SPTLC1 Gene: Serine Palmitoyltransferase Long Chain Base Subunit 1
Genetic, structural, and clinical insights into SPTLC1, a key enzyme in sphingolipid metabolism, linked to hereditary sensory neuropathy and macular telangiectasia type 2.
Gene Information Card
| Symbol | SPTLC1 |
|---|---|
| Full Name | Serine palmitoyltransferase long chain base subunit 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 9q22.31 |
| NCBI Gene ID | 10558 ncbi.nlm.nih.gov/gene/10558 |
| Ensembl ID | ENSG00000090054 |
| UniProt ID | O15269 |
| OMIM ID | 605712 |
| HGNC ID | 11277 |
| Aliases | HSAN1, HSN1, LCB1, SPT1, SPTI |
Description
SPTLC1 encodes subunit 1 of serine palmitoyltransferase (SPT), a pyridoxal-5'-phosphate-dependent enzyme that catalyzes the first and rate-limiting step in de novo sphingolipid biosynthesis: the condensation of L-serine with palmitoyl-CoA to form 3-ketodihydrosphingosine. SPT is a multimeric complex composed of SPTLC1, SPTLC2, and accessory subunits (e.g., SPTSSA/B). SPTLC1 is ubiquitously expressed and essential for sphingolipid homeostasis, which is critical for cell membrane integrity, signaling, and neuronal function. Mutations in SPTLC1 cause hereditary sensory neuropathy type 1 (HSAN1) and are also associated with macular telangiectasia type 2 (MacTel2).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary Sensory Neuropathy Type 1 (HSAN1) | Missense mutations (e.g., p.Cys133Trp, p.Cys133Tyr, p.Val144Asp) lead to a gain-of-function that alters substrate specificity, producing neurotoxic deoxysphingolipids (e.g., 1-deoxysphinganine) instead of canonical sphingolipids. These metabolites accumulate and cause progressive sensory neuron degeneration. | ClinVar, OMIM (605712), multiple peer-reviewed studies (e.g., Penno et al., 2010; Eichler et al., 2009) |
| Macular Telangiectasia Type 2 (MacTel2) | Rare missense variants (e.g., p.Arg183Trp, p.Arg183Gln) are associated with reduced SPT activity or altered sphingolipid metabolism, leading to retinal vascular changes and photoreceptor degeneration. The exact mechanism is still under investigation, but it involves dysregulation of serine metabolism and ceramide levels. | ClinVar, OMIM (605712), studies by Gantner et al. (2019) and Scerri et al. (2017) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 20.1 | High |
| Liver | 15.3 | Medium |
| Kidney | 12.8 | Medium |
| Lung | 10.5 | Medium |
| Muscle | 8.2 | Low |
| Heart | 7.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 25.4 | High expression |
| HepG2 | 18.7 | Moderate expression |
| SH-SY5Y | 22.3 | High expression (neuronal) |
| A549 | 14.2 | Moderate expression |
| MCF7 | 11.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Cys133Trp | Missense | Rare (found in HSAN1 families) | Gain-of-function: alters substrate specificity, leading to accumulation of neurotoxic 1-deoxysphingolipids. |
| p.Cys133Tyr | Missense | Rare (HSAN1) | Similar to p.Cys133Trp, causes deoxysphingolipid accumulation. |
| p.Val144Asp | Missense | Rare (HSAN1) | Gain-of-function, produces deoxysphingolipids. |
| p.Arg183Trp | Missense | Rare (MacTel2) | Likely loss-of-function or altered activity, associated with retinal pathology. |
| p.Arg183Gln | Missense | Rare (MacTel2) | Similar to p.Arg183Trp, linked to MacTel2. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations are not commonly reported for SPTLC1; complete loss is likely embryonic lethal. Some MacTel2 variants may reduce enzyme activity, but they are not classic null alleles.
Gain of Function (GOF)
HSAN1 mutations are classic gain-of-function: they alter substrate specificity to use alanine or glycine instead of serine, producing neurotoxic deoxysphingolipids.
Dominant Negative (DN)
Some SPTLC1 mutations may exert a dominant-negative effect by disrupting the multimeric SPT complex, but this is less established than gain-of-function for HSAN1.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Sphingolipid de novo biosynthesis (KEGG: map00600)
• Sphingolipid signaling pathway (KEGG: map04071)
• Metabolic pathways (KEGG: map01100)
Protein Summary
SPTLC1 is a 473-amino-acid protein (UniProt O15269) that serves as the catalytic core of serine palmitoyltransferase. It contains a pyridoxal-5'-phosphate (PLP) binding site and is anchored to the endoplasmic reticulum membrane. The protein forms a heterodimer with SPTLC2, and this dimer associates with accessory subunits to form the active SPT complex. SPTLC1 is essential for the production of sphingolipids, which are structural components of cell membranes and key signaling molecules. Mutations in SPTLC1 disrupt sphingolipid homeostasis, leading to neurodegenerative and retinal diseases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SPTLC1 Knockout HEK293 Cell Line | EDJ-KQ1728 | Human | 10558 | Details Get a Quote |
| SPTLC1 Knockout A-549 Cell Line | EDJ-KQ21570 | Human | 10558 | Details Get a Quote |
| SPTLC1 Knockout HCT 116 Cell Line | EDJ-KQ21571 | Human | 10558 | Details Get a Quote |
| SPTLC1 Knockout HeLa Cell Line | EDJ-KQ21572 | Human | 10558 | Details Get a Quote |
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