Human Gene ATN1 (uc001qrx.1) Description and Page Index
  Description: Homo sapiens atrophin 1 (ATN1), transcript variant 2, mRNA.
RefSeq Summary (NM_001940): 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].
Transcript (Including UTRs)
   Position: hg19 chr12:7,037,480-7,053,815 Size: 16,336 Total Exon Count: 10 Strand: +
Coding Region
   Position: hg19 chr12:7,043,165-7,050,943 Size: 7,779 Coding Exon Count: 9 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesGeneReviewsModel Information
Data last updated: 2013-06-15

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr12:7,037,480-7,053,815)mRNA (may differ from genome)Protein (1190 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
neXtProtOMIMPubMedReactomeStanford SOURCETreefam

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=Atrophin-1; AltName: Full=Dentatorubral-pallidoluysian atrophy protein;
FUNCTION: Transcriptional corepressor. Recruits NR2E1 to repress transcription. Promotes vascular smooth cell (VSMC) migration and orientation (By similarity). Corepressor of MTG8 transcriptional repression. Has some intrinsic repression activity which is independent of the number of poly-Asn (polyQ) repeats.
SUBUNIT: Interacts with NR2E1; the interaction represses the transcriptional activity of NR2E1. Interacts (via its N-terminus) with FAT1 (via a C-terminus domain) (By similarity). Interacts with BAIAP2, WWP1, WWP2, WWP3 and RERE. Interacts (via its N- terminus) with MTG8; the interaction enhances transcriptional repression of MTG8.
INTERACTION: Q12805:EFEMP1; NbExp=3; IntAct=EBI-945980, EBI-536772; O95967:EFEMP2; NbExp=3; IntAct=EBI-945980, EBI-743414; Q9HAU0:PLEKHA5; NbExp=2; IntAct=EBI-945980, EBI-945934; P61289:PSME3; NbExp=3; IntAct=EBI-945980, EBI-355546; Q9NWB1:RBFOX1; NbExp=2; IntAct=EBI-945980, EBI-945906; Q9P2R6:RERE; NbExp=3; IntAct=EBI-945980, EBI-948076; Q15654:TRIP6; NbExp=2; IntAct=EBI-945980, EBI-742327;
SUBCELLULAR LOCATION: Nucleus. Cytoplasm, perinuclear region. Cell junction (By similarity). Note=Shuttles between nucleus and cytoplasm. Colocalizes with FAT1 in the perinuclear area, at cell- cell junctions and leading edges of cells (By similarity). Colocalizes with MTG8 in discrete nuclear dots. Proteolytic fragment F1 appears to remain in nucleus. Fragment F2 is exported into the cytoplasm. Fragment F2 from mutant sequences with longer poly-Asn (polyQ) tracts are additionally located to the cytoplasmic membrane and to certain organelles.
TISSUE SPECIFICITY: Widely expressed in various tissues including heart, lung, kidney, ovary, testis, prostate, placenta, skeletal Low levels in the liver, thymus and leukocytes. In the adult brain, broadly expressed in amygdala, caudate nucleus, corpus callosum, hippocampus, hypothalamus, substantia nigra, subthalamic nucleus, and thalamus. High levels in fetal tissues, especially brain.
PTM: Phosphorylated in vitro by MAPK8/JNK1 on Ser-739. Mutant ATN1 sequences with expanded poly-Asn (polyQ) traits are more slowly phosphorylated.
PTM: Proteolytically cleaved, probably in the nucleus, to produce two C-terminal fragments of 140 kDa (F1) and 125 kDa (F2) each containing poly-Asn (polyQ) tracts. F2 is produced by cleavage by caspases and is exported into the cytoplasm. In vitro, cleavage increases with an increase in the number of polyQ tracts. C- terminal proteolytic products appear to be the cause of cell toxicity. In vitro cleavage at Asp-109.
POLYMORPHISM: The poly-Gln region of ATN1 is highly polymorphic (7 to 23 repeats) in the normal population and is expanded to about 49-75 repeats in DRPLA and HRS patients. Longer expansions result in earlier onset and more severe clinical manifestations of the disease.
DISEASE: Defects in ATN1 are the cause of dentatorubral- pallidoluysian atrophy (DRPLA) [MIM:125370]. DRPLA is an autosomal dominant neurodegenerative disorder characterized by a loss of neurons in the dentate nucleus, rubrum, glogus pallidus and Luys'body. Clinical features are myoclonus epilepsy, dementia, and cerebellar ataxia. Onset of the disease occurs usually in the second decade of life and death in the fourth.
SEQUENCE CAUTION: Sequence=BAA07534.1; Type=Frameshift; Positions=961, 970, 977, 980, 983, 1005;
WEB RESOURCE: Name=GeneReviews; URL="";

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): ATN1
CDC HuGE Published Literature: ATN1
Positive Disease Associations: myotonic dystrophy type 1 , schizophrenia
Related Studies:
  1. myotonic dystrophy type 1
    Savic, D. et al. 2001, Is the 31 CAG repeat allele of the spinocerebellar ataxia 1 (SCA1) gene locus non-specifically associated with trinucleotide expansion diseases?, Psychiatric genetics. 2001 Dec;11(4):201-5. [PubMed 11807410]
    Allele frequency distributions for all tested loci were similar in these three groups with the exception of the SCA1 locus. In DM1 patients, the SCA1 allele with 31 CAG repeats account for 40.4% of all chromosomes tested, which is significantly higher than in two other groups (11.3% in healthy controls and 6.6% in the group of non-triplet diseased patients; P < 0.001, Fisher's exact test). This is consistent with our previous findings in HD patients. The absence of this association in non-triplet diseases as well as in healthy controls could indicate a possible role of this SCA1 allele with 31 repeats in triplet diseases. Here we discuss a possible role of the SCA1 region in pathological trinucleotide repeat expansions.
  2. schizophrenia
    Morris-Rosendahl DJ et al. 1997, Analysis of the CAG repeats in the SCA1 and B37 genes in schizophrenic and bipolar I disorder patients: tentative association between B37 and schizophrenia., American journal of medical genetics. 1997 May;74(3):324-30. [PubMed 9184318]

-  MalaCards Disease Associations
  MalaCards Gene Search: ATN1
Diseases sorted by gene-association score: dentatorubro-pallidoluysian atrophy* (1389), spinocerebellar ataxia 1 (17), spinocerebellar ataxia 17 (15), cerebellar ataxia (11), early myoclonic encephalopathy (11), autosomal dominant cerebellar ataxia (11), machado-joseph disease (7), spinocerebellar ataxia 12 (6), hereditary ataxia (6), progressive relapsing multiple sclerosis (5), huntington disease (4), leukoencephalopathy with vanishing white matter (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 203.84 RPKM in Ovary
Total median expression: 4502.25 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
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-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -85.60230-0.372 Picture PostScript Text
3' UTR -1156.262872-0.403 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR017993 - Atrophin-1
IPR002951 - Atrophin-like

Pfam Domains:
PF03154 - Atrophin-1 family

ModBase Predicted Comparative 3D Structure on P54259
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
Gene SorterGene Sorter    
 Protein Sequence    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0003714 transcription corepressor activity
GO:0005515 protein binding
GO:0019904 protein domain specific binding

Biological Process:
GO:0000122 negative regulation of transcription from RNA polymerase II promoter
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0007417 central nervous system development
GO:0051402 neuron apoptotic process

Cellular Component:
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0016363 nuclear matrix
GO:0030054 cell junction
GO:0048471 perinuclear region of cytoplasm

-  Descriptions from all associated GenBank mRNAs
  BC051795 - Homo sapiens atrophin 1, mRNA (cDNA clone MGC:57647 IMAGE:4181592), complete cds.
D31840 - Homo sapiens DRPLA mRNA, complete cds.
JD125055 - Sequence 106079 from Patent EP1572962.
D38529 - Homo sapiens mRNA for DRPLA protein, complete cds.
JD560143 - Sequence 541167 from Patent EP1572962.
U23851 - Human atrophin-1 mRNA, complete cds.
JD357640 - Sequence 338664 from Patent EP1572962.
JD287941 - Sequence 268965 from Patent EP1572962.
JD200210 - Sequence 181234 from Patent EP1572962.
EU446506 - Synthetic construct Homo sapiens clone IMAGE:100070339; IMAGE:100011715; FLH258371.01L atrophin 1 (ATN1) gene, encodes complete protein.
AB209345 - Homo sapiens mRNA for atrophin-1 variant protein.
Z22814 - H.sapiens ORF, complete CDS.
L10377 - Human (clone CTG-B37) mRNA sequence.
JD478915 - Sequence 459939 from Patent EP1572962.
JD403225 - Sequence 384249 from Patent EP1572962.
JD230495 - Sequence 211519 from Patent EP1572962.
JD457840 - Sequence 438864 from Patent EP1572962.
JD102772 - Sequence 83796 from Patent EP1572962.
JD283474 - Sequence 264498 from Patent EP1572962.
JD290143 - Sequence 271167 from Patent EP1572962.
JD122723 - Sequence 103747 from Patent EP1572962.
JD376507 - Sequence 357531 from Patent EP1572962.
AK310266 - Homo sapiens cDNA, FLJ17308.
M17910 - Human U7 small nuclear RNA (snRNP).
JA532848 - Sequence 1 from Patent WO2011113889.
DQ578235 - Homo sapiens piRNA piR-46347, complete sequence.
AK311912 - Homo sapiens cDNA, FLJ92178.
BC009925 - Homo sapiens chromosome 12 open reading frame 57, mRNA (cDNA clone MGC:4750 IMAGE:3537206), complete cds.
KJ895251 - Synthetic construct Homo sapiens clone ccsbBroadEn_04645 C12orf57 gene, encodes complete protein.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein P54259 (Reactome details) participates in the following event(s):

R-HSA-6807077 NR2E1 associated with transcription repressors binds PTEN promoter
R-HSA-8943724 Regulation of PTEN gene transcription
R-HSA-6807070 PTEN Regulation
R-HSA-1257604 PIP3 activates AKT signaling
R-HSA-9006925 Intracellular signaling by second messengers
R-HSA-162582 Signal Transduction

-  Other Names for This Gene
  Alternate Gene Symbols: ATN1_HUMAN, D12S755E, DRPLA, NM_001940, NP_001931, P54259, Q99495, Q99621, Q9UEK7
UCSC ID: uc001qrx.1
RefSeq Accession: NM_001940
Protein: P54259 (aka ATN1_HUMAN)
CCDS: CCDS31734.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene ATN1:
ataxias (Hereditary Ataxia Overview)
drpla (DRPLA)
dystonia-ov (Hereditary Dystonia Overview)

-  Gene Model Information
category: coding nonsense-mediated-decay: no RNA accession: NM_001940.3
exon count: 10CDS single in 3' UTR: no RNA size: 4360
ORF size: 3573CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 6150.00frame shift in genome: no % Coverage: 99.63
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: yes # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.