ATXN8OS

Chr 13ADMulti

ATXN8 opposite strand lncRNA

Also known as: KLHL1AS, NCRNA00003, SCA8

NCBI Gene: 6315 ENSG00000230223 UniProt: P0DMR3 OMIM: 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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM

This gene is an antisense transcript to the KLHL1 gene (homolog to the Drosophila KELCH gene); it does not itself appear to be protein coding. A TAC/TGC trinucleotide repeat expansion that is incorporated into this gene transcript, but not the KLHL1 transcript, causes spinocerebellar ataxia type 8. Presumably the expansion interferes with normal antisense function of this transcript. [provided by RefSeq, Oct 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

MultiplemechanismAD/Multi2 OMIM phenotypes

Clinical Summary— ATXN8OS

📋

ClinVar Variants

2 unique Pathogenic / Likely Pathogenic· 20 VUS of 44 total submissions

💊

Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

📖

GeneReview available — ATXN8OS

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

This gene — mechanism propensity

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.1

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

References

1.PMID 19680539 ↗

ClinVar Variant Classifications

44 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic2

VUS20

Likely Benign8

Benign12

Likely Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	2	0	2
VUS	20	0	0	20
Likely Benign	0	6	2	8
Benign	0	11	1	12
Total	20	19	3	42

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

View in ClinVar →

59 pathogenic / likely-pathogenic (of 87) ClinVar copy-number / structural variants overlap ATXN8OS — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →