ATXN7

Chr 3AD

ataxin 7

Also known as: ADCAII, OPCA3, SCA7, SGF73

NCBI Gene: 6314 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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

The autosomal dominant cerebellar ataxias (ADCA) are a heterogeneous group of neurodegenerative disorders characterized by progressive degeneration of the cerebellum, brain stem and spinal cord. Clinically, ADCA has been divided into three groups: ADCA types I-III. ADCAI is genetically heterogeneous, with five genetic loci, designated spinocerebellar ataxia (SCA) 1, 2, 3, 4 and 6, being assigned to five different chromosomes. ADCAII, which always presents with retinal degeneration (SCA7), and ADCAIII often referred to as the 'pure' cerebellar syndrome (SCA5), are most likely homogeneous disorders. Several SCA genes have been cloned and shown to contain CAG repeats in their coding regions. ADCA is caused by the expansion of the CAG repeats, producing an elongated polyglutamine tract in the corresponding protein. The expanded repeats are variable in size and unstable, usually increasing in size when transmitted to successive generations. This locus has been mapped to chromosome 3, and it has been determined that the diseased allele associated with spinocerebellar ataxia-7 contains 37-306 CAG repeats (near the N-terminus), compared to 4-35 in the normal allele. The encoded protein is a component of the SPT3/TAF9/GCN5 acetyltransferase (STAGA) and TBP-free TAF-containing (TFTC) chromatin remodeling complexes, and it thus plays a role in transcriptional regulation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2016]

GeneReviews 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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ClinVar Variants

4 unique Pathogenic / Likely Pathogenic· 193 VUS of 252 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 — ATXN7

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

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.

ClinVar Variant Classifications

252 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

Likely Pathogenic2

VUS193

Likely Benign22

Benign11

Conflicting4

Pathogenic

Likely Pathogenic

193

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	1	1	0	2
Likely Pathogenic	1	1	0	0	2
VUS	2	187	3	1	193
Likely Benign	0	13	3	6	22
Benign	0	5	4	2	11
Conflicting	—				4
Total	3	207	11	9	234

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

View in ClinVar →

10 pathogenic / likely-pathogenic (of 17) ClinVar copy-number / structural variants overlap ATXN7 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →