Spinocerebellar ataxia type 26

Summary

Spinocerebellar ataxia type 26 (MONDO:0012246) is a disease caused by EEF2 (GenCC Strong), with 1 cohort gene and 1 clinical trial.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: EEF2 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 16
• Phenotypes (HPO): 15
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		1	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

15 HPO clinical features (Orphanet curated; top 15 by frequency):

HPO ID	Term	Frequency
HP:0001151	Impaired horizontal smooth pursuit	Very frequent (80-99%)
HP:0001260	Dysarthria	Very frequent (80-99%)
HP:0002070	Limb ataxia	Very frequent (80-99%)
HP:0002073	Progressive cerebellar ataxia	Very frequent (80-99%)
HP:0007240	Progressive gait ataxia	Very frequent (80-99%)
HP:0000639	Nystagmus	Frequent (30-79%)
HP:0000641	Dysmetric saccades	Frequent (30-79%)
HP:0001272	Cerebellar atrophy	Frequent (30-79%)
HP:0002078	Truncal ataxia	Frequent (30-79%)
HP:0003487	Babinski sign	Occasional (5-29%)
HP:0007034	Generalized hyperreflexia	Occasional (5-29%)
HP:0001250	Seizure	Excluded (0%)
HP:0002380	Fasciculations	Excluded (0%)
HP:0003470	Paralysis	Excluded (0%)
HP:0003474	Somatic sensory dysfunction	Excluded (0%)

Identifiers

Disease identifiers

Field	Value
Canonical name	spinocerebellar ataxia type 26
Mondo ID	MONDO:0012246
MeSH	C537203
OMIM	609306
Orphanet	101112
DOID	DOID:0050975
ICD-11	586976339
SNOMED CT	718769009
UMLS	C1836395
MedGen	373077
GARD	0009995
Is cancer (heuristic)	no

Also known as: SCA26 · spinocerebellar ataxia 26 · spinocerebellar ataxia type 26

Data availability: 16 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › autosomal dominant cerebellar ataxia › autosomal dominant cerebellar ataxia type III › spinocerebellar ataxia type 26

Related subtypes (9): spinocerebellar ataxia type 31, spinocerebellar ataxia type 6, spinocerebellar ataxia type 5, spinocerebellar ataxia type 11, spinocerebellar ataxia type 30, spinocerebellar ataxia type 38, spinocerebellar ataxia type 41, spinocerebellar ataxia type 42, spinocerebellar ataxia 45

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

16 retrieved; paginated sample, class counts are floors:

10 uncertain significance, 3 benign, 1 likely pathogenic, 1 conflicting classifications of pathogenicity, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
66077	NM_001961.4(EEF2):c.1787C>A (p.Pro596His)	EEF2	Pathogenic	criteria provided, single submitter
1696864	NM_001961.4(EEF2):c.2314G>A (p.Glu772Lys)	EEF2	Likely pathogenic	no assertion criteria provided
585829	NM_001961.4(EEF2):c.2241G>A (p.Val747=)	EEF2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1696627	NM_001961.4(EEF2):c.949_950delinsAG (p.Glu317Arg)	EEF2	Uncertain significance	criteria provided, single submitter
1699353	NM_001961.4(EEF2):c.1359G>A (p.Met453Ile)	EEF2	Uncertain significance	criteria provided, single submitter
1805894	NM_001961.4(EEF2):c.463C>A (p.Leu155Met)	EEF2	Uncertain significance	criteria provided, single submitter
2412766	NM_001961.4(EEF2):c.442del (p.Ala148fs)	EEF2	Uncertain significance	criteria provided, single submitter
2441180	NM_001961.4(EEF2):c.1130C>T (p.Pro377Leu)	EEF2	Uncertain significance	criteria provided, single submitter
2627502	NM_001961.4(EEF2):c.1480A>T (p.Met494Leu)	EEF2	Uncertain significance	criteria provided, single submitter
3901980	NM_001961.4(EEF2):c.2123C>T (p.Thr708Ile)	EEF2	Uncertain significance	criteria provided, single submitter
441103	NM_001961.4(EEF2):c.1979A>G (p.Asn660Ser)	EEF2	Uncertain significance	criteria provided, single submitter
4759481	NM_001961.4(EEF2):c.1800C>G (p.Asn600Lys)	EEF2	Uncertain significance	criteria provided, single submitter
4081896	NC_000019.10:g.3936565_4932966dup	LOC111828491	Uncertain significance	no assertion criteria provided
1255372	NM_001961.4(EEF2):c.1150+15T>C	EEF2	Benign	criteria provided, multiple submitters, no conflicts
128958	NM_001961.4(EEF2):c.1632T>C (p.His544=)	EEF2	Benign	criteria provided, multiple submitters, no conflicts
128959	NM_001961.4(EEF2):c.2190T>C (p.Tyr730=)	LOC130063169	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · 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
EEF2	Strong	Autosomal dominant	spinocerebellar ataxia type 26	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
EEF2	Orphanet:101112	Spinocerebellar ataxia type 26

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
EEF2	HGNC:3214	ENSG00000167658	P13639	Elongation factor 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
EEF2	Elongation factor 2	Catalyzes the GTP-dependent ribosomal translocation step during translation elongation.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
EEF2	Enzyme (other)	yes	3.6.5.3	EFG_V-like, T_Tr_GTP-bd_dom, EFTu-like_2

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
cartilage tissue	1
parotid gland	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
EEF2	301	ubiquitous	marker	parotid gland, cartilage tissue, stromal cell of endometrium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
EEF2	8,196

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
EEF2	P13639	31

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways 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.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Uptake and function of diphtheria toxin	1	1903.3×	0.002	EEF2
Synthesis of diphthamide-EEF2	1	1427.5×	0.002	EEF2
Protein methylation	1	671.8×	0.002	EEF2
Peptide chain elongation	1	126.9×	0.010	EEF2
Neutrophil degranulation	1	23.1×	0.043	EEF2

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
translation at postsynapse	1	16852.0×	9e-04	EEF2
response to folic acid	1	2407.4×	0.003	EEF2
cellular response to brain-derived neurotrophic factor stimulus	1	1872.4×	0.003	EEF2
translational elongation	1	1203.7×	0.003	EEF2
positive regulation of cytoplasmic translation	1	991.3×	0.003	EEF2
glial cell proliferation	1	887.0×	0.003	EEF2
skeletal muscle contraction	1	510.7×	0.004	EEF2
response to hydrogen peroxide	1	468.1×	0.004	EEF2
skeletal muscle cell differentiation	1	343.9×	0.005	EEF2
response to ischemia	1	251.5×	0.006	EEF2
hematopoietic progenitor cell differentiation	1	237.3×	0.006	EEF2
positive regulation of translation	1	227.7×	0.006	EEF2
response to estradiol	1	198.3×	0.006	EEF2
response to endoplasmic reticulum stress	1	166.8×	0.007	EEF2
response to ethanol	1	146.5×	0.007	EEF2
response to xenobiotic stimulus	1	69.1×	0.014	EEF2

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
EEF2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
EEF2	26	Binding:26

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
EEF2	3.6.5.3	protein-synthesizing GTPase

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	1	EEF2
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
EEF2	26	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford