ATXN1

Chr 6AD

ataxin 1

Also known as: ATX1, D6S504E, SCA1

NCBI Gene: 6310ENSG00000124788UniProt: P54253OMIM: 601556

ATXN1 encodes a chromatin-binding factor that represses Notch signaling and may be involved in RNA metabolism and brain development. Mutations cause spinocerebellar ataxia type 1 (SCA1), an autosomal dominant cerebellar ataxia characterized by progressive degeneration of the cerebellum, brainstem and spinal cord. The pathogenic mechanism involves expansion of CAG repeats (40-83 repeats versus 6-39 normal) in the coding region, producing an elongated polyglutamine tract in the protein.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
MultiplemechanismADLOEUF 0.321 OMIM phenotype
Clinical Summary— ATXN1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.97). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
20 unique Pathogenic / Likely Pathogenic· 55 VUS of 125 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.32LOEUF
pLI 0.975
Z-score 4.03
OE 0.12 (0.06–0.32)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
1.25Z-score
OE missense 0.84 (0.78–0.91)
434 obs / 513.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.12 (0.06–0.32)
0≤0.351.4
Missense OE0.84 (0.78–0.91)
0≤0.61.4
Synonymous OE1.16
0≤1.21.6
LoF obs/exp: 3 / 24.6Missense obs/exp: 434 / 513.8Syn Z: -1.98
DN
0.2598th %ile
GOF
0.2398th %ile
LOF
0.83top 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.

LOFprediction above median · 1 literature citation · LOEUF 0.32
GOF1 literature citation

Literature Evidence

GOFToxic gain-of-function mutations in ATXN1 cause the neurodegenerative disorder spinocerebellar ataxia type 1 (SCA1).PMID:33478569
LOFHaploinsufficiency of two histone modifier genes on 6p22.3, ATXN1 and JARID2, is associated with intellectual disability.PMID:23294540

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

125 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17
Likely Pathogenic3
VUS55
Likely Benign29
Benign16
Conflicting5
17
Pathogenic
3
Likely Pathogenic
55
VUS
29
Likely Benign
16
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
17
0
17
Likely Pathogenic
0
0
3
0
3
VUS
3
38
13
1
55
Likely Benign
0
19
3
7
29
Benign
1
10
1
4
16
Conflicting
—5
Total4673712125

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ATXN1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients