Spinocerebellar ataxia type 2

disease

On this page

Also known as ALS13amyotrophic lateral sclerosis 13ATXN2 autosomal dominant cerebellar ataxia type Iautosomal dominant cerebellar ataxia type I caused by mutation in ATXN2olivopontocerebellar atrophy Holguin typeOPCA2SCA 2SCA2spinocerebellar ataxia 2spinocerebellar ataxia Cuban typespinocerebellar ataxia with slow eye movementsWadia swami syndrome

Summary

Spinocerebellar ataxia type 2 (MONDO:0008458) is a disease caused by ATXN2 (GenCC Definitive), with 1 cohort gene and 15 clinical trials. Top therapeutic interventions include lithium carbonate, riluzole, and troriluzole.

At a glance

Prevalence: 1-9 / 100 000 (Worldwide) [Orphanet-validated]
Causal gene: ATXN2 (GenCC Definitive)
Cohort genes: 1
ClinVar variants: 22
Phenotypes (HPO): 27
Clinical trials: 15

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000	1.5	Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

27 HPO clinical features (Orphanet curated; top 27 by frequency):

HPO ID	Term	Frequency
HP:0002073	Progressive cerebellar ataxia	Very frequent (80-99%)
HP:0045007	Abnormality of the substantia nigra	Very frequent (80-99%)
HP:0000514	Slow saccadic eye movements	Frequent (30-79%)
HP:0000623	Supranuclear ophthalmoplegia	Frequent (30-79%)
HP:0000639	Nystagmus	Frequent (30-79%)
HP:0000726	Dementia	Frequent (30-79%)
HP:0001260	Dysarthria	Frequent (30-79%)
HP:0001265	Hyporeflexia	Frequent (30-79%)
HP:0001290	Generalized hypotonia	Frequent (30-79%)
HP:0001332	Dystonia	Frequent (30-79%)
HP:0002066	Gait ataxia	Frequent (30-79%)
HP:0002072	Chorea	Frequent (30-79%)
HP:0002174	Postural tremor	Frequent (30-79%)
HP:0002380	Fasciculations	Frequent (30-79%)
HP:0003133	Abnormality of the spinocerebellar tracts	Frequent (30-79%)
HP:0003394	Muscle spasm	Frequent (30-79%)
HP:0006955	Olivopontocerebellar hypoplasia	Frequent (30-79%)
HP:0008311	Spinal cord posterior columns myelin loss	Frequent (30-79%)
HP:0012082	Cerebellar Purkinje layer atrophy	Frequent (30-79%)
HP:0025461	Abnormal cell morphology	Frequent (30-79%)
HP:0030186	Kinetic tremor	Frequent (30-79%)
HP:0000597	Ophthalmoparesis	Occasional (5-29%)
HP:0001300	Parkinsonism	Occasional (5-29%)
HP:0002120	Cerebral cortical atrophy	Occasional (5-29%)
HP:0002536	Abnormal cortical gyration	Occasional (5-29%)
HP:0006801	Hyperactive deep tendon reflexes	Occasional (5-29%)
HP:0012762	Cerebral white matter atrophy	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	spinocerebellar ataxia type 2
Mondo ID	MONDO:0008458
OMIM	183090
Orphanet	98756
DOID	DOID:0050955, DOID:0060204
ICD-11	1232187870
NCIT	C148315
SNOMED CT	715751004
UMLS	C0752121
MedGen	155704
GARD	0004072
Is cancer (heuristic)	no

Also known as: ALS13 · amyotrophic lateral sclerosis 13 · ATXN2 autosomal dominant cerebellar ataxia type I · autosomal dominant cerebellar ataxia type I caused by mutation in ATXN2 · olivopontocerebellar atrophy Holguin type · OPCA2 · SCA 2 · SCA2 · spinocerebellar ataxia 2 · spinocerebellar ataxia Cuban type · spinocerebellar ataxia type 2 · spinocerebellar ataxia with slow eye movements · Wadia swami syndrome

Data availability: 22 ClinVar variants · 4 GenCC gene-disease records · 21 cell lines.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › spinal cord disorder › anterior horn disorder › amyotrophic lateral sclerosis › familial amyotrophic lateral sclerosis › spinocerebellar ataxia type 2

Subtypes (1): spinocerebellar degeneration with slow eye movements

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

22 retrieved; paginated sample, class counts are floors:

8 benign, 7 uncertain significance, 2 likely pathogenic, 1 pathogenic, 1 benign/likely benign, 1 pathogenic; risk factor, 1 not provided, 1 likely pathogenic; risk factor

ClinVar	Variant (HGVS)	Gene	Classification	Review
3238749	NM_001372574.1(ATXN2):c.18GCA[43] (p.Gln28_Pro29insGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGln)	ATXN2	Pathogenic	criteria provided, single submitter
929858	NM_002973.4(ATXN2):c.16CAG[33_?] (p.6Gln[33_?])	ATXN2	Pathogenic; risk factor	no assertion criteria provided
3775779	NM_001372574.1(ATXN2):c.18GCA[38] (p.Gln28_Pro29insGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGln)	ATXN2	Likely pathogenic	criteria provided, single submitter
3779390	NM_001372574.1(ATXN2):c.30_58del (p.Gln11fs)	ATXN2	Likely pathogenic	criteria provided, single submitter
976652	NM_001372574.1(ATXN2):c.18GCA[28] (p.Gln14_Gln28dup)	ATXN2	Likely pathogenic; risk factor	criteria provided, multiple submitters, no conflicts
1298295	NM_001372574.1(ATXN2):c.494T>C (p.Met165Thr)	ATXN2	Uncertain significance	no assertion criteria provided
2439421	NM_001372574.1(ATXN2):c.1648C>G (p.Pro550Ala)	ATXN2	Uncertain significance	criteria provided, single submitter
3391095	NM_001372574.1(ATXN2):c.682T>G (p.Leu228Val)	ATXN2	Uncertain significance	criteria provided, single submitter
3775376	NM_001372574.1(ATXN2):c.18GCA[33] (p.Gln28_Pro29insGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGln)	ATXN2	Uncertain significance	criteria provided, single submitter
4277660	NM_001372574.1(ATXN2):c.56_57insGCAGC (p.Gln21fs)	ATXN2	Uncertain significance	criteria provided, single submitter
802894	NM_001372574.1(ATXN2):c.-266C>T	ATXN2	Uncertain significance	criteria provided, single submitter
930922	NM_001372574.1(ATXN2):c.1921A>C (p.Lys641Gln)	ATXN2	Uncertain significance	criteria provided, single submitter
128507	NM_001372574.1(ATXN2):c.-162C>G	ATXN2	Benign	criteria provided, single submitter
128508	NM_001372574.1(ATXN2):c.-91C>T	ATXN2	Benign	criteria provided, single submitter
128509	NM_001372574.1(ATXN2):c.42G>A (p.Gln14=)	ATXN2	Benign	criteria provided, single submitter
522365	NM_001372574.1(ATXN2):c.3043-12G>A	ATXN2	Benign	criteria provided, single submitter
522366	NM_001372574.1(ATXN2):c.289-11dup	ATXN2	Benign	no assertion criteria provided
522367	NM_001372574.1(ATXN2):c.289-11del	ATXN2	Benign/Likely benign	no assertion criteria provided
522368	NM_001372574.1(ATXN2):c.59AGC[8] (p.Gln28del)	ATXN2	Benign	criteria provided, single submitter
522370	NM_001372574.1(ATXN2):c.57A>G (p.Gln19=)	ATXN2	Benign	criteria provided, single submitter
930944	NM_001372574.1(ATXN2):c.3322A>G (p.Met1108Val)	ATXN2	Benign	criteria provided, single submitter
929859	NM_002973.4(ATXN2):c.16CAG[22_31] (p.6Gln[22_31])	ATXN2	not provided	no classification provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
ATXN2	Definitive	Autosomal dominant	spinocerebellar ataxia type 2	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ATXN2	Orphanet:803	Amyotrophic lateral sclerosis
ATXN2	Orphanet:98756	Spinocerebellar ataxia type 2

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ATXN2	HGNC:10555	ENSG00000204842	Q99700	Ataxin-2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ATXN2	Ataxin-2	Involved in EGFR trafficking, acting as negative regulator of endocytic EGFR internalization at the plasma membrane.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ATXN2	Other/Unknown	no		LsmAD_domain, PAM2_motif, LSM_dom_sf

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
buccal mucosa cell	1
colonic epithelium	1
olfactory bulb	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ATXN2	286	ubiquitous	marker	buccal mucosa cell, colonic epithelium, olfactory bulb

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ATXN2	3,360

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ATXN2	Q99700	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
RNA metabolic process	1	2808.7×	0.001	ATXN2
RNA transport	1	1532.0×	0.001	ATXN2
negative regulation of receptor internalization	1	1203.7×	0.001	ATXN2
P-body assembly	1	1053.2×	0.001	ATXN2
stress granule assembly	1	601.9×	0.002	ATXN2
regulation of translation	1	218.9×	0.005	ATXN2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ATXN2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
ATXN2	5	Binding:3, Functional:2

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	ATXN2

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
ATXN2	5	—

Clinical trials & evidence

Clinical trials

Clinical trials: 15.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	8
PHASE3	3
PHASE2	3
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03408080	PHASE3	ACTIVE_NOT_RECRUITING	Open Pilot Trial of BHV-4157
NCT03701399	PHASE3	ACTIVE_NOT_RECRUITING	Troriluzole in Adult Participants With Spinocerebellar Ataxia
NCT03347344	PHASE3	COMPLETED	Clinical Trial With Riluzole in Spinocerebellar Ataxia Type 2 (ATRIL)
NCT03378414	PHASE2	NOT_YET_RECRUITING	Umbilical Cord Mesenchymal Stem Cells Therapy (19#iSCLife®-SA) for Patients With Spinocerebellar Ataxia
NCT00998634	PHASE2	COMPLETED	Safety and Tolerability of Lithium in Spinocerebellar Ataxia 2 (SCA2)
NCT04301284	PHASE2	WITHDRAWN	Study of CAD-1883 for Spinocerebellar Ataxia
NCT06672445	PHASE1	RECRUITING	Study of ARO-ATXN2 Injection in Adults With Spinocerebellar Ataxia Type 2
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT05826171	Not specified	ACTIVE_NOT_RECRUITING	Priming Motor Learning Through Exercise in People With Spinocerebellar Ataxia
NCT01060371	Not specified	UNKNOWN	Natural History Study of and Genetic Modifiers in Spinocerebellar Ataxias
NCT01470729	Not specified	COMPLETED	Biomarkers in Autosomal Dominant Cerebellar Ataxia
NCT03120013	Not specified	COMPLETED	Rehabilitative Trial With Cerebello-Spinal tDCS in Neurodegenerative Ataxia
NCT04153110	Not specified	COMPLETED	Cerebello-Spinal tDCS as Rehabilitative Intervention in Neurodegenerative Ataxia
NCT04268147	Not specified	COMPLETED	Instrumented Data Exchange for Ataxia Study
NCT04288128	Not specified	COMPLETED	Integrated Functional Evaluation of the Cerebellum

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
LITHIUM CARBONATE	4	1
RILUZOLE	4	1
TRORILUZOLE	3	3
RIMTUZALCAP	2	1

Cohort genes: ATXN2
Drugs: Lithium Carbonate, Riluzole, Troriluzole