ATXN1
Basic information
Region (hg38): 6:16299111-16761491
Previous symbols: [ "SCA1" ]
Links
Phenotypes
GenCC
Source:
- spinocerebellar ataxia type 1 (Moderate), mode of inheritance: AD
- spinocerebellar ataxia type 1 (Supportive), mode of inheritance: AD
- spinocerebellar ataxia type 1 (Strong), mode of inheritance: AD
Clinical Genomic Database
Source:
Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
---|---|---|---|---|---|
Spinocerebellar ataxia 1 | AD | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Neurologic | 8275090; 8358429; 7951322; 8198139; 8037204; 8615077; 10424816; 11973625; 14967775; 16133185; 15747371; 18262566; 18685131; 20301363 |
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the ATXN1 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
---|---|---|---|---|---|---|
synonymous | 15 | |||||
missense | 45 | 55 | ||||
nonsense | 2 | |||||
start loss | 0 | |||||
frameshift | 1 | |||||
inframe indel | 17 | |||||
splice donor/acceptor (+/-2bp) | 0 | |||||
splice region | 0 | |||||
non coding | 1 | |||||
Total | 0 | 0 | 51 | 24 | 16 |
Variants in ATXN1
This is a list of pathogenic ClinVar variants found in the ATXN1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
Position | Type | Phenotype | Significance | ClinVar |
---|---|---|---|---|
6-16306340-C-T | Inborn genetic diseases • ATXN1-related disorder | Conflicting classifications of pathogenicity (Aug 11, 2022) | ||
6-16306357-A-G | Inborn genetic diseases | Uncertain significance (Oct 04, 2022) | ||
6-16306360-C-A | Inborn genetic diseases | Uncertain significance (Dec 27, 2022) | ||
6-16306438-C-T | Inborn genetic diseases | Uncertain significance (Jul 12, 2022) | ||
6-16306508-A-G | Inborn genetic diseases | Likely benign (Nov 09, 2023) | ||
6-16306520-G-A | not specified | Likely benign (-) | ||
6-16306563-G-A | Likely benign (Jul 01, 2023) | |||
6-16306607-C-T | Inborn genetic diseases | Uncertain significance (Mar 16, 2022) | ||
6-16306625-C-T | Inborn genetic diseases | Uncertain significance (Apr 01, 2024) | ||
6-16306627-G-A | Spinocerebellar ataxia type 1 • not specified | Likely benign (Oct 30, 2017) | ||
6-16306634-C-T | Inborn genetic diseases | Conflicting classifications of pathogenicity (Mar 29, 2022) | ||
6-16306700-CG-C | Uncertain significance (Apr 18, 2022) | |||
6-16306746-T-C | ATXN1-related disorder | Benign (Aug 14, 2019) | ||
6-16306853-C-T | Inborn genetic diseases | Uncertain significance (Nov 07, 2023) | ||
6-16326380-C-A | Benign (Jun 25, 2021) | |||
6-16326440-G-A | ATXN1-related disorder | Likely benign (May 09, 2019) | ||
6-16326468-C-T | Inborn genetic diseases | Uncertain significance (Mar 21, 2023) | ||
6-16326507-C-A | Spinocerebellar ataxia type 1 | Uncertain significance (Aug 13, 2019) | ||
6-16326616-C-T | Benign (Jul 01, 2022) | |||
6-16326617-G-A | Inborn genetic diseases | Uncertain significance (Nov 08, 2022) | ||
6-16326620-G-T | Inborn genetic diseases | Uncertain significance (May 30, 2024) | ||
6-16326633-C-T | Uncertain significance (Jul 01, 2016) | |||
6-16326641-A-G | Inborn genetic diseases | Uncertain significance (Jan 19, 2024) | ||
6-16326660-G-A | Uncertain significance (Aug 07, 2017) | |||
6-16326676-T-C | ATXN1-related disorder | Likely benign (Apr 01, 2022) |
GnomAD
Source:
Gene | Type | Bio Type | Transcript | Coding Exons | Length |
---|---|---|---|---|---|
ATXN1 | protein_coding | protein_coding | ENST00000244769 | 2 | 462380 |
pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
---|---|---|---|---|---|---|
0.975 | 0.0250 | 125674 | 24 | 28 | 125726 | 0.000207 |
Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
---|---|---|---|---|---|---|
Missense | 1.25 | 434 | 514 | 0.845 | 0.0000353 | 5214 |
Missense in Polyphen | 105 | 172.15 | 0.60994 | 1741 | ||
Synonymous | -1.98 | 290 | 250 | 1.16 | 0.0000211 | 1750 |
Loss of Function | 4.03 | 3 | 24.6 | 0.122 | 0.00000117 | 259 |
LoF frequencies by population
Ethnicity | Sum of pLOFs | p |
---|---|---|
African & African-American | 0.00154 | 0.00107 |
Ashkenazi Jewish | 0.000408 | 0.000198 |
East Asian | 0.000681 | 0.000272 |
Finnish | 0.000292 | 0.000231 |
European (Non-Finnish) | 0.000287 | 0.000114 |
Middle Eastern | 0.000681 | 0.000272 |
South Asian | 0.000855 | 0.000392 |
Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Chromatin-binding factor that repress Notch signaling in the absence of Notch intracellular domain by acting as a CBF1 corepressor. Binds to the HEY promoter and might assist, along with NCOR2, RBPJ-mediated repression. Binds RNA in vitro. May be involved in RNA metabolism (PubMed:21475249). In concert with CIC and ATXN1L, involved in brain development (By similarity). {ECO:0000250|UniProtKB:P54254, ECO:0000269|PubMed:21475249}.;
- Disease
- DISEASE: Spinocerebellar ataxia 1 (SCA1) [MIM:164400]: Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to cerebellum degeneration with variable involvement of the brainstem and spinal cord. SCA1 belongs to the autosomal dominant cerebellar ataxias type I (ADCA I) which are characterized by cerebellar ataxia in combination with additional clinical features like optic atrophy, ophthalmoplegia, bulbar and extrapyramidal signs, peripheral neuropathy and dementia. SCA1 is caused by expansion of a CAG repeat in the coding region of ATXN1. Longer expansions result in earlier onset and more severe clinical manifestations of the disease. {ECO:0000269|PubMed:7647801, ECO:0000269|PubMed:7951322, ECO:0000269|PubMed:8634720}. Note=The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by expansion of the polyglutamine tract to about 40-83 repeats, causing accumulation in neurons and exerting toxicity. {ECO:0000269|PubMed:7647801, ECO:0000269|PubMed:8634720}.;
Recessive Scores
- pRec
- 0.429
Intolerance Scores
- loftool
- 0.0948
- rvis_EVS
- -0.52
- rvis_percentile_EVS
- 20.94
Haploinsufficiency Scores
- pHI
- 0.973
- hipred
- Y
- hipred_score
- 0.825
- ghis
- 0.509
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.934
Gene Damage Prediction
All | Recessive | Dominant | |
---|---|---|---|
Mendelian | Medium | Medium | Medium |
Primary Immunodeficiency | Medium | Medium | Medium |
Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Atxn1
- Phenotype
- mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; skeleton phenotype; muscle phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); growth/size/body region phenotype; homeostasis/metabolism phenotype;
Gene ontology
- Biological process
- negative regulation of transcription by RNA polymerase II;RNA processing;brain development;learning;memory;social behavior;negative regulation of transcription, DNA-templated;lung alveolus development;nuclear export
- Cellular component
- nucleus;nucleoplasm;nucleolus;cytoplasm;cytosol;nuclear matrix;nuclear inclusion body
- Molecular function
- DNA binding;protein binding;protein C-terminus binding;poly(U) RNA binding;poly(G) binding;identical protein binding;protein self-association