ACO1 (Aconitase 1) Gene: Function, Mutations, and Disease Associations
Comprehensive biomedical resource for the ACO1 gene encoding cytosolic aconitase/iron regulatory protein 1 (IRP1)
Gene Information Card
| Symbol | ACO1 |
|---|---|
| Full Name | Aconitase 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 9p21.1 |
| NCBI Gene ID | 48 ncbi.nlm.nih.gov/gene/48 |
| Ensembl ID | ENSG00000134982 |
| UniProt ID | P21399 |
| OMIM ID | 100880 |
| HGNC ID | 114 |
| Aliases | IREB1, IREBP1, IRP1, ACONS |
Description
ACO1 encodes the cytosolic aconitase 1, also known as iron regulatory protein 1 (IRP1). This bifunctional protein acts as an aconitase in the tricarboxylic acid cycle, interconverting citrate and isocitrate, and as an iron-responsive element (IRE)-binding protein that regulates iron homeostasis by controlling the translation or stability of mRNAs involved in iron uptake, storage, and utilization. The switch between enzymatic and RNA-binding activities is regulated by cellular iron levels and reactive oxygen species.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Iron-refractory iron deficiency anemia (IRIDA) | Loss of IRP1 function disrupts iron-responsive element binding, impairing iron absorption and utilization. | ClinVar; PMID: 23351997 |
| Hereditary hyperferritinemia-cataract syndrome (HHCS) | Gain-of-function mutations in IRP1 increase ferritin translation, leading to hyperferritinemia and cataract formation. | ClinVar; PMID: 23351997 |
| Neurodegeneration with brain iron accumulation (NBIA) | Altered IRP1 activity contributes to iron dyshomeostasis in the brain. | OMIM; PMID: 23351997 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | High |
| Brain | 8.3 | Medium |
| Heart | 7.1 | Medium |
| Kidney | 6.8 | Medium |
| Skeletal Muscle | 5.2 | Medium |
| Lung | 4.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 10.2 | Hepatocellular carcinoma cell line |
| SH-SY5Y | 7.8 | Neuroblastoma cell line |
| HEK293 | 6.5 | Embryonic kidney cell line |
| K562 | 5.1 | Chronic myelogenous leukemia cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1868G>A (p.Arg623Gln) | Missense | 0.001% (gnomAD) | Reduced aconitase activity; associated with IRIDA |
| c.2414A>G (p.Asn805Ser) | Missense | 0.0005% (gnomAD) | Impaired IRE-binding; linked to HHCS |
| c.1A>G (p.Met1Val) | Start loss | <0.001% (gnomAD) | Loss of protein expression; severe IRIDA |
Mutation functional classification
Loss of Function (LOF)
Missense and start-loss mutations (e.g., p.Arg623Gln, p.Met1Val) reduce aconitase activity or IRE-binding, leading to iron-refractory iron deficiency anemia (IRIDA).
Gain of Function (GOF)
Mutations such as p.Asn805Ser enhance IRE-binding affinity, increasing ferritin translation and causing hereditary hyperferritinemia-cataract syndrome (HHCS).
Dominant Negative (DN)
No dominant-negative mutations have been reported for ACO1.
View complete mutation data：
Gene Ontology (GO)
| • GO:0003994 – aconitate hydratase activity | • GO:0005737 – cytoplasm |
| • GO:0006099 – tricarboxylic acid cycle | • GO:0006879 – cellular iron ion homeostasis |
| • GO:0030350 – iron-responsive element binding | • GO:0042802 – identical protein binding |
Pathways
• KEGG: hsa00020 – Citrate cycle (TCA cycle)
• Reactome: R-HSA-71403 – Citric acid cycle (TCA cycle)
• Reactome: R-HSA-917937 – Iron uptake and transport
Protein Summary
Aconitase 1 (ACO1) is a 889-amino-acid cytosolic protein that functions as a bifunctional enzyme/RNA-binding regulator. In iron-replete conditions, it assembles a [4Fe-4S] cluster and catalyzes the isomerization of citrate to isocitrate. Under iron-deplete conditions, the cluster disassembles, converting the protein into IRP1, which binds to iron-responsive elements (IREs) in the 5' or 3' UTRs of target mRNAs (e.g., ferritin, transferrin receptor) to post-transcriptionally regulate iron metabolism. The protein is highly conserved and expressed in most tissues.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ACO1 Knockout HEK293 Cell Line | EDJ-KQ3552 | Human | 48 | Details Get a Quote |
| TACO1 Knockout HEK293 Cell Line | EDJ-KQ10972 | Human | 51204 | Details Get a Quote |
| MACO1 Knockout HEK293 Cell Line | EDJ-KQ14170 | Human | 55219 | Details Get a Quote |
| MACO1 Knockout A-549 Cell Line | EDJ-KQ44101 | Human | 55219 | Details Get a Quote |
| MACO1 Knockout HCT 116 Cell Line | EDJ-KQ44102 | Human | 55219 | Details Get a Quote |
| MACO1 Knockout HeLa Cell Line | EDJ-KQ44103 | Human | 55219 | Details Get a Quote |
| ACO1 Knockout A-549 Cell Line | EDJ-KQ25408 | Human | 48 | Details Get a Quote |
| ACO1 Knockout HCT 116 Cell Line | EDJ-KQ25409 | Human | 48 | Details Get a Quote |
| ACO1 Knockout HeLa Cell Line | EDJ-KQ25410 | Human | 48 | Details Get a Quote |
| TACO1 Knockout A-549 Cell Line | EDJ-KQ38793 | Human | 51204 | Details Get a Quote |
| TACO1 Knockout HCT 116 Cell Line | EDJ-KQ38794 | Human | 51204 | Details Get a Quote |
| TACO1 Knockout HeLa Cell Line | EDJ-KQ38795 | Human | 51204 | Details Get a Quote |
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