TISIDB

Summary
Symbol	AOX1
Name	aldehyde oxidase 1
Aliases	AO; azaheterocycle hydroxylase; Aldehyde oxidase
Chromosomal Location	2q33
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	PF01315 Aldehyde oxidase and xanthine dehydrogenase PF02738 Molybdopterin-binding domain of aldehyde dehydrogenase PF03450 CO dehydrogenase flavoprotein C-terminal domain PF00941 FAD binding domain in molybdopterin dehydrogenase PF00111 2Fe-2S iron-sulfur cluster binding domain PF01799 [2Fe-2S] binding domain
Function	Oxidase with broad substrate specificity, oxidizing aromatic azaheterocycles, such as N1-methylnicotinamide, N-methylphthalazinium and phthalazine, as well as aldehydes, such as benzaldehyde, retinal, pyridoxal, and vanillin. Plays a key role in the metabolism of xenobiotics and drugs containing aromatic azaheterocyclic substituents. Participates in the bioactivation of prodrugs such as famciclovir, catalyzing the oxidation step from 6-deoxypenciclovir to penciclovir, which is a potent antiviral agent. Is probably involved in the regulation of reactive oxygen species homeostasis. May be a prominent source of superoxide generation via the one-electron reduction of molecular oxygen. Also may catalyze nitric oxide (NO) production via the reduction of nitrite to NO with NADH or aldehyde as electron donor. May play a role in adipogenesis.

> Gene Ontology [ TOP ]
Biological Process	GO:0006144 purine nucleobase metabolic process GO:0006145 purine nucleobase catabolic process GO:0006766 vitamin metabolic process GO:0006767 water-soluble vitamin metabolic process GO:0009112 nucleobase metabolic process GO:0009115 xanthine catabolic process GO:0019439 aromatic compound catabolic process GO:0042816 vitamin B6 metabolic process GO:0044270 cellular nitrogen compound catabolic process GO:0046110 xanthine metabolic process GO:0046113 nucleobase catabolic process GO:0046700 heterocycle catabolic process GO:0072523 purine-containing compound catabolic process GO:0072524 pyridine-containing compound metabolic process GO:0072593 reactive oxygen species metabolic process GO:1901361 organic cyclic compound catabolic process GO:1901565 organonitrogen compound catabolic process
Molecular Function	GO:0004031 aldehyde oxidase activity GO:0004854 xanthine dehydrogenase activity GO:0005506 iron ion binding GO:0009055 electron carrier activity GO:0016614 oxidoreductase activity, acting on CH-OH group of donors GO:0016623 oxidoreductase activity, acting on the aldehyde or oxo group of donors, oxygen as acceptor GO:0016725 oxidoreductase activity, acting on CH or CH2 groups GO:0016726 oxidoreductase activity, acting on CH or CH2 groups, NAD or NADP as acceptor GO:0016903 oxidoreductase activity, acting on the aldehyde or oxo group of donors GO:0043546 molybdopterin cofactor binding GO:0048037 cofactor binding GO:0050660 flavin adenine dinucleotide binding GO:0050662 coenzyme binding GO:0051287 NAD binding GO:0051536 iron-sulfur cluster binding GO:0051537 2 iron, 2 sulfur cluster binding GO:0051540 metal cluster binding
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04630 Jak-STAT signaling pathway hsa00280 Valine, leucine and isoleucine degradation hsa00350 Tyrosine metabolism hsa00380 Tryptophan metabolism hsa00750 Vitamin B6 metabolism hsa00760 Nicotinate and nicotinamide metabolism hsa00830 Retinol metabolism hsa00982 Drug metabolism - cytochrome P450 hsa01100 Metabolic pathways
Reactome	R-HSA-1430728: Metabolism R-HSA-196854: Metabolism of vitamins and cofactors R-HSA-196849: Metabolism of water-soluble vitamins and cofactors R-HSA-964975: Vitamins B6 activation to pyridoxal phosphate

Summary
Symbol	AOX1
Name	aldehyde oxidase 1
Aliases	AO; azaheterocycle hydroxylase; Aldehyde oxidase
Chromosomal Location	2q33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between AOX1 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	AOX1
Name	aldehyde oxidase 1
Aliases	AO; azaheterocycle hydroxylase; Aldehyde oxidase
Chromosomal Location	2q33
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 AOX1 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	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	AOX1
Name	aldehyde oxidase 1
Aliases	AO; azaheterocycle hydroxylase; Aldehyde oxidase
Chromosomal Location	2q33
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 AOX1 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	0.068	0.923
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.275	0.818
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.052	0.952
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.392	0.507
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.933	0.617
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.288	0.898
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.763	0.325
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.615	0.626
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.731	0.632
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.024	0.99
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	0.748	0.76
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.769	0.0105

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of AOX1 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	7.1	0	7.1	0.452
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	10	0	10	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	11.1	6.8	4.3	0.443
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	11.1	8.5	2.6	0.702
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	14.3	5.9	8.4	0.613
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	15.4	9.1	6.3	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	5.3	3.7	1.6	1
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	6.2	0	6.2	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	7.7	-7.7	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	8.3	-8.3	1

Summary
Symbol	AOX1
Name	aldehyde oxidase 1
Aliases	AO; azaheterocycle hydroxylase; Aldehyde oxidase
Chromosomal Location	2q33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of AOX1. 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	AOX1
Name	aldehyde oxidase 1
Aliases	AO; azaheterocycle hydroxylase; Aldehyde oxidase
Chromosomal Location	2q33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of AOX1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by AOX1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	AOX1
Name	aldehyde oxidase 1
Aliases	AO; azaheterocycle hydroxylase; Aldehyde oxidase
Chromosomal Location	2q33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of AOX1. 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	AOX1
Name	aldehyde oxidase 1
Aliases	AO; azaheterocycle hydroxylase; Aldehyde oxidase
Chromosomal Location	2q33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of AOX1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	AOX1
Name	aldehyde oxidase 1
Aliases	AO; azaheterocycle hydroxylase; Aldehyde oxidase
Chromosomal Location	2q33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between AOX1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	AOX1
Name	aldehyde oxidase 1
Aliases	AO; azaheterocycle hydroxylase; Aldehyde oxidase
Chromosomal Location	2q33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting AOX1 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting AOX1.

ID	Name	Drug Type	Targets	#Targets
DB03516	Eniluracil	Small Molecule	AOX1, DPYD, XDH	3

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