ATXN7L3

Chr 17

ataxin 7 like 3

Also known as: HATONS, SGF11

NCBI Gene: 56970 ENSG00000087152 UniProt: Q14CW9

The ATXN7L3 protein is a component of the SAGA transcriptional regulatory complex that enables histone deubiquitination and chromatin remodeling to activate gene transcription. Mutations cause autosomal recessive cone-rod dystrophy, a progressive retinal degeneration affecting both cone and rod photoreceptors. This gene is highly constrained against loss-of-function variants in the general population.

ResearchSummary from RefSeq, UniProt

Enables transcription coactivator activity. Involved in positive regulation of DNA-templated transcription and regulation of transcription by RNA polymerase II. Located in nucleus. Part of DUBm complex and SAGA complex. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.20

Clinical Summary— ATXN7L3

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

2 unique Pathogenic / Likely Pathogenic· 42 VUS of 60 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.20LOEUF

pLI 0.999

Z-score 4.37

OE 0.04 (0.01–0.20)

Highly constrained

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

Missense Constraint?

2.05Z-score

OE missense 0.61 (0.53–0.70)

134 obs / 219.5 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.04 (0.01–0.20)

0≤0.351.4

Missense OE?0.61 (0.53–0.70)

0≤0.61.4

Synonymous OE?1.09

0≤1.21.6

LoF obs/exp: 1 / 24.2Missense obs/exp: 134 / 219.5Syn Z: -0.67

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

moderateATXN7L3-related developmental delay, hypotonia and facial dysmorphismLOFAD

This gene — mechanism propensity

0.2898th %ile

GOF

0.1799th %ile

LOF

0.85top 5%

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

LOFprediction above median · LOEUF 0.20

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

60 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

Likely Pathogenic1

VUS42

Likely Benign4

Benign2

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	1	0	1
Likely Pathogenic	0	1	0	0	1
VUS	6	25	11	0	42
Likely Benign	0	1	1	2	4
Benign	0	0	2	0	2
Total	6	27	15	2	50

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

View in ClinVar →

9 pathogenic / likely-pathogenic (of 11) ClinVar copy-number / structural variants overlap ATXN7L3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →