Cerebellar ataxia: genes and variants

Genes linked to Cerebellar ataxia

• MFN2: Mitofusin-2

  It promotes outer-mitochondrial-membrane fusion and coordinates mitochondrial transport, distribution, and contacts with other organelles. Pathogenic variants are a major cause of Charcot-Marie-Tooth disease type 2A and related axonal neuropathies.

  1 disease-causing and 0 uncertain variants in MFN2 are linked to Cerebellar ataxia.

• SCN8A: Sodium channel protein type 8 subunit alpha

  The protein forms Nav1.6, a voltage-gated sodium channel that sets the threshold and propagation of neuronal action potentials. It is widely important for neuronal excitability, and SCN8A variants are associated with developmental and epileptic encephalopathies.

  1 disease-causing and 0 uncertain variants in SCN8A are linked to Cerebellar ataxia.

• SPTBN2: Spectrin beta chain, non-erythrocytic 2

  It organizes the neuronal membrane cytoskeleton and is particularly important for Purkinje-cell structure and signaling in the cerebellum. Dominant variants cause spinocerebellar ataxia type 5 or early-onset developmental ataxia, while biallelic variants can cause a more severe SCAR phenotype.

  1 disease-causing and 0 uncertain variants in SPTBN2 are linked to Cerebellar ataxia.

Weakly linked (only a few uncertain records): CACNA1A, NPC1, COQ8A, DNM1, DNMT1, FAT2, GJB1, KCNJ10 and 1 more.

Known disease-causing variants in Cerebellar ataxia

Same protein, different disease

• Spinocerebellar ataxia type 6 is also caused by SPTBN2 variants; they fall mostly in different places as the Cerebellar ataxia variants (9 disease-causing).
• Charcot-Marie-Tooth disease is also caused by MFN2 variants; they fall mostly in different places as the Cerebellar ataxia variants (86 disease-causing).
• Charcot-Marie-Tooth disease type 2A2 is also caused by MFN2 variants; they fall mostly in different places as the Cerebellar ataxia variants (32 disease-causing).
• Charcot-Marie-Tooth disease, axonal, autosomal recessive, type 2a2b; is also caused by MFN2 variants; they fall mostly in different places as the Cerebellar ataxia variants (9 disease-causing).
• Neuropathy, hereditary motor and sensory, type 6A is also caused by MFN2 variants; they fall mostly in different places as the Cerebellar ataxia variants (6 disease-causing).
• Hereditary motor and sensory neuropathy with optic atrophy is also caused by MFN2 variants; they fall mostly in different places as the Cerebellar ataxia variants (3 disease-causing).
• Early-infantile DEE is also caused by SCN8A variants; they fall mostly in different places as the Cerebellar ataxia variants (90 disease-causing).
• Cognitive impairment with or without cerebellar ataxia is also caused by SCN8A variants; they fall mostly in different places as the Cerebellar ataxia variants (22 disease-causing).
• Seizures, benign familial infantile, 3 is also caused by SCN8A variants; they fall mostly in different places as the Cerebellar ataxia variants (12 disease-causing).
• Complex neurodevelopmental disorder is also caused by SCN8A variants; they fall mostly in different places as the Cerebellar ataxia variants (8 disease-causing).
• Autosomal recessive inheritance is also caused by SCN8A variants; they fall mostly in different places as the Cerebellar ataxia variants (3 disease-causing).

Diseases related to Cerebellar ataxia

• Early-infantile DEE, also linked to SCN8A
• Charcot-Marie-Tooth disease, also linked to MFN2
• Seizures, benign familial infantile, 3, also linked to SCN8A
• Amyotrophic lateral sclerosis, also linked to SCN8A
• Cardiac arrhythmia, also linked to SCN8A
• Complex neurodevelopmental disorder, also linked to SCN8A
• Spinocerebellar ataxia type 6, also linked to SPTBN2
• Charcot-Marie-Tooth disease type 2A2, also linked to MFN2
• Cognitive impairment with or without cerebellar ataxia, also linked to SCN8A
• Epilepsy, also linked to SCN8A
• Auditory neuropathy, also linked to MFN2
• Charcot-Marie-Tooth disease, axonal, autosomal recessive, type 2a2b;, also linked to MFN2

Frequently asked questions

Which genes are linked to Cerebellar ataxia?

In CATVariant, Cerebellar ataxia is linked to 3 analyzed proteins: MFN2 (Mitofusin-2), SCN8A (Sodium channel protein type 8 subunit alpha) and SPTBN2 (Spectrin beta chain, non-erythrocytic 2).

How many genetic variants are linked to Cerebellar ataxia?

14 variants: 3 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 6 are of uncertain significance or have conflicting reports.

Which uncertain variants in Cerebellar 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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