ATXN2

ataxin 2

Basic information

Region (hg38): 12:111443484-111599676

Previous symbols: [ "SCA2", "TNRC13" ]

Links

ENSG00000204842 ∙ NCBI:6311 ∙ OMIM:601517 ∙ HGNC:10555 ∙ Uniprot:Q99700 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• spinocerebellar ataxia type 2 (Definitive), mode of inheritance: AD
• spinocerebellar ataxia type 2 (Supportive), mode of inheritance: AD
• spinocerebellar ataxia type 2 (Strong), mode of inheritance: AD
• spinocerebellar ataxia type 2 (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spinocerebellar ataxia 2	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	8896557; 8896555; 8896556; 10735276; 9779806; 10993999; 11761482; 12210804; 12451209; 12671950; 15254952; 14732617; 15747371; 17568014; 17923635; 19676102; 20301452; 21610160; 21562247; 21880993; 21934711
In some individuals, the phenotype may include L-dopa responsive parkinsonism; Homozygosity/compound heterozygosity has been reported

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ATXN2 gene.

• Inborn genetic diseases (57 variants)
• not provided (35 variants)
• not specified (11 variants)
• Spinocerebellar ataxia type 2 (5 variants)
• Amyotrophic lateral sclerosis (2 variants)
• SH2B3-related condition (2 variants)
• Primary myelofibrosis;Thrombocythemia 1;Primary familial polycythemia due to EPO receptor mutation (1 variants)
• Hereditary cancer (1 variants)
• Thrombocythemia 1;Primary familial polycythemia due to EPO receptor mutation;Primary myelofibrosis (1 variants)
• Hereditary cancer-predisposing syndrome (1 variants)
• Thrombocythemia 1 (1 variants)
• Primary familial polycythemia due to EPO receptor mutation (1 variants)
• GM3 synthase deficiency (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ATXN2 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			2	5	1	8
missense			53	3	2	58
nonsense						0
start loss						0
frameshift						0
inframe indel				3	3	6
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding	1	1	15	3	10	30
Total	1	1	70	14	16

Variants in ATXN2

This is a list of pathogenic ClinVar variants found in the ATXN2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
12-111444796-G-A			Benign (May 01, 2023)
12-111446485-G-C			Benign (Jan 10, 2019)
12-111446611-T-C			Benign (Jan 10, 2019)
12-111446743-G-C		not specified	Likely benign (Dec 22, 2022)
12-111446775-C-G		Inborn genetic diseases	Uncertain significance (Mar 14, 2023)
12-111446790-T-C		not specified	Conflicting classifications of pathogenicity (Jan 27, 2022)
12-111446801-C-T		not specified	Uncertain significance (Aug 24, 2022)
12-111446804-T-C		Primary familial polycythemia due to EPO receptor mutation;Primary myelofibrosis;Thrombocythemia 1	Benign (Nov 30, 2023)
12-111446814-G-A		not specified	Uncertain significance (May 04, 2022)
12-111446815-G-A		not specified	Benign (Oct 17, 2018)
12-111446832-A-G		Inborn genetic diseases	Uncertain significance (Sep 22, 2023)
12-111447011-C-T		SH2B3-related disorder	Uncertain significance (Sep 11, 2023)
12-111447014-TCGGAGTGCACA-T			Uncertain significance (May 04, 2017)
12-111447026-G-C		Inborn genetic diseases	Uncertain significance (Oct 06, 2022)
12-111447138-G-A		Inborn genetic diseases	Uncertain significance (Feb 27, 2023)
12-111447315-CATCTT-C		SH2B3-related disorder	Likely benign (Jan 24, 2024)
12-111447330-G-A		Inborn genetic diseases	Uncertain significance (Dec 20, 2022)
12-111447339-C-T		not specified • SH2B3-related disorder	Benign/Likely benign (Apr 01, 2024)
12-111447360-C-T		Inborn genetic diseases	Uncertain significance (Oct 03, 2022)
12-111447372-C-T		Inborn genetic diseases	Uncertain significance (Oct 29, 2021)
12-111447395-C-T		Multiple myeloma	Likely pathogenic (Aug 31, 2019)
12-111447445-G-A			Likely benign (Apr 06, 2023)
12-111447462-C-A		Inborn genetic diseases	Uncertain significance (Oct 25, 2023)
12-111447491-G-A		Primary familial polycythemia due to EPO receptor mutation • Thrombocythemia 1	Pathogenic/Likely pathogenic (Jan 10, 2024)
12-111447506-G-A		Primary myelofibrosis;Thrombocythemia 1;Primary familial polycythemia due to EPO receptor mutation	Uncertain significance (Oct 31, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ATXN2	protein_coding	protein_coding	ENST00000377617	25	147463

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.853	0.147	125698	0	50	125748	0.000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.35	466	632	0.737	0.0000344	8428
Missense in Polyphen		173	288.34	0.59999		3409
Synonymous	0.675	225	238	0.944	0.0000150	2678
Loss of Function	5.48	11	54.8	0.201	0.00000267	687

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000418	0.000418
Ashkenazi Jewish	0.00180	0.00179
East Asian	0.0000580	0.0000544
Finnish	0.0000510	0.0000462
European (Non-Finnish)	0.000143	0.000141
Middle Eastern	0.0000580	0.0000544
South Asian	0.0000327	0.0000327
Other	0.000336	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in EGFR trafficking, acting as negative regulator of endocytic EGFR internalization at the plasma membrane. {ECO:0000269|PubMed:18602463}.
• Disease: DISEASE: Spinocerebellar ataxia 2 (SCA2) [MIM:183090]: 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. SCA2 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. SCA2 is characterized by hyporeflexia, myoclonus and action tremor and dopamine-responsive parkinsonism. In some patients, SCA2 presents as pure familial parkinsonism without cerebellar signs. {ECO:0000269|PubMed:8896555, ECO:0000269|PubMed:8896556, ECO:0000269|PubMed:8896557}. Note=The disease is caused by mutations affecting the gene represented in this entry. SCA2 is caused by expansion of a CAG repeat resulting in about 36 to 52 repeats in some patients. Longer expansions result in earlier the expansion, onset of the disease.; DISEASE: Amyotrophic lateral sclerosis 13 (ALS13) [MIM:183090]: A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5- 10% of the cases. {ECO:0000269|PubMed:20740007}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. An increased risk for developing amyotrophic lateral sclerosis seems to be conferred by CAG repeat intermediate expansions greater than 23 but below the threshold for developing spinocerebellar ataxia.
• Pathway: Parkinsons Disease Pathway;EGF-EGFR Signaling Pathway;EGFR1 (Consensus)

Recessive Scores

• pRec: 0.250

Intolerance Scores

• loftool: 0.374
• rvis_EVS: -1
• rvis_percentile_EVS: 8.54

Haploinsufficiency Scores

• pHI: 0.901
• hipred: Y
• hipred_score: 0.825
• ghis: 0.601

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.572

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Atxn2
• Phenotype: adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; growth/size/body region phenotype; homeostasis/metabolism phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system 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); reproductive system 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)

Gene ontology

• Biological process: negative regulation of receptor internalization;regulation of translation;regulation of cytoplasmic mRNA processing body assembly;RNA metabolic process;cytoplasmic mRNA processing body assembly;stress granule assembly;RNA transport
• Cellular component: cytoplasm;Golgi apparatus;trans-Golgi network;cytosol;polysome;cytoplasmic stress granule;membrane;perinuclear region of cytoplasm;ribonucleoprotein complex
• Molecular function: RNA binding;epidermal growth factor receptor binding;protein binding;protein C-terminus binding