IDH1

Protein identityUniProt · HPA

UniProt accession

O75874

Gene

IDH1

Ensembl

ENSG00000138413

Chromosome

2

Canonical length

414 aa

Protein class

Cancer-related genes, Citric acid cycle related proteins, Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Metabolic proteins, Plasma proteins, Predicted intracellular proteins

Subcellular location

Nuclear bodies,Cytosol

Quaternary structure

Homodimer

OverviewNCBI Gene

Isocitrate dehydrogenases catalyze the oxidative decarboxylation of isocitrate to 2-oxoglutarate. These enzymes belong to two distinct subclasses, one of which utilizes NAD(+) as the electron acceptor and the other NADP(+). Five isocitrate dehydrogenases have been reported: three NAD(+)-dependent isocitrate dehydrogenases, which localize to the mitochondrial matrix, and two NADP(+)-dependent isocitrate dehydrogenases, one of which is mitochondrial and the other predominantly cytosolic. Each NADP(+)-dependent isozyme is a homodimer. The protein encoded by this gene is the NADP(+)-dependent isocitrate dehydrogenase found in the cytoplasm and peroxisomes. It contains the PTS-1 peroxisomal targeting signal sequence. The presence of this enzyme in peroxisomes suggests roles in the regeneration of NADPH for intraperoxisomal reductions, such as the conversion of 2, 4-dienoyl-CoAs to 3-enoyl-CoAs, as well as in peroxisomal reactions that consume 2-oxoglutarate, namely the alpha-hydroxylation of phytanic acid. The cytoplasmic enzyme serves a significant role in cytoplasmic NADPH production. Alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Sep 2013]

Canonical amino-acid sequenceUniProt

414 residues, UniProt reviewed canonical sequence.

>O75874|IDH1
     1  MSKKISGGSV VEMQGDEMTR IIWELIKEKL IFPYVELDLH SYDLGIENRD ATNDQVTKDA
    61  AEAIKKHNVG VKCATITPDE KRVEEFKLKQ MWKSPNGTIR NILGGTVFRE AIICKNIPRL
   121  VSGWVKPIII GRHAYGDQYR ATDFVVPGPG KVEITYTPSD GTQKVTYLVH NFEEGGGVAM
   181  GMYNQDKSIE DFAHSSFQMA LSKGWPLYLS TKNTILKKYD GRFKDIFQEI YDKQYKSQFE
   241  AQKIWYEHRL IDDMVAQAMK SEGGFIWACK NYDGDVQSDS VAQGYGSLGM MTSVLVCPDG
   301  KTVEAEAAHG TVTRHYRMYQ KGQETSTNPI ASIFAWTRGL AHRAKLDNNK ELAFFANALE
   361  EVSIETIEAG FMTKDLAACI KGLPNVQRSD YLNTFEFMDK LGENLKIKLA QAKL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against IDH1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.24

Highest tissue expression

501 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about IDH1.

Disease | AllUniProt

Conditions IDH1 is implicated in, by any mechanism.

• Glioma (GLM) MIM:137800

Disease | GeneticClinVar

6 pathogenic / likely-pathogenic of 489 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Enchondromatosis
• Neoplasm
• Glioma susceptibility 1
• Astrocytoma IDH-mutant
• Acute myeloid leukemia

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.33

gnomAD pLI

0

gnomAD missense Z

0.6

DepMap mean gene effect

-0.09

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• 2-oxoglutarate metabolic process
• female gonad development
• glutathione metabolic process
• glyoxylate cycle
• isocitrate metabolic process
• NADP+ metabolic process
• NADPH regeneration
• regulation of phospholipid biosynthetic process
• response to oxidative stress
• response to steroid hormone
• tricarboxylic acid cycle
• regulation of phospholipid catabolic process

Molecular functions

• cadherin binding
• identical protein binding
• isocitrate dehydrogenase (NADP+) activity
• magnesium ion binding
• NAD binding
• NADP binding
• protein homodimerization activity

Cellular components

• cytoplasm
• cytosol
• extracellular exosome
• extracellular region
• ficolin-1-rich granule lumen
• mitochondrion
• peroxisomal matrix
• peroxisome
• secretory granule lumen
• tertiary granule lumen

Protein domainsUniProt · Pfam · InterPro

• Isocitrate dehydrogenase NADP-dependent
• Isocitrate/isopropylmalate dehydrogenase, conserved site
• Isopropylmalate dehydrogenase-like domain
• Isocitrate/isopropylmalate dehydrogenase

KeywordsUniProt

• Acetylation
• Cytoplasm
• Glyoxylate bypass
• Magnesium
• Manganese
• Metal-binding
• NADP
• Oxidoreductase
• Peroxisome
• Phosphoprotein
• Tricarboxylic acid cycle

InteractionsUniProt · HPA

Protein binding partners of IDH1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CALM1