Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2: genes and variants

Genes linked to Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2

• SETX: Helicase senataxin

  It resolves RNA-DNA hybrids and supports transcription termination, RNA processing, and genome stability, particularly in long-lived neurons. Different pathogenic mechanisms cause ataxia with oculomotor apraxia type 2 or juvenile amyotrophic lateral sclerosis type 4.

  17 disease-causing and 577 uncertain variants in SETX are linked to Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2.

Where Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 variants cluster

• SETX UPF1-type SF1B helicase ATP-binding (positions 1933–2254): 7 of 17 disease-causing changes, 3.4× more than its size predicts.

Known disease-causing variants in Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2

Which prediction tools work for Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2

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

• PolyPhen-2: 92 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• CATVariant: 91 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 90 out of 100
• CADD: 89 out of 100
• phyloP: 86 out of 100
• REVEL: 86 out of 100 (learned from overlapping clinical labels, so this is optimistic)

Diseases related to Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2

• Hereditary spastic paraplegia, also linked to SETX
• Amyotrophic lateral sclerosis, also linked to SETX
• Spastic ataxia, also linked to SETX

Frequently asked questions

Which genes are linked to Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2?

In CATVariant, Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 is linked to 1 analyzed protein: SETX (Helicase senataxin).

How many genetic variants are linked to Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2?

805 variants: 17 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 577 are of uncertain significance or have conflicting reports.

Which uncertain variants in Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 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 Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2?

Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 0.90, based on 15 disease-causing and 191 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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