TISIDB

Summary
Symbol	ARHGEF18
Name	Rho/Rac guanine nucleotide exchange factor (GEF) 18
Aliases	P114-RhoGEF; KIAA0521; MGC15913; Rho-specific guanine nucleotide exchange factor p114; 114 kDa Rho-specific ......
Chromosomal Location	19p13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway

> Subcellular Location, Domain and Function [ TOP ]
Subcellular Location	Cytoplasm Cytoplasm, cytoskeleton Apical cell membrane
Domain	PF00169 PH domain PF00621 RhoGEF domain
Function	Acts as guanine nucleotide exchange factor (GEF) for RhoA GTPases. Its activation induces formation of actin stress fibers. Also act as a GEF for RAC1, inducing production of reactive oxygen species (ROS). Does not act as a GEF for CDC42. The G protein beta-gamma (Gbetagamma) subunits of heterotrimeric G proteins act as activators, explaining the integrated effects of LPA and other G-protein coupled receptor agonists on actin stress fiber formation, cell shape change and ROS production. Required for EPB41L4B-mediated regulation of the circumferential actomyosin belt in epithelial cells (PubMed:22006950).

> Gene Ontology [ TOP ]
Biological Process	GO:0007178 transmembrane receptor protein serine/threonine kinase signaling pathway GO:0007179 transforming growth factor beta receptor signaling pathway GO:0007265 Ras protein signal transduction GO:0007266 Rho protein signal transduction GO:0008360 regulation of cell shape GO:0022604 regulation of cell morphogenesis GO:0035023 regulation of Rho protein signal transduction GO:0046578 regulation of Ras protein signal transduction GO:0051056 regulation of small GTPase mediated signal transduction GO:0071559 response to transforming growth factor beta GO:0071560 cellular response to transforming growth factor beta stimulus
Molecular Function	GO:0005085 guanyl-nucleotide exchange factor activity GO:0005088 Ras guanyl-nucleotide exchange factor activity GO:0005089 Rho guanyl-nucleotide exchange factor activity
Cellular Component	GO:0016324 apical plasma membrane GO:0045177 apical part of cell

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04530 Tight junction
Reactome	R-HSA-204998: Cell death signalling via NRAGE, NRIF and NADE R-HSA-416482: G alpha (12/13) signalling events R-HSA-388396: GPCR downstream signaling R-HSA-193648: NRAGE signals death through JNK R-HSA-194840: Rho GTPase cycle R-HSA-162582: Signal Transduction R-HSA-372790: Signaling by GPCR R-HSA-194315: Signaling by Rho GTPases R-HSA-170834: Signaling by TGF-beta Receptor Complex R-HSA-166520: Signalling by NGF R-HSA-2173791: TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) R-HSA-193704: p75 NTR receptor-mediated signalling

> KEGG and Reactome Pathway

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KEGG

hsa04530 Tight junction

Reactome

R-HSA-204998: Cell death signalling via NRAGE, NRIF and NADE
R-HSA-416482: G alpha (12/13) signalling events
R-HSA-388396: GPCR downstream signaling
R-HSA-193648: NRAGE signals death through JNK
R-HSA-194840: Rho GTPase cycle
R-HSA-162582: Signal Transduction
R-HSA-372790: Signaling by GPCR
R-HSA-194315: Signaling by Rho GTPases
R-HSA-170834: Signaling by TGF-beta Receptor Complex
R-HSA-166520: Signalling by NGF
R-HSA-2173791: TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition)
R-HSA-193704: p75 NTR receptor-mediated signalling

Summary
Symbol	ARHGEF18
Name	Rho/Rac guanine nucleotide exchange factor (GEF) 18
Aliases	P114-RhoGEF; KIAA0521; MGC15913; Rho-specific guanine nucleotide exchange factor p114; 114 kDa Rho-specific ......
Chromosomal Location	19p13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between ARHGEF18 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.

> Text Mining [ TOP ]
There is no record.

Summary
Symbol	ARHGEF18
Name	Rho/Rac guanine nucleotide exchange factor (GEF) 18
Aliases	P114-RhoGEF; KIAA0521; MGC15913; Rho-specific guanine nucleotide exchange factor p114; 114 kDa Rho-specific ......
Chromosomal Location	19p13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.

> High-throughput Screening

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Statistical results of ARHGEF18 in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	Second most enriched score: 0.65	Sensitive to T cell-mediated killing
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	ARHGEF18
Name	Rho/Rac guanine nucleotide exchange factor (GEF) 18
Aliases	P114-RhoGEF; KIAA0521; MGC15913; Rho-specific guanine nucleotide exchange factor p114; 114 kDa Rho-specific ......
Chromosomal Location	19p13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders

> Expression difference between responders and non-responders

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Points in the above scatter plot represent the expression difference of ARHGEF18 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	0.071	0.741
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.228	0.89
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.045	0.971
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.13	0.704
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.2	0.916
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.041	0.986
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.301	0.37
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.4	0.78
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.13	0.938
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.556	0.61
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	0.432	0.791
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.011	0.897

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of ARHGEF18 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	5.9	-5.9	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	7.1	-7.1	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	0	1.4	-1.4	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	0	1.7	-1.7	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	5.9	-1.1	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	12.5	0	12.5	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	9.1	-9.1	0.458
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	11.1	6.2	4.9	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	11.1	-11.1	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	25	0	25	0.364
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	2.6	7.4	-4.8	0.565
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	7.7	-3.2	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	7.1	-7.1	0.467
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	9.1	0	9.1	0.458
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	16.7	0	16.7	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	ARHGEF18
Name	Rho/Rac guanine nucleotide exchange factor (GEF) 18
Aliases	P114-RhoGEF; KIAA0521; MGC15913; Rho-specific guanine nucleotide exchange factor p114; 114 kDa Rho-specific ......
Chromosomal Location	19p13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of ARHGEF18. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.

> Lymphocyte [ TOP ]

Summary
Symbol	ARHGEF18
Name	Rho/Rac guanine nucleotide exchange factor (GEF) 18
Aliases	P114-RhoGEF; KIAA0521; MGC15913; Rho-specific guanine nucleotide exchange factor p114; 114 kDa Rho-specific ......
Chromosomal Location	19p13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of ARHGEF18. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by ARHGEF18. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	ARHGEF18
Name	Rho/Rac guanine nucleotide exchange factor (GEF) 18
Aliases	P114-RhoGEF; KIAA0521; MGC15913; Rho-specific guanine nucleotide exchange factor p114; 114 kDa Rho-specific ......
Chromosomal Location	19p13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of ARHGEF18. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	ARHGEF18
Name	Rho/Rac guanine nucleotide exchange factor (GEF) 18
Aliases	P114-RhoGEF; KIAA0521; MGC15913; Rho-specific guanine nucleotide exchange factor p114; 114 kDa Rho-specific ......
Chromosomal Location	19p13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of ARHGEF18 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	ARHGEF18
Name	Rho/Rac guanine nucleotide exchange factor (GEF) 18
Aliases	P114-RhoGEF; KIAA0521; MGC15913; Rho-specific guanine nucleotide exchange factor p114; 114 kDa Rho-specific ......
Chromosomal Location	19p13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between ARHGEF18 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	ARHGEF18
Name	Rho/Rac guanine nucleotide exchange factor (GEF) 18
Aliases	P114-RhoGEF; KIAA0521; MGC15913; Rho-specific guanine nucleotide exchange factor p114; 114 kDa Rho-specific ......
Chromosomal Location	19p13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting ARHGEF18 collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

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