ARHGEF2

Summary

ARHGEF2 (Rho/Rac guanine nucleotide exchange factor 2, HGNC:682) is a protein-coding gene on chromosome 1q22, encoding Rho guanine nucleotide exchange factor 2 (Q92974). Activates Rho-GTPases by promoting the exchange of GDP for GTP.

Rho GTPases play a fundamental role in numerous cellular processes that are initiated by extracellular stimuli that work through G protein coupled receptors. The encoded protein may form complex with G proteins and stimulate rho-dependent signals. Alternatively spliced transcript variants encoding different isoforms have been identified.

Source: NCBI Gene 9181 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder with midbrain and hindbrain malformations (Limited, GenCC)
• GWAS associations: 19
• Clinical variants (ClinVar): 175 total — 1 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 28
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001162383

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:682
Approved symbol	ARHGEF2
Name	Rho/Rac guanine nucleotide exchange factor 2
Location	1q22
Locus type	gene with protein product
Status	Approved
Aliases	LFP40, GEF-H1, KIAA0651, P40, Lfc, GEFH1
Ensembl gene	ENSG00000116584
Ensembl biotype	protein_coding
OMIM	607560
Entrez	9181

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 15 protein_coding, 4 retained_intron, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000313667, ENST00000313695, ENST00000361247, ENST00000423422, ENST00000462460, ENST00000465079, ENST00000470541, ENST00000470874, ENST00000470975, ENST00000471589, ENST00000474428, ENST00000476273, ENST00000477754, ENST00000487755, ENST00000495070, ENST00000497907, ENST00000608543, ENST00000609707, ENST00000673475, ENST00000696600, ENST00000696601, ENST00000873828, ENST00000873829, ENST00000927873

RefSeq mRNA: 6 — MANE Select: NM_001162383 NM_001162383, NM_001162384, NM_001350110, NM_001350111, NM_001350112, NM_004723

CCDS: CCDS1125, CCDS53375, CCDS53376

Canonical transcript exons

ENST00000361247 — 22 exons

Exon	Start	End
ENSE00000788585	155951741	155951776
ENSE00000788586	155951919	155951986
ENSE00000788587	155952116	155952235
ENSE00001853199	155946854	155948015
ENSE00001856287	155978365	155978547
ENSE00003488715	155952628	155952828
ENSE00003703255	155957713	155957882
ENSE00003703478	155966820	155966887
ENSE00003703730	155969156	155969300
ENSE00003703944	155965631	155965760
ENSE00003704391	155965303	155965412
ENSE00003704588	155951483	155951533
ENSE00003705139	155954902	155954969
ENSE00003705612	155966416	155966479
ENSE00003706783	155961661	155961909
ENSE00003709716	155950829	155951272
ENSE00003709770	155962105	155962222
ENSE00003710595	155958320	155958396
ENSE00003711203	155962933	155963183
ENSE00003711330	155962593	155962718
ENSE00003721437	155950299	155950482
ENSE00003787884	155964988	155965131

Expression profiles

Bgee: expression breadth ubiquitous, 297 present calls, max score 98.07.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 52.1624 / max 777.2739, expressed in 1824 samples.

FANTOM5 promoters (32 alternative TSS)

Promoter ID	TPM avg	Samples expressed
15023	27.4400	1811
15025	6.3654	1565
15020	4.5192	1486
15024	4.2054	1587
15021	2.6594	1027
15009	1.0321	89
15041	0.9909	176
15019	0.9123	124
15004	0.7435	417
15008	0.4707	64

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
inferior vagus X ganglion	UBERON:0005363	98.07	gold quality
ganglionic eminence	UBERON:0004023	97.96	gold quality
corpus callosum	UBERON:0002336	97.90	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.48	gold quality
olfactory bulb	UBERON:0002264	97.43	gold quality
spinal cord	UBERON:0002240	97.26	gold quality
blood	UBERON:0000178	97.22	gold quality
granulocyte	CL:0000094	97.10	gold quality
sural nerve	UBERON:0015488	96.96	gold quality
upper lobe of left lung	UBERON:0008952	96.92	gold quality
right lung	UBERON:0002167	96.85	gold quality
subthalamic nucleus	UBERON:0001906	96.84	gold quality
upper lobe of lung	UBERON:0008948	96.83	gold quality
inferior olivary complex	UBERON:0002127	96.77	gold quality
prefrontal cortex	UBERON:0000451	96.76	gold quality
cardia of stomach	UBERON:0001162	96.69	gold quality
Brodmann (1909) area 10	UBERON:0013541	96.66	gold quality
globus pallidus	UBERON:0001875	96.63	gold quality
medial globus pallidus	UBERON:0002477	96.61	gold quality
middle frontal gyrus	UBERON:0002702	96.60	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.59	gold quality
lateral globus pallidus	UBERON:0002476	96.54	gold quality
cerebellar hemisphere	UBERON:0002245	96.47	gold quality
cerebellar cortex	UBERON:0002129	96.45	gold quality
bone marrow cell	CL:0002092	96.26	gold quality
cortical plate	UBERON:0005343	96.23	gold quality
cerebellum	UBERON:0002037	96.17	gold quality
dorsal plus ventral thalamus	UBERON:0001897	96.11	gold quality
lung	UBERON:0002048	96.09	gold quality
stromal cell of endometrium	CL:0002255	96.08	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	14.49
E-CURD-114	yes	6.93

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXC1, TGFB2

miRNA regulators (miRDB)

50 targeting ARHGEF2, 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-9-5P	100.00	72.28	2361
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-23A-5P	99.94	65.39	468
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-1255A	99.74	68.09	744
HSA-MIR-1255B-5P	99.74	68.16	741
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-4255	99.72	67.70	1541
HSA-MIR-670-5P	99.67	69.94	1565
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-150-3P	99.43	70.51	920
HSA-MIR-135A-5P	99.36	71.85	1601
HSA-MIR-135B-5P	99.36	71.63	1613
HSA-MIR-6809-5P	99.13	68.45	1223
HSA-MIR-7160-5P	99.11	67.17	2207
HSA-MIR-4695-5P	99.06	64.87	1151
HSA-MIR-181A-2-3P	98.91	67.60	1168

Literature-anchored findings (GeneRIF, showing 40)

• GEF-H1 is regulated by an interaction with microtubules. (PMID:11912491)
• PAK4 mediates morphological changes through regulation of GEF-H1 (PMID:15827085)
• GEF-H1 expression level strongly correlated with p53 status in a panel of 32 cancer cell lines, and GEF-H1 induction caused activation of RhoA. Growth of mutant p53 cells was dependent on GEF-H1 expression. (PMID:16778209)
• These results identify a GEF-H1-dependent mechanism to modulate localized RhoA activation during cytokinesis under the control of mitotic kinases. (PMID:17488622)
• These studies reveal a critical role for a GEF-H1/RhoA/ROCK/MLC signaling pathway in mediating nocodazole-induced cell contractility. (PMID:18287519)
• This study establishes GEF-H1 as a critical organizer of key structural and signaling components of cell migration through the localized regulation of RhoA activity at the cell leading edge. (PMID:19625450)
• Lfc is a phosphorylated protein and demonstrate that 14-3-3 interacts directly and in a phosphorylation-dependent manner with Lfc. (PMID:19667072)
• Data indicate that GEF-H1 is a target and functional effector of TGF-beta by orchestrating Rho signaling to regulate gene expression and cell migration. (PMID:20089843)
• Heparin inhibits pulmonary artery smooth muscle cell proliferation through GEF-H1/RhoA/ROCK/p27 signaling pathway. (PMID:20558775)
• GEF-H1 is a new component of a syndecan signaling complex that is differentially expressed in brain metastatic melanoma cells compared to corresponding non-metastatic counterparts (PMID:20803552)
• the TNF-alpha-induced activation of the ERK/GEF-H1/RhoA pathway in tubular cells is mediated through Src- and TACE-dependent EGFR activation. (PMID:21212278)
• GEFH1 was identified as binding partner for the BAR domain of ASAP1.GEFH1 is a negative regulator of podosomes. (PMID:21352810)
• These data suggest that Par1b-phosphorylation regulates turnover of GEF-H1 localization by regulating its interaction with microtubules, which may contribute to cell polarization. (PMID:21513698)
• GEF-H1 mediated the activation of Rip2 during signaling by NOD2, but not in the presence of the 3020insC variant of NOD2 associated with Crohn’s disease. GEF-H1 functioned downstream of NOD2 as part of Rip2-containing signaling complexes. (PMID:21887730)
• Study shows that hPTTG1 is a transcription factor that triggers the GEF-H1/RhoA pathway to accelerate breast cancer invasion and metastasis. In human invasive breast carcinoma, hPTTG1 is overexpressed and is correlated to GEF-H1 expression. (PMID:22002306)
• Polarity-regulating kinase partitioning-defective 1b (PAR1b) phosphorylates guanine nucleotide exchange factor H1 (GEF-H1) to regulate RhoA-dependent actin cytoskeletal reorganization. (PMID:22072711)
• Results show that LPS-induced NF-kappaB activation and IL-8 synthesis in endothelial cells are regulated by the MyD88 pathway and GEF-H1-RhoA pathway. (PMID:22226472)
• Lipopolysaccharide-induced ICAM-1 synthesis in human umbilical vein endothelial cells is regulated by GEF-H1/RhoA-dependent signaling pathway via activation of p38 and NF-kappaB. (PMID:22226621)
• LPS rapidly upregulates GEF-H1 expression. Activated Rho-associated kinase by GEF-H1 subsequently activates p38 and ERK1/2, thereby increasing IL-6/TNF-alpha expression in endothelial cells. (PMID:22301607)
• Data indicate that highly aggressive spindle-shaped 231BR3 cells changed to a round cell morphology associated with expression of the small GTPase guanine nucleotide exchange factor-H1 (GEF-H1). (PMID:22513363)
• extracellular matrix stiffness regulates RhoA through microtubule destabilization and the subsequent release and activation of GEF-H1. (PMID:22593214)
• Our findings underscore a potent oncogenic role for GEF-H1 in promoting the metastatic potentials of hepatocellular carcinoma, possibly through activation of RhoA signalling. (PMID:22847784)
• present evidence that depletion of GEF-H1, a guanine nucleotide exchange factor for Rho proteins, affects vesicle trafficking (PMID:22898781)
• vincristine activates GEF-H1/RhoA/ROCK/MLC signaling. (PMID:23057787)
• CAMSAP3-anchored non-centrosomal microtubules capture GEF-H1 more efficiently than other microtubules do. (PMID:23432781)
• ERK binds to the Rho exchange factor GEF-H1 and phosphorylates it on S959, causing inhibition of GEF-H1 activity and a consequent decrease in RhoA activity. (PMID:24043311)
• This study investigated a novel mechanism of vascular barrier protection by ANP via modulation of GEF-H1 function. (PMID:24352660)
• The RhoGEF GEF-H1 is required for oncogenic RAS signaling via KSR-1. (PMID:24525234)
• Paxillin-GEF-H1-p42/44-MAPK module as a regulator of pathological mechanotransduction. (PMID:24706358)
• TGF-beta regulates LARG and GEF-H1 during epithelial-mesenchymal transition to affect stiffening response to force and cell invasion. (PMID:25143398)
• Results supported that miR-512-3p could inhibit tumor cell adhesion, migration, and invasion by regulating the RAC1 activity via DOCK3 in NSCLC A549 and H1299 cell lines. (PMID:25687035)
• data suggest that the induction of SGK1 through treatment with dexamethasone alters MT dynamics to increase Sec5-GEF-H1 interactions, which promote GEF-H1 targeting to adhesion sites. (PMID:26359301)
• By stimulating cofilin/PP2A-mediated dephosphorylation of the guanine nucleotide exchange factor GEF-H1. (PMID:26759237)
• this study reports the crystal structure of human GEF-H1 PH domain to 2.45 A resolution. (PMID:26820534)
• regulation of c-Src trafficking requires both microtubules and actin polymerization, and GEF-H1 coordinates c-Src trafficking, acting as a molecular switch between these two mechanisms (PMID:26866809)
• Overexpression of miR-194 downregulates the GEF-H1/RhoA pathway, inhibits melanoma cancer cell proliferation and metastasis. Furthermore, miR-194 expression is negatively associated with tumor-node-metastasis (TNM) stages (PMID:27573550)
• depletion induces phosphorylation of the microtubule-associated GEF-H1 on Ser886, and thereby promotes RhoA activity and actin stress fiber assembly. (PMID:28096473)
• human brain malformation is recapitulated in Arhgef2 mutant mice and identify an aberrant migration of distinct components of the precerebellar system as a pathomechanism underlying the midbrain-hindbrain phenotype. Our results highlight the crucial function of ARHGEF2 in human brain development and identify a mutation in ARHGEF2 as novel cause of a neurodevelopmental disorder. (PMID:28453519)
• Authors identified a regulatory switch controlled by MARK3 that couples microtubules to the actin cytoskeleton to establish epithelial cell polarity through ARHGEF2. (PMID:29089450)
• role for RASSF1A in tunneling nanotube formation between cells through GEFH1/Rab11 pathway control (PMID:30305100)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	arhgef2a	ENSDARG00000040380
danio_rerio	arhgef2b	ENSDARG00000075819
mus_musculus	Arhgef2	ENSMUSG00000028059
rattus_norvegicus	Arhgef2	ENSRNOG00000020027
drosophila_melanogaster	RhoGEF2	FBGN0023172
drosophila_melanogaster	cyst	FBGN0032796
caenorhabditis_elegans		WBGENE00006468
caenorhabditis_elegans	prhg-1	WBGENE00022391

Paralogs (8): PLEKHG6 (ENSG00000008323), ARHGEF1 (ENSG00000076928), ARHGEF18 (ENSG00000104880), ARHGEF11 (ENSG00000132694), ARHGEF3 (ENSG00000163947), NET1 (ENSG00000173848), ARHGEF12 (ENSG00000196914), ARHGEF28 (ENSG00000214944)

Protein

Protein identifiers

Rho guanine nucleotide exchange factor 2 — Q92974 (reviewed: Q92974)

Alternative names: Guanine nucleotide exchange factor H1, Microtubule-regulated Rho-GEF, Proliferating cell nucleolar antigen p40

All UniProt accessions (12): A0A1Y8EN19, A0A5F9ZI21, A0A8Q3SIN5, A0A8Q3SIV8, Q92974, V9GY94, V9GYF0, V9GYF5, V9GYG5, V9GYM8, V9GZ14, V9GZ58

UniProt curated annotations — full annotation on UniProt →

Function. Activates Rho-GTPases by promoting the exchange of GDP for GTP. May be involved in epithelial barrier permeability, cell motility and polarization, dendritic spine morphology, antigen presentation, leukemic cell differentiation, cell cycle regulation, innate immune response, and cancer. Binds Rac-GTPases, but does not seem to promote nucleotide exchange activity toward Rac-GTPases, which was uniquely reported in PubMed:9857026. May stimulate instead the cortical activity of Rac. Inactive toward CDC42, TC10, or Ras-GTPases. Forms an intracellular sensing system along with NOD1 for the detection of microbial effectors during cell invasion by pathogens. Required for RHOA and RIP2 dependent NF-kappaB signaling pathways activation upon S.flexneri cell invasion. Involved not only in sensing peptidoglycan (PGN)-derived muropeptides through NOD1 that is independent of its GEF activity, but also in the activation of NF-kappaB by Shigella effector proteins (IpgB2 and OspB) which requires its GEF activity and the activation of RhoA. Involved in innate immune signaling transduction pathway promoting cytokine IL6/interleukin-6 and TNF secretion in macrophage upon stimulation by bacterial peptidoglycans; acts as a signaling intermediate between NOD2 receptor and RIPK2 kinase. Contributes to the tyrosine phosphorylation of RIPK2 through Src tyrosine kinase leading to NF-kappaB activation by NOD2. Overexpression activates Rho-, but not Rac-GTPases, and increases paracellular permeability. Involved in neuronal progenitor cell division and differentiation. Involved in the migration of precerebellar neurons.

Subunit / interactions. Found in a complex composed at least of ARHGEF2, NOD2 and RIPK2. Interacts with RIPK2; the interaction mediates tyrosine phosphorylation of RIPK2 by Src kinase CSK. Interacts with RIPK1 and RIPK3. Interacts with YWHAZ/14-3-3 zeta; when phosphorylated at Ser-886. Interacts with the kinases PAK4, AURKA and MAPK1. Interacts with RHOA and RAC1. Interacts with NOD1. Interacts (via the N-terminal zinc finger) with CAPN6 (via domain II). Interacts with DYNLT1.

Subcellular location. Cytoplasm. Cytoskeleton. Cell junction. Tight junction. Golgi apparatus. Spindle. Cell projection. Ruffle membrane. Cytoplasmic vesicle.

Post-translational modifications. Phosphorylation of Ser-886 by PAK1 induces binding to protein YWHAZ, promoting its relocation to microtubules and the inhibition of its activity. Phosphorylated by AURKA and CDK1 during mitosis, which negatively regulates its activity. Phosphorylation by MAPK1 or MAPK3 increases nucleotide exchange activity. Phosphorylation by PAK4 releases GEF-H1 from the microtubules. Phosphorylated on serine, threonine and tyrosine residues in a RIPK2-dependent manner.

Disease relevance. Neurodevelopmental disorder with midbrain and hindbrain malformations (NEDMHM) [MIM:617523] An autosomal recessive neurodevelopmental disorder characterized by intellectual disability, speech delay, mild microcephaly, midbrain-hindbrain malformations, and variable dysmorphic features. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The DH (DBL-homology) domain interacts with and promotes loading of GTP on RhoA. Promotes tyrosine phosphorylation of RIPK2. The PH domain has no affinity for phosphoinositides suggesting that it does not interact directly with membranes. The phorbol-ester/DAG-type zinc-finger and the C-terminal coiled-coil domains (606-986) are both important for association with microtubules.

Induction. Up-regulated by bacterial peptidoglycans stimulation, such as muramyl dipeptide and in biopsies from inflamed mucosal areas of Crohn’s disease patients.

Isoforms (3)

UniProt ID	Names	Canonical?
Q92974-1	1	yes
Q92974-2	2
Q92974-3	3

RefSeq proteins (6): NP_001155855, NP_001155856, NP_001337039, NP_001337040, NP_001337041, NP_004714 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000219	DH_dom	Domain
IPR001849	PH_domain	Domain
IPR002219	PKC_DAG/PE	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR035899	DBL_dom_sf	Homologous_superfamily
IPR037806	ARHGEF2_PH	Domain
IPR041020	PH_16	Domain
IPR046349	C1-like_sf	Homologous_superfamily
IPR051632	Rho_GEF	Family

Pfam: PF00621, PF17838

UniProt features (88 total): modified residue 31, helix 19, strand 10, mutagenesis site 9, region of interest 3, sequence conflict 3, turn 3, domain 2, compositionally biased region 2, splice variant 2, coiled-coil region 2, chain 1, zinc finger region 1

Structure

Experimental structures (PDB)

60 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
7G83	X-RAY DIFFRACTION	1.31
7G8T	X-RAY DIFFRACTION	1.39
8BNT	X-RAY DIFFRACTION	1.4
7G82	X-RAY DIFFRACTION	1.41
7G8B	X-RAY DIFFRACTION	1.42
7G8F	X-RAY DIFFRACTION	1.42
7G8R	X-RAY DIFFRACTION	1.44
7G8V	X-RAY DIFFRACTION	1.45
7G94	X-RAY DIFFRACTION	1.47
7G8K	X-RAY DIFFRACTION	1.49
7G8A	X-RAY DIFFRACTION	1.5
7G8Z	X-RAY DIFFRACTION	1.51
7G81	X-RAY DIFFRACTION	1.51
7G95	X-RAY DIFFRACTION	1.55
7G8Q	X-RAY DIFFRACTION	1.56
7G8O	X-RAY DIFFRACTION	1.58
7G8L	X-RAY DIFFRACTION	1.6
7G8S	X-RAY DIFFRACTION	1.6
7G8H	X-RAY DIFFRACTION	1.67
7G80	X-RAY DIFFRACTION	1.67
7G93	X-RAY DIFFRACTION	1.69
7G86	X-RAY DIFFRACTION	1.7
7G8X	X-RAY DIFFRACTION	1.71
7G85	X-RAY DIFFRACTION	1.74
7G8Y	X-RAY DIFFRACTION	1.75
7G99	X-RAY DIFFRACTION	1.78
7G8E	X-RAY DIFFRACTION	1.79
7G84	X-RAY DIFFRACTION	1.81
7G88	X-RAY DIFFRACTION	1.87
7G92	X-RAY DIFFRACTION	1.87

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92974-F1	69.91	0.38

Functional residue map

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

Post-translational modifications (31): 109, 122, 129, 133, 137, 143, 151, 163, 172, 174, 177, 353, 645, 648, 679, 691, 696, 711, 782, 886 …

Mutagenesis-validated functional residues (9):

Position	Phenotype
53	abolishes microtubule binding, increased activity in vitro.
143	abolishes phosphorylation by pak4, self aggregation in the cytoplasm. increases activity; when associated with a-896.
394	reduces phosphorylation level, normal microtubule localization and activity.
679	reduces phosphorylation level.
886	normal activity.
886	increases activity. abolishes nucleotide exchange activity; when associated with d-960.
896	abolishes phosphorylation by pak4, self aggregation in the cytoplasm. increases activity; when associated with a-143.
960	normal activity.
960	increases activity. abolishes nucleotide exchange activity; when associated with d-886.

Function

Pathways and Gene Ontology

Reactome pathways

13 pathways

ID	Pathway
R-HSA-193648	NRAGE signals death through JNK
R-HSA-416482	G alpha (12/13) signalling events
R-HSA-8980692	RHOA GTPase cycle
R-HSA-9013026	RHOB GTPase cycle
R-HSA-162582	Signal Transduction
R-HSA-193704	p75 NTR receptor-mediated signalling
R-HSA-194315	Signaling by Rho GTPases
R-HSA-204998	Cell death signalling via NRAGE, NRIF and NADE
R-HSA-372790	Signaling by GPCR
R-HSA-388396	GPCR downstream signalling
R-HSA-73887	Death Receptor Signaling
R-HSA-9012999	RHO GTPase cycle
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 484 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, GGGACCA_MIR133A_MIR133B, CREL_01, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, BROWNE_HCMV_INFECTION_6HR_DN, HNF3ALPHA_Q6, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_RESPONSE_TO_PEPTIDE, GOBP_POSITIVE_REGULATION_OF_NEURON_DIFFERENTIATION, AAGCCAT_MIR135A_MIR135B, MAZ_Q6, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, REACTOME_NRAGE_SIGNALS_DEATH_THROUGH_JNK

GO Biological Process (26): cell morphogenesis (GO:0000902), intracellular protein transport (GO:0006886), actin filament organization (GO:0007015), negative regulation of microtubule depolymerization (GO:0007026), positive regulation of interleukin-6 production (GO:0032755), positive regulation of tumor necrosis factor production (GO:0032760), regulation of Rho protein signal transduction (GO:0035023), regulation of cell population proliferation (GO:0042127), innate immune response (GO:0045087), positive regulation of neuron differentiation (GO:0045666), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of peptidyl-tyrosine phosphorylation (GO:0050731), regulation of small GTPase mediated signal transduction (GO:0051056), obsolete positive regulation of NF-kappaB transcription factor activity (GO:0051092), asymmetric neuroblast division (GO:0055059), negative regulation of necroptotic process (GO:0060546), cellular response to muramyl dipeptide (GO:0071225), cellular response to tumor necrosis factor (GO:0071356), cellular hyperosmotic response (GO:0071474), negative regulation of extrinsic apoptotic signaling pathway via death domain receptors (GO:1902042), negative regulation of intrinsic apoptotic signaling pathway in response to osmotic stress (GO:1902219), positive regulation of neuron migration (GO:2001224), immune system process (GO:0002376), nervous system development (GO:0007399), cell differentiation (GO:0030154), cell division (GO:0051301)

GO Molecular Function (6): guanyl-nucleotide exchange factor activity (GO:0005085), microtubule binding (GO:0008017), zinc ion binding (GO:0008270), small GTPase binding (GO:0031267), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (16): cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), spindle (GO:0005819), cytosol (GO:0005829), cytoskeleton (GO:0005856), microtubule (GO:0005874), bicellular tight junction (GO:0005923), focal adhesion (GO:0005925), cytoplasmic vesicle (GO:0031410), vesicle (GO:0031982), ruffle membrane (GO:0032587), protein-containing complex (GO:0032991), plasma membrane (GO:0005886), membrane (GO:0016020), cell projection (GO:0042995), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Signal Transduction	3
RHO GTPase cycle	2
Cell death signalling via NRAGE, NRIF and NADE	1
GPCR downstream signalling	1
Death Receptor Signaling	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
p75 NTR receptor-mediated signalling	1
Signaling by GPCR	1
Signaling by Rho GTPases	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cytoplasm	3
microtubule cytoskeleton	2
intracellular membraneless organelle	2
anatomical structure morphogenesis	1
intracellular protein localization	1
protein transport	1
intracellular transport	1
actin cytoskeleton organization	1
supramolecular fiber organization	1
microtubule depolymerization	1
negative regulation of microtubule polymerization or depolymerization	1
regulation of microtubule depolymerization	1
negative regulation of protein depolymerization	1
negative regulation of supramolecular fiber organization	1
positive regulation of cytokine production	1
interleukin-6 production	1
regulation of interleukin-6 production	1
tumor necrosis factor production	1
regulation of tumor necrosis factor production	1
positive regulation of tumor necrosis factor superfamily cytokine production	1
Rho protein signal transduction	1
regulation of small GTPase mediated signal transduction	1
cell population proliferation	1
regulation of cellular process	1
immune response	1
defense response to symbiont	1
neuron differentiation	1
positive regulation of cell differentiation	1
regulation of neuron differentiation	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
positive regulation of protein phosphorylation	1
peptidyl-tyrosine phosphorylation	1
regulation of peptidyl-tyrosine phosphorylation	1
small GTPase-mediated signal transduction	1
regulation of intracellular signal transduction	1
asymmetric cell division	1
cell fate commitment	1

Protein interactions and networks

STRING

1686 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARHGEF2	CGN	Q9P2M7	947
ARHGEF2	RHOA	P06749	936
ARHGEF2	CGNL1	Q0VF96	924
ARHGEF2	EXOC2	Q96KP1	908
ARHGEF2	CDC42	P21181	847
ARHGEF2	DYNLT1	P63172	799
ARHGEF2	RHOC	P08134	797
ARHGEF2	CAPN6	Q9Y6Q1	794
ARHGEF2	RABIF	P47224	792
ARHGEF2	PXN	P49023	770
ARHGEF2	RHOB	P01121	770
ARHGEF2	AKT1	P31749	750
ARHGEF2	TJP2	Q9UDY2	703
ARHGEF2	YWHAH	Q04917	697
ARHGEF2	ARHGEF7	Q14155	680

IntAct

187 interactions, top by confidence:

A	B	Type	Score
RHOA	ARHGEF11	psi-mi:“MI:0914”(association)	0.900
PPP2R1A	STRN	psi-mi:“MI:0914”(association)	0.880
RPP25L	ARHGEF2	psi-mi:“MI:0915”(physical association)	0.870
ARHGEF2	RPP25L	psi-mi:“MI:0915”(physical association)	0.870
ANKRD28	PPP6C	psi-mi:“MI:0914”(association)	0.870
PPP6C	ANKRD28	psi-mi:“MI:0914”(association)	0.870
ARHGEF2	YWHAZ	psi-mi:“MI:0914”(association)	0.860
YWHAZ	ARHGEF2	psi-mi:“MI:0915”(physical association)	0.860
ARHGEF2	YWHAG	psi-mi:“MI:0915”(physical association)	0.860
YWHAB	PIK3C2A	psi-mi:“MI:0914”(association)	0.800
RHOA	ARHGEF2	psi-mi:“MI:0915”(physical association)	0.740
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
WDR5	MEN1	psi-mi:“MI:0914”(association)	0.710
CEP170	KIF2A	psi-mi:“MI:2364”(proximity)	0.650
ARHGEF2	YWHAE	psi-mi:“MI:0915”(physical association)	0.650
USE1	NBAS	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
YWHAB	BLTP3B	psi-mi:“MI:2364”(proximity)	0.610
YWHAB	BLTP3B	psi-mi:“MI:0914”(association)	0.610
IGF1R	PIK3R2	psi-mi:“MI:2364”(proximity)	0.590
YWHAE	PIK3C2A	psi-mi:“MI:0914”(association)	0.570

BioGRID (329): RPP25L (Two-hybrid), ARHGEF2 (Affinity Capture-RNA), ARHGEF2 (Affinity Capture-RNA), ARHGEF2 (Affinity Capture-MS), ARHGEF2 (Affinity Capture-MS), ARHGEF2 (Affinity Capture-MS), ARHGEF2 (Affinity Capture-MS), ARHGEF2 (Affinity Capture-MS), ARHGEF2 (Co-fractionation), KLC2 (Co-fractionation), PRDX1 (Co-fractionation), PSME3 (Co-fractionation), ARHGEF2 (Affinity Capture-Western), MARK2 (Affinity Capture-Western), MARK2 (Reconstituted Complex)

ESM2 similar proteins: A1A4I4, A1A5B6, A4D2P6, B2DCZ9, B4F7F3, O00192, O08773, O08874, O08908, O35465, O43566, O62683, O75808, O95049, P70268, P97492, Q0QWG9, Q12851, Q14164, Q14318, Q16512, Q16513, Q3B7U9, Q3KR56, Q3MII6, Q3UFB7, Q5FVC2, Q60875, Q61161, Q63433, Q63788, Q6P5Z2, Q6PFQ7, Q6V7V2, Q6ZT62, Q7Z5H3, Q865S3, Q8BWW9, Q8IYK8, Q8K045

Diamond homologs: B2DCZ9, E9Q394, F1M3G7, P0C6P5, P97433, Q12802, Q5FVC2, Q60875, Q6P9R4, Q6ZSZ5, Q865S3, Q8N1W1, Q92974, Q9NZN5, Q61210, Q92888, Q9Z1I6, Q8R4H2

SIGNOR signaling

20 interactions.

A	Effect	B	Mechanism
PKN1	down-regulates	ARHGEF2	phosphorylation
MAPK3	up-regulates	ARHGEF2	phosphorylation
MARK2	down-regulates	ARHGEF2	phosphorylation
MAPK1	up-regulates	ARHGEF2	phosphorylation
PAK1	down-regulates	ARHGEF2	phosphorylation
ARHGEF2	“up-regulates activity”	RHOA	“guanine nucleotide exchange factor”
Gbeta	up-regulates	ARHGEF2	phosphorylation
ERK1/2	up-regulates	ARHGEF2	phosphorylation
CyclinB/CDK1	“down-regulates activity”	ARHGEF2	phosphorylation
AURKA	“down-regulates activity”	ARHGEF2	phosphorylation
AURKB	“down-regulates activity”	ARHGEF2	phosphorylation
MARK3	“up-regulates activity”	ARHGEF2	phosphorylation
DYNLT1	“down-regulates activity”	ARHGEF2	binding
SRC	“up-regulates activity”	ARHGEF2	phosphorylation
PAK4	“down-regulates activity”	ARHGEF2	phosphorylation
CAMK1	“up-regulates activity”	ARHGEF2	phosphorylation
NEK9	“up-regulates activity”	ARHGEF2	phosphorylation
PPP1R9B	“up-regulates activity”	ARHGEF2	binding
PPP1R9A	“up-regulates activity”	ARHGEF2	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 175 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
Activation of BAD and translocation to mitochondria	7	44.4×	5e-09
Signaling by GSK3beta mutants	7	44.4×	5e-09
CTNNB1 S33 mutants aren’t phosphorylated	7	44.4×	5e-09
CTNNB1 S37 mutants aren’t phosphorylated	7	44.4×	5e-09
CTNNB1 S45 mutants aren’t phosphorylated	7	44.4×	5e-09
CTNNB1 T41 mutants aren’t phosphorylated	7	44.4×	5e-09
Beta-catenin phosphorylation cascade	7	39.2×	1e-08
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	39.2×	1e-08

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of MAP kinase activity	5	21.3×	1e-03
peptidyl-tyrosine phosphorylation	6	16.6×	1e-03
cell surface receptor protein tyrosine kinase signaling pathway	9	10.3×	3e-04
protein autophosphorylation	8	7.7×	3e-03
intracellular protein localization	9	6.2×	4e-03
cell migration	11	4.5×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	112
Likely benign	17
Benign	10

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
427795	NM_001162383.2(ARHGEF2):c.1545+1del	Pathogenic
4845829	NM_001162383.2(ARHGEF2):c.2527G>T (p.Glu843Ter)	Likely pathogenic

SpliceAI

3203 predictions. Top by Δscore:

Variant	Effect	Δscore
1:155948011:AAAGT:A	acceptor_gain	1.0000
1:155948012:AAGT:A	acceptor_gain	1.0000
1:155948013:AGT:A	acceptor_gain	1.0000
1:155948014:GT:G	acceptor_gain	1.0000
1:155948015:TCT:T	acceptor_loss	1.0000
1:155948016:C:CC	acceptor_gain	1.0000
1:155950337:T:TA	donor_gain	1.0000
1:155950478:CTGGG:C	acceptor_gain	1.0000
1:155950479:TGGG:T	acceptor_gain	1.0000
1:155950480:GGG:G	acceptor_gain	1.0000
1:155950481:GG:G	acceptor_gain	1.0000
1:155950483:C:CA	acceptor_loss	1.0000
1:155950483:C:CC	acceptor_gain	1.0000
1:155950485:G:C	acceptor_gain	1.0000
1:155950485:G:GC	acceptor_gain	1.0000
1:155950490:C:CT	acceptor_gain	1.0000
1:155950491:A:T	acceptor_gain	1.0000
1:155950492:G:C	acceptor_gain	1.0000
1:155950492:G:GC	acceptor_gain	1.0000
1:155950823:CCTTA:C	donor_loss	1.0000
1:155950824:CTTA:C	donor_loss	1.0000
1:155951740:CCT:C	donor_gain	1.0000
1:155951774:ATCC:A	acceptor_loss	1.0000
1:155951775:TCCT:T	acceptor_loss	1.0000
1:155951777:C:CA	acceptor_loss	1.0000
1:155951778:T:A	acceptor_loss	1.0000
1:155951915:CTA:C	donor_loss	1.0000
1:155951916:TACC:T	donor_loss	1.0000
1:155951917:A:AC	donor_gain	1.0000
1:155951917:AC:A	donor_gain	1.0000

AlphaMissense

6382 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:155957811:A:C	F539L	1.000
1:155957811:A:T	F539L	1.000
1:155957813:A:G	F539L	1.000
1:155966840:A:G	C86R	1.000
1:155966859:A:C	C79W	1.000
1:155966860:C:G	C79S	1.000
1:155966860:C:T	C79Y	1.000
1:155966861:A:G	C79R	1.000
1:155966861:A:T	C79S	1.000
1:155966868:G:C	H76Q	1.000
1:155966868:G:T	H76Q	1.000
1:155966870:G:C	H76D	1.000
1:155966885:A:G	C71R	1.000
1:155969160:G:C	C68W	1.000
1:155969161:C:G	C68S	1.000
1:155969161:C:T	C68Y	1.000
1:155969162:A:G	C68R	1.000
1:155969162:A:T	C68S	1.000
1:155969167:A:G	L66P	1.000
1:155969196:A:C	C56W	1.000
1:155969197:C:G	C56S	1.000
1:155969197:C:T	C56Y	1.000
1:155969198:A:G	C56R	1.000
1:155969198:A:T	C56S	1.000
1:155969205:G:C	C53W	1.000
1:155969206:C:G	C53S	1.000
1:155969206:C:T	C53Y	1.000
1:155969207:A:G	C53R	1.000
1:155969207:A:T	C53S	1.000
1:155969239:A:G	F42S	1.000

dbSNP variants (sampled 300 via entrez): RS1000216692 (1:155975653 C>G,T), RS1000255798 (1:155980911 C>T), RS1000311177 (1:155946673 T>A,G), RS1000361967 (1:155947135 A>G), RS1000416499 (1:155947499 C>T), RS1000545826 (1:155952543 C>G,T), RS1000574527 (1:155954362 C>A), RS1000578033 (1:155962208 G>A,T), RS1000635517 (1:155961845 A>C,G), RS1000660123 (1:155947444 C>A), RS1000817755 (1:155974802 C>G,T), RS1001002659 (1:155980745 T>G), RS1001110010 (1:155960149 A>C,T), RS1001227354 (1:155974323 C>T), RS1001278227 (1:155973982 C>T)

Disease associations

OMIM: gene MIM:607560 | disease phenotypes: MIM:617523, MIM:615355

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder with midbrain and hindbrain malformations	Limited	Autosomal recessive

Mondo (4): neurodevelopmental disorder with midbrain and hindbrain malformations (MONDO:0056797), myoepithelial tumor (MONDO:0002380), Noonan syndrome 8 (MONDO:0014143), microcephaly (MONDO:0001149)

Orphanet (1): Noonan syndrome (Orphanet:648)

HPO phenotypes

28 total (29 of 28 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000343	Long philtrum
HP:0000483	Astigmatism
HP:0000486	Strabismus
HP:0000494	Downslanted palpebral fissures
HP:0000508	Ptosis
HP:0000527	Long eyelashes
HP:0000543	Optic disc pallor
HP:0000646	Amblyopia
HP:0000649	Abnormality of visual evoked potentials
HP:0000750	Delayed speech and language development
HP:0000988	Skin rash
HP:0001249	Intellectual disability
HP:0001252	Hypotonia
HP:0001265	Hyporeflexia
HP:0001270	Motor delay
HP:0001320	Cerebellar vermis hypoplasia
HP:0001500	Broad finger
HP:0002162	Low posterior hairline
HP:0002359	Frequent falls
HP:0003577	Congenital onset
HP:0006610	Wide intermamillary distance
HP:0006958	Abnormal auditory evoked potentials
HP:0007811	Horizontal pendular nystagmus
HP:0011451	Primary microcephaly
HP:0012110	Hypoplasia of the pons
HP:0000252	Microcephaly

GWAS associations

19 associations (top):

Study	Trait	p-value
GCST001663_1	Amyotrophic lateral sclerosis (age of onset)	1.000000e-06
GCST004131_70	Inflammatory bowel disease	6.000000e-08
GCST004132_44	Crohn’s disease	2.000000e-07
GCST007294_124	Body fat distribution (trunk fat ratio)	8.000000e-35
GCST007294_3	Body fat distribution (trunk fat ratio)	6.000000e-21
GCST007294_50	Body fat distribution (trunk fat ratio)	1.000000e-15
GCST007295_17	Body fat distribution (leg fat ratio)	3.000000e-13
GCST007295_37	Body fat distribution (leg fat ratio)	7.000000e-17
GCST007295_72	Body fat distribution (leg fat ratio)	1.000000e-28
GCST008822_2	Neuritic plaque	6.000000e-06
GCST010696_19	Cortical thickness (min-P)	2.000000e-10
GCST010697_10	Cortical surface area (min-P)	3.000000e-10
GCST010698_59	Subcortical volume (min-P)	9.000000e-10
GCST010699_20	Brain morphology (min-P)	7.000000e-10
GCST010700_5	Cortical thickness (MOSTest)	8.000000e-17
GCST010701_66	Cortical surface area (MOSTest)	1.000000e-09
GCST010702_43	Subcortical volume (MOSTest)	3.000000e-10
GCST010703_253	Brain morphology (MOSTest)	4.000000e-14
GCST010989_184	Body size at age 10	3.000000e-10

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004847	age at onset
EFO:0004341	body fat distribution
EFO:0006798	neuritic plaque measurement
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness
EFO:0009819	comparative body size at age 10, self-reported

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D009208	Myoepithelioma	C04.557.435.585

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725018 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
7.32	Kd	48.42	nM	CHEMBL5653589
7.32	ED50	48.42	nM	CHEMBL5653589
7.12	Kd	76	nM	MOLIBRESIB
6.66	IC50	220	nM	MOLIBRESIB
5.02	Kd	9510	nM	CHEMBL3752910
5.02	ED50	9510	nM	CHEMBL3752910

PubChem BioAssay actives

4 with measured affinity, of 11 total; 3 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-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147886: Binding affinity to human ARHGEF2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0484	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2179207: Binding affinity against ARHGEF2 (unknown origin) assessed as apparent dissociation constant incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	kd	0.0760	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147886: Binding affinity to human ARHGEF2 incubated for 45 mins by Kinobead based pull down assay	kd	9.5097	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, affects expression, decreases expression	5
Valproic Acid	decreases expression, affects expression, affects cotreatment	5
bisphenol A	affects expression, decreases expression, increases expression	4
Cisplatin	affects expression, decreases expression, decreases reaction, increases reaction	3
Tunicamycin	increases expression	3
Cyclosporine	increases expression	3
Benzo(a)pyrene	decreases expression, increases expression	2
Smoke	decreases expression	2
Tretinoin	increases expression	2
Cadmium Chloride	increases expression	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
methylselenic acid	increases expression	1
decabromobiphenyl ether	increases expression	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	increases expression	1
flubendazole	decreases expression	1
perfluorooctanoic acid	increases expression	1
coumarin	affects phosphorylation	1
hydroquinone	increases expression	1
muconaldehyde	decreases expression	1
ciglitazone	affects binding, increases expression	1
S-(1,2-dichlorovinyl)cysteine	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	decreases ADP-ribosylation	1
CGP 52608	affects binding, increases reaction	1
chloropicrin	affects expression	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5650928	Binding	Binding affinity to human ARHGEF2 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

2 cell lines: 1 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1JX	Abcam HeLa ARHGEF2 KO	Cancer cell line	Female
CVCL_D8ZE	Ubigene HEK293 ARHGEF2 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03600649	PHASE1	UNKNOWN	Clinical Trial of SP-2577 (Seclidemstat) in Patients With Relapsed or Refractory Ewing or Ewing-related Sarcomas
NCT05266196	PHASE1/PHASE2	UNKNOWN	A Rollover Protocol to Allow for Continued Access to the LSD1 Inhibitor Seclidemstat (SP-2577)
NCT06239272	PHASE1/PHASE2	RECRUITING	NRSTS2021, A Risk Adapted Study Evaluating Maintenance Pazopanib, Limited Margin, Dose-Escalated Radiation Therapy and Selinexor in Non-Rhabdomyosarcoma Soft Tissue Sarcoma (NRSTS)
NCT06625190	PHASE1/PHASE2	RECRUITING	Alpha/Beta T and B Cell Depletion With Zoledronic Acid for Solid Tumors
NCT06244420	Not specified	COMPLETED	Malignant Myoepithelioma of Bone and Soft Tissues: Diagnostic Imaging and Histology in Relation to Prognosis
NCT05518188	PHASE1/PHASE2	RECRUITING	Melpida: Recombinant Adeno-associated Virus (serotype 9) Encoding a Codon Optimized Human AP4M1 Transgene (hAP4M1opt)
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