Ornithine carbamoyltransferase deficiency: genes and variants

Genes linked to Ornithine carbamoyltransferase deficiency

• OTC: Ornithine transcarbamylase, mitochondrial

  It combines ornithine with carbamoyl phosphate in the mitochondrial urea cycle, allowing toxic nitrogen to be converted ultimately to urea. Loss-of-function variants cause X-linked OTC deficiency and can produce life-threatening hyperammonemia.

  135 disease-causing and 141 uncertain variants in OTC are linked to Ornithine carbamoyltransferase deficiency.

Known disease-causing variants in Ornithine carbamoyltransferase deficiency

Showing 60 of 135.

Uncertain variants in Ornithine carbamoyltransferase deficiency that look disease-causing

Which prediction tools work for Ornithine carbamoyltransferase deficiency

How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).

• CATVariant: 91 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• PolyPhen-2: 89 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• MetaLR: 87 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 82 out of 100

Diseases related to Ornithine carbamoyltransferase deficiency

• Likely inborn error of metabolism, also linked to OTC

Frequently asked questions

Which genes are linked to Ornithine carbamoyltransferase deficiency?

In CATVariant, Ornithine carbamoyltransferase deficiency is linked to 1 analyzed protein: OTC (Ornithine transcarbamylase, mitochondrial).

How many genetic variants are linked to Ornithine carbamoyltransferase deficiency?

312 variants: 135 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 141 are of uncertain significance or have conflicting reports.

Which uncertain variants in Ornithine carbamoyltransferase deficiency look disease-causing?

17 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example OTC M268I, OTC A140V, OTC G162A, OTC G39D and OTC D126E. These are leads for expert review, not diagnoses.

Which variant effect predictor works best for Ornithine carbamoyltransferase deficiency?

Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 0.82, based on 132 disease-causing and 8 harmless variants).

About this data

Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.

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