Hereditary ataxia: genes and variants

Genes linked to Hereditary ataxia

• ATP1A3: Sodium/potassium-transporting ATPase subunit alpha-3

  It rapidly restores neuronal sodium and potassium gradients after repetitive firing, making it particularly important in highly active neurons. Pathogenic variants cause overlapping syndromes including alternating hemiplegia of childhood, rapid-onset dystonia-parkinsonism, and CAPOS syndrome.

  1 disease-causing and 0 uncertain variants in ATP1A3 are linked to Hereditary ataxia.

• NKX2-1: Homeobox protein Nkx-2.1

  It controls developmental and tissue-specific gene programs in lung, thyroid, and basal ganglia. Haploinsufficiency causes brain-lung-thyroid syndrome, variably combining chorea or developmental movement disorder, neonatal respiratory disease, and thyroid dysfunction.

  1 disease-causing and 0 uncertain variants in NKX2-1 are linked to Hereditary ataxia.

• SPG7: Mitochondrial inner membrane m-AAA protease component paraplegin

  It participates in mitochondrial inner-membrane protein quality control and respiratory homeostasis as part of the m-AAA protease machinery. Biallelic pathogenic variants cause SPG7-related disease, commonly presenting with spastic ataxia, optic neuropathy, or progressive gait impairment.

  0 disease-causing and 0 uncertain variants in SPG7 are linked to Hereditary ataxia.

Weakly linked (only a few uncertain records): SPTBN2, ABCD1, ADCY5, ARID1B, HMBS, KCNA1, KCNQ5, KIF11 and 7 more.

Known disease-causing variants in Hereditary ataxia

Same protein, different disease

• Brain-lung-thyroid syndrome is also caused by NKX2-1 variants; they fall mostly in different places as the Hereditary ataxia variants (14 disease-causing).
• Benign hereditary chorea is also caused by NKX2-1 variants; they fall mostly in different places as the Hereditary ataxia variants (4 disease-causing).
• Alternating hemiplegia of childhood is also caused by ATP1A3 variants; they fall mostly in different places as the Hereditary ataxia variants (23 disease-causing).
• Cerebellar ataxia-areflexia-pes cavus-optic atrophy-sensorineural hearing loss syndrome is also caused by ATP1A3 variants; they fall mostly in different places as the Hereditary ataxia variants (18 disease-causing).
• ATP1A3-associated neurological disorder is also caused by ATP1A3 variants; they fall mostly in different places as the Hereditary ataxia variants (4 disease-causing).

Diseases related to Hereditary ataxia

• Hereditary spastic paraplegia, also linked to SPG7
• Alternating hemiplegia of childhood, also linked to ATP1A3
• Cerebellar ataxia-areflexia-pes cavus-optic atrophy-sensorineural hearing loss syndrome, also linked to ATP1A3
• Brain-lung-thyroid syndrome, also linked to NKX2-1
• Multiple myeloma, also linked to NKX2-1
• Hereditary pancreatitis, also linked to SPG7
• Spastic ataxia, also linked to SPG7
• Mitochondrial disease, also linked to SPG7
• Possible mitochondrial disorder - nuclear genes, also linked to SPG7
• Thyroid cancer, nonmedullary, 2, also linked to NKX2-1
• Mitochondrial DNA maintenance disorder, also linked to SPG7
• Benign hereditary chorea, also linked to NKX2-1

Frequently asked questions

Which genes are linked to Hereditary ataxia?

In CATVariant, Hereditary ataxia is linked to 3 analyzed proteins: ATP1A3 (Sodium/potassium-transporting ATPase subunit alpha-3), NKX2-1 (Homeobox protein Nkx-2.1) and SPG7 (Mitochondrial inner membrane m-AAA protease component paraplegin).

How many genetic variants are linked to Hereditary ataxia?

20 variants: 2 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 13 are of uncertain significance or have conflicting reports.

Which uncertain variants in Hereditary ataxia 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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