ASAH2
protein-codingN-acylsphingosine amidohydrolase 2
Gene summary
Ceramidases (EC 3.5.1.23), such as ASAH2, catalyze hydrolysis of the N-acyl linkage of ceramide, a second messenger in a variety of cellular events, to produce sphingosine. Sphingosine exerts both mitogenic and apoptosis-inducing activities, and its phosphorylated form functions as an intra- and intercellular second messenger (see MIM 603730) (Mitsutake et al., 2001 [PubMed 11328816]).[supplied by OMIM, Mar 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~96.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ASAH2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_019893.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 40 | 1 | 41 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 40 | 1 | 0 | 41 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_063946.2 | 20 | MANE Select | |
| Ensembl | ENSP00000506746.1 | 20 | MANE Select | |
| RefSeq | NP_001137446.1 | 19 | Standard | |
| Ensembl | ENSP00000329886.6 | 19 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Sphingolipid signaling pathway - Homo sapiens (human)
- Sphingolipid metabolism - Homo sapiens (human)
- Sphingolipid Metabolism
- Metabolism of lipids
- Metabolism
Biological Process
- sphingosine metabolic process
- ceramide metabolic process
- apoptotic process
- response to organic substance
- long-chain fatty acid biosynthetic process
Molecular Function
- calcium ion binding
- zinc ion binding
- N-acylsphingosine amidohydrolase activity
- ceramidase activity
Cellular Component
- extracellular region
- mitochondrion
- plasma membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000395526
- Coding exons
- 20
- Length
- 65833
- Individuals with no LoFs
- 124583
- Homozygous LoFs
- 9
- Heterozygous LoFs
- 1156
- Defined
- 125748
- p
- 0.00464
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.346 | 123 | 134 | 0.916 | 0.00000686 | 5076 |
| Missense (PolyPhen) | 38 | 39.644 | 0.95852 | 1949 | ||
| Synonymous | -1.46 | 62 | 49.0 | 1.27 | 0.00000246 | 1516 |
| Loss of Function | 1.32 | 5 | 9.36 | 0.534 | 5.62e-7 | 480 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.012 | 0.012 | notable |
| Latino/Admixed American | 0.0011 | 0.0011 | notable |
| Ashkenazi Jewish | 0.0040 | 0.0040 | notable |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0.0086 | 0.0086 | notable |
| European (Non-Finnish) | 0.0058 | 0.0058 | notable |
| South Asian | 0.00085 | 0.00085 | rare |
| Other | 0.0039 | 0.0038 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Hydrolyzes the sphingolipid ceramide into sphingosine and free fatty acid at an optimal pH of 6.5-8.5 (PubMed:10781606, PubMed:26190575). Acts as a key regulator of sphingolipid signaling metabolites by generating sphingosine at the cell surface. Acts as a repressor of apoptosis both by reducing C16- ceramide, thereby preventing ceramide-induced apoptosis, and generating sphingosine, a precursor of the antiapoptotic factor sphingosine 1-phosphate. Probably involved in the digestion of dietary sphingolipids in intestine by acting as a key enzyme for the catabolism of dietary sphingolipids and regulating the levels of bioactive sphingolipid metabolites in the intestinal tract. {ECO:0000269|PubMed:10781606, ECO:0000269|PubMed:15946935, ECO:0000269|PubMed:16061940, ECO:0000269|PubMed:26190575}.;
Recessive Scores
- pRec
- 0.129
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.168
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |