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

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

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 (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	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

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