Menu
GeneBe

ATXN2

ataxin 2

Basic information

Region (hg38): 12:111443484-111599676

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

Links

ENSG00000204842NCBI:6311OMIM:601517HGNC:10555Uniprot:Q99700AlphaFoldGenCCjaxSfariGnomADPubmed

Phenotypes

GenCC

Source: genCC

  • spinocerebellar ataxia type 2 (Definitive), mode of inheritance: AD
  • spinocerebellar ataxia type 2 (Supportive), 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 (40 variants)
  • not specified (22 variants)
  • not provided (17 variants)
  • Spinocerebellar ataxia type 2 (13 variants)
  • Amyotrophic lateral sclerosis (2 variants)
  • Tip-toe gait (1 variants)
  • Thrombocythemia 1;Primary familial polycythemia due to EPO receptor mutation;Primary myelofibrosis (1 variants)
  • Hereditary cancer-predisposing syndrome (1 variants)
  • Multiple myeloma (1 variants)
  • Thrombocythemia 1 (1 variants)
  • Primary familial polycythemia due to EPO receptor mutation (1 variants)
  • GM3 synthase deficiency (1 variants)
  • Primary familial polycythemia due to EPO receptor mutation;Primary myelofibrosis;Thrombocythemia 1 (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.

Variant type Pathogenic Likely pathogenic VUS Likely benign Benign Sum
synonymous 2 3 5
missense 1 40 3 2 46
nonsense 0
start loss 0
frameshift 1 1 2
inframe indel 0
splice variant 1 1
non coding 2 1 11 7 11 32
Total 2 2 55 13 14

Highest pathogenic variant AF is 0.000222

Variants in ATXN2

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

Position Type Phenotype Significance ClinVar
12-111444796-G-A Benign (May 01, 2023)link
12-111446485-G-C Benign (Jan 10, 2019)link
12-111446611-T-C Benign (Jan 10, 2019)link
12-111446743-G-C not specified Likely benign (Dec 22, 2022)link
12-111446775-C-G Inborn genetic diseases Uncertain significance (Mar 14, 2023)link
12-111446790-T-C not specified Benign (Apr 06, 2021)link
12-111446801-C-T not specified Uncertain significance (Aug 24, 2022)link
12-111446804-T-C Thrombocythemia 1;Primary familial polycythemia due to EPO receptor mutation;Primary myelofibrosis Benign (May 16, 2022)link
12-111446814-G-A not specified Uncertain significance (May 04, 2022)link
12-111446815-G-A not specified Benign (Oct 17, 2018)link
12-111447014-TCGGAGTGCACA-T Uncertain significance (May 04, 2017)link
12-111447026-G-C Inborn genetic diseases Uncertain significance (Oct 06, 2022)link
12-111447138-G-A Inborn genetic diseases Uncertain significance (Feb 27, 2023)link
12-111447330-G-A Inborn genetic diseases Uncertain significance (Dec 20, 2022)link
12-111447339-C-T not specified Likely benign (Jun 23, 2021)link
12-111447360-C-T Inborn genetic diseases Uncertain significance (Oct 03, 2022)link
12-111447372-C-T Inborn genetic diseases Uncertain significance (Oct 29, 2021)link
12-111447395-C-T Multiple myeloma Likely pathogenic (Aug 31, 2019)link
12-111447491-G-A Thrombocythemia 1 • Primary familial polycythemia due to EPO receptor mutation Pathogenic (Mar 16, 2018)link
12-111447506-G-A Primary familial polycythemia due to EPO receptor mutation;Primary myelofibrosis;Thrombocythemia 1 Uncertain significance (Oct 31, 2018)link
12-111447535-GA-G Hereditary cancer-predisposing syndrome Pathogenic (Oct 19, 2020)link
12-111447547-ATGGGG-A not specified Benign (Feb 06, 2020)link
12-111447547-A-ATGGGG not specified Likely benign (Jul 30, 2021)link
12-111447568-T-G Benign (Jan 10, 2019)link
12-111447746-C-T Inborn genetic diseases Uncertain significance (May 04, 2023)link

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