Spinocerebellar ataxia type 38

Summary

Spinocerebellar ataxia type 38 (MONDO:0014417) is a disease caused by ELOVL5 (GenCC Strong), with 1 cohort gene and 1 clinical trial. Top therapeutic interventions include artenimol and doconexent.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: ELOVL5 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 16
• Phenotypes (HPO): 11
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		4	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

11 HPO clinical features (Orphanet curated; top 11 by frequency):

HPO ID	Term	Frequency
HP:0000639	Nystagmus	Very frequent (80-99%)
HP:0001260	Dysarthria	Very frequent (80-99%)
HP:0001288	Gait disturbance	Very frequent (80-99%)
HP:0002066	Gait ataxia	Very frequent (80-99%)
HP:0000514	Slow saccadic eye movements	Frequent (30-79%)
HP:0001272	Cerebellar atrophy	Frequent (30-79%)
HP:0003474	Somatic sensory dysfunction	Frequent (30-79%)
HP:0009830	Peripheral neuropathy	Frequent (30-79%)
HP:0002460	Distal muscle weakness	Occasional (5-29%)
HP:0000708	Atypical behavior	Very rare (<1-4%)
HP:0001337	Tremor	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	spinocerebellar ataxia type 38
Mondo ID	MONDO:0014417
OMIM	615957
Orphanet	423296
DOID	DOID:0050985
SNOMED CT	734021001
UMLS	C4518337
MedGen	1379865
GARD	0012369
Is cancer (heuristic)	no

Also known as: SCA38 · spinocerebellar ataxia 38 · spinocerebellar ataxia type 38

Data availability: 16 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › inherited lipid metabolism disorder › disorder of phospholipids, sphingolipids and fatty acids biosynthesis › spinocerebellar ataxia type 38

Related subtypes (16): Sengers syndrome, Sjogren-Larsson syndrome, Barth syndrome, megaconial type congenital muscular dystrophy, hereditary spastic paraplegia 39, PHARC syndrome, congenital ichthyosis-intellectual disability-spastic quadriplegia syndrome, 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome, progressive encephalopathy with leukodystrophy due to DECR deficiency, progressive myoclonic epilepsy type 8, neutral lipid storage disease, fatty acid hydroxylase-associated neurodegeneration, hereditary sensory and autonomic neuropathy type 1, GM3 synthase deficiency, nephrotic syndrome 14, autosomal recessive complex spastic paraplegia due to kennedy pathway dysfunction

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:

12 uncertain significance, 2 pathogenic, 1 conflicting classifications of pathogenicity, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
144075	NM_021814.5(ELOVL5):c.689G>T (p.Gly230Val)	ELOVL5	Pathogenic	no assertion criteria provided
144076	NM_021814.5(ELOVL5):c.214C>G (p.Leu72Val)	ELOVL5	Pathogenic	no assertion criteria provided
210935	NM_021814.5(ELOVL5):c.698A>G (p.Tyr233Cys)	ELOVL5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1298314	NM_021814.5(ELOVL5):c.490G>A (p.Gly164Ser)	ELOVL5	Uncertain significance	no assertion criteria provided
1705602	NM_021814.5(ELOVL5):c.692G>T (p.Trp231Leu)	ELOVL5	Uncertain significance	criteria provided, multiple submitters, no conflicts
1806222	NM_021814.5(ELOVL5):c.246+3859C>G	ELOVL5	Uncertain significance	criteria provided, single submitter
2441211	NM_021814.5(ELOVL5):c.694T>C (p.Leu232=)	ELOVL5	Uncertain significance	criteria provided, single submitter
2441212	NM_021814.5(ELOVL5):c.332G>A (p.Arg111His)	ELOVL5	Uncertain significance	criteria provided, multiple submitters, no conflicts
3627044	NM_021814.5(ELOVL5):c.304G>A (p.Ala102Thr)	ELOVL5	Uncertain significance	criteria provided, multiple submitters, no conflicts
3773712	NM_021814.5(ELOVL5):c.140G>A (p.Trp47Ter)	ELOVL5	Uncertain significance	criteria provided, single submitter
3892082	NM_021814.5(ELOVL5):c.246+3856G>A	ELOVL5	Uncertain significance	criteria provided, single submitter
4073422	NM_021814.5(ELOVL5):c.871G>T (p.Val291Leu)	ELOVL5	Uncertain significance	criteria provided, single submitter
4293109	NM_021814.5(ELOVL5):c.247-1009C>T	ELOVL5	Uncertain significance	criteria provided, single submitter
931695	NM_021814.5(ELOVL5):c.577C>T (p.Arg193Cys)	ELOVL5	Uncertain significance	criteria provided, multiple submitters, no conflicts
984690	NM_021814.5(ELOVL5):c.235A>T (p.Met79Leu)	ELOVL5	Uncertain significance	criteria provided, single submitter
691282	NM_021814.5(ELOVL5):c.246+3891C>T	ELOVL5	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
ELOVL5	Strong	Autosomal dominant	spinocerebellar ataxia type 38	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ELOVL5	Orphanet:423296	Spinocerebellar ataxia type 38

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
ELOVL5	HGNC:21308	ENSG00000012660	Q9NYP7	Very long chain fatty acid elongase 5	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ELOVL5	Very long chain fatty acid elongase 5	Catalyzes the first and rate-limiting reaction of the four reactions that constitute the long-chain fatty acids elongation cycle.

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)
ELOVL5	Other/Unknown	no		ELO_fam, ELOVL5

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
mammary duct	1
secondary oocyte	1
seminal vesicle	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ELOVL5	294	ubiquitous	marker	seminal vesicle, secondary oocyte, mammary duct

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ELOVL5	2,384

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ELOVL5	Q9NYP7	82.53

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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
Linoleic acid (LA) metabolism	1	1142.0×	0.003	ELOVL5
alpha-linolenic acid (ALA) metabolism	1	713.8×	0.003	ELOVL5
Synthesis of very long-chain fatty acyl-CoAs	1	456.8×	0.003	ELOVL5
MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis	1	82.8×	0.012	ELOVL5

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
fatty acid elongation, monounsaturated fatty acid	1	2407.4×	0.002	ELOVL5
fatty acid elongation, polyunsaturated fatty acid	1	2407.4×	0.002	ELOVL5
fatty acid elongation, saturated fatty acid	1	2106.5×	0.002	ELOVL5
very long-chain fatty acid biosynthetic process	1	1296.3×	0.002	ELOVL5
positive regulation of fatty acid biosynthetic process	1	1296.3×	0.002	ELOVL5
alpha-linolenic acid metabolic process	1	887.0×	0.002	ELOVL5
long-chain fatty-acyl-CoA biosynthetic process	1	842.6×	0.002	ELOVL5
linoleic acid metabolic process	1	702.2×	0.002	ELOVL5
unsaturated fatty acid biosynthetic process	1	648.1×	0.002	ELOVL5
long-chain fatty acid biosynthetic process	1	443.5×	0.002	ELOVL5
sphingolipid biosynthetic process	1	358.6×	0.003	ELOVL5

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
ELOVL5	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
ELOVL5	5	Binding:5

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	ELOVL5

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)
ELOVL5	5	—

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
NCT03109626	Not specified	COMPLETED	Docosahexaenoic Acid (DHA) Replacement for Treatment in Spinocerebellar Ataxia 38

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ARTENIMOL	4	1
DOCONEXENT	3	1