ACER3: Alkaline Ceramidase 3
A key regulator of sphingolipid metabolism involved in leukodystrophy and cancer
Gene Information Card
| Symbol | ACER3 |
|---|---|
| Full Name | Alkaline Ceramidase 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 11q13.5 |
| NCBI Gene ID | 55331 ncbi.nlm.nih.gov/gene/55331 |
| Ensembl ID | ENSG00000149131 |
| UniProt ID | Q9H7Z7 |
| OMIM ID | 617105 |
| HGNC ID | 16066 |
| Aliases | PHCA, ALKCDase3, APHC, ASAH3L |
Description
ACER3 encodes alkaline ceramidase 3, a membrane-bound enzyme that catalyzes the hydrolysis of ceramide into sphingosine and free fatty acids, preferentially acting on unsaturated long-chain ceramides (C18:1, C20:1, C20:4). It plays a critical role in sphingolipid homeostasis, cell signaling, and apoptosis. Mutations in ACER3 cause leukodystrophy, and altered expression is implicated in various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Leukodystrophy, progressive, with leukoencephalopathy and developmental delay | Loss-of-function mutations impair ceramide hydrolysis, leading to accumulation of unsaturated ceramides and disruption of myelin maintenance | OMIM #617105, ClinVar |
| Hepatocellular carcinoma | Overexpression of ACER3 promotes cell proliferation and resistance to apoptosis via altered sphingolipid signaling | COSMIC, PubMed studies |
| Colorectal cancer | Upregulation associated with poor prognosis; modulates ceramide/sphingosine-1-phosphate balance | COSMIC, PubMed studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 8.2 | Medium |
| Liver | 6.5 | Medium |
| Kidney | 5.1 | Low |
| Lung | 4.3 | Low |
| Heart | 3.8 | Low |
| Testis | 2.9 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 7.1 | Hepatocellular carcinoma cell line |
| A549 | 5.4 | Lung adenocarcinoma cell line |
| HEK293 | 4.8 | Embryonic kidney cells |
| SH-SY5Y | 6.2 | Neuroblastoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.103C>T (p.Arg35Ter) | Nonsense | Rare | Loss of function; associated with leukodystrophy |
| c.200T>C (p.Leu67Pro) | Missense | Rare | Loss of function; reduced ceramidase activity |
| c.487G>A (p.Gly163Arg) | Missense | Rare | Loss of function; impaired protein stability |
Mutation functional classification
Loss of Function (LOF)
Nonsense and missense mutations (e.g., p.Arg35Ter, p.Leu67Pro) reduce or abolish enzymatic activity, leading to ceramide accumulation and leukodystrophy.
Gain of Function (GOF)
Not reported in germline; overexpression in cancers may confer gain-of-function through increased sphingosine-1-phosphate production.
Dominant Negative (DN)
Not documented for ACER3.
View complete mutation data：
Gene Ontology (GO)
| • GO:0017040 - ceramidase activity | • GO:0046513 - ceramide metabolic process |
| • GO:0006672 - ceramide biosynthetic process | • GO:0016021 - integral component of membrane |
| • GO:0005783 - endoplasmic reticulum |
Pathways
• Sphingolipid metabolism (Reactome: R-HSA-428157)
• Sphingosine-1-phosphate signaling (Reactome: R-HSA-428930)
Protein Summary
Alkaline ceramidase 3 (ACER3) is a 297-amino acid integral membrane protein localized to the endoplasmic reticulum. It catalyzes the hydrolysis of ceramide to sphingosine, with a preference for unsaturated long-chain ceramides. The enzyme is involved in regulating cellular levels of bioactive sphingolipids, influencing cell survival, proliferation, and differentiation. ACER3 is expressed in brain, liver, and kidney, and its dysfunction is linked to neurological disorders and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ACER3 Knockout HEK293 Cell Line | EDJ-KQ2859 | Human | 55331 | Details Get a Quote |
| ACER3 Knockout A-549 Cell Line | EDJ-KQ23880 | Human | 55331 | Details Get a Quote |
| ACER3 Knockout HCT 116 Cell Line | EDJ-KQ23881 | Human | 55331 | Details Get a Quote |
| ACER3 Knockout HeLa Cell Line | EDJ-KQ23882 | Human | 55331 | Details Get a Quote |
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