TISIDB

Summary
Symbol	LTA4H
Name	leukotriene A4 hydrolase
Aliases	LTA-4 hydrolase; Leukotriene A(4) hydrolase; Leukotriene A-4 hydrolase
Chromosomal Location	12q22
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.
Domain	PF09127 Leukotriene A4 hydrolase PF01433 Peptidase family M1
Function	Epoxide hydrolase that catalyzes the final step in the biosynthesis of the proinflammatory mediator leukotriene B4. Has also aminopeptidase activity.

> Gene Ontology [ TOP ]
Biological Process	GO:0006631 fatty acid metabolic process GO:0006633 fatty acid biosynthetic process GO:0006636 unsaturated fatty acid biosynthetic process GO:0006690 icosanoid metabolic process GO:0006691 leukotriene metabolic process GO:0016053 organic acid biosynthetic process GO:0019370 leukotriene biosynthetic process GO:0033559 unsaturated fatty acid metabolic process GO:0043171 peptide catabolic process GO:0044283 small molecule biosynthetic process GO:0046394 carboxylic acid biosynthetic process GO:0046456 icosanoid biosynthetic process GO:0072330 monocarboxylic acid biosynthetic process GO:1901565 organonitrogen compound catabolic process
Molecular Function	GO:0004177 aminopeptidase activity GO:0004301 epoxide hydrolase activity GO:0004463 leukotriene-A4 hydrolase activity GO:0008235 metalloexopeptidase activity GO:0008237 metallopeptidase activity GO:0008238 exopeptidase activity GO:0016801 hydrolase activity, acting on ether bonds GO:0016803 ether hydrolase activity GO:0033218 amide binding GO:0042277 peptide binding GO:0070006 metalloaminopeptidase activity
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa00590 Arachidonic acid metabolism hsa01100 Metabolic pathways
Reactome	R-HSA-2142753: Arachidonic acid metabolism R-HSA-168256: Immune System R-HSA-168249: Innate Immune System R-HSA-1430728: Metabolism R-HSA-556833: Metabolism of lipids and lipoproteins R-HSA-6798695: Neutrophil degranulation R-HSA-2142691: Synthesis of Leukotrienes (LT) and Eoxins (EX)

Summary
Symbol	LTA4H
Name	leukotriene A4 hydrolase
Aliases	LTA-4 hydrolase; Leukotriene A(4) hydrolase; Leukotriene A-4 hydrolase
Chromosomal Location	12q22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between LTA4H 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	LTA4H
Name	leukotriene A4 hydrolase
Aliases	LTA-4 hydrolase; Leukotriene A(4) hydrolase; Leukotriene A-4 hydrolase
Chromosomal Location	12q22
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 LTA4H 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	logFC: 1.07; FDR: 0.001770	Sensitive to T cell-mediated killing
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
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	LTA4H
Name	leukotriene A4 hydrolase
Aliases	LTA-4 hydrolase; Leukotriene A(4) hydrolase; Leukotriene A-4 hydrolase
Chromosomal Location	12q22
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 LTA4H 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	0.229	0.31
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.156	0.949
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.285	0.871
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.155	0.567
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.12	0.951
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.199	0.936
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.183	0.677
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.045	0.981
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.466	0.826
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.402	0.828
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	0.811	0.777
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.03	0.676

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of LTA4H 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	0	0	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	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	3.7	4.1	-0.4	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	3.7	5.1	-1.4	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	0	4.8	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	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	2.6	0	2.6	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	0	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	6.2	0	6.2	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	LTA4H
Name	leukotriene A4 hydrolase
Aliases	LTA-4 hydrolase; Leukotriene A(4) hydrolase; Leukotriene A-4 hydrolase
Chromosomal Location	12q22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of LTA4H. 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	LTA4H
Name	leukotriene A4 hydrolase
Aliases	LTA-4 hydrolase; Leukotriene A(4) hydrolase; Leukotriene A-4 hydrolase
Chromosomal Location	12q22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of LTA4H. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by LTA4H. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	LTA4H
Name	leukotriene A4 hydrolase
Aliases	LTA-4 hydrolase; Leukotriene A(4) hydrolase; Leukotriene A-4 hydrolase
Chromosomal Location	12q22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of LTA4H. 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	LTA4H
Name	leukotriene A4 hydrolase
Aliases	LTA-4 hydrolase; Leukotriene A(4) hydrolase; Leukotriene A-4 hydrolase
Chromosomal Location	12q22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of LTA4H expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	LTA4H
Name	leukotriene A4 hydrolase
Aliases	LTA-4 hydrolase; Leukotriene A(4) hydrolase; Leukotriene A-4 hydrolase
Chromosomal Location	12q22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between LTA4H and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	LTA4H
Name	leukotriene A4 hydrolase
Aliases	LTA-4 hydrolase; Leukotriene A(4) hydrolase; Leukotriene A-4 hydrolase
Chromosomal Location	12q22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting LTA4H collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting LTA4H.

ID	Name	Drug Type	Targets	#Targets
DB01197	Captopril	Small Molecule	ACE, BDKRB1, LTA4H, MMP2, MMP9	5
DB02062	N-[3-[(1-Aminoethyl)(Hydroxy)Phosphoryl]-2-(1,1'-Biphenyl-4-Ylmethyl)Propanoyl]Alanine	Small Molecule	LTA4H, MME	2
DB02352	3-(Benzyloxy)Pyridin-2-Amine	Small Molecule	LTA4H, MAPK14	2
DB03366	Imidazole	Small Molecule	AK2, CYCS, DMC1, GPHN, LTA4H, MB, MYO1E, NOS2, PIM1	9
DB03424	Ubenimex	Small Molecule	LTA4H	1
DB05177	DG051	Small Molecule	LTA4H	1
DB06828	5-[2-(1H-pyrrol-1-yl)ethoxy]-1H-indole	Small Molecule	LTA4H	1
DB06851	N-(pyridin-3-ylmethyl)aniline	Small Molecule	LTA4H	1
DB06917	(4-fluorophenyl)(pyridin-4-yl)methanone	Small Molecule	LTA4H	1
DB07094	1-(2,2'-bithiophen-5-yl)methanamine	Small Molecule	LTA4H	1
DB07099	N-[4-(benzyloxy)phenyl]glycinamide	Small Molecule	LTA4H	1
DB07102	(2S)-2-amino-5-oxo-5-[(4-phenylmethoxyphenyl)amino]pentanoic acid	Small Molecule	LTA4H	1
DB07104	4-amino-N-[4-(benzyloxy)phenyl]butanamide	Small Molecule	LTA4H	1
DB07196	N-methyl-1-(2-thiophen-2-ylphenyl)methanamine	Small Molecule	LTA4H	1
DB07237	{4-[(2R)-pyrrolidin-2-ylmethoxy]phenyl}(4-thiophen-3-ylphenyl)methanone	Small Molecule	LTA4H	1
DB07258	(R)-pyridin-4-yl[4-(2-pyrrolidin-1-ylethoxy)phenyl]methanol	Small Molecule	LTA4H	1
DB07259	1-(4-thiophen-2-ylphenyl)methanamine	Small Molecule	LTA4H	1
DB07260	N-benzyl-4-[(2R)-pyrrolidin-2-ylmethoxy]aniline	Small Molecule	LTA4H	1
DB07292	4-(2-amino-1,3-thiazol-4-yl)phenol	Small Molecule	LTA4H	1
DB08040	N-[(2R)-2-benzyl-4-(hydroxyamino)-4-oxobutanoyl]-L-alanine	Small Molecule	LTA4H	1
DB08466	5-[2-(4-hydroxyphenyl)ethyl]benzene-1,3-diol	Small Molecule	LTA4H	1
DB11781	Tosedostat	Small Molecule	LTA4H, NPEPPS	2

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