ASAH1-related sphingolipidosis

Summary

ASAH1-related sphingolipidosis (MONDO:0100524) is a disease with 1 cohort gene and 1 clinical trial.

At a glance

• Cohort genes: 1
• ClinVar variants: 2
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	ASAH1-related sphingolipidosis
Mondo ID	MONDO:0100524
GARD	0026262
Is cancer (heuristic)	no

Also known as: acid ceramidase deficiency · ASAH1-related disorders · ASAH1-related sphingolipidosis

Data availability: 2 ClinVar variants.

Disease family

An umbrella term covering 2 Mondo subtypes.

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 › lysosomal lipid storage disorder › sphingolipidosis › ASAH1-related sphingolipidosis

Related subtypes (10): Niemann-Pick disease, Krabbe disease, sea-blue histiocyte syndrome, mucosulfatidosis, Fabry disease, gangliosidosis, autosomal recessive cerebellar ataxia with late-onset spasticity, Gaucher disease, metachromatic leukodystrophy, PSAP-related sphingolipidosis

Subtypes (2): spinal muscular atrophy-progressive myoclonic epilepsy syndrome, Farber lipogranulomatosis

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:

1 uncertain significance, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
433108	NM_004315.6(ASAH1):c.35G>C (p.Arg12Pro)	ASAH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3780054	NM_177924.5(ASAH1):c.1163G>A (p.Cys388Tyr)	ASAH1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

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

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ASAH1	Orphanet:2590	Spinal muscular atrophy-progressive myoclonic epilepsy syndrome
ASAH1	Orphanet:333	Farber 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
ASAH1	HGNC:735	ENSG00000104763	Q13510	Acid ceramidase	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ASAH1	Acid ceramidase	Lysosomal ceramidase that hydrolyzes sphingolipid ceramides into sphingosine and free fatty acids at acidic pH.

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)
ASAH1	Enzyme (other)	yes	3.5.1.23	Acid_ceramidase-like, Acid_ceramidase_N, CBAH/NAAA_C

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
heart right ventricle	1
pancreatic ductal cell	1
visceral pleura	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ASAH1	302	ubiquitous	marker	heart right ventricle, visceral pleura, pancreatic ductal cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ASAH1	2,633

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ASAH1	Q13510	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 12. 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
Regulation of MITF-M-dependent genes involved in lysosome biogenesis and autophagy	1	671.8×	0.014	ASAH1
Glycosphingolipid metabolism	1	300.5×	0.014	ASAH1
Glycosphingolipid catabolism	1	292.8×	0.014	ASAH1
MITF-M-dependent gene expression	1	181.3×	0.014	ASAH1
Sphingolipid metabolism	1	167.9×	0.014	ASAH1
MITF-M-regulated melanocyte development	1	114.2×	0.018	ASAH1
Metabolism of lipids	1	31.6×	0.054	ASAH1
Innate Immune System	1	25.5×	0.058	ASAH1
Neutrophil degranulation	1	23.1×	0.058	ASAH1
Developmental Biology	1	14.5×	0.083	ASAH1
Immune System	1	13.0×	0.084	ASAH1
Metabolism	1	11.6×	0.086	ASAH1

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
regulation of programmed necrotic cell death	1	16852.0×	5e-04	ASAH1
ceramide catabolic process	1	2407.4×	0.002	ASAH1
regulation of steroid biosynthetic process	1	1532.0×	0.002	ASAH1
sphingosine biosynthetic process	1	1053.2×	0.002	ASAH1
ceramide biosynthetic process	1	421.3×	0.004	ASAH1
keratinocyte differentiation	1	247.8×	0.005	ASAH1
fatty acid metabolic process	1	193.7×	0.006	ASAH1
cellular response to tumor necrosis factor	1	163.6×	0.006	ASAH1

Therapeutics

Drug target analysis

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

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
ASAH1	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CARMOFUR	2	ASAH1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
ASAH1	111	Binding:108, Functional:3

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ASAH1	3.5.1.23	ceramidase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
ASAH1	111

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

1 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.

Compound	Max phase	Cohort target (bioactivity)
CARMOFUR	2	ASAH1

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	1	ASAH1
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

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
NCT03233841	Not specified	COMPLETED	Farber Disease Natural History Study