SPTLC2 Gene: Serine Palmitoyltransferase Long Chain Base Subunit 2
Genetic insights into SPTLC2: from hereditary sensory neuropathy to sphingolipid metabolism
Gene Information Card
| Symbol | SPTLC2 |
|---|---|
| Full Name | serine palmitoyltransferase long chain base subunit 2 |
| Gene Type | protein coding |
| Chromosomal Location | 14q24.3 |
| NCBI Gene ID | 9517 ncbi.nlm.nih.gov/gene/9517 |
| Ensembl ID | ENSG00000100596 |
| UniProt ID | O15270 |
| OMIM ID | 605713 |
| HGNC ID | 11278 |
| Aliases | hLCB2, LCB2, SPT2 |
Description
SPTLC2 encodes a subunit of serine palmitoyltransferase (SPT), the enzyme catalyzing the first and rate-limiting step in de novo sphingolipid biosynthesis. This enzyme converts L-serine and palmitoyl-CoA to 3-ketodihydrosphingosine. SPT is a multimeric complex composed of SPTLC1, SPTLC2, and accessory subunits. Mutations in SPTLC2 are associated with hereditary sensory and autonomic neuropathy type 1 (HSAN1), a progressive neurodegenerative disorder. The gene is widely expressed and plays a critical role in sphingolipid homeostasis, impacting cell membrane integrity and signaling.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary sensory and autonomic neuropathy type 1 (HSAN1) | Missense mutations (e.g., p.A182P, p.V359M) alter substrate specificity, leading to accumulation of neurotoxic deoxysphingolipids (e.g., 1-deoxysphinganine) that impair neuronal function. | ClinVar and OMIM (605713) list pathogenic variants; functional studies confirm altered SPT activity. |
| Charcot-Marie-Tooth disease (CMT) – some cases | Rare SPTLC2 variants may cause peripheral neuropathy with features overlapping HSAN1, likely via similar deoxysphingolipid toxicity. | Case reports in PubMed; not yet a major CMT gene, but emerging evidence. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.3 | Medium |
| Liver | 8.7 | Medium |
| Kidney | 7.9 | Medium |
| Testis | 6.5 | Low |
| Lung | 5.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.2 | High expression |
| HEK293 | 12.8 | High expression |
| HepG2 | 10.1 | Moderate expression |
| SH-SY5Y | 9.4 | Moderate expression |
| A549 | 6.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.A182P | Missense | Rare (found in HSAN1 families) | Alters substrate specificity, increases deoxysphingolipid production |
| p.V359M | Missense | Rare (HSAN1) | Similar to A182P, causes neurotoxic lipid accumulation |
| p.I504F | Missense | Reported in CMT-like phenotype | Potential loss of normal SPT function, but exact mechanism under study |
Mutation functional classification
Loss of Function (LOF)
Complete loss-of-function mutations are rare; some variants may reduce SPT activity, but haploinsufficiency is not a common disease mechanism.
Gain of Function (GOF)
Most pathogenic missense mutations are gain-of-function in terms of producing deoxysphingolipids, not increased canonical SPT activity.
Dominant Negative (DN)
Mutant subunits may incorporate into the SPT complex and alter its function, but evidence for classic dominant-negative effect is limited; rather, they act as neomorphic alleles.
View complete mutation data：
Gene Ontology (GO)
| • serine C-palmitoyltransferase activity | • pyridoxal phosphate binding |
| • sphingolipid biosynthetic process | • membrane |
| • endoplasmic reticulum |
Pathways
• Sphingolipid metabolism
• De novo sphingolipid biosynthesis
• Sphingosine and sphingosine-1-phosphate metabolism
Protein Summary
SPTLC2 is a 63 kDa protein with 562 amino acids, containing a pyridoxal phosphate (PLP) binding site essential for catalytic activity. It forms a heterodimer with SPTLC1, and the complex is anchored to the endoplasmic reticulum membrane. The protein is ubiquitously expressed, with higher levels in brain and liver. Pathogenic mutations in SPTLC2 disrupt substrate specificity, leading to the production of atypical deoxysphingolipids that are toxic to sensory neurons. This underlies the pathophysiology of HSAN1. The protein is also implicated in metabolic regulation and cellular stress responses.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SPTLC2 Knockout HEK293 Cell Line | EDJ-KQ1729 | Human | 9517 | Details Get a Quote |
| SPTLC2 Knockout HCT 116 Cell Line | EDJ-KQ20223 | Human | 9517 | Details Get a Quote |
| SPTLC2 Knockout A-549 Cell Line | EDJ-KQ21573 | Human | 9517 | Details Get a Quote |
| SPTLC2 Knockout HeLa Cell Line | EDJ-KQ21574 | Human | 9517 | Details Get a Quote |
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