TISIDB

Summary
Symbol	ALDH4A1
Name	aldehyde dehydrogenase 4 family, member A1
Aliases	P5CDh; P5CD; L-glutamate gamma-semialdehyde dehydrogenase; P5C dehydrogenase; aldehyde dehydrogenase family ......
Chromosomal Location	1p36
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	Mitochondrion matrix.
Domain	PF00171 Aldehyde dehydrogenase family
Function	Irreversible conversion of delta-1-pyrroline-5-carboxylate (P5C), derived either from proline or ornithine, to glutamate. This is a necessary step in the pathway interconnecting the urea and tricarboxylic acid cycles. The preferred substrate is glutamic gamma-semialdehyde, other substrates include succinic, glutaric and adipic semialdehydes.

> Gene Ontology [ TOP ]
Biological Process	GO:0006520 cellular amino acid metabolic process GO:0006536 glutamate metabolic process GO:0006537 glutamate biosynthetic process GO:0006560 proline metabolic process GO:0006561 proline biosynthetic process GO:0006562 proline catabolic process GO:0006575 cellular modified amino acid metabolic process GO:0008652 cellular amino acid biosynthetic process GO:0009063 cellular amino acid catabolic process GO:0009064 glutamine family amino acid metabolic process GO:0009065 glutamine family amino acid catabolic process GO:0009084 glutamine family amino acid biosynthetic process GO:0010133 proline catabolic process to glutamate GO:0016053 organic acid biosynthetic process GO:0016054 organic acid catabolic process GO:0019470 4-hydroxyproline catabolic process GO:0019471 4-hydroxyproline metabolic process GO:0042219 cellular modified amino acid catabolic process GO:0043648 dicarboxylic acid metabolic process GO:0043650 dicarboxylic acid biosynthetic process GO:0044282 small molecule catabolic process GO:0044283 small molecule biosynthetic process GO:0046394 carboxylic acid biosynthetic process GO:0046395 carboxylic acid catabolic process GO:1901565 organonitrogen compound catabolic process GO:1901605 alpha-amino acid metabolic process GO:1901606 alpha-amino acid catabolic process GO:1901607 alpha-amino acid biosynthetic process
Molecular Function	GO:0003842 1-pyrroline-5-carboxylate dehydrogenase activity GO:0004029 aldehyde dehydrogenase (NAD) activity GO:0009055 electron carrier activity GO:0016620 oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor GO:0016645 oxidoreductase activity, acting on the CH-NH group of donors GO:0016646 oxidoreductase activity, acting on the CH-NH group of donors, NAD or NADP as acceptor GO:0016903 oxidoreductase activity, acting on the aldehyde or oxo group of donors
Cellular Component	GO:0005759 mitochondrial matrix

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa00250 Alanine, aspartate and glutamate metabolism hsa00330 Arginine and proline metabolism hsa01100 Metabolic pathways
Reactome	R-HSA-6788656: Histidine, lysine, phenylalanine, tyrosine, proline and tryptophan catabolism R-HSA-1430728: Metabolism R-HSA-71291: Metabolism of amino acids and derivatives R-HSA-70688: Proline catabolism

Summary
Symbol	ALDH4A1
Name	aldehyde dehydrogenase 4 family, member A1
Aliases	P5CDh; P5CD; L-glutamate gamma-semialdehyde dehydrogenase; P5C dehydrogenase; aldehyde dehydrogenase family ......
Chromosomal Location	1p36
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between ALDH4A1 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	ALDH4A1
Name	aldehyde dehydrogenase 4 family, member A1
Aliases	P5CDh; P5CD; L-glutamate gamma-semialdehyde dehydrogenase; P5C dehydrogenase; aldehyde dehydrogenase family ......
Chromosomal Location	1p36
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 ALDH4A1 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	ALDH4A1
Name	aldehyde dehydrogenase 4 family, member A1
Aliases	P5CDh; P5CD; L-glutamate gamma-semialdehyde dehydrogenase; P5C dehydrogenase; aldehyde dehydrogenase family ......
Chromosomal Location	1p36
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 ALDH4A1 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	0.912	0.0261
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	1.184	0.517
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.721	0.561
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.017	0.972
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.415	0.808
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.555	0.775
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.298	0.429
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.543	0.668
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.066	0.966
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.109	0.948
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	0.264	0.912
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.125	0.428

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of ALDH4A1 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	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	4.8	0	4.8	1
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	7.7	0	7.7	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	11.1	12.5	-1.4	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	14.3	10.7	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	4.5	0	4.5	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	ALDH4A1
Name	aldehyde dehydrogenase 4 family, member A1
Aliases	P5CDh; P5CD; L-glutamate gamma-semialdehyde dehydrogenase; P5C dehydrogenase; aldehyde dehydrogenase family ......
Chromosomal Location	1p36
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of ALDH4A1. 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	ALDH4A1
Name	aldehyde dehydrogenase 4 family, member A1
Aliases	P5CDh; P5CD; L-glutamate gamma-semialdehyde dehydrogenase; P5C dehydrogenase; aldehyde dehydrogenase family ......
Chromosomal Location	1p36
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of ALDH4A1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by ALDH4A1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	ALDH4A1
Name	aldehyde dehydrogenase 4 family, member A1
Aliases	P5CDh; P5CD; L-glutamate gamma-semialdehyde dehydrogenase; P5C dehydrogenase; aldehyde dehydrogenase family ......
Chromosomal Location	1p36
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of ALDH4A1. 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	ALDH4A1
Name	aldehyde dehydrogenase 4 family, member A1
Aliases	P5CDh; P5CD; L-glutamate gamma-semialdehyde dehydrogenase; P5C dehydrogenase; aldehyde dehydrogenase family ......
Chromosomal Location	1p36
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of ALDH4A1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	ALDH4A1
Name	aldehyde dehydrogenase 4 family, member A1
Aliases	P5CDh; P5CD; L-glutamate gamma-semialdehyde dehydrogenase; P5C dehydrogenase; aldehyde dehydrogenase family ......
Chromosomal Location	1p36
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between ALDH4A1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	ALDH4A1
Name	aldehyde dehydrogenase 4 family, member A1
Aliases	P5CDh; P5CD; L-glutamate gamma-semialdehyde dehydrogenase; P5C dehydrogenase; aldehyde dehydrogenase family ......
Chromosomal Location	1p36
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting ALDH4A1 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting ALDH4A1.

ID	Name	Drug Type	Targets	#Targets
DB00157	NADH	Small Molecule	AASS, ACADS, ADH1A, ADH1B, ADH1C, ADH4, ADH5, ADH7, AKR1B1, AKR1C1 ......	144

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