mild Canavan disease

Summary

mild Canavan disease (MONDO:0017831) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Europe) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 2
• Phenotypes (HPO): 16

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	<1 / 1 000 000		Europe	Validated

Signs & symptoms

Clinical features (HPO)

16 HPO clinical features (Orphanet curated; top 16 by frequency):

HPO ID	Term	Frequency
HP:0001270	Motor delay	Frequent (30-79%)
HP:0001328	Specific learning disability	Frequent (30-79%)
HP:0002465	Poor speech	Frequent (30-79%)
HP:0011342	Mild global developmental delay	Frequent (30-79%)
HP:0012379	Abnormal enzyme/coenzyme activity	Frequent (30-79%)
HP:0000256	Macrocephaly	Occasional (5-29%)
HP:0000510	Rod-cone dystrophy	Occasional (5-29%)
HP:0000750	Delayed speech and language development	Occasional (5-29%)
HP:0001250	Seizure	Occasional (5-29%)
HP:0001252	Hypotonia	Occasional (5-29%)
HP:0001347	Hyperreflexia	Occasional (5-29%)
HP:0002421	Poor head control	Occasional (5-29%)
HP:0002493	Upper motor neuron dysfunction	Occasional (5-29%)
HP:0003487	Babinski sign	Occasional (5-29%)
HP:0012751	Abnormal basal ganglia MRI signal intensity	Occasional (5-29%)
HP:0040196	Mild microcephaly	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	mild Canavan disease
Mondo ID	MONDO:0017831
Orphanet	314918
UMLS	C4017127
MedGen	865564
GARD	0017438
Is cancer (heuristic)	no

Also known as: juvenile Canavan disease

Data availability: 2 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › inborn aminoacylase deficiency › Canavan disease › mild Canavan disease

Related subtypes (1): severe Canavan disease

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

2 retrieved; paginated sample, class counts are floors:

2 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1700565	NM_000049.4(ASPA):c.526G>A (p.Gly176Ser)	ASPA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2616	NM_000049.4(ASPA):c.212G>A (p.Arg71His)	ASPA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · 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
ASPA	Definitive	Autosomal recessive	Canavan disease	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ASPA	Orphanet:314911	Severe Canavan disease
ASPA	Orphanet:314918	Mild Canavan disease

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
ASPA	HGNC:756	ENSG00000108381	P45381	Aspartoacylase	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ASPA	Aspartoacylase	Catalyzes the deacetylation of N-acetylaspartic acid (NAA) to produce acetate and L-aspartate.

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)
ASPA	Enzyme (other)	yes	3.5.1.15	Aste_AspA_hybrid_dom, Aspartoacylase, AspA/AstE_fam

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
corpus callosum	1
medial globus pallidus	1
nephron tubule	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ASPA	238	broad	marker	corpus callosum, nephron tubule, medial globus pallidus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ASPA	680

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ASPA	P45381	8

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
Aspartate and asparagine metabolism	1	1038.2×	0.003	ASPA
Metabolism of amino acids and derivatives	1	67.6×	0.022	ASPA
Metabolism	1	11.6×	0.086	ASPA

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
acetate metabolic process	1	16852.0×	1e-04	ASPA
aspartate metabolic process	1	2106.5×	5e-04	ASPA

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ASPA	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ASPA	3.5.1.15	aspartoacylase

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	ASPA
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)
ASPA	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.