Likely inborn error of metabolism: genes and variants

Genes linked to Likely inborn error of metabolism

• 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.

  2 disease-causing and 1 uncertain variants in OTC are linked to Likely inborn error of metabolism.

• ALDH5A1: Succinate-semialdehyde dehydrogenase, mitochondrial

  1 disease-causing and 0 uncertain variants in ALDH5A1 are linked to Likely inborn error of metabolism.

• MMUT: Methylmalonyl-CoA mutase, mitochondrial

  It converts methylmalonyl-CoA to succinyl-CoA in mitochondria using adenosylcobalamin as a cofactor. Biallelic loss-of-function variants cause isolated methylmalonic acidemia, which can lead to metabolic acidosis, hyperammonemia, neurologic injury, and chronic kidney disease.

  1 disease-causing and 0 uncertain variants in MMUT are linked to Likely inborn error of metabolism.

Weakly linked (only a few uncertain records): MCCC2.

Known disease-causing variants in Likely inborn error of metabolism

Same protein, different disease

• Ornithine carbamoyltransferase deficiency is also caused by OTC variants; they fall mostly in different places as the Likely inborn error of metabolism variants (135 disease-causing).
• Succinate-semialdehyde dehydrogenase deficiency is also caused by ALDH5A1 variants; they fall mostly in different places as the Likely inborn error of metabolism variants (55 disease-causing).
• Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency is also caused by MMUT variants; they fall mostly in different places as the Likely inborn error of metabolism variants (55 disease-causing).
• Methylmalonic aciduria due to complete methylmalonyl-CoA mutase deficiency is also caused by MMUT variants; they fall mostly in different places as the Likely inborn error of metabolism variants (53 disease-causing).
• Methylmalonic acidemia is also caused by MMUT variants; they fall mostly in different places as the Likely inborn error of metabolism variants (32 disease-causing).

Diseases related to Likely inborn error of metabolism

• Ornithine carbamoyltransferase deficiency, also linked to OTC
• Succinate-semialdehyde dehydrogenase deficiency, also linked to ALDH5A1
• Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency, also linked to MMUT
• Methylmalonic aciduria due to complete methylmalonyl-CoA mutase deficiency, also linked to MMUT
• Methylmalonic acidemia, also linked to MMUT
• Epilepsy, also linked to ALDH5A1
• Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins, also linked to MMUT

Frequently asked questions

Which genes are linked to Likely inborn error of metabolism?

In CATVariant, Likely inborn error of metabolism is linked to 3 analyzed proteins: OTC (Ornithine transcarbamylase, mitochondrial), ALDH5A1 (Succinate-semialdehyde dehydrogenase, mitochondrial) and MMUT (Methylmalonyl-CoA mutase, mitochondrial).

How many genetic variants are linked to Likely inborn error of metabolism?

6 variants: 4 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 2 are of uncertain significance or have conflicting reports.

Which uncertain variants in Likely inborn error of metabolism look disease-causing?

None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.

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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