ATXN10

Chr 22AD

ataxin 10

Also known as: ATX10, E46L, HUMEEP, SCA10

This protein regulates cytokinesis, stimulates protein glycosylation, and induces neuritogenesis by activating the Ras-MAP kinase pathway while supporting cerebellar neuron survival. Expansion of an ATTCT repeat in this gene causes spinocerebellar ataxia 10, an autosomal dominant progressive cerebellar disorder. The gene is highly intolerant to loss-of-function variants (pLI 0.0003, LOEUF 0.697), indicating it is essential for normal cellular function.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismADLOEUF 0.701 OMIM phenotype
Clinical SummaryATXN10
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
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GeneReview available — ATXN10
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.70LOEUF
pLI 0.000
Z-score 2.69
OE 0.41 (0.250.70)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.33Z-score
OE missense 1.06 (0.961.17)
270 obs / 255.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.41 (0.250.70)
00.351.4
Missense OE1.06 (0.961.17)
00.61.4
Synonymous OE1.00
01.21.6
LoF obs/exp: 10 / 24.3Missense obs/exp: 270 / 255.4Syn Z: 0.04
DN
0.6746th %ile
GOF
0.5465th %ile
LOF
0.2484th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOF1 literature citation

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

GOFHeterozygous mutants were overtly normal and did not develop SCA10 phenotype CONCLUSION: A simple gain of function or loss of function of ATXN10 is unlikely to be the major pathogenic mechanism contributing to the spinocerebellar ataxia type 10 phenotype.PMID:16924013

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ATXN10 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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