IREB2

Chr 15AR

iron responsive element binding protein 2

Also known as: ACO3, IRE-BP 2, IRE-BP2, IRP2, IRP2AD, NDCAMA

NCBI Gene: 3658 ENSG00000136381 UniProt: P48200 OMIM: 147582

This protein binds to iron-responsive elements in mRNAs to regulate cellular iron homeostasis by controlling translation of ferritin and stability of transferrin receptor mRNA. Biallelic mutations cause autosomal recessive neurodegeneration with early-onset choreoathetoid movements and microcytic anemia. The gene is highly constrained against loss-of-function variants (pLI 0.999), suggesting that complete loss of protein function is poorly tolerated.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is an RNA-binding protein that acts to regulate iron levels in the cells by regulating the translation and stability of mRNAs that affect iron homeostasis under conditions when iron is depleted. When iron levels are low, this protein binds to iron-responsive elements (IRES), stem-loop structures located either in the 5' or 3' UTRs. Binding to the 5' UTR represses translation, while binding to the 3' UTR inhibits mRNA degradation. When iron is found in the cell, this protein is degraded in a F-box and leucine rich repeat protein 5-dependent manner. Variants in this gene have been associated with lung cancer and chronic obstructive pulmonary disease (COPD). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2017]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Neurodegeneration, early-onset, with choreoathetoid movements and microcytic anemiaMIM #618451

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.22

LOEUF· LoF intol.

LOF

Mechanism· predicted