.98
9LXH	ELECTRON MICROSCOPY	7.52

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P84095-F1	93.84	0.87

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 (4): 10–17; 28–35; 57–61; 115–118

Post-translational modifications (5): 188, 188, 39, 138, 180

Glycosylation sites (2): 35, 35

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-114604	GPVI-mediated activation cascade
R-HSA-1257604	PIP3 activates AKT signaling
R-HSA-2219530	Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-5625970	RHO GTPases activate KTN1
R-HSA-6798695	Neutrophil degranulation
R-HSA-6811558	PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-9013408	RHOG GTPase cycle

MSigDB gene sets: 345 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, CHIBA_RESPONSE_TO_TSA_UP, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_CELL_CHEMOTAXIS, GOBP_SYNAPSE_ASSEMBLY, GOCC_SECRETORY_GRANULE, MODULE_151, LFA1_Q6, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, SP3_Q3, MODULE_45, GOBP_ACTIVATION_OF_GTPASE_ACTIVITY, MAZ_Q6, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION

GO Biological Process (16): actin filament organization (GO:0007015), establishment or maintenance of cell polarity (GO:0007163), Rho protein signal transduction (GO:0007266), positive regulation of cell population proliferation (GO:0008284), regulation of cell shape (GO:0008360), Rac protein signal transduction (GO:0016601), actin cytoskeleton organization (GO:0030036), cortical cytoskeleton organization (GO:0030865), regulation of actin cytoskeleton organization (GO:0032956), positive regulation of DNA-templated transcription (GO:0045893), cell chemotaxis (GO:0060326), activation of GTPase activity (GO:0090630), regulation of postsynapse assembly (GO:0150052), regulation of ruffle assembly (GO:1900027), positive regulation of protein localization to plasma membrane (GO:1903078), small GTPase-mediated signal transduction (GO:0007264)

GO Molecular Function (5): GTPase activity (GO:0003924), GTP binding (GO:0005525), protein kinase binding (GO:0019901), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (12): endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), focal adhesion (GO:0005925), secretory granule membrane (GO:0030667), cytoplasmic vesicle (GO:0031410), cell projection (GO:0042995), extracellular exosome (GO:0070062), postsynapse (GO:0098794), glutamatergic synapse (GO:0098978), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Platelet activation, signaling and aggregation	1
Intracellular signaling by second messengers	1
PI3K/AKT Signaling in Cancer	1
RHO GTPase Effectors	1
Innate Immune System	1
Negative regulation of the PI3K/AKT network	1
RHO GTPase cycle	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
actin cytoskeleton organization	2
small GTPase-mediated signal transduction	2
cytoskeleton organization	2
cytoplasm	2
synapse	2
supramolecular fiber organization	1
cellular process	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
regulation of cell morphogenesis	1
regulation of biological quality	1
actin filament-based process	1
regulation of actin filament-based process	1
regulation of cytoskeleton organization	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
chemotaxis	1
cell migration	1
cellular response to chemical stimulus	1
positive regulation of GTPase activity	1
regulation of synapse assembly	1
postsynapse assembly	1
regulation of postsynapse organization	1
ruffle assembly	1
regulation of plasma membrane bounded cell projection assembly	1
protein localization to plasma membrane	1
regulation of protein localization to plasma membrane	1
positive regulation of protein localization to cell periphery	1
positive regulation of protein localization to membrane	1
intracellular signaling cassette	1
ribonucleoside triphosphate phosphatase activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
kinase binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

89 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
	RHOG	psi-mi:“MI:0915”(physical association)	0.660
	RHOG	psi-mi:“MI:0407”(direct interaction)	0.660
RHOG	ELMO1	psi-mi:“MI:0915”(physical association)	0.620
ELMO1	RHOG	psi-mi:“MI:0915”(physical association)	0.620
UNC13D	RHOG	psi-mi:“MI:0915”(physical association)	0.540
	RHOG	psi-mi:“MI:0915”(physical association)	0.540
	RHOG	psi-mi:“MI:0407”(direct interaction)	0.540
UNC13D	RHOG	psi-mi:“MI:0403”(colocalization)	0.540
NT5E	SCAMP1	psi-mi:“MI:0914”(association)	0.530
GPS1	PXDNL	psi-mi:“MI:0914”(association)	0.530
	AP3D1	psi-mi:“MI:0914”(association)	0.460
TUBA1A	TUBAL3	psi-mi:“MI:2364”(proximity)	0.420
SDC1	ILVBL	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (935): RHOG (Affinity Capture-MS), RHOG (Two-hybrid), RHOG (Affinity Capture-MS), RHOG (Affinity Capture-MS), RHOG (Affinity Capture-MS), RHOG (Two-hybrid), RHOG (Affinity Capture-MS), RHOG (Affinity Capture-RNA), RHOG (Affinity Capture-MS), RHOG (Affinity Capture-MS), RHOG (Affinity Capture-MS), RHOG (Affinity Capture-MS), RHOG (Affinity Capture-MS), RHOG (Proximity Label-MS), ELMOD2 (Reconstituted Complex)

ESM2 similar proteins: C4YDI6, O04369, O42825, P06780, P08134, P0CY33, P19073, P22122, P34148, P34149, P60766, P60952, P60953, P62745, P62746, P62747, P84095, P84096, P84097, P92978, Q007T2, Q01112, Q03206, Q05062, Q09914, Q16YG0, Q17031, Q1RMJ6, Q22038, Q24814, Q2KJ93, Q35638, Q38902, Q38912, Q3ZBW5, Q40220, Q4R4R6, Q5RCK9, Q62159, Q6DHE8

Diamond homologs: A0A286QZ36, A5D7J5, C4YDI6, O04369, O76321, O82480, O82481, O88931, O94103, O96390, P01122, P08134, P0CY33, P15153, P17081, P19073, P24406, P34144, P34145, P34146, P34147, P34148, P34149, P34150, P40792, P40793, P48148, P48554, P60763, P60764, P60766, P60952, P60953, P61585, P61586, P61589, P62998, P62999, P63000, P63001

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 88 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
RHOG GTPase cycle	5	13.7×	4e-03
RAC1 GTPase cycle	7	7.9×	4e-03
Neutrophil degranulation	11	4.7×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of translation	5	13.2×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	15
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

325 predictions. Top by Δscore:

Variant	Effect	Δscore
11:3828203:TGAC:T	acceptor_gain	1.0000
11:3828205:ACC:A	acceptor_loss	1.0000
11:3828207:C:CC	acceptor_gain	1.0000
11:3828207:CTGTG:C	acceptor_loss	1.0000
11:3828214:CAGA:C	acceptor_gain	1.0000
11:3828217:A:AC	acceptor_gain	1.0000
11:3828217:A:C	acceptor_gain	1.0000
11:3828202:GTGAC:G	acceptor_gain	0.9900
11:3828204:GAC:G	acceptor_gain	0.9900
11:3828205:AC:A	acceptor_gain	0.9900
11:3828206:CC:C	acceptor_gain	0.9900
11:3828209:G:GC	acceptor_gain	0.9900
11:3840888:CCTCA:C	donor_loss	0.9900
11:3840889:CTCAC:C	donor_loss	0.9900
11:3840890:TCACC:T	donor_loss	0.9900
11:3840892:ACC:A	donor_loss	0.9900
11:3840893:C:CA	donor_loss	0.9900
11:3828215:A:T	acceptor_gain	0.9800
11:3839371:A:AC	donor_gain	0.9800
11:3839372:C:CC	donor_gain	0.9800
11:3828209:G:C	acceptor_gain	0.9600
11:3840892:A:AC	donor_gain	0.9500
11:3840893:C:CC	donor_gain	0.9500
11:3839361:A:AT	donor_gain	0.9200
11:3828207:CTGT:C	acceptor_gain	0.9000
11:3828207:C:A	acceptor_gain	0.8900
11:3840763:TGG:T	donor_gain	0.8900
11:3840616:T:C	donor_gain	0.8800
11:3828203:TGACC:T	acceptor_gain	0.8700
11:3828205:ACCT:A	acceptor_gain	0.8700

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000052163 (11:3827227 A>C,G,T), RS1000080275 (11:3831892 C>A,G), RS1000246406 (11:3836549 A>C), RS1000394994 (11:3842112 C>T), RS1000660146 (11:3831291 C>T), RS1001280123 (11:3838588 A>T), RS1001442416 (11:3827174 C>T), RS1001470822 (11:3842022 G>C), RS1001977092 (11:3830097 C>A,T), RS1002085618 (11:3836110 T>C), RS1002372502 (11:3833555 T>A), RS1002436609 (11:3836431 T>A,C), RS1002548900 (11:3840460 C>G), RS1002672191 (11:3828817 T>A,C), RS1002860022 (11:3830480 C>A)

Disease associations

OMIM: gene MIM:179505 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
hereditary hemophagocytic lymphohistiocytosis	Moderate	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
hemophagocytic lymphohistiocytosis due to RhoG deficiency	Moderate	AR

Mondo (1): hereditary hemophagocytic lymphohistiocytosis (MONDO:0015541)

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST010725_20	Malaria	4.000000e-69
GCST010725_33	Malaria	2.000000e-67
GCST010725_51	Malaria	1.000000e-55
GCST90002389_460	Lymphocyte percentage of white cells	6.000000e-10
GCST90002400_630	Plateletcrit	2.000000e-13
GCST90027899_7	Eosinophilic esophagitis	1.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007985	platelet crit

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression	3
sodium arsenite	affects cotreatment, decreases expression	2
bisphenol S	affects expression, increases expression	2
Benzo(a)pyrene	decreases methylation, affects methylation	2
Nickel	increases expression	2
Tobacco Smoke Pollution	increases expression, affects expression	2
Tretinoin	affects cotreatment, decreases expression, increases expression	2
bisphenol F	increases expression	1
triphenyl phosphate	affects expression	1
arsenite	affects binding, increases reaction	1
tetrabromobisphenol A	decreases expression	1
pyrrolidine dithiocarbamic acid	affects cotreatment, decreases reaction, increases expression	1
ochratoxin A	affects binding	1
aflatoxin B2	increases methylation	1
calfactant	affects cotreatment, increases expression	1
bisphenol B	increases expression	1
bisphenol AF	increases expression	1
Sunitinib	increases expression	1
Zoledronic Acid	increases expression	1
Arsenic	affects methylation	1
Aspirin	decreases expression	1
Diuron	decreases expression	1
Doxorubicin	decreases expression	1
Environmental Pollutants	affects expression	1
Ivermectin	decreases expression	1
Selenium	increases expression	1
Smoke	decreases expression	1
Tetradecanoylphorbol Acetate	affects cotreatment, decreases reaction, increases expression	1
Vitamin E	increases expression	1
Mifepristone	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3G1	Abcam HEK293T RHOG KO	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05744063	PHASE4	COMPLETED	A Post-authorization Study to Describe the Safety and Efficacy of Emapalumab for the Treatment of pHLH in Treatment Experienced Chinese Patients
NCT03312751	PHASE3	COMPLETED	Study to Assess the Efficacy and Safety of Emapalumab in Primary Haemophagocytic Lymphohistiocytosis
NCT00368355	PHASE2	COMPLETED	T Cell Depletion for Recipients of HLA Haploidentical Related Donor Stem Cell Grafts
NCT01494103	PHASE1	ACTIVE_NOT_RECRUITING	Administration of Donor T Cells With the Caspase-9 Suicide Gene
NCT03827343	Not specified	ACTIVE_NOT_RECRUITING	Retrospective Study of Immunotherapy Related Toxicities and Factors Impacting Outcomes in Children and Adults With Cancer
NCT06587191	Not specified	ACTIVE_NOT_RECRUITING	Emapalumab Efficacy in Children With Primary Hemophagocytic Lymphohistiocytosis