ATXN7

Chr 3AD

ataxin 7

ENSG00000163635 UniProt: O15265 OMIM: 607640

The protein acts as a component of the SAGA transcription coactivator complex, mediating gene activation and microtubule cytoskeleton stabilization. Mutations cause spinocerebellar ataxia 7 (SCA7), an autosomal dominant progressive cerebellar ataxia that uniquely includes retinal degeneration among the spinocerebellar ataxias. The gene is highly constrained against loss-of-function variants, and the disorder involves CAG repeat expansion with anticipation across generations.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Acts as a component of the SAGA (aka STAGA) transcription coactivator-HAT complex (PubMed:15932940, PubMed:18206972). Mediates the interaction of SAGA complex with the CRX and is involved in CRX-dependent gene activation (PubMed:15932940, PubMed:18206972). Probably involved in tethering the deubiquitination module within the SAGA complex (PubMed:24493646). Necessary for microtubule cytoskeleton stabilization (PubMed:22100762). Involved in neurodegeneration (PubMed:9288099)

OMIM ResearchGenerating clinical summary…

DNmechanismADLOEUF 0.331 OMIM phenotype

Clinical Summary— ATXN7

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.96). One damaged copy is likely sufficient to cause disease.

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Clinical Trials

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

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Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.33LOEUF

pLI 0.960

Z-score 4.43

OE 0.16 (0.08–0.33)

Highly constrained

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

Missense Constraint?

-0.62Z-score

OE missense 1.08 (1.00–1.16)

544 obs / 504.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.16 (0.08–0.33)

0≤0.351.4

Missense OE?1.08 (1.00–1.16)

0≤0.61.4

Synonymous OE?1.07

0≤1.21.6

LoF obs/exp: 5 / 32.1Missense obs/exp: 544 / 504.6Syn Z: -0.84

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveATXN7-related spinocerebellar ataxiaDNAD

This gene — mechanism propensity

0.2897th %ile

GOF

0.2198th %ile

LOF

0.88top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.33

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.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.