ATXN1

ataxin 1

Basic information

Region (hg38): 6:16299111-16761491

Previous symbols: [ "SCA1" ]

Links

ENSG00000124788 ∙ NCBI:6310 ∙ OMIM:601556 ∙ HGNC:10548 ∙ Uniprot:P54253 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 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: CGD

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 ClinVar and linked to the ATXN1 gene.

• Inborn genetic diseases (32 variants)
• not provided (20 variants)
• not specified (11 variants)
• Spinocerebellar ataxia type 1 (8 variants)
• Tip-toe gait (2 variants)

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			1	3	3	7
missense			35	3	3	41
nonsense			2			2
start loss						0
frameshift			1			1
inframe indel			2	2	3	7
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					1	1
Total	0	0	41	8	10

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)
6-16306627-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)
6-16326633-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)
6-16326736-G-A			Likely benign (Mar 01, 2022)
6-16326748-C-G		Tip-toe gait	Uncertain significance (Dec 08, 2020)

GnomAD

Source: gnomAD

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: dbNSFP

• 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