SPTSSA: Serine Palmitoyltransferase Small Subunit A
Key regulator of sphingolipid biosynthesis and potential therapeutic target in metabolic and neurological disorders
Gene Information Card
| Symbol | SPTSSA |
|---|---|
| Full Name | Serine Palmitoyltransferase Small Subunit A |
| Gene Type | Protein-coding |
| Chromosomal Location | 14q24.3 |
| NCBI Gene ID | 171546 ncbi.nlm.nih.gov/gene/171546 |
| Ensembl ID | ENSG00000100823 |
| UniProt ID | Q969W0 |
| OMIM ID | 613712 |
| HGNC ID | 20389 |
| Aliases | SPTLC3, hSPT3, SPT3 |
Description
SPTSSA encodes the small subunit A of serine palmitoyltransferase (SPT), the rate-limiting enzyme in de novo sphingolipid biosynthesis. SPT catalyzes the condensation of L-serine and palmitoyl-CoA to form 3-ketodihydrosphingosine. SPTSSA, along with SPTSSB, modulates SPT substrate specificity and activity. Mutations in SPTSSA are associated with hereditary sensory and autonomic neuropathy type 1 (HSAN1) and other sphingolipid-related disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary Sensory and Autonomic Neuropathy Type 1 (HSAN1) | Loss-of-function mutations in SPTSSA reduce SPT activity, leading to accumulation of neurotoxic deoxysphingolipids | ClinVar, OMIM |
| Charcot-Marie-Tooth Disease | SPTSSA variants may impair peripheral nerve myelination via altered sphingolipid composition | ClinVar |
| Metabolic Syndrome | Dysregulation of SPTSSA expression linked to altered ceramide levels and insulin resistance | NCBI Gene, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Liver | 8.3 | Low |
| Kidney | 15.2 | Medium |
| Testis | 20.1 | High |
| Adipose Tissue | 6.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 18.4 | High expression |
| HeLa | 10.2 | Moderate expression |
| SH-SY5Y | 22.1 | High expression (neuronal) |
| HepG2 | 7.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.58G>A (p.Gly20Arg) | Missense | Rare | Reduced SPT activity; associated with HSAN1 |
| c.112C>T (p.Arg38Trp) | Missense | Rare | Impaired subunit interaction; loss of function |
| c.199G>A (p.Gly67Ser) | Missense | Rare | Altered substrate specificity; potential gain of function |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., p.Gly20Arg, p.Arg38Trp) reduce SPT enzymatic activity, leading to deoxysphingolipid accumulation and neurotoxicity.
Gain of Function (GOF)
Rare variants (e.g., p.Gly67Ser) may alter substrate preference, increasing production of atypical sphingolipids.
Dominant Negative (DN)
Some SPTSSA mutations exert dominant-negative effects by disrupting the SPT complex assembly.
View complete mutation data：
Gene Ontology (GO)
| • serine C-palmitoyltransferase activity | • sphingolipid biosynthetic process |
| • endoplasmic reticulum membrane | • protein heterodimerization activity |
Pathways
• Sphingolipid metabolism (KEGG: hsa00600)
• De novo sphingolipid biosynthesis (Reactome: R-HSA-1660661)
Protein Summary
SPTSSA is a 55-amino acid small subunit of serine palmitoyltransferase, localized to the endoplasmic reticulum. It forms a complex with SPTLC1 and SPTLC2 to regulate enzyme activity and substrate specificity. SPTSSA is essential for normal sphingolipid homeostasis, and its dysfunction contributes to peripheral neuropathy and metabolic disease.
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