IREB2

Chr 15AR

iron responsive element binding protein 2

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

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.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.221 OMIM phenotype
Clinical SummaryIREB2
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.22LOEUF
pLI 1.000
Z-score 5.98
OE 0.11 (0.060.22)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.03Z-score
OE missense 0.75 (0.690.81)
378 obs / 506.8 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.11 (0.060.22)
00.351.4
Missense OE0.75 (0.690.81)
00.61.4
Synonymous OE1.02
01.21.6
LoF obs/exp: 6 / 53.0Missense obs/exp: 378 / 506.8Syn Z: -0.22
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
moderateIREB2-related neurodevelopmental disorderOTHERAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.4587th %ile
GOF
0.4677th %ile
LOF
0.64top 25%

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

IREB2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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