TISIDB

Summary
Symbol	ALDH1A1
Name	aldehyde dehydrogenase 1 family, member A1
Aliases	RALDH1; retinaldehyde dehydrogenase 1; PUMB1; ALDH1; ALDH-E1; ALDH11; HEL-9; HEL-S-53e; HEL12; ALDH class 1; ......
Chromosomal Location	9q21.13
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, cytosol
Domain	PF00171 Aldehyde dehydrogenase family
Function	Can convert/oxidize retinaldehyde to retinoic acid. Binds free retinal and cellular retinol-binding protein-bound retinal (By similarity). May have a broader specificity and oxidize other aldehydes in vivo (PubMed:19296407, PubMed:26373694, PubMed:25450233).

> Gene Ontology [ TOP ]
Biological Process	GO:0001523 retinoid metabolic process GO:0005996 monosaccharide metabolic process GO:0006000 fructose metabolic process GO:0006001 fructose catabolic process GO:0006066 alcohol metabolic process GO:0006067 ethanol metabolic process GO:0006069 ethanol oxidation GO:0006081 cellular aldehyde metabolic process GO:0006720 isoprenoid metabolic process GO:0006721 terpenoid metabolic process GO:0010817 regulation of hormone levels GO:0016052 carbohydrate catabolic process GO:0016101 diterpenoid metabolic process GO:0019318 hexose metabolic process GO:0019320 hexose catabolic process GO:0019682 glyceraldehyde-3-phosphate metabolic process GO:0034308 primary alcohol metabolic process GO:0034754 cellular hormone metabolic process GO:0042445 hormone metabolic process GO:0042572 retinol metabolic process GO:0044282 small molecule catabolic process GO:0044723 single-organism carbohydrate metabolic process GO:0044724 single-organism carbohydrate catabolic process GO:0046365 monosaccharide catabolic process GO:0061624 fructose catabolic process to hydroxyacetone phosphate and glyceraldehyde-3-phosphate GO:1901615 organic hydroxy compound metabolic process
Molecular Function	GO:0001758 retinal dehydrogenase activity GO:0004029 aldehyde dehydrogenase (NAD) activity GO:0005096 GTPase activator activity GO:0005497 androgen binding GO:0008047 enzyme activator activity GO:0016620 oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor GO:0016903 oxidoreductase activity, acting on the aldehyde or oxo group of donors GO:0018479 benzaldehyde dehydrogenase (NAD+) activity GO:0030695 GTPase regulator activity GO:0042562 hormone binding GO:0060589 nucleoside-triphosphatase regulator activity
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa00830 Retinol metabolism hsa01100 Metabolic pathways
Reactome	R-HSA-211859: Biological oxidations R-HSA-71384: Ethanol oxidation R-HSA-70350: Fructose catabolism R-HSA-5652084: Fructose metabolism R-HSA-1430728: Metabolism R-HSA-71387: Metabolism of carbohydrates R-HSA-211945: Phase 1 - Functionalization of compounds R-HSA-5365859: RA biosynthesis pathway R-HSA-162582: Signal Transduction R-HSA-5362517: Signaling by Retinoic Acid

Summary
Symbol	ALDH1A1
Name	aldehyde dehydrogenase 1 family, member A1
Aliases	RALDH1; retinaldehyde dehydrogenase 1; PUMB1; ALDH1; ALDH-E1; ALDH11; HEL-9; HEL-S-53e; HEL12; ALDH class 1; ......
Chromosomal Location	9q21.13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between ALDH1A1 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

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Literatures describing the relation between ALDH1A1 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
21856769	Breast Carcinoma; Head and Neck Cell Carcinoma; Pancreas Carcinoma	Promote immunity	Adoptive therapy with ALDH1A1-specific CD8(+) T cells eliminated ALDH(bright) cells, inhibited tumor growth and metastases, or prolonged survival of xenograft-bearing immunodeficient mice.

Summary
Symbol	ALDH1A1
Name	aldehyde dehydrogenase 1 family, member A1
Aliases	RALDH1; retinaldehyde dehydrogenase 1; PUMB1; ALDH1; ALDH-E1; ALDH11; HEL-9; HEL-S-53e; HEL12; ALDH class 1; ......
Chromosomal Location	9q21.13
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 ALDH1A1 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	ALDH1A1
Name	aldehyde dehydrogenase 1 family, member A1
Aliases	RALDH1; retinaldehyde dehydrogenase 1; PUMB1; ALDH1; ALDH-E1; ALDH11; HEL-9; HEL-S-53e; HEL12; ALDH class 1; ......
Chromosomal Location	9q21.13
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 ALDH1A1 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	0.1	0.888
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.002	0.999
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.165	0.928
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	1.208	0.107
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	1.24	0.491
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	1.163	0.578
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.105	0.858
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.709	0.694
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.82	0.713
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.823	0.768
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	0.837	0.844
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.203	0.431

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of ALDH1A1 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	1.4	2.3	0.469
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	1.7	2	0.532
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	5.9	-5.9	0.447
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	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	0	6.2	-6.2	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	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	0	0	0	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	0	0	0	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	ALDH1A1
Name	aldehyde dehydrogenase 1 family, member A1
Aliases	RALDH1; retinaldehyde dehydrogenase 1; PUMB1; ALDH1; ALDH-E1; ALDH11; HEL-9; HEL-S-53e; HEL12; ALDH class 1; ......
Chromosomal Location	9q21.13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of ALDH1A1. 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	ALDH1A1
Name	aldehyde dehydrogenase 1 family, member A1
Aliases	RALDH1; retinaldehyde dehydrogenase 1; PUMB1; ALDH1; ALDH-E1; ALDH11; HEL-9; HEL-S-53e; HEL12; ALDH class 1; ......
Chromosomal Location	9q21.13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of ALDH1A1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by ALDH1A1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	ALDH1A1
Name	aldehyde dehydrogenase 1 family, member A1
Aliases	RALDH1; retinaldehyde dehydrogenase 1; PUMB1; ALDH1; ALDH-E1; ALDH11; HEL-9; HEL-S-53e; HEL12; ALDH class 1; ......
Chromosomal Location	9q21.13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of ALDH1A1. 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	ALDH1A1
Name	aldehyde dehydrogenase 1 family, member A1
Aliases	RALDH1; retinaldehyde dehydrogenase 1; PUMB1; ALDH1; ALDH-E1; ALDH11; HEL-9; HEL-S-53e; HEL12; ALDH class 1; ......
Chromosomal Location	9q21.13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of ALDH1A1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	ALDH1A1
Name	aldehyde dehydrogenase 1 family, member A1
Aliases	RALDH1; retinaldehyde dehydrogenase 1; PUMB1; ALDH1; ALDH-E1; ALDH11; HEL-9; HEL-S-53e; HEL12; ALDH class 1; ......
Chromosomal Location	9q21.13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between ALDH1A1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	ALDH1A1
Name	aldehyde dehydrogenase 1 family, member A1
Aliases	RALDH1; retinaldehyde dehydrogenase 1; PUMB1; ALDH1; ALDH-E1; ALDH11; HEL-9; HEL-S-53e; HEL12; ALDH class 1; ......
Chromosomal Location	9q21.13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting ALDH1A1 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting ALDH1A1.

ID	Name	Drug Type	Targets	#Targets
DB00157	NADH	Small Molecule	AASS, ACADS, ADH1A, ADH1B, ADH1C, ADH4, ADH5, ADH7, AKR1B1, AKR1C1 ......	144
DB00162	Vitamin A	Small Molecule	ALDH1A1, ALDH1A2, ALDH1A3, APOD, DHRS3, DHRS4, HPGDS, LRAT, RBP1, ......	18
DB00755	Tretinoin	Small Molecule	ALDH1A1, ALDH1A2, CYP26A1, CYP26B1, CYP26C1, GPRC5A, HPGDS, LCN1, ......	19
DB04447	1,4-Dithiothreitol	Small Molecule	ALDH1A1, AXIN1, CAMK2A, GSTZ1, HMGCR, LGALS1, MSRA, PPIB, TPI1, TR ......	10

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