CERS6: Ceramide Synthase 6 – Sphingolipid Metabolism and Disease
Key enzyme in de novo ceramide synthesis, implicated in cancer, diabetes, and neurological disorders
Gene Information Card
| Symbol | CERS6 |
|---|---|
| Full Name | ceramide synthase 6 |
| Gene Type | protein-coding |
| Chromosomal Location | 2q24.3 |
| NCBI Gene ID | 253782 ncbi.nlm.nih.gov/gene/253782 |
| Ensembl ID | ENSG00000172292 |
| UniProt ID | Q6ZMG9 |
| OMIM ID | 615335 |
| HGNC ID | HGNC:23825 |
| Aliases | LASS6, CERS5, FLJ10769, MGC138290 |
Description
CERS6 (ceramide synthase 6) encodes a member of the ceramide synthase family, which catalyzes the synthesis of ceramides with specific fatty acyl chain lengths (primarily C16 and C14). Ceramides are key bioactive sphingolipids involved in cell signaling, apoptosis, differentiation, and stress responses. CERS6 is highly expressed in brain, kidney, and testis, and its dysregulation is linked to cancer progression, insulin resistance, and neurodegenerative diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | Altered ceramide composition promotes cell survival and proliferation | COSMIC; PMID: 25691811 |
| Type 2 diabetes | CERS6-mediated ceramide accumulation impairs insulin signaling | PMID: 24684822 |
| Alzheimer's disease | Increased CERS6 expression correlates with amyloid-beta pathology | PMID: 29100055 |
| Hepatocellular carcinoma | CERS6 upregulation associated with poor prognosis | PMID: 30348673 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | High |
| Kidney | 8.3 | Medium |
| Testis | 15.1 | High |
| Liver | 4.2 | Low |
| Lung | 3.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 9.8 | Embryonic kidney cells |
| SH-SY5Y | 14.2 | Neuroblastoma cell line |
| HepG2 | 5.6 | Hepatocellular carcinoma |
| MCF7 | 7.1 | Breast cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1015C>T (p.Arg339Trp) | Missense | 0.01% (gnomAD) | Unknown functional impact |
| c.1246G>A (p.Val416Met) | Missense | 0.005% (gnomAD) | Predicted damaging (SIFT) |
| c.1489_1490insA (p.Thr497Asnfs*5) | Frameshift | Rare | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense variants (e.g., p.Thr497Asnfs*5) predicted to truncate the protein, abolishing ceramide synthase activity.
Gain of Function (GOF)
Not well characterized; some missense variants may increase enzyme activity but require functional validation.
Dominant Negative (DN)
No confirmed dominant-negative mutations reported in CERS6.
View complete mutation data：
Gene Ontology (GO)
| • transferase activity (GO:0016747) | • ceramide synthase activity (GO:0017025) |
| • ceramide biosynthetic process (GO:0006672) | • endoplasmic reticulum (GO:0005783) |
| • cytoplasm (GO:0005737) |
Pathways
• Sphingolipid metabolism (Reactome: R-HSA-428157)
• De novo ceramide synthesis (KEGG: map00600)
Protein Summary
CERS6 is a 488-amino acid transmembrane protein localized to the endoplasmic reticulum. It catalyzes the acylation of sphingoid bases to form ceramides, preferentially using C16-CoA. The protein contains a conserved TLC (TRAM, Lag1, CLN8) domain essential for enzymatic activity. CERS6 plays a critical role in regulating cellular ceramide levels and sphingolipid homeostasis, impacting apoptosis, autophagy, and insulin sensitivity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CERS6 Knockout HEK293 Cell Line | EDJ-KQ1736 | Human | 253782 | Details Get a Quote |
| CERS6 Knockout A-549 Cell Line | EDJ-KQ21580 | Human | 253782 | Details Get a Quote |
| CERS6 Knockout HCT 116 Cell Line | EDJ-KQ21581 | Human | 253782 | Details Get a Quote |
| CERS6 Knockout HeLa Cell Line | EDJ-KQ21582 | Human | 253782 | Details Get a Quote |
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