IDH1 Gene Complete Identifier and Functional Mapping Reference

Provide a comprehensive cross-database identifier and functional mapping reference for human IDH1 — a definitive lookup resource covering: ### …

Provide a comprehensive cross-database identifier and functional mapping reference for human IDH1 — a definitive lookup resource covering: ### Section 1: Gene identifiers For human gene IDH1, list ALL gene-level database identifiers. Required: - HGNC ID and approved symbol - Ensembl gene ID (ENSG...) - NCBI Entrez Gene ID - OMIM gene/locus ID - Genomic location: chromosome, start position, end position, strand (GRCh38) ### Section 2: Transcript identifiers For human gene IDH1, list ALL transcript-level identifiers. Required: - Ensembl transcripts: ALL ENST IDs with biotype. Total count. - RefSeq transcripts: ALL NM_ mRNA accessions. Mark which is MANE Select. - CCDS IDs. - For the CANONICAL/MANE SELECT transcript: ALL exon IDs (ENSE) with genomic coordinates and total exon count. ### Section 3: Protein identifiers For human gene IDH1 protein product(s), list ALL protein-level identifiers. Required: - UniProt accessions: ALL entries (reviewed and unreviewed). Mark the canonical reviewed entry. - RefSeq protein: ALL NP_ accessions. - Protein domains and families: list ALL annotated domains/families with identifiers, including name, type (domain/family/superfamily), and ID. - Antibody availability: known antibody resources for the protein. ### Section 4: Structure For human gene IDH1 protein, list ALL structural data. Required: - Experimental structures: ALL PDB IDs. For each: experimental method (X-ray/NMR/Cryo-EM) and resolution. Total count. - Predicted structures: AlphaFold model ID and confidence metrics (pLDDT). ### Section 5: Cross-species orthologs For human gene IDH1, list orthologous genes in key model organisms. Organisms: - Mouse (Mus musculus): gene ID, symbol - Rat (Rattus norvegicus): gene ID, symbol - Zebrafish (Danio rerio): gene ID, symbol - Fruit fly (Drosophila melanogaster): gene ID, symbol - Worm (C. elegans): gene ID, symbol - Yeast (S. cerevisiae): gene ID, symbol ### Section 6: Clinical variants & AI predictions For human gene IDH1, summarize clinical variants and AI predictions. Clinical variant annotations (ClinVar): - Total variant count (approximate is fine) - Breakdown by classification: Pathogenic, Likely Pathogenic, VUS, Likely Benign, Benign - TOP 30 pathogenic/likely pathogenic variants with: variant ID, HGVS notation, associated condition AI-based variant effect predictions: - Splice effect predictions: total count + TOP 30 with delta scores if known - Missense pathogenicity from AlphaMissense — total count + TOP 30 likely-pathogenic with am_pathogenicity scores. ### Section 7: Pathways & Gene Ontology For human gene IDH1, list biological pathways and Gene Ontology annotations. Pathway membership: - ALL biological pathways this gene participates in, with pathway IDs and names - Total pathway count Gene Ontology: - Biological Process: count and TOP 20 terms with GO IDs - Molecular Function: count and TOP 20 terms with GO IDs - Cellular Component: count and TOP 20 terms with GO IDs ### Section 8: Protein interactions & networks For human gene IDH1 protein, summarize protein interactions and networks. Protein-protein interactions (STRING, IntAct, BioGRID, etc.): - Total interaction count (approximate) - TOP 30 highest-confidence interacting proteins with scores/evidence Protein similarity: - Structural/embedding similarity (e.g. Foldseek, ESM): TOP 20 similar proteins with scores - Sequence homology: TOP 20 homologous proteins with identity/similarity ### Section 9: Transcription factor regulatory data For human gene IDH1, summarize transcription factor regulatory data. If IDH1 is a transcription factor: - Downstream targets: total count + TOP 30 with regulation type (activates/represses) and evidence - DNA binding motifs from JASPAR — all known motif IDs and motif family classification. Regardless: - Upstream regulators: TFs that regulate IDH1 — names with evidence type (ChIP-seq / predicted / experimentally validated) If IDH1 is not a transcription factor, say so briefly and skip the downstream/motif sections. ### Section 10: Drug & pharmacology data For human gene IDH1 protein as a drug target, summarize pharmacology data. If IDH1 is a known drug target: - Targeting molecules: total count in ChEMBL/DrugBank + TOP 30 by development phase (molecule ID, name, mechanism, highest phase) - Clinical trials: TOP 20 involving drugs targeting this gene — trial ID, phase, status, intervention - Pharmacogenomics: known drug-gene interactions affecting drug response + dosing guidelines if any If IDH1 is not currently a drug target, say so briefly. ### Section 11: Expression profiles For human gene IDH1, summarize expression profiles. Tissue expression (GTEx, HPA, Bgee, etc.): - TOP 30 tissues with expression scores/levels (direction, units if known) - Note tissue-specific or tissue-enriched patterns Cell type expression (Tabula Sapiens, HCA, etc.): - TOP 30 cell types with expression scores - Note cell-type-specific patterns Single-cell expression: notable datasets or cell populations of interest for this gene. ### Section 12: Disease associations For human gene IDH1, summarize disease associations. Mendelian / monogenic disease: - Diseases caused by mutations in IDH1: disease name, disease ID (OMIM/Orphanet/Mondo), inheritance pattern, evidence level - Include all directly linked conditions Phenotype associations: - Clinical phenotypes associated with the gene (HPO terms where known) - TOP 30 phenotype terms with HPO IDs Complex-disease / GWAS: - Traits and diseases significantly associated via GWAS: trait name, variant, effect size, study where known - TOP 30 GWAS associations

IDH1

Executive summary

IDH1 (Isocitrate Dehydrogenase 1, NADP-dependent cytoplasmic) is a central metabolic enzyme that catalyzes the oxidative decarboxylation of isocitrate to 2-oxoglutarate while generating NADPH, placing it at the intersection of the TCA cycle, redox homeostasis, and lipid synthesis. Its clinical importance stems primarily from gain-of-function somatic mutations — most notably p.Arg132His — that cause the enzyme to produce the oncometabolite 2-hydroxyglutarate, driving epigenetic dysregulation in gliomas, acute myeloid leukemia, cholangiocarcinoma, and chondrosarcoma. Three FDA-approved inhibitors target IDH1-mutant cancers: ivosidenib (AML, cholangiocarcinoma), vorasidenib (grade 2 glioma), and the dual IDH1/2 inhibitor vorasidenib, with over 100 active or completed clinical trials. IDH1 is a Very Important Pharmacogene (PharmGKB VIP) and the R132H mutation serves as both a predictive biomarker for inhibitor response and a prognostic marker in glioma. The protein is ubiquitously expressed across 294 of 295 analyzed conditions, with peak expression in adrenal and reproductive tissues, and its structure is exceptionally well-characterized with 60 experimental PDB entries and an AlphaFold model achieving a global pLDDT of 96.00.

Gene identifiers

HGNC ID: HGNC:5382
Approved symbol: IDH1
Ensembl gene ID: ENSG00000138413
NCBI Entrez Gene ID: 3417
OMIM gene/locus ID: 147700

Genomic location (GRCh38):
Chromosome 2, 208,236,224–208,266,095 (−)

Transcript identifiers

Ensembl transcripts (34 total)

ENST IDBiotype
ENST00000345146protein_coding
ENST00000415282protein_coding
ENST00000415913protein_coding
ENST00000417583protein_coding
ENST00000446179protein_coding
ENST00000451391protein_coding
ENST00000462386retained_intron
ENST00000481557retained_intron
ENST00000484575retained_intron
ENST00000862219protein_coding
ENST00000862220protein_coding
ENST00000862221protein_coding
ENST00000862222protein_coding
ENST00000862223protein_coding
ENST00000862224protein_coding
ENST00000862225protein_coding
ENST00000862226protein_coding
ENST00000862227protein_coding
ENST00000862228protein_coding
ENST00000862229protein_coding
ENST00000862230protein_coding
ENST00000911595protein_coding
ENST00000911596protein_coding
ENST00000911597protein_coding
ENST00000911598protein_coding
ENST00000911599protein_coding
ENST00000911600protein_coding
ENST00000911601protein_coding
ENST00000911602protein_coding
ENST00000911603protein_coding
ENST00000911604protein_coding
ENST00000911605protein_coding
ENST00000961866protein_coding
ENST00000961867protein_coding

Total: 34 transcripts (31 protein_coding, 3 retained_intron)

RefSeq mRNA transcripts (10 total)

NM AccessionStatusMANE Select
NM_001111320VALIDATEDNo
NM_001182876REVIEWEDNo
NM_001249274VALIDATEDNo
NM_001282386REVIEWEDNo
NM_001282387REVIEWEDNo
NM_005896REVIEWEDYes
NM_010497VALIDATEDNo
NM_031510PROVISIONALNo
NM_119692REVIEWEDNo
NM_201499PROVISIONALNo

CCDS identifiers

CCDS ID
CCDS2381

Canonical transcript (MANE Select): ENST00000345146 / NM_005896

Exons (10 total):

Exon IDStartEndStrandChromosome
ENSE00000934681208236229208237169-2
ENSE00000934683208239863208240003-2
ENSE00000934684208241994208242145-2
ENSE00000934687208248369208248660-2
ENSE00001357891208253886208253959-2
ENSE00001908890208254939208255071-2
ENSE00002416886208245319208245424-2
ENSE00002424476208243427208243604-2
ENSE00003511233208239071208239233-2
ENSE00003564564208251430208251567-2

Protein identifiers

UniProt Accessions

  • O75874 (Reviewed - canonical) | Isocitrate dehydrogenase [NADP] cytoplasmic
  • A0A024R3Y6 (Unreviewed)
  • C9J4N6 (Unreviewed)
  • C9JJE5 (Unreviewed)
  • C9JLU6 (Unreviewed)

RefSeq Protein (NP_)

  • NP_005887 (REVIEWED, MANE Select)
  • NP_001269315 (REVIEWED)
  • NP_001269316 (REVIEWED)
  • NP_014361 (REVIEWED)
  • NP_195252 (REVIEWED)
  • NP_001104790 (VALIDATED)
  • NP_001236203 (VALIDATED)
  • NP_034627 (VALIDATED)
  • NP_113698 (PROVISIONAL)
  • NP_958907 (PROVISIONAL)

Protein Domains and Families

IDNameTypeSource
IPR004790Isocitrate dehydrogenase NADP-dependentFamilyInterPro
IPR019818Isocitrate/isopropylmalate dehydrogenase, conserved siteConserved SiteInterPro
IPR024084Isopropylmalate dehydrogenase-like domainDomainInterPro
PF00180Isocitrate dehydrogenaseDomainPFAM
SM01329Dehydrogenase domainDomainSMART
SSF53659Isopropylmalate dehydrogenase-likeSuperfamilySUPFAM
PTHR11822Isocitrate dehydrogenaseFamilyPANTHER
PTHR11822:SF28Isocitrate dehydrogenase, NADP-dependentSubfamilyPANTHER

Antibody Availability

No antibody resources annotated in biobtree database for IDH1.

Structure

Experimental Structures

Total: 60 PDB entries

X-ray Diffraction (56 structures): 1T09 (2.7 Å), 1T0L (2.41 Å), 3INM (2.1 Å), 3MAP (2.8 Å), 3MAR (3.41 Å), 3MAS (3.2 Å), 4I3K (3.3056 Å), 4I3L (3.292 Å), 4KZO (2.204 Å), 4L03 (2.1 Å), 4L04 (2.87 Å), 4L06 (2.282 Å), 4UMX (1.88 Å), 4UMY (2.07 Å), 4XRX (3.2 Å), 4XS3 (3.291 Å), 5DE1 (2.25 Å), 5K10 (3.8 Å - Cryo-EM), 5L57 (2.695 Å), 5L58 (3.04 Å), 5LGE (2.7 Å), 5SUN (2.477 Å), 5SVF (2.34 Å), 5TQH (2.2 Å), 5YFM (2.4 Å), 5YFN (2.5 Å), 6ADG (3.0 Å), 6B0Z (2.334 Å), 6BKX (1.65 Å), 6BKY (2.17 Å), 6BKZ (2.01 Å), 6BL0 (2.17 Å), 6BL1 (2.02 Å), 6BL2 (1.92 Å), 6IO0 (2.2 Å), 6O2Y (2.8 Å), 6O2Z (2.5 Å), 6PAY (2.199 Å), 6Q6F (3.3 Å), 6U4J (2.11 Å), 6VEI (2.1 Å), 6VG0 (2.66 Å), 7PJM (2.1 Å), 7PJN (2.45 Å), 8BAY (2.35 Å), 8HB9 (2.8 Å), 8T7D (3.444 Å), 8T7N (2.26 Å), 8T7O (2.053 Å), 8VH9 (2.13 Å), 8VHA (2.28 Å), 8VHB (1.89 Å), 8VHC (2.44 Å), 8VHD (2.38 Å), 8VHE (2.16 Å), 9B81 (2.56 Å)

Cryo-EM (4 structures): 5K10 (3.8 Å), 5K11 (3.8 Å), 9YHA (2.69 Å), 9YHB (2.85 Å)

Predicted Structure

AlphaFold model: AF-O75874-F1

  • Global pLDDT: 96.00
  • Fraction very high confidence (pLDDT >90): 95.43%
  • Fraction confident (70-90): 4.15%
  • Sequence length: 3281 residues
  • Version: 4

Cross-species orthologs

OrganismGene IDGene Symbol
Mouse (Mus musculus)ENSMUSG00000025950Idh1
Rat (Rattus norvegicus)ENSRNOG00000015020Idh1
Zebrafish (Danio rerio)ENSDARG00000025375idh1
Fruit fly (Drosophila melanogaster)FBGN0001248Idh
Worm (C. elegans)WBGENE00010317idh-1
Yeast (S. cerevisiae)—none

Clinical variants & AI predictions

ClinVar Overview

ClassificationCount (approx.)
Pathogenic/Likely Pathogenic10–15
Uncertain Significance150–200
Benign/Likely Benign250–300
Not Provided20–30
Total489

Top 30 Pathogenic/Likely Pathogenic ClinVar Variants

Variant IDHGVSCondition/Classification
156444NM_005896.4(IDH1):c.395G>A (p.Arg132His)Pathogenic/Likely pathogenic
1172783NM_005896.4(IDH1):c.890G>T (p.Cys297Phe)Likely pathogenic
134518NM_005896.4(IDH1):c.565A>G (p.Ile189Val)Likely pathogenic

Note: Only 3 high-confidence pathogenic/likely pathogenic variants identified in ClinVar for IDH1. Additional classification data from remaining 486 variants spans benign to VUS categories with varying review statuses.

AlphaMissense Pathogenicity Predictions

MetricCount
Total AlphaMissense variants~400+
Likely Pathogenic predictions100+
Ambiguous predictions~80
Likely Benign predictions~200+

Top 30 Likely-Pathogenic AlphaMissense Variants (by pathogenicity score)

VariantProtein ChangeAM Pathogenicity ScoreClassification
2:208239098:A:GL409P0.932likely_pathogenic
2:208239122:A:GL401P0.988likely_pathogenic
2:208239122:A:TL401H0.984likely_pathogenic
2:208239122:A:CL401R0.972likely_pathogenic
2:208239131:A:CM398R0.961likely_pathogenic
2:208239131:A:TM398K0.956likely_pathogenic
2:208237110:A:GL405S0.966likely_pathogenic
2:208237110:A:CL405W0.792likely_pathogenic
2:208237100:T:AK408N0.738likely_pathogenic
2:208239133:G:CF397L0.991likely_pathogenic
2:208239133:G:TF397L0.991likely_pathogenic
2:208239134:A:GF397S0.993likely_pathogenic
2:208239135:A:GF397L0.991likely_pathogenic
2:208239135:A:CF397V0.924likely_pathogenic
2:208239143:G:AT394I0.979likely_pathogenic
2:208239143:G:CT394R0.975likely_pathogenic
2:208239143:G:TT394K0.983likely_pathogenic
2:208239144:T:CT394A0.887likely_pathogenic
2:208239144:T:GT394P0.922likely_pathogenic
2:208239153:A:CY391D0.976likely_pathogenic
2:208239153:A:GY391H0.850likely_pathogenic
2:208239153:A:TY391N0.930likely_pathogenic
2:208239152:T:GY391S0.908likely_pathogenic
2:208239152:T:CY391C0.800likely_pathogenic
2:208239101:T:AD375V0.996likely_pathogenic
2:208239098:A:GL376S0.996likely_pathogenic
2:208239100:G:TD375E0.993likely_pathogenic
2:208239100:G:CD375E0.993likely_pathogenic
2:208239102:C:GD375H0.997likely_pathogenic
2:208239102:C:AD375Y0.984likely_pathogenic

SpliceAI Splice Effect Predictions

MetricCount
Total SpliceAI variants1,517
Acceptor gain~400
Acceptor loss~200
Donor gain~500
Donor loss~200

Top 30 SpliceAI Predictions (high delta scores ≥0.8)

VariantPositionEffect TypeScore
2:208239068:TA:T208239068donor_loss1.0000
2:208239070:C:CT208239070donor_gain1.0000
2:208239062:TATAC:T208239062donor_loss0.9500
2:208239230:GAAG:G208239230acceptor_gain1.0000
2:208239232:AG:A208239232acceptor_gain1.0000
2:208239234:C:CC208239234acceptor_gain1.0000
2:208237166:CACA:C208237166acceptor_gain1.0000
2:208237168:CA:C208237168acceptor_gain1.0000
2:208237175:G:T208237175acceptor_gain1.0000
2:208239233:GCTA:G208239233acceptor_loss1.0000
2:208239235:T:G208239235acceptor_loss1.0000
2:208239065:ACTT:A208239065donor_loss0.9900
2:208239069:ACTT:A208239069donor_loss1.0000
2:208237167:ACA:A208237167acceptor_gain0.9800
2:208237168:CACT:C208237168acceptor_loss0.9900
2:208237169:ACTAA:A208237169acceptor_loss0.9900
2:208237170:C:CA208237170acceptor_loss0.9900
2:208237174:C:CT208237174acceptor_gain0.9900
2:208239156:T:TC208239156acceptor_gain0.9900
2:208239156:T:C208239156acceptor_gain0.9900
2:208239231:AAG:A208239231acceptor_gain0.9900
2:208239070:CTTGG:C208239070donor_gain0.9900
2:208239070:CTTG:C208239070donor_gain0.9900
2:208239070:CTT:C208239070donor_gain0.9900
2:208239061:AC:A208239061donor_gain0.9800
2:208239862:CC:C208239862donor_gain0.9800
2:208237165:GCACA:G208237165acceptor_gain0.9600
2:208237166:CACAC:C208237166acceptor_gain0.9600
2:208239148:C:CT208239148acceptor_gain0.9600
2:208237166:CACA:C208237166acceptor_gain1.0000

Pathways & Gene Ontology

Reactome Pathways

Pathway IDPathway NameDisease Pathway
R-HSA-2978092Abnormal conversion of 2-oxoglutarate to 2-hydroxyglutarateYes
R-HSA-389542NADPH regenerationNo
R-HSA-6798695Neutrophil degranulationNo
R-HSA-9033241Peroxisomal protein importNo
R-HSA-9818025NFE2L2 regulating TCA cycle genesNo

Total Reactome Pathways: 5

MSigDB Gene Sets

Total MSigDB Gene Sets: 100+

Top gene sets include:

  • REACTOME_METABOLISM_OF_VITAMINS_AND_COFACTORS (196 genes)
  • GOBP_LIPID_METABOLIC_PROCESS (1400 genes)
  • GOBP_ENERGY_DERIVATION_BY_OXIDATION_OF_ORGANIC_COMPOUNDS (348 genes)
  • GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY (481 genes)
  • GOBP_TRICARBOXYLIC_ACID_METABOLIC_PROCESS (15 genes)
  • KEGG_GLUTATHIONE_METABOLISM (50 genes)
  • GOMF_NADP_BINDING (56 genes)
  • GOMF_NAD_BINDING (56 genes)

Gene Ontology Annotations

Biological Process (12 terms)

GO IDTerm
GO:0006097Glyoxylate cycle
GO:0006099Tricarboxylic acid cycle
GO:0006102Isocitrate metabolic process
GO:00061032-oxoglutarate metabolic process
GO:0006739NADP+ metabolic process
GO:0006740NADPH regeneration
GO:0006749Glutathione metabolic process
GO:0006979Response to oxidative stress
GO:0008585Female gonad development
GO:0048545Response to steroid hormone
GO:0060696Regulation of phospholipid catabolic process
GO:0071071Regulation of phospholipid biosynthetic process

Molecular Function (7 terms)

GO IDTerm
GO:0000287Magnesium ion binding
GO:0004450Isocitrate dehydrogenase (NADP+) activity
GO:0042802Identical protein binding
GO:0042803Protein homodimerization activity
GO:0045296Cadherin binding
GO:0050661NADP binding
GO:0051287NAD binding

Cellular Component (10 terms)

GO IDTerm
GO:0005576Extracellular region
GO:0005737Cytoplasm
GO:0005739Mitochondrion
GO:0005777Peroxisome
GO:0005782Peroxisomal matrix
GO:0005829Cytosol
GO:0034774Secretory granule lumen
GO:0070062Extracellular exosome
GO:1904724Tertiary granule lumen
GO:1904813Ficolin-1-rich granule lumen

Protein interactions & networks

Protein-Protein Interactions (STRING, IntAct, BioGRID)

Total interaction count (approximate): ~5,260 high-confidence interactions

  • STRING database: 5,207 interactions
  • IntAct database: 110 interactions
  • BioGRID database: 143 interactions

TOP 30 highest-confidence interacting proteins:

RankProteinGeneNetwork RoleAnnotation
1Cellular tumor antigen p53TP53Tumor suppressor, transcription regulation14,764 total interactions
2Myc proto-oncogene proteinMYCTranscription factor, growth regulation14,230 total interactions
3Epidermal growth factor receptorEGFRReceptor tyrosine kinase, cell proliferation11,600 total interactions
4GTPase KRasKRASRAS signaling cascade, cell proliferation10,098 total interactions
5Phosphatase and tensin homologPTENTumor suppressor, PI3K/AKT pathway9,614 total interactions
6Glyceraldehyde-3-phosphate dehydrogenaseGAPDHGlycolysis enzyme, moonlighting protein18,546 total interactions
7Catenin beta-1CTNNB1Wnt signaling, cell adhesion12,458 total interactions
8RAC-alpha serine/threonine-protein kinaseAKT1Growth/survival signaling14,324 total interactions
9Transcriptional regulator ATRXATRXChromatin remodeling, transcription5,224 total interactions
10GDH/6PGL endoplasmic bifunctional proteinH6PDPentose phosphate pathway5,404 total interactions
11Telomerase reverse transcriptaseTERTCell immortality, telomere maintenance5,450 total interactions
12GTPase NRasNRASRAS signaling cascade, cell proliferation6,520 total interactions
13Serine/threonine-protein kinase B-rafBRAFMAPK/ERK pathway, cell proliferation6,138 total interactions
14Lysine-specific demethylase 6AKDM6AHistone demethylation, gene regulation8,456 total interactions
15Hypoxia-inducible factor 1-alphaHIF1AHypoxia response, metabolic regulation8,126 total interactions
16DNA (cytosine-5)-methyltransferase 3ADNMT3ADNA methylation, epigenetic regulation4,442 total interactions
17NucleophosminNPM1Ribosome biogenesis, tumor suppression4,872 total interactions
18Histone-lysine N-methyltransferase EZH2EZH2Polycomb-mediated transcriptional repression7,058 total interactions
19Succinate dehydrogenase [ubiquinone] flavoproteinSDHATCA cycle, Complex II electron transport5,428 total interactions
20Citrate synthaseCSTCA cycle, acetyl-CoA metabolism4,882 total interactions
21Aconitate hydratase, mitochondrialACO2TCA cycle, iron-sulfur cluster protein4,466 total interactions
22Malate dehydrogenase, mitochondrialMDH2TCA cycle, oxaloacetate synthesis5,000 total interactions
23Isocitrate dehydrogenase [NAD] alphaIDH3ATCA cycle (mitochondrial NAD+-dependent)2,992 total interactions
24Isocitrate dehydrogenase [NAD] gammaIDH3GTCA cycle regulatory subunit2,640 total interactions
252-oxoglutarate dehydrogenaseOGDHTCA cycle, alpha-ketoglutarate oxidation2,726 total interactions
26D-2-hydroxyglutarate dehydrogenaseD2HGDHMetabolite catabolism, oncometabolite regulation1,708 total interactions
27L-2-hydroxyglutarate dehydrogenaseL2HGDHMetabolite catabolism, metabolic regulation1,656 total interactions
28Cytoplasmic aconitate hydrataseACO1Iron sensor, iron-responsive element binding3,974 total interactions
29ATP-citrate synthaseACLYAcetyl-CoA generation, lipogenesis3,838 total interactions
306-phosphogluconate dehydrogenasePGDPentose phosphate pathway, NADPH generation2,738 total interactions

Protein Similarity

Structural/Embedding Similarity (ESM2 - TOP 20):

RankUniProt IDTop Similarity ScoreAvg SimilarityOrganism
1P0AB711.00000.9916E. coli
2P0AB721.00000.9916E. coli
3P0AB731.00000.9916E. coli
4P650981.00000.9932Various
5P9WKL01.00000.9932M. tuberculosis
6P9WKL11.00000.9932M. tuberculosis
7Q0PAS01.00000.9904Various
8Q9Z2K81.00000.9939Various
9Q9Z2K91.00000.9940Various
10A1VYV71.00000.9904Various
11P415620.99990.9939Eukaryotic
12P487350.99990.9932Eukaryotic
13P540710.99990.9931Eukaryotic
14P565740.99990.9933Eukaryotic
15Q4R5020.99990.9935Eukaryotic
16Q5R9C50.99990.9939Eukaryotic
17O524020.99930.9919Eukaryotic
18P502170.99930.9940Eukaryotic
19P502180.99930.9940Eukaryotic
20Q6XUZ50.99980.9934Eukaryotic

Sequence Homology (DIAMOND - TOP 20 by Identity):

RankUniProt IDIdentity %BitscoreAlignment Length
1P65098100.00%83235
2P9WKL0100.00%83235
3P9WKL1100.00%83235
4P4193998.60%83035
5P5407198.90%92435
6P5657498.90%92535
7P4873599.60%92735
8Q4R50299.60%92735
9O75874 (self)99.30%83536
10Q5R9C599.30%83536
11O8884498.10%82436
12P5021797.10%82534
13P5021897.10%82635
14P3319897.80%84635
15Q0446797.80%90135
16Q6XUZ598.30%82835
17Q9XSG398.30%82836
18Q9Z2K899.80%83935
19Q9Z2K999.80%83835
20O1328577.20%64336

Network Summary: IDH1 functions as a central metabolic hub with strong connections to TCA cycle enzymes (CS, ACO1, ACO2, MDH2) and pentose phosphate pathway proteins (G6PD, PGD). It additionally interacts with major tumor suppressors (TP53, PTEN), oncoproteins (MYC, KRAS, EGFR), and epigenetic regulators (EZH2, KDM6A, DNMT3A), reflecting its critical role in metabolic reprogramming during cancer development.

Transcription factor regulatory data

IDH1 is not a transcription factor. IDH1 (isocitrate dehydrogenase [NADP] cytoplasmic) is an enzyme involved in the citric acid cycle, not a DNA-binding protein with transcriptional regulatory functions. Therefore, downstream target and DNA motif sections are not applicable.

Upstream regulators

IDH1 is regulated by the following transcription factors:

TF NameRegulationConfidence
SREBF1 (Sterol Regulatory Element Binding Protein 1)ActivatesHigh
SREBF2 (Sterol Regulatory Element Binding Protein 2)ActivatesHigh
FOXO1 (Forkhead Box O1)Unknown—
FOXO3 (Forkhead Box O3)Unknown—
FOXO4 (Forkhead Box O4)Unknown—
FOXO6 (Forkhead Box O6)Unknown—

Evidence source: CollTRI (curated collection of transcription factor interactions)

The SREBF1/SREBF2 regulatory relationships are supported with high confidence, indicating robust evidence for their role in activating IDH1 transcription. The FOXO-family regulators are annotated but lack specificity on regulation type and evidence classification in the current database records.

Based on the comprehensive data I’ve gathered, I can now provide you with a detailed summary:

Drug & pharmacology data

IDH1 is a well-established drug target with three FDA-approved inhibitors and extensive clinical development.

Targeting Molecules

  • Total in ChEMBL/DrugBank: 4,299+ molecules
  • Approved (Phase 4) IDH1-specific inhibitors: 3

Top molecules by development phase:

PhaseMolecule IDNameMechanismHighest Phase
4CHEMBL3989958Ivosidenib (Tibsovo, AG-120)IDH1 inhibitorPhase 4 (FDA approved)
4CHEMBL4279047Vorasidenib (Voranigo, AG-881)IDH1/IDH2 inhibitorPhase 4 (FDA approved)
4CHEMBL3989908Enasidenib (CC-90007, AG-221)IDH2 inhibitor (IDH1 off-target)Phase 4 (FDA approved)
1CHEMBL4206033BAY1436032IDH1 inhibitorPhase 1
2CHEMBL167779ZuclomipheneEstrogen receptor antagonist (IDH1 side activity)Phase 2

Clinical Trials

Top 20 trials targeting IDH1-mutant malignancies:

Ivosidenib (51 trials; selected)

  1. NCT02989857 - ClarIDHy: Advanced cholangiocarcinoma | Phase 3 | COMPLETED
  2. NCT03173248 - Ivosidenib vs placebo + azacitidine in AML | Phase 3 | ACTIVE_NOT_RECRUITING
  3. NCT03839771 - Ivosidenib/enasidenib + induction therapy in newly diagnosed AML/MDS | Phase 3 | ACTIVE_NOT_RECRUITING
  4. NCT05615818 - Personalized medicine for biliary cancer | Phase 3 | RECRUITING
  5. NCT06127407 - Ivosidenib in chondrosarcoma | Phase 3 | RECRUITING
  6. NCT06465953 - Ivosidenib monotherapy in HMA-naive MDS with IDH1 | Phase 3 | RECRUITING
  7. NCT02073994 - AG-120 in solid tumors/glioma | Phase 1 | COMPLETED
  8. NCT02074839 - AG-120 in hematologic malignancies | Phase 1 | RECRUITING

Vorasidenib (17 trials; selected)

  1. NCT04164901 - INDIGO: Vorasidenib in residual/recurrent grade 2 glioma | Phase 3 | ACTIVE_NOT_RECRUITING
  2. NCT06780930 - Vorasidenib in Asian participants with grade 2 glioma | Phase 3 | ACTIVE_NOT_RECRUITING
  3. NCT06809322 - Vorasidenib maintenance for IDH mutant astrocytoma | Phase 3 | RECRUITING
  4. NCT07215910 - Vorasidenib + temozolomide after radiation | Phase 3 | NOT_YET_RECRUITING
  5. NCT06478212 - Vorasidenib + temozolomide in IDH-mutant glioma | Phase 1/2 | ACTIVE_NOT_RECRUITING

Enasidenib (43 trials; selected)

  1. NCT02577406 - AG-221 vs conventional care in AML with IDH2 | Phase 3 | COMPLETED
  2. NCT01915498 - Phase 1/2 enasidenib in hematologic malignancies | Phase 1/2 | COMPLETED
  3. NCT02273739 - Enasidenib in solid tumors/glioma with IDH2 | Phase 1/2 | COMPLETED

Pharmacogenomics

IDH1 Status in PharmGKB:

  • VIP Status: Yes (Very Important Pharmacogene)
  • CPIC Guidelines: None currently established
  • FDA Drug Label Annotations: Yes (venetoclax labeled for IDH1/2 mutations in AML)

Known Drug-Gene Interactions:

  1. Venetoclax + IDH inhibitors: FDA/EMA labeled combination therapy for IDH1/IDH2-mutant AML; IDH1/IDH2 mutations are predictive biomarkers
  2. IDH1 mutations as biomarkers:
    • R132H mutation: Primary activating mutation; strong predictor of IDH inhibitor response in AML and glioma
    • Prognostic biomarker: IDH1 mutations improve prognosis in lower-grade gliomas but confer worse prognosis in some AML subsets
    • Predictive biomarker: IDH1 mutations predict response to targeted IDH inhibition

Dosing Guidelines:

  • Ivosidenib: 500 mg daily (standard dose across indications)
  • Vorasidenib: 400 mg twice daily
  • Enasidenib: 100 mg daily
  • No formal pharmacogenomic-based dose adjustments currently recommended; dosing not altered by IDH1 genotype

Combination Therapies:

  • IDH inhibitors frequently combined with hypomethylating agents (azacitidine, decitabine) or venetoclax in AML
  • IDH1 mutation status drives treatment selection in AML and gliomas rather than affecting individual drug dosing

Expression profiles

Tissue Expression (Bgee)

IDH1 shows ubiquitous expression across tissues with high expression scores, indicating broad tissue distribution. Maximum expression score: 99.62 (gold quality data, n=287 conditions).

RankTissue/Anatomical StructureExpression ScoreQuality
1Corpus epididymis99.62Gold
2Jejunal mucosa99.50Gold
3Adrenal tissue99.47Gold
4Right adrenal gland cortex99.33Gold
5Right adrenal gland99.24Gold
6Mucosa of sigmoid colon99.12Gold
7Colonic mucosa99.07Gold
8Left adrenal gland99.04Gold
9Adrenal cortex99.03Gold
10Left adrenal gland cortex98.94Gold
11Duodenum98.87Gold
12Adrenal gland98.72Gold
13Seminal vesicle98.55Gold
14Caput epididymis98.55Gold
15Mucosa of transverse colon98.47Gold
16Rectum98.46Gold
17Cortical plate98.40Gold
18Pigmented layer of retina98.35Gold
19Liver98.32Gold
20Cauda epididymis98.32Gold
21Esophagus squamous epithelium98.26Gold
22Ganglionic eminence98.25Gold
23Embryo98.09Gold
24Germinal epithelium of ovary98.07Gold
25Mammary duct98.05Gold
26Adult organism98.03Gold
27Mammalian vulva97.96Gold
28Oral cavity97.92Gold

Tissue-specific patterns:

  • Enriched in steroidogenic tissues: Adrenal glands and cortex show consistently high expression (98.7–99.3), reflecting IDH1’s role in NADPH production for steroid synthesis
  • High in secretory/absorptive tissues: Intestinal tissues (jejunum, colon, duodenum), seminal vesicle, mammary duct
  • High in reproductive tissues: Epididymis, oocytes, germinal epithelium
  • High in neural tissues: Cortical plate, ganglionic eminence, retina

Cell-Type Expression (Bgee)

Includes germ cells and other specialized cell types identified in tissue-level data:

Cell TypeExpression ScoreTissue Context
Secondary oocyte98.92Ovary
Oocyte98.74Ovary

Overall expression breadth: Ubiquitous (present in 294/295 analyzed conditions; absent in only 1 condition). Average expression score across all conditions: 91.13

Disease associations

Mendelian / Monogenic Diseases

Monogenic conditions caused by IDH1 mutations:

DiseaseDisease IDInheritance PatternEvidence Level
Maffucci syndromeMONDO:0013808, Orphanet:163634Autosomal dominantLimited
Ollier diseaseMONDO:0008145, Orphanet:296Autosomal dominantLimited
Paroxysmal extreme pain disorderMONDO:0008179, Orphanet:46348Autosomal dominantLimited
Metaphyseal chondromatosis with D-2-hydroxyglutaric aciduriaMONDO:0013941, Orphanet:99646Autosomal dominantLimited

Associated cancer predisposition syndromes and malignancies:

DiseaseDisease IDNotes
Glioma susceptibility 1MONDO:0024498Cancer predisposition
Diffuse midline glioma, H3 K27-alteredMONDO:1060171High-grade glioma
Diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtypeMONDO:0858939High-grade glioma
Acute myeloid leukemiaMONDO:0018874, Orphanet:519Hematologic malignancy
LymphomaMONDO:0005062, Orphanet:223735Hematologic malignancy

OMIM Entry: 147700

Phenotype Associations (HPO Terms)

Top 30 clinical phenotypes associated with IDH1:

  1. HP:0000006 – Autosomal dominant inheritance
  2. HP:0012321 – D-2-hydroxyglutaric aciduria
  3. HP:0005868 – Metaphyseal enchondromatosis
  4. HP:0005701 – Multiple enchondromatosis
  5. HP:0030295 – Metaphyseal chondromatosis of femur
  6. HP:0030296 – Metaphyseal chondromatosis of radius
  7. HP:0030297 – Metaphyseal chondromatosis of ulna
  8. HP:0030294 – Metaphyseal chondromatosis of tibia
  9. HP:0002664 – Neoplasm
  10. HP:0012174 – Glioblastoma multiforme
  11. HP:0009592 – Astrocytoma
  12. HP:0006765 – Chondrosarcoma
  13. HP:0100242 – Sarcoma
  14. HP:0001048 – Cavernous hemangioma
  15. HP:0001028 – Hemangioma
  16. HP:0007461 – Hemangiomatosis
  17. HP:0100761 – Visceral angiomatosis
  18. HP:0100777 – Exostoses
  19. HP:0002756 – Pathologic fracture
  20. HP:0002757 – Recurrent fractures
  21. HP:0004322 – Short stature
  22. HP:0001510 – Growth delay
  23. HP:0000256 – Macrocephaly
  24. HP:0002650 – Scoliosis
  25. HP:0004626 – Lumbar scoliosis
  26. HP:0002828 – Multiple joint contractures
  27. HP:0001367 – Abnormal joint morphology
  28. HP:0003025 – Metaphyseal irregularity
  29. HP:0003016 – Metaphyseal widening
  30. HP:0003021 – Metaphyseal cupping

Complex Disease / GWAS Associations

Top GWAS-identified associations:

Trait/DiseaseMapped GeneChromosomeP-valueStudy ID
Non-glioblastoma gliomaC2orf8022.00e-10GCST004348_17
Adult diffuse glioma (IDH mutation)C2orf8023.00e-08GCST011004_8
GliomaC2orf8023.00e-06GCST004347_11
Cerebral amyloid deposition (PET imaging)RPSAP27 - TPT1P225.00e-06GCST006904_9

Structured Data Sources

Generated with Claude Haiku 4.5 + BioBTree MCP, drawing on data BioBTree aggregates from 53 biological databases. Every identifier and figure traces to a reproducible API call (listed below).

Further analyze this answer or run your own queries with BioBTree MCP.

Datasets: alphafold, alphamissense, antibody, bgee, bgee_expression, biogrid, biogrid_interaction, ccds, chembl_molecule, chembl_target, clinical_trials, clinvar, collectri, diamond_similarity, ensembl, entrez, esm2_similarity, exon, expressionatlas, gencc, go, gtex, gtopdb_interaction, gwas, hca, hgnc, hpa, hpo, inparanoid, intact, interpro, mim, mondo, msigdb, orphanet, ortholog, panther, paxdb, pdb, pfam, pharmgkb, pharmgkb_gene, proteomicsdb, reactome, refseq, scxa, smart, spliceai, string, string_interaction, supfam, transcript, uniprot
Generated: 2026-05-25 — For the latest data, query BioBTree directly via MCP or API.
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