ACO1

Chr 9

aconitase 1

Also known as: ACONS, HEL60, IREB1, IREBP, IREBP1, IRP1

NCBI Gene: 48 ENSG00000122729 UniProt: P21399 OMIM: 100880

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.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is a bifunctional, cytosolic protein that functions as an essential enzyme in the TCA cycle and interacts with mRNA to control the levels of iron inside cells. When cellular iron levels are high, this protein binds to a 4Fe-4S cluster and functions as an aconitase. Aconitases are iron-sulfur proteins that function to catalyze the conversion of citrate to isocitrate. When cellular iron levels are low, the protein binds to iron-responsive elements (IREs), which are stem-loop structures found in the 5' UTR of ferritin mRNA, and in the 3' UTR of transferrin receptor mRNA. When the protein binds to IRE, it results in repression of translation of ferritin mRNA, and inhibition of degradation of the otherwise rapidly degraded transferrin receptor mRNA. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. Alternative splicing results in multiple transcript variants [provided by RefSeq, Jan 2014]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.93

LOEUF

Mechanism· predicted