ATXN2
Chr 12ADMultiataxin 2
Also known as: ATX2, SCA2, TNRC13
The ATXN2 protein localizes to the endoplasmic reticulum and plasma membrane where it regulates endocytosis, modulates mTOR signaling, and controls ribosomal translation and mitochondrial function. Pathogenic expansions of the polyglutamine tract (normally 14-31 residues) cause autosomal dominant spinocerebellar ataxia type 2 when expanded to 32-200 residues, while intermediate expansions increase susceptibility to amyotrophic lateral sclerosis. The pathogenic mechanism involves loss of normal protein function due to the expanded polyglutamine tract.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Moderately missense-constrained (top ~2.5%)
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
251 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 1 | 8 | 0 | 9 |
Likely Pathogenic | 1 | 1 | 0 | 0 | 2 |
VUS | 1 | 107 | 55 | 1 | 164 |
Likely Benign | 5 | 10 | 8 | 7 | 30 |
Benign | 0 | 5 | 7 | 3 | 15 |
Conflicting | — | 5 | |||
| Total | 7 | 124 | 78 | 11 | 225 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ATXN2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools