TISIDB

Summary
Symbol	LDHA
Name	lactate dehydrogenase A
Aliases	GSD11; HEL-S-133P; LDHM; PIG19; LDH muscle subunit; LDH-A; LDH-M; cell proliferation-inducing gene 19 protei ......
Chromosomal Location	11p15.1
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	PF02866 lactate/malate dehydrogenase PF00056 lactate/malate dehydrogenase
Function	-

> Gene Ontology [ TOP ]
Biological Process	GO:0000302 response to reactive oxygen species GO:0001666 response to hypoxia GO:0006089 lactate metabolic process GO:0006090 pyruvate metabolic process GO:0006091 generation of precursor metabolites and energy GO:0006096 glycolytic process GO:0006165 nucleoside diphosphate phosphorylation GO:0006732 coenzyme metabolic process GO:0006733 oxidoreduction coenzyme metabolic process GO:0006757 ATP generation from ADP GO:0006979 response to oxidative stress GO:0007584 response to nutrient GO:0009116 nucleoside metabolic process GO:0009119 ribonucleoside metabolic process GO:0009123 nucleoside monophosphate metabolic process GO:0009126 purine nucleoside monophosphate metabolic process GO:0009132 nucleoside diphosphate metabolic process GO:0009135 purine nucleoside diphosphate metabolic process GO:0009141 nucleoside triphosphate metabolic process GO:0009144 purine nucleoside triphosphate metabolic process GO:0009150 purine ribonucleotide metabolic process GO:0009161 ribonucleoside monophosphate metabolic process GO:0009167 purine ribonucleoside monophosphate metabolic process GO:0009179 purine ribonucleoside diphosphate metabolic process GO:0009185 ribonucleoside diphosphate metabolic process GO:0009199 ribonucleoside triphosphate metabolic process GO:0009205 purine ribonucleoside triphosphate metabolic process GO:0009743 response to carbohydrate GO:0009746 response to hexose GO:0009749 response to glucose GO:0009991 response to extracellular stimulus GO:0010035 response to inorganic substance GO:0014074 response to purine-containing compound GO:0016052 carbohydrate catabolic process GO:0019362 pyridine nucleotide metabolic process GO:0019674 NAD metabolic process GO:0031667 response to nutrient levels GO:0034284 response to monosaccharide GO:0036293 response to decreased oxygen levels GO:0042278 purine nucleoside metabolic process GO:0042493 response to drug GO:0042542 response to hydrogen peroxide GO:0043627 response to estrogen GO:0044723 single-organism carbohydrate metabolic process GO:0044724 single-organism carbohydrate catabolic process GO:0046031 ADP metabolic process GO:0046034 ATP metabolic process GO:0046128 purine ribonucleoside metabolic process GO:0046496 nicotinamide nucleotide metabolic process GO:0046683 response to organophosphorus GO:0046939 nucleotide phosphorylation GO:0048569 post-embryonic animal organ development GO:0051186 cofactor metabolic process GO:0051591 response to cAMP GO:0070482 response to oxygen levels GO:0072524 pyridine-containing compound metabolic process GO:1901657 glycosyl compound metabolic process
Molecular Function	GO:0004457 lactate dehydrogenase activity GO:0004459 L-lactate dehydrogenase activity GO:0016614 oxidoreductase activity, acting on CH-OH group of donors GO:0016616 oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor GO:0045296 cadherin binding GO:0048037 cofactor binding GO:0050662 coenzyme binding GO:0050839 cell adhesion molecule binding GO:0051287 NAD binding GO:0098631 protein binding involved in cell adhesion GO:0098632 protein binding involved in cell-cell adhesion GO:0098641 cadherin binding involved in cell-cell adhesion
Cellular Component	GO:0005913 cell-cell adherens junction

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04066 HIF-1 signaling pathway hsa04922 Glucagon signaling pathway hsa00010 Glycolysis / Gluconeogenesis hsa00270 Cysteine and methionine metabolism hsa00620 Pyruvate metabolism hsa00640 Propanoate metabolism hsa01100 Metabolic pathways
Reactome	R-HSA-1430728: Metabolism R-HSA-70268: Pyruvate metabolism R-HSA-71406: Pyruvate metabolism and Citric Acid (TCA) cycle R-HSA-1428517: The citric acid (TCA) cycle and respiratory electron transport

Summary
Symbol	LDHA
Name	lactate dehydrogenase A
Aliases	GSD11; HEL-S-133P; LDHM; PIG19; LDH muscle subunit; LDH-A; LDH-M; cell proliferation-inducing gene 19 protei ......
Chromosomal Location	11p15.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between LDHA 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 LDHA and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
27641098	Melanoma	Inhibit immunity (T cell function)	Elevated lactate dehydrogenase A (LDHA) expression is associated with poor outcome in tumor patients. Database analyses revealed negative correlations between LDHA expression and T cell activation markers in human melanoma patients.
28446465	Lung Carcinoma	Inhibit immunity (T cell function)	Our results suggest that expressions of LDH-A and lactate by macrophage in the tumor microenvironment are major drivers of T-cell immunosuppression, strongly supporting the concept of targeting stromal LDH-A as an effective strategy to blunt tumoral immune escape.
16837029	Endometrial adenocarcinoma	Inhibit immunity	Endometrial adenocarcinomas displayed LDH-5 expression in 31/68 (45.5%) cases with those having a high LDH-5 expression being connected with a low lymphocytic response; this may suggest an important role of LDH-5 and, presumably, lactate release in tumor escape from host immuno-surveillance.

Summary
Symbol	LDHA
Name	lactate dehydrogenase A
Aliases	GSD11; HEL-S-133P; LDHM; PIG19; LDH muscle subunit; LDH-A; LDH-M; cell proliferation-inducing gene 19 protei ......
Chromosomal Location	11p15.1
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 LDHA 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	LDHA
Name	lactate dehydrogenase A
Aliases	GSD11; HEL-S-133P; LDHM; PIG19; LDH muscle subunit; LDH-A; LDH-M; cell proliferation-inducing gene 19 protei ......
Chromosomal Location	11p15.1
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 LDHA 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	0.158	0.639
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.575	0.889
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.139	0.962
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.05	0.903
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.415	0.87
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.638	0.844
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.171	0.78
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.289	0.916
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.024	0.993
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.15	0.962
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	0.355	0.943
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.109	0.376

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of LDHA 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	0	3.7	0.27
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	0	3.7	0.314
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	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	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	LDHA
Name	lactate dehydrogenase A
Aliases	GSD11; HEL-S-133P; LDHM; PIG19; LDH muscle subunit; LDH-A; LDH-M; cell proliferation-inducing gene 19 protei ......
Chromosomal Location	11p15.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of LDHA. 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	LDHA
Name	lactate dehydrogenase A
Aliases	GSD11; HEL-S-133P; LDHM; PIG19; LDH muscle subunit; LDH-A; LDH-M; cell proliferation-inducing gene 19 protei ......
Chromosomal Location	11p15.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of LDHA. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by LDHA. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	LDHA
Name	lactate dehydrogenase A
Aliases	GSD11; HEL-S-133P; LDHM; PIG19; LDH muscle subunit; LDH-A; LDH-M; cell proliferation-inducing gene 19 protei ......
Chromosomal Location	11p15.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of LDHA. 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	LDHA
Name	lactate dehydrogenase A
Aliases	GSD11; HEL-S-133P; LDHM; PIG19; LDH muscle subunit; LDH-A; LDH-M; cell proliferation-inducing gene 19 protei ......
Chromosomal Location	11p15.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of LDHA expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	LDHA
Name	lactate dehydrogenase A
Aliases	GSD11; HEL-S-133P; LDHM; PIG19; LDH muscle subunit; LDH-A; LDH-M; cell proliferation-inducing gene 19 protei ......
Chromosomal Location	11p15.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between LDHA and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	LDHA
Name	lactate dehydrogenase A
Aliases	GSD11; HEL-S-133P; LDHM; PIG19; LDH muscle subunit; LDH-A; LDH-M; cell proliferation-inducing gene 19 protei ......
Chromosomal Location	11p15.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting LDHA collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting LDHA.

ID	Name	Drug Type	Targets	#Targets
DB00157	NADH	Small Molecule	AASS, ACADS, ADH1A, ADH1B, ADH1C, ADH4, ADH5, ADH7, AKR1B1, AKR1C1 ......	144
DB02483	Etheno-Nad	Small Molecule	BST1, LDHA	2
DB02701	Nicotinamide	Small Molecule	BST1, LDHA, PARP1, SIRT5	4
DB03940	Oxamic Acid	Small Molecule	LDHA, LDHB	2
DB09118	Stiripentol	Small Molecule	GABRA1, GABRA2, GABRA3, GABRA4, GABRA5, GABRA6, GABRB1, GABRB2, GA ......	18
DB09130	Copper	Small Molecule	A1BG, ACTG1, ACTN1, ACY1, AFM, AGT, AHCY, AHSG, AKR1A1, ANXA4, ANX ......	141
DB11638	Artenimol	Small Molecule	ACTG1, ALB, ALDH7A1, ALDOA, ANXA2, ATP5A1, ATP5L, ATP5O, CAST, CCT ......	79

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