Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins: genes and variants

Genes linked to Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins

• TRMU: Mitochondrial tRNA-specific 2-thiouridylase 1

  A mitochondrial tRNA-modifying enzyme that adds sulfur to wobble-position uridines in several mitochondrial tRNAs. This modification supports accurate mitochondrial protein synthesis, and TRMU variants are associated with aminoglycoside-related deafness and transient infantile liver failure.

  12 disease-causing and 34 uncertain variants in TRMU are linked to Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins.

• 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 Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins.

Known disease-causing variants in Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins

Which prediction tools work for Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins

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

• REVEL: 93 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 92 out of 100
• PolyPhen-2: 91 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• phyloP: 90 out of 100
• AlphaMissense: 89 out of 100
• CADD: 88 out of 100
• CATVariant: 84 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• ESM1b (LLR): 80 out of 100

Same protein, different disease

• Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency is also caused by MMUT variants; they fall mostly in different places as the Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins 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 Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins variants (53 disease-causing).
• Methylmalonic acidemia is also caused by MMUT variants; they fall mostly in different places as the Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins variants (32 disease-causing).

Diseases related to Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins

• 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
• Aminoglycoside-induced deafness, also linked to TRMU
• Likely inborn error of metabolism, also linked to MMUT

Frequently asked questions

Which genes are linked to Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins?

In CATVariant, Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins is linked to 2 analyzed proteins: TRMU (Mitochondrial tRNA-specific 2-thiouridylase 1) and MMUT (Methylmalonyl-CoA mutase, mitochondrial).

How many genetic variants are linked to Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins?

70 variants: 13 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 34 are of uncertain significance or have conflicting reports.

Which uncertain variants in Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins look disease-causing?

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

Which variant effect predictor works best for Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins?

Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 0.92, based on 12 disease-causing and 20 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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