ATXN8OS

Chr 13ADMulti

ATXN8 opposite strand lncRNA

Also known as: KLHL1AS, NCRNA00003, SCA8

NCBI Gene: 6315ENSG00000230223UniProt: P0DMR3OMIM: 603680

ATXN8OS is a non-protein-coding antisense transcript to the KLHL1 gene that normally regulates gene expression through antisense mechanisms. Trinucleotide repeat expansions in this transcript cause spinocerebellar ataxia type 8, a late-onset progressive cerebellar disorder characterized by gait ataxia, dysarthria, and abnormal eye movements. The condition follows autosomal dominant inheritance with reduced penetrance and anticipation.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM
MultiplemechanismAD/Multi2 OMIM phenotypes
Clinical Summary— ATXN8OS
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ClinVar Variants
61 unique Pathogenic / Likely Pathogenic· 46 VUS of 130 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
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GeneReview available — ATXN8OS
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

DN
0.6841th %ile
GOF
0.6345th %ile
LOF
0.4628th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). The Badonyi & Marsh model scores dominant-negative highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports gain-of-function. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median · 1 literature citation
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Literature Evidence

GOFDaughters et al. (2009) presented evidence that the expanded CTG repeat in the ATXN8OS gene is transcribed into an mRNA with an expanded CUG repeat, conferring a toxic gain of function that plays a role in the SCA8 phenotype.PMID:19680539

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

130 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic59
Likely Pathogenic2
VUS46
Likely Benign9
Benign12
59
Pathogenic
2
Likely Pathogenic
46
VUS
9
Likely Benign
12
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
59
0
59
Likely Pathogenic
0
0
2
0
2
VUS
0
20
26
0
46
Likely Benign
0
0
7
2
9
Benign
0
0
11
1
12
Total0201053128

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

View in ClinVar →

Protein Context — Lollipop Plot

ATXN8OS · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
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