Menu
GeneBe

ATXN2

ataxin 2

Basic information

Region (hg38): 12:111443484-111599676

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

Links

ENSG00000204842NCBI:6311OMIM:601517HGNC:10555Uniprot:Q99700AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

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

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Spinocerebellar ataxia 2ADGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingNeurologic8896557; 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
clinvar
5
clinvar
1
clinvar
8
missense
53
clinvar
3
clinvar
2
clinvar
58
nonsense
0
start loss
0
frameshift
0
inframe indel
3
clinvar
3
clinvar
6
splice donor/acceptor (+/-2bp)
0
splice region
0
non coding
1
clinvar
1
clinvar
15
clinvar
3
clinvar
10
clinvar
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)2570848
12-111446485-G-C Benign (Jan 10, 2019)1246850
12-111446611-T-C Benign (Jan 10, 2019)1281022
12-111446743-G-C not specified Likely benign (Dec 22, 2022)2443260
12-111446775-C-G Inborn genetic diseases Uncertain significance (Mar 14, 2023)2462938
12-111446790-T-C not specified Conflicting classifications of pathogenicity (Jan 27, 2022)1336175
12-111446801-C-T not specified Uncertain significance (Aug 24, 2022)2443261
12-111446804-T-C Primary familial polycythemia due to EPO receptor mutation;Primary myelofibrosis;Thrombocythemia 1 Benign (Nov 30, 2023)1265448
12-111446814-G-A not specified Uncertain significance (May 04, 2022)1685101
12-111446815-G-A not specified Benign (Oct 17, 2018)733920
12-111447011-C-T SH2B3-related condition Uncertain significance (Sep 11, 2023)2634485
12-111447014-TCGGAGTGCACA-T Uncertain significance (May 04, 2017)501688
12-111447026-G-C Inborn genetic diseases Uncertain significance (Oct 06, 2022)2369926
12-111447138-G-A Inborn genetic diseases Uncertain significance (Feb 27, 2023)2456290
12-111447315-CATCTT-C SH2B3-related condition Likely benign (Jan 24, 2024)3045593
12-111447330-G-A Inborn genetic diseases Uncertain significance (Dec 20, 2022)2369292
12-111447339-C-T SH2B3-related condition • not specified Likely benign (Jun 23, 2021)732661
12-111447360-C-T Inborn genetic diseases Uncertain significance (Oct 03, 2022)2315035
12-111447372-C-T Inborn genetic diseases Uncertain significance (Oct 29, 2021)2377564
12-111447395-C-T Multiple myeloma Likely pathogenic (Aug 31, 2019)800348
12-111447445-G-A Likely benign (Apr 06, 2023)2920899
12-111447491-G-A Primary familial polycythemia due to EPO receptor mutation • Thrombocythemia 1 Pathogenic/Likely pathogenic (Jan 10, 2024)619973
12-111447506-G-A Primary myelofibrosis;Thrombocythemia 1;Primary familial polycythemia due to EPO receptor mutation Uncertain significance (Oct 31, 2018)501686
12-111447535-GA-G Hereditary cancer-predisposing syndrome Pathogenic (Oct 19, 2020)1805838
12-111447546-TATGGG-T SH2B3-related condition Likely benign (Feb 09, 2024)3054073

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
ATXN2protein_codingprotein_codingENST00000377617 25147463
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.8530.1471256980501257480.000199
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense2.354666320.7370.00003448428
Missense in Polyphen173288.340.599993409
Synonymous0.6752252380.9440.00001502678
Loss of Function5.481154.80.2010.00000267687

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0004180.000418
Ashkenazi Jewish0.001800.00179
East Asian0.00005800.0000544
Finnish0.00005100.0000462
European (Non-Finnish)0.0001430.000141
Middle Eastern0.00005800.0000544
South Asian0.00003270.0000327
Other0.0003360.000326

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

AllRecessiveDominant
MendelianHighHighHigh
Primary ImmunodeficiencyHighHighHigh
CancerHighHighHigh

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