ATXN10

Chr 22AD

ataxin 10

Also known as: ATX10, E46L, HUMEEP, SCA10

NCBI Gene: 25814 ENSG00000130638 UniProt: Q9UBB4 OMIM: 611150

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a protein that may function in neuron survival, neuron differentiation, and neuritogenesis. These roles may be carried out via activation of the mitogen-activated protein kinase cascade. Expansion of an ATTCT repeat from 9-32 copies to 800-4500 copies in an intronic region of this locus has been associated with spinocerebellar ataxia, type 10. Alternatively spliced transcript variants have been described.[provided by RefSeq, Jul 2016]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Spinocerebellar ataxia 10MIM #603516

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Spinocerebellar ataxia 10; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.70

LOEUF

Multiple*

Mechanism· predicted

📖

GeneReview available — ATXN10

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.70LOEUF

pLI 0.000

Z-score 2.69

OE 0.41 (0.25–0.70)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.33Z-score

OE missense 1.06 (0.96–1.17)

270 obs / 255.4 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.41 (0.25–0.70)

0≤0.351.4

Missense OE?1.06 (0.96–1.17)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 10 / 24.3Missense obs/exp: 270 / 255.4Syn Z: 0.04

Background carrier burden — how many people carry a rare variant somewhere in ATXN10?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 83

697 rare PASS variants

Rare truncating (LoF)

1 in 1,600

113 rare PASS variants

Rare synonymous (reference)

1 in 200

282 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ATXN10. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 110	1 in 2,100
South Asian	~43k	1 in 100	1 in 1,100
Remaining (unassigned)	~30k	1 in 77	1 in 1,900
European (Finnish)	~27k	1 in 290	1 in 2,600
Admixed American	~22k	1 in 85	1 in 2,800
African / African American	~21k	1 in 60	1 in 700
East Asian	~20k	1 in 67	1 in 470
Ashkenazi Jewish	~13k	1 in 360	1 in 1,300
Middle Eastern	~2,884	1 in 84	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 12 coding exons well covered in gnomAD exomes and genomes.? see exons ↓