Optic atrophy: genes and variants

Genes linked to Optic atrophy

• 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.

  7 disease-causing and 2 uncertain variants in OPA1 are linked to Optic atrophy.

• ABCA4: Retinal-specific phospholipid-transporting ATPase ABCA4

  It flips retinal-derived lipid adducts across photoreceptor disc membranes so they can be cleared during the visual cycle. Biallelic loss-of-function variants cause Stargardt disease and can also produce cone-rod dystrophy or retinitis pigmentosa.

  1 disease-causing and 5 uncertain variants in ABCA4 are linked to Optic atrophy.

• ABCC6: ATP-binding cassette sub-family C member 6

  Its ATP-dependent transport activity in liver and other tissues is required indirectly for maintaining extracellular pyrophosphate, a major inhibitor of inappropriate mineralization. Loss-of-function variants cause pseudoxanthoma elasticum and can promote calcification of skin, retina, and arteries.

  1 disease-causing and 0 uncertain variants in ABCC6 are linked to Optic atrophy.

• WDR45: WD repeat domain phosphoinositide-interacting protein 4

  It participates in early autophagosome formation and cellular recycling pathways, with neurons particularly vulnerable to its dysfunction. De novo or mosaic loss-of-function variants cause beta-propeller protein-associated neurodegeneration, with childhood developmental delay followed by progressive dystonia, parkinsonism, and brain iron accumulation.

  1 disease-causing and 0 uncertain variants in WDR45 are linked to Optic atrophy.

Weakly linked (only a few uncertain records): CRB1, MFN2, CEP290, EYS, IFT172, ISCA2, PROS1 and WDR19.

Where Optic atrophy variants cluster

• OPA1 Dynamin-type G (positions 285–561): 4 of 7 disease-causing changes, 2.0× more than its size predicts.

Known disease-causing variants in Optic atrophy

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 variants (13 disease-causing).
• Optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy is also caused by OPA1 variants; they fall mostly in different places as the Optic atrophy variants (10 disease-causing).
• Severe early-childhood-onset retinal dystrophy is also caused by ABCA4 variants; they fall mostly in different places as the Optic atrophy variants (148 disease-causing).
• ABCA4-related retinopathy is also caused by ABCA4 variants; they fall mostly in different places as the Optic atrophy variants (60 disease-causing).
• Retinitis pigmentosa is also caused by ABCA4 variants; they fall mostly in different places as the Optic atrophy variants (58 disease-causing).
• Stargardt disease is also caused by ABCA4 variants; they fall mostly in different places as the Optic atrophy variants (41 disease-causing).
• Age related macular degeneration 9 is also caused by ABCA4 variants; they fall mostly in different places as the Optic atrophy variants (41 disease-causing).
• Autosomal recessive inherited pseudoxanthoma elasticum is also caused by ABCC6 variants; they fall mostly in different places as the Optic atrophy variants (67 disease-causing).
• Arterial calcification, generalized, of infancy, 2 is also caused by ABCC6 variants; they fall mostly in different places as the Optic atrophy variants (25 disease-causing).
• Pseudoxanthoma elasticum, forme fruste is also caused by ABCC6 variants; they fall mostly in different places as the Optic atrophy variants (21 disease-causing).
• Neurodegeneration with brain iron accumulation is also caused by WDR45 variants; they fall mostly in different places as the Optic atrophy variants (15 disease-causing).

Diseases related to Optic atrophy

• Retinitis pigmentosa, also linked to ABCA4
• Leber congenital amaurosis, also linked to ABCA4
• Severe early-childhood-onset retinal dystrophy, also linked to ABCA4
• Autosomal recessive inherited pseudoxanthoma elasticum, also linked to ABCC6
• ABCA4-related retinopathy, also linked to ABCA4
• Stargardt disease, also linked to ABCA4
• Cone-rod dystrophy, also linked to ABCA4
• Age related macular degeneration 9, also linked to ABCA4
• Arterial calcification, generalized, of infancy, 2, also linked to ABCC6
• Pseudoxanthoma elasticum, forme fruste, also linked to ABCC6
• Neurodegeneration with brain iron accumulation, also linked to WDR45
• Retinal disorder, also linked to ABCA4

Frequently asked questions

Which genes are linked to Optic atrophy?

In CATVariant, Optic atrophy is linked to 4 analyzed proteins: OPA1 (Dynamin-like GTPase OPA1, mitochondrial), ABCA4 (Retinal-specific phospholipid-transporting ATPase ABCA4), ABCC6 (ATP-binding cassette sub-family C member 6) and WDR45 (WD repeat domain phosphoinositide-interacting protein 4).

How many genetic variants are linked to Optic atrophy?

35 variants: 10 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 17 are of uncertain significance or have conflicting reports.

Which uncertain variants in Optic atrophy 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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