Entrez Gene

General information | Expression | Regulation | Mutation | Interaction

Basic Information
Gene ID	3417
Name	IDH1
Synonymous	IDCD\|IDH\|IDP\|IDPC\|PICD;isocitrate dehydrogenase 1 (NADP+), soluble;IDH1;isocitrate dehydrogenase 1 (NADP+), soluble
Definition	NADP(+)-specific ICDH\|NADP-dependent isocitrate dehydrogenase, cytosolic\|NADP-dependent isocitrate dehydrogenase, peroxisomal\|isocitrate dehydrogenase [NADP] cytoplasmic\|oxalosuccinate decarboxylase
Position	2q33.3
Gene type	protein-coding
Source	Count: 1; Generif
Sentence	Abstract
"IDH1 appears to function as a tumor suppressor that, when mutationally inactivated, contributes to tumorigenesis in part through induction of the HIF-1 pathway"	Heterozygous mutations in the gene encoding isocitrate dehydrogenase-1 (IDH1) occur in certain human brain tumors, but their mechanistic role in tumor development is unknown. We have shown that tumor-derived IDH1 mutations impair the enzyme's affinity for its substrate and dominantly inhibit wild-type IDH1 activity through the formation of catalytically inactive heterodimers. Forced expression of mutant IDH1 in cultured cells reduces formation of the enzyme product, alpha-ketoglutarate (alpha-KG), and increases the levels of hypoxia-inducible factor subunit HIF-1alpha, a transcription factor that facilitates tumor growth when oxygen is low and whose stability is regulated by alpha-KG. The rise in HIF-1alpha levels was reversible by an alpha-KG derivative. HIF-1alpha levels were higher in human gliomas harboring an IDH1 mutation than in tumors without a mutation. Thus, IDH1 appears to function as a tumor suppressor that, when mutationally inactivated, contributes to tumorigenesis in part through induction of the HIF-1 pathway.