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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
ATN1
atrophin 1
Chromosome 12 Β· 12p13.31
NCBI Gene: 1822Ensembl: ENSG00000111676.16HGNC: HGNC:3033UniProt: P54259
116PubMed Papers
22Diseases
0Drugs
11Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
nucleusnucleoplasmprotein domain specific bindingneuron apoptotic processcongenital hypotonia, epilepsy, developmental delay, and digital anomaliesdentatorubral-pallidoluysian atrophyDentatorubral pallidoluysian atrophygenetic disorder
✦AI Summary

ATN1 encodes atrophin-1, a transcriptional corepressor that functions as a nuclear protein involved in transcriptional regulation and neurodevelopmental processes 1. The protein acts as a corepressor through recruitment of NR2E1 and interaction with transcriptional machinery to regulate gene expression 1. ATN1 contains a polyglutamine (polyQ) tract encoded by CAG repeats in exon 5, and pathogenic expansions of these repeats cause dentatorubral-pallidoluysian atrophy (DRPLA), a rare autosomal dominant neurodegenerative disorder characterized by cerebellar ataxia, myoclonus, epilepsy, dementia, and psychiatric symptoms 2. Additionally, heterozygous variants in the HX repeat motif of ATN1 cause CHEDDA syndrome (congenital hypotonia, epilepsy, developmental delay, and digital anomalies), a distinct neurodevelopmental condition 3. In DRPLA pathogenesis, expanded polyQ-containing atrophin-1 accumulates diffusely in neuronal nuclei, leading to nuclear dysfunction, protein aggregation, and neuronal loss particularly affecting the globus pallidus and brainstem nuclei 14. Whole genome sequencing shows high sensitivity (97.3%) and specificity (99.6%) for detecting ATN1 repeat expansions clinically 5. Currently, no disease-modifying treatments exist for DRPLA 2.

Sources cited
1
ATN1 encodes atrophin-1, a nuclear transcriptional coregulator; DRPLA caused by CAG repeat expansion resulting in polyQ stretches; mutant atrophin-1 accumulates in neuronal nuclei affecting multiple CNS regions
PMID: 21827919
2
DRPLA characterized by myoclonus, epilepsy, ataxia, dementia; CAG repeat expansion in ATN1 causes neuronal intranuclear inclusions and variable neuronal loss in specific brain regions; no disease-modifying treatments available
PMID: 30410817
3
Heterozygous variants in HX repeat motif of ATN1 cause CHEDDA syndrome with developmental delay, speech delay, and dysmorphic features
PMID: 36251950
4
Expanded polyQ-containing atrophin-1 shows proteolytic processing, nuclear accumulation, and protein aggregation contributing to pathogenesis in DRPLA models
PMID: 10434299
5
Whole genome sequencing for ATN1 repeat expansion detection shows 97.3% sensitivity and 99.6% specificity with high clinical utility
PMID: 35182509
Disease Associationsβ“˜22
congenital hypotonia, epilepsy, developmental delay, and digital anomaliesOpen Targets
0.75Strong
dentatorubral-pallidoluysian atrophyOpen Targets
0.64Moderate
Dentatorubral pallidoluysian atrophyOpen Targets
0.46Moderate
genetic disorderOpen Targets
0.19Weak
Intellectual disabilityOpen Targets
0.12Weak
Hydrocephalus with stenosis of the aqueduct of SylviusOpen Targets
0.12Weak
X-linked hydrocephalus with stenosis of the aqueduct of SylviusOpen Targets
0.12Weak
diabetes mellitusOpen Targets
0.11Weak
type 1 diabetes mellitusOpen Targets
0.11Weak
experimental autoimmune encephalomyelitisOpen Targets
0.09Suggestive
Neck painOpen Targets
0.09Suggestive
Alzheimer diseaseOpen Targets
0.09Suggestive
neuropathyOpen Targets
0.08Suggestive
atherosclerosisOpen Targets
0.08Suggestive
infectionOpen Targets
0.07Suggestive
severe combined immunodeficiencyOpen Targets
0.07Suggestive
chronic obstructive pulmonary diseaseOpen Targets
0.07Suggestive
Huntington diseaseOpen Targets
0.07Suggestive
neoplasmOpen Targets
0.05Suggestive
sialadenitisOpen Targets
0.05Suggestive
Congenital hypotonia, epilepsy, developmental delay, and digital anomaliesUniProt
Dentatorubral-pallidoluysian atrophyUniProt
Pathogenic Variants11
NM_001940.4(ATN1):c.3178C>T (p.His1060Tyr)Likely pathogenic
not provided|Congenital hypotonia, epilepsy, developmental delay, and digital anomalies
β˜…β˜…β˜†β˜†2024β†’ Residue 1060
NM_001940.4(ATN1):c.3182TGCACC[3] (p.1061LH[3])Pathogenic
Congenital hypotonia, epilepsy, developmental delay, and digital anomalies|Dentatorubral-pallidoluysian atrophy|not provided
β˜…β˜…β˜†β˜†2024
NM_001940.4(ATN1):c.3165_3176del (p.Ile1057_His1060del)Pathogenic
Congenital hypotonia, epilepsy, developmental delay, and digital anomalies|not provided
β˜…β˜…β˜†β˜†2023β†’ Residue 1057
NM_001940.4(ATN1):c.3155A>C (p.His1052Pro)Pathogenic
Congenital hypotonia, epilepsy, developmental delay, and digital anomalies|not provided
β˜…β˜…β˜†β˜†2021β†’ Residue 1052
GRCh38/hg38 12p13.31(chr12:6909787-6934028)x1Likely pathogenic
Congenital hypotonia, epilepsy, developmental delay, and digital anomalies
β˜…β˜†β˜†β˜†2024
NM_001940.4(ATN1):c.3182TGCACC[1] (p.1061LH[1])Likely pathogenic
Congenital hypotonia, epilepsy, developmental delay, and digital anomalies|not provided|ATN1-related disorder
β˜…β˜†β˜†β˜†2021
NM_001940.4(ATN1):c.3172C>T (p.His1058Tyr)Pathogenic
Congenital ATN1 related disorder|Congenital hypotonia, epilepsy, developmental delay, and digital anomalies|ATN1-related disorder
β˜…β˜†β˜†β˜†β†’ Residue 1058
NM_001940.4(ATN1):c.3167A>C (p.His1056Pro)Likely pathogenic
Congenital hypotonia, epilepsy, developmental delay, and digital anomalies
β˜†β˜†β˜†β˜†2021β†’ Residue 1056
NM_001940.4(ATN1):c.3185A>G (p.His1062Arg)Pathogenic
Congenital hypotonia, epilepsy, developmental delay, and digital anomalies|Congenital ATN1 related disorder
β˜†β˜†β˜†β˜†2019β†’ Residue 1062
NM_001940.4(ATN1):c.3160C>A (p.His1054Asn)Pathogenic
Congenital ATN1 related disorder|Congenital hypotonia, epilepsy, developmental delay, and digital anomalies
β˜†β˜†β˜†β˜†2019β†’ Residue 1054
NM_001940.4(ATN1):c.3188T>G (p.Leu1063Arg)Pathogenic
Congenital ATN1 related disorder
β˜†β˜†β˜†β˜†2018β†’ Residue 1063
View on ClinVar β†—
Related Genes
ATXN2Protein interaction97%QKIProtein interaction97%NR2E1Protein interaction95%ATXN3Protein interaction91%ATXN7Protein interaction90%HTTProtein interaction89%
Tissue Expression6 tissues
Ovary
100%
Lung
36%
Brain
32%
Heart
24%
Liver
18%
Bone Marrow
6%
Gene Interaction Network
Click a node to explore
ATN1ATXN2QKINR2E1ATXN3ATXN7HTT
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt P54259
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.35Moderately Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.24 [0.16–0.35]
RankingsWhere ATN1 stands among ~20K protein-coding genes
  • #4,073of 20,598
    Most Researched116 Β· top quartile
  • #2,750of 5,498
    Most Pathogenic Variants11
  • #1,555of 17,882
    Most Constrained (LOEUF)0.35 Β· top 10%
Genes detectedATN1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
PMID: 20301664
1.00
2
Whole genome sequencing for the diagnosis of neurological repeat expansion disorders in the UK: a retrospective diagnostic accuracy and prospective clinical validation study.
PMID: 35182509
Lancet Neurol Β· 2022
0.90
3
Dentatorubral-pallidoluysian Atrophy: An Update.
PMID: 30410817
Tremor Other Hyperkinet Mov (N Y) Β· 2018
0.80
4
MAGI2/S-SCAM outside brain.
PMID: 25637633
J Biochem Β· 2015
0.70
5
Dentatorubral-pallidoluysian atrophy.
PMID: 21827919
Handb Clin Neurol Β· 2012
0.60