Optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy: genes and variants

Genes linked to Optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy

• OPA1: Dynamin-like GTPase OPA1, mitochondrial

  A mitochondrial dynamin-related GTPase that fuses inner mitochondrial membranes and shapes cristae. By maintaining mitochondrial architecture and respiratory-chain function, it supports cell energy production, and OPA1 variants cause inherited optic-atrophy syndromes.

  10 disease-causing and 12 uncertain variants in OPA1 are linked to Optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy.

Where Optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy variants cluster

• OPA1 Dynamin-type G (positions 285–561): 5 of 10 disease-causing changes, 1.7× more than its size predicts.

Known disease-causing variants in Optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy

Which prediction tools work for Optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy

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

• EVE: 88 out of 100
• AlphaMissense: 88 out of 100
• SIFT: 87 out of 100
• CATVariant: 87 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• PolyPhen-2: 87 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• MetaLR: 81 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• MutPred2: 81 out of 100 (learned from overlapping clinical labels, so this is optimistic)

Same protein, different disease

• Autosomal dominant optic atrophy classic form is also caused by OPA1 variants; they fall mostly in different places as the Optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy variants (13 disease-causing).
• Optic atrophy is also caused by OPA1 variants; they fall mostly in different places as the Optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy variants (7 disease-causing).

Diseases related to Optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy

• Auditory neuropathy, also linked to OPA1
• Autosomal dominant optic atrophy classic form, also linked to OPA1
• Optic atrophy, also linked to OPA1
• Mitochondrial DNA depletion syndrome 14B (cardioencephalomyopathic type), also linked to OPA1

Frequently asked questions

Which genes are linked to Optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy?

In CATVariant, Optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy is linked to 1 analyzed protein: OPA1 (Dynamin-like GTPase OPA1, mitochondrial).

How many genetic variants are linked to Optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy?

33 variants: 10 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 12 are of uncertain significance or have conflicting reports.

Which uncertain variants in Optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy 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 Optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy?

Among tools not trained on clinical labels, EVE separates this disease's known disease-causing variants from harmless ones best (AUROC 0.88, based on 9 disease-causing and 26 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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