TISIDB

Summary
Symbol	IDH1
Name	isocitrate dehydrogenase 1 (NADP+), soluble
Aliases	HEL-216; HEL-S-26; IDCD; IDPC; PICD; NADP-dependent isocitrate dehydrogenase, cytosolic; NADP-dependent isoc ......
Chromosomal Location	2q34
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 Peroxisome
Domain	PF00180 Isocitrate/isopropylmalate dehydrogenase
Function	-

> Gene Ontology [ TOP ]
Biological Process	GO:0006091 generation of precursor metabolites and energy GO:0006097 glyoxylate cycle GO:0006099 tricarboxylic acid cycle GO:0006102 isocitrate metabolic process GO:0006103 2-oxoglutarate metabolic process GO:0006575 cellular modified amino acid metabolic process GO:0006644 phospholipid metabolic process GO:0006732 coenzyme metabolic process GO:0006733 oxidoreduction coenzyme metabolic process GO:0006739 NADP metabolic process GO:0006740 NADPH regeneration GO:0006749 glutathione metabolic process GO:0006790 sulfur compound metabolic process GO:0006979 response to oxidative stress GO:0007548 sex differentiation GO:0008406 gonad development GO:0008585 female gonad development GO:0008654 phospholipid biosynthetic process GO:0009060 aerobic respiration GO:0009395 phospholipid catabolic process GO:0009894 regulation of catabolic process GO:0015980 energy derivation by oxidation of organic compounds GO:0016042 lipid catabolic process GO:0019216 regulation of lipid metabolic process GO:0019362 pyridine nucleotide metabolic process GO:0031329 regulation of cellular catabolic process GO:0043648 dicarboxylic acid metabolic process GO:0044242 cellular lipid catabolic process GO:0044262 cellular carbohydrate metabolic process GO:0044723 single-organism carbohydrate metabolic process GO:0045137 development of primary sexual characteristics GO:0045333 cellular respiration GO:0046434 organophosphate catabolic process GO:0046487 glyoxylate metabolic process GO:0046496 nicotinamide nucleotide metabolic process GO:0046545 development of primary female sexual characteristics GO:0046660 female sex differentiation GO:0046890 regulation of lipid biosynthetic process GO:0048545 response to steroid hormone GO:0048608 reproductive structure development GO:0050994 regulation of lipid catabolic process GO:0051186 cofactor metabolic process GO:0060696 regulation of phospholipid catabolic process GO:0061458 reproductive system development GO:0071071 regulation of phospholipid biosynthetic process GO:0072350 tricarboxylic acid metabolic process GO:0072524 pyridine-containing compound metabolic process GO:1903725 regulation of phospholipid metabolic process
Molecular Function	GO:0000287 magnesium ion binding GO:0004448 isocitrate dehydrogenase activity GO:0004450 isocitrate dehydrogenase (NADP+) 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:0050661 NADP binding GO:0050662 coenzyme binding GO:0050839 cell adhesion molecule binding GO:0051287 NAD binding GO:0051990 (R)-2-hydroxyglutarate dehydrogenase activity 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:0005777 peroxisome GO:0005782 peroxisomal matrix GO:0005913 cell-cell adherens junction GO:0031907 microbody lumen GO:0042579 microbody GO:0044438 microbody part GO:0044439 peroxisomal part

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04146 Peroxisome hsa00020 Citrate cycle (TCA cycle) hsa00480 Glutathione metabolism hsa01100 Metabolic pathways hsa01200 Carbon metabolism hsa01210 2-Oxocarboxylic acid metabolism hsa01230 Biosynthesis of amino acids
Reactome	R-HSA-2978092: Abnormal conversion of 2-oxoglutarate to 2-hydroxyglutarate R-HSA-1643685: Disease R-HSA-5668914: Diseases of 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-389542: NADPH regeneration R-HSA-6798695: Neutrophil degranulation R-HSA-390918: Peroxisomal lipid metabolism

Summary
Symbol	IDH1
Name	isocitrate dehydrogenase 1 (NADP+), soluble
Aliases	HEL-216; HEL-S-26; IDCD; IDPC; PICD; NADP-dependent isocitrate dehydrogenase, cytosolic; NADP-dependent isoc ......
Chromosomal Location	2q34
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between IDH1 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 IDH1 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
28465358	Glioma	Promote immunity (T cell function)	Also, we showed that IDH1 mutations caused down-regulation of leukocyte chemotaxis, resulting in repression of the tumor-associated immune system.
25043048	Glioma	Promote immunity (infiltration)	From an immunological perspective, IDH1(R132H) represents a potential target for immunotherapy as it is a tumour-specific potential neoantigen with high uniformity and penetrance expressed in all tumour cells.
29628290	all cancer types	Promote immunity	Specific driver mutations correlated with lower (CTNNB1, NRAS, or IDH1) or higher (BRAF, TP53, or CASP8) leukocyte levels across all cancers.

Summary
Symbol	IDH1
Name	isocitrate dehydrogenase 1 (NADP+), soluble
Aliases	HEL-216; HEL-S-26; IDCD; IDPC; PICD; NADP-dependent isocitrate dehydrogenase, cytosolic; NADP-dependent isoc ......
Chromosomal Location	2q34
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 IDH1 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	IDH1
Name	isocitrate dehydrogenase 1 (NADP+), soluble
Aliases	HEL-216; HEL-S-26; IDCD; IDPC; PICD; NADP-dependent isocitrate dehydrogenase, cytosolic; NADP-dependent isoc ......
Chromosomal Location	2q34
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 IDH1 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	-0.025	0.923
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.049	0.984
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.007	0.997
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.155	0.789
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.251	0.896
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.662	0.771
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.011	0.982
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.009	0.996
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.132	0.953
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.054	0.975
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	0.402	0.88
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.254	0.0975

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of IDH1 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	1.4	-1.4	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	1.7	-1.7	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	3.7	-3.7	0.415
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	7.7	-7.7	0.371
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	1

Summary
Symbol	IDH1
Name	isocitrate dehydrogenase 1 (NADP+), soluble
Aliases	HEL-216; HEL-S-26; IDCD; IDPC; PICD; NADP-dependent isocitrate dehydrogenase, cytosolic; NADP-dependent isoc ......
Chromosomal Location	2q34
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of IDH1. 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	IDH1
Name	isocitrate dehydrogenase 1 (NADP+), soluble
Aliases	HEL-216; HEL-S-26; IDCD; IDPC; PICD; NADP-dependent isocitrate dehydrogenase, cytosolic; NADP-dependent isoc ......
Chromosomal Location	2q34
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of IDH1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by IDH1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	IDH1
Name	isocitrate dehydrogenase 1 (NADP+), soluble
Aliases	HEL-216; HEL-S-26; IDCD; IDPC; PICD; NADP-dependent isocitrate dehydrogenase, cytosolic; NADP-dependent isoc ......
Chromosomal Location	2q34
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of IDH1. 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	IDH1
Name	isocitrate dehydrogenase 1 (NADP+), soluble
Aliases	HEL-216; HEL-S-26; IDCD; IDPC; PICD; NADP-dependent isocitrate dehydrogenase, cytosolic; NADP-dependent isoc ......
Chromosomal Location	2q34
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of IDH1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	IDH1
Name	isocitrate dehydrogenase 1 (NADP+), soluble
Aliases	HEL-216; HEL-S-26; IDCD; IDPC; PICD; NADP-dependent isocitrate dehydrogenase, cytosolic; NADP-dependent isoc ......
Chromosomal Location	2q34
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between IDH1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	IDH1
Name	isocitrate dehydrogenase 1 (NADP+), soluble
Aliases	HEL-216; HEL-S-26; IDCD; IDPC; PICD; NADP-dependent isocitrate dehydrogenase, cytosolic; NADP-dependent isoc ......
Chromosomal Location	2q34
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting IDH1 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting IDH1.

ID	Name	Drug Type	Targets	#Targets
DB01727	Isocitric Acid	Small Molecule	ACO2, IDH1, IDH2	3
DB03461	2'-Monophosphoadenosine 5'-Diphosphoribose	Small Molecule	ADH1B, AKR1A1, AKR1B1, AKR1B10, AKR1C1, AKR1C2, AKR1C3, BLVRB, CRY ......	28

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