IDH1
Chr 2isocitrate dehydrogenase (NADP(+)) 1
Also known as: HEL-216, HEL-S-26, IDCD, IDH, IDP, IDPC, PICD
The enzyme catalyzes the NADP-dependent oxidative decarboxylation of isocitrate to 2-oxoglutarate and plays a critical role in generating NADPH, an important cofactor in biosynthesis pathways. Mutations cause autosomal recessive retinal dystrophy with early childhood onset, primarily affecting vision and retinal function. The gene is highly constrained against loss-of-function variants, indicating that such mutations are likely to be pathogenic.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
The highest-scoring mechanism for this gene is dominant-negative.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
300 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 13 | 0 | 13 |
Likely Pathogenic | 0 | 1 | 0 | 0 | 1 |
VUS | 0 | 154 | 6 | 0 | 160 |
Likely Benign | 0 | 3 | 0 | 86 | 89 |
Benign | 0 | 0 | 17 | 1 | 18 |
| Total | 0 | 158 | 36 | 87 | 281 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
IDH1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Niraparib In Recurrent IDH 1/2 Gliomas
ACTIVE NOT RECRUITINGTesting Addition of an Anti-cancer Drug, Vorasidenib to Temozolomide, After Radiation for Advanced Brain Cancer
NOT YET RECRUITINGRegistry of Patients With MPNs in Taiwan
ACTIVE NOT RECRUITINGMulticenter, Platform-type Clinical Study of Refractory/Recurrent Acute Myeloid Leukemia
RECRUITINGPrevalence Of Germline Gene Mutations In Patients With Myeloproliferative Neoplasms With Family History
NOT YET RECRUITINGAG-120 in People With IDH1 Mutant Chondrosarcoma
ACTIVE NOT RECRUITINGA Study of Gilteritinib in Combination With Ivosidenib or Enasidenib in People With Acute Myeloid Leukemia (AML)
RECRUITINGIvosidenib in Participants With Locally Advanced or Metastatic Conventional Chondrosarcoma Untreated or Previously Treated With 1 Systemic Treatment Regimen
RECRUITINGIDH Targeted/Non- Targeted vs Non-targeted/IDH-targeted Approaches in the Treatment of Newly Diagnosed IDH Mutated AML Patients Not Candidates for Intensive Induction Therapy (I- DATA Study)
RECRUITINGhSTAR GBM (Hematopoetic Stem Cell (HPC) Rescue for GBM)
RECRUITINGOBServatory of Compassionate Use of IVOsidenib in France for Patients With Acute Myeloid Leukemia
RECRUITINGCPX-351 and Ivosidenib for the Treatment of IDH1 Mutated Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome
RECRUITINGExternal Resources
Links to major genomics databases and tools