ATN1

Chr 12AD

atrophin 1

Also known as: B37, CHEDDA, D12S755E, DRPLA, HRS, NOD

NCBI Gene: 1822ENSG00000111676UniProt: P54259OMIM: 607462

Dentatorubral pallidoluysian atrophy (DRPLA) is a rare neurodegenerative disorder characterized by cerebellar ataxia, myoclonic epilepsy, choreoathetosis, and dementia. The disorder is related to the expansion from 7-35 copies to 49-93 copies of a trinucleotide repeat (CAG/CAA) within this gene. The encoded protein includes a serine repeat and a region of alternating acidic and basic amino acids, as well as the variable glutamine repeat. Alternative splicing results in two transcripts variants that encode the same protein. [provided by RefSeq, Jul 2016]

GeneReviewsOMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Congenital hypotonia, epilepsy, developmental delay, and digital anomaliesMIM #618494
AD
Dentatorubral-pallidoluysian atrophyMIM #125370
AD

Clinical highlights

Gene-disease validity (ClinGen)
dentatorubral-pallidoluysian atrophy · ADDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.
3
Active trials
22
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.19
LOEUF· LoF intol.
Multiple*
Mechanism· predicted
📖
GeneReview available — ATN1
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?
0.19LOEUF
pLI 1.000
Z-score 5.42
OE 0.07 (0.03–0.19)
Highly constrained

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

Missense Constraint?
1.76Z-score
OE missense 0.81 (0.76–0.87)
567 obs / 698.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.07 (0.03–0.19)
0≤0.351.4
Missense OE?0.81 (0.76–0.87)
0≤0.61.4
Synonymous OE?0.91
0≤1.21.6
LoF obs/exp: 3 / 40.0Missense obs/exp: 567 / 698.0Syn Z: 1.25

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

ATN1 · protein map & ClinVar variants

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

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients