IDH1 (O75874) variants and mutations

IDH1 (also known as O75874) is a human protein-coding gene encoding an isocitrate dehydrogenase [NADP] cytoplasmic protein. It normally generates alpha-ketoglutarate and NADPH in the cytosol and peroxisomes. Recurrent cancer-associated variants at R132 acquire the ability to produce D-2-hydroxyglutarate, an oncometabolite that rewires epigenetic regulation in glioma, leukemia, and other tumors. This analysis covers 1,522 IDH1 variants and mutations. Of these, 0.5% have pathogenic or likely pathogenic clinical classifications, 51% have computational variant effect predictions from REVEL and MutPred, and 35% have population-specific frequency data. Disease context includes colorectal cancer and glioma samples. Example IDH1 variants include S2C, S2F, and S2P.

Variant analysis overview

Gene: IDH1
Protein: O75874
UniProt accession: O75874
Organism: Homo sapiens
Variants analyzed: 1522
Variant scope: all variants
Completed: 2026-08-09

Variant and mutation evidence

Variant composition: 1,334 unspecified-consequence records; 1 stop retained variant; 1 stop lost; 73 synonymous variants; 65 missense variants; 14 frameshift variants; 11 stop-gained variants; 5 in-frame deletions; 1 in-frame insertions; 5 splice-region variants; 2 protein altering variant; 10 substitution
Clinical classifications: 8 pathogenic or likely pathogenic; 58 benign or likely benign; 341 uncertain-significance; 60 other clinical labels.
Computational signals: 188 REVEL high-risk; 42 MutPred high-risk.
Variant classes: 1,352 missense; 73 synonymous; 91 truncating or splice.
Prediction scores: 779 variants have prediction scores (51% of the analyzed set).
Literature: 101 publications are represented in the literature summary.

Clinical, disease, and population context

Clinical evidence: 5 records have expert-only or criteria-backed evidence.
Clinical annotations: 479 variants have clinical annotations.
Population evidence: 615 variants have population-frequency evidence.
Disease context: 25 disease associations are represented. Top associations: colorectal cancer and glioma samples.

Protein structure and variant hotspots

Protein features: 13 binding sites; 10 post-translational modification sites.
Ancestry evidence: 535 variants have ancestry-specific frequency data.
PTM context: 32 variants overlap post-translational modification sites.
3D hotspots: 2 hotspot clusters were identified. Clusters at residues 15-306 (intolerant, 13 variants); residues 289-399 (intolerant, 25 variants).
Allosteric analysis: 13 functional sites were identified.
gnomAD gene constraint: pLI 0.00 (tolerant of loss-of-function variation); LOEUF 0.72; missense Z-score 1.78.

Data sources

Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.

Notable IDH1 variants

Examples include S2C, S2F, S2P, S2T, S2Y, K3*, K3Q, K4I. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.

IDH1 analysis run — IDH1 (1,522 variants) — completed 2026-08-09