ACO1
Chr 9aconitase 1
Also known as: ACONS, HEL60, IREB1, IREBP, IREBP1, IRP1
The encoded protein functions as both a cytosolic aconitase that catalyzes the conversion of citrate to isocitrate in the TCA cycle and as an iron-responsive element-binding protein that regulates cellular iron homeostasis by controlling translation and stability of iron-related mRNAs. Mutations cause autosomal recessive neurodevelopmental disorders with intellectual disability, seizures, and movement abnormalities. The phenotypes reflect disruption of both mitochondrial energy metabolism and cellular iron regulation affecting primarily the nervous system.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
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
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
ACO1 · 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
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools