Affinage

SPTLC1

Serine palmitoyltransferase 1 · UniProt O15269

Length
473 aa
Mass
52.7 kDa
Annotated
2026-04-28
64 papers in source corpus 23 papers cited in narrative 22 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SPTLC1 encodes the LCB1 subunit of serine palmitoyltransferase (SPT), an ER-resident heterodimeric enzyme that catalyzes the PLP-dependent condensation of L-serine with palmitoyl-CoA to form 3-ketosphinganine — the first and rate-limiting step of de novo sphingolipid biosynthesis (PMID:2066332, PMID:8058731, PMID:9405408). SPTLC1 is an integral ER membrane protein with a single N-terminal transmembrane domain that mediates interaction with ORMDL regulatory proteins controlling SPT oligomerization and homeostatic activity, while its cytosolic C-terminal PDZ-binding motif recruits Par3 to modulate enzyme activity and cell migration (PMID:12464627, PMID:30529276, PMID:19592499). SPTLC1 activity is negatively regulated by ABL kinase-mediated phosphorylation at Tyr164, and conditional deletion in specific tissues disrupts lipid raft formation, VEGF signaling in endothelial cells, and myeloid differentiation in bone marrow progenitors (PMID:23629659, PMID:36197001, PMID:31751474). Missense mutations in SPTLC1 cause hereditary sensory and autonomic neuropathy type I (HSAN1) through a gain-of-function shift in substrate specificity toward L-alanine, generating neurotoxic 1-deoxysphingolipids, whereas transmembrane-domain mutations linked to ALS disrupt ORMDL-mediated suppression and cause unrestrained sphingolipid synthesis (PMID:19923297, PMID:26681808, PMID:37348646).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1991 High

    Identification of LCB1 as an SPT component resolved the genetic basis of a previously known enzyme-deficient yeast mutant and revealed that the sphingolipid biosynthetic enzyme belongs to the PLP-dependent alpha-oxoamine synthase family.

    Evidence Molecular cloning and complementation of lcb1-defective S. cerevisiae strains restoring SPT activity

    PMID:2066332

    Open questions at the time
    • Whether LCB1 alone is sufficient for catalysis or requires additional subunits was unknown
    • Mammalian ortholog not yet cloned
  2. 1994 High

    Demonstrating that SPT requires co-overexpression of both LCB1 and LCB2 for elevated activity established the obligate heterodimeric architecture of the enzyme, resolving why single-subunit overexpression was insufficient.

    Evidence Yeast co-overexpression of LCB1 and LCB2 with enzyme activity measurements

    PMID:8058731

    Open questions at the time
    • Stoichiometry and active-site architecture unresolved
    • Mammalian complex not yet characterized
  3. 1998 High

    Reciprocal co-immunoprecipitation of mammalian SPTLC1 and SPTLC2 with co-purifying SPT activity confirmed that the heterodimeric enzyme architecture is conserved from yeast to mammals, enabling biochemical studies in human cells.

    Evidence Co-IP and affinity pulldown of endogenous SPTLC1/2 from mammalian cells with activity assays

    PMID:9405408 PMID:9837968

    Open questions at the time
    • Active-site location within the heterodimer not mapped
    • Membrane topology and ER retention mechanism unknown
  4. 2002 High

    Determining that SPTLC1 has a single N-terminal transmembrane domain with lumen-facing N-terminus and that it is required for SPTLC2 protein stability resolved both the membrane topology and the structural basis for obligate heterodimerization.

    Evidence Epitope-tag orientation analysis, subcellular fractionation, and SPTLC1-null CHO cell rescue

    PMID:12464627

    Open questions at the time
    • ER retention signals not identified
    • Relationship of topology to catalytic mechanism unresolved
  5. 2002 High

    HSN1 mutations in SPTLC1 (C133Y/W, V144D) were shown to dominantly reduce SPT activity by ~50% and to cluster near the predicted PLP-binding site at the LCB1–LCB2 interface, establishing the first mechanistic link between SPTLC1 mutations, active-site disruption, and hereditary neuropathy.

    Evidence Yeast dominance tests, enzyme activity assays, structural modeling, co-IP confirming retained LCB2 interaction

    PMID:11242106 PMID:11242114 PMID:11781309

    Open questions at the time
    • No high-resolution structure of the eukaryotic enzyme
    • Whether activity reduction alone explains neuronal toxicity was unclear
  6. 2009 High

    Discovery that HSN1 mutations shift SPT substrate specificity from serine to alanine/glycine, generating neurotoxic 1-deoxysphingolipids, fundamentally reframed the disease mechanism from simple loss-of-function to a toxic gain-of-function, and rescue by wild-type SPTLC1 overexpression validated the model in vivo.

    Evidence Transgenic mouse double-transgenic rescue, lipid mass spectrometry, bacterial SPT crystal structures of equivalent mutations

    PMID:19376777 PMID:19923297

    Open questions at the time
    • No crystal structure of mammalian SPT to confirm active-site rearrangement
    • Downstream mechanisms of deoxysphingolipid neurotoxicity unknown
  7. 2009 High

    Identification of a C-terminal PDZ-binding motif in SPTLC1 that recruits Par3 to regulate SPT activity and MCP-1-driven chemotaxis revealed a previously unrecognized link between sphingolipid biosynthesis and cell polarity/migration signaling.

    Evidence PDZ domain array screen, co-IP of endogenous Par3–SPTLC1/2 complex, siRNA knockdown reducing SPT activity and chemotaxis in monocytes

    PMID:19592499

    Open questions at the time
    • Whether Par3 modulates SPT at the active-site level or via localization is unknown
    • Relevance in non-immune cell types not tested
  8. 2013 High

    ABL kinase-dependent phosphorylation of SPTLC1 at Tyr164 was shown to inhibit SPT activity, connecting sphingolipid metabolism to oncogenic tyrosine kinase signaling and explaining a mechanism by which BCR-ABL protects cells from ceramide-driven apoptosis.

    Evidence ER microsome phosphoproteomics, in vitro ABL kinase assay, Y164F mutagenesis with SPT activity and apoptosis readouts

    PMID:23629659

    Open questions at the time
    • Whether other kinases phosphorylate this site in vivo
    • Structural basis for how Y164 phosphorylation inhibits catalysis unknown
  9. 2015 High

    Systematic profiling of 11 HSAN1 SPTLC1 mutants confirmed that deoxysphingolipid overproduction occurs without proportional loss of canonical serine-based activity, establishing the substrate-shift as a universal feature of HSAN1 mutations and enabling structure–severity correlations.

    Evidence Stable isotope labelling SPT activity assay across mutant panel, homology modeling

    PMID:26681808

    Open questions at the time
    • No mammalian SPT structure for definitive active-site mapping
    • Mutant-specific differences in substrate preference not fully explained structurally
  10. 2018 High

    Mapping the ORMDL interaction interface to the first transmembrane domain of Lcb1/SPTLC1 resolved how homeostatic sphingolipid sensing controls SPT: ORM proteins bind the TMD to promote SPT oligomerization and suppress activity, a mechanism later found disrupted in ALS-linked mutations.

    Evidence TMD1 deletion/replacement mutagenesis in yeast, co-IP for ORM binding, fluorescence imaging of SPT oligomers

    PMID:30529276

    Open questions at the time
    • High-resolution structure of the SPTLC1–ORMDL complex not yet available
    • Whether ORMDL regulation involves allosteric or steric inhibition unresolved
  11. 2022 High

    Endothelial-specific SPTLC1 knockout demonstrated that de novo sphingolipid synthesis is essential for lipid raft integrity, VEGF receptor signaling, and developmental angiogenesis, extending SPTLC1 function beyond neurobiology to vascular biology.

    Evidence EC-specific Cre-lox knockout in mice, retinal vascular imaging, VEGF signaling assays, lipidomics

    PMID:36197001

    Open questions at the time
    • Whether sphingolipid species other than ceramide mediate the vascular phenotype is unclear
    • Relevance to adult pathological angiogenesis not tested
  12. 2023 Medium

    An ALS-linked SPTLC1 p.L38R mutation in the first transmembrane domain was shown to disrupt ORMDL binding and release homeostatic suppression, causing globally elevated sphingolipid synthesis — establishing a gain-of-function mechanism mechanistically distinct from the HSAN1 substrate shift.

    Evidence Plasma lipidomics, HEK293 expression with SPT activity assay, genetic characterization

    PMID:37348646

    Open questions at the time
    • ORMDL interaction loss inferred from activity data rather than direct binding assay
    • Whether all ALS-linked TMD mutations share this mechanism needs confirmation
    • No in vivo model for SPTLC1-ALS

Open questions

Synthesis pass · forward-looking unresolved questions
  • A high-resolution structure of the human SPTLC1–SPTLC2–ORMDL holoenzyme complex and the molecular basis for how TMD mutations versus active-site-proximal mutations produce mechanistically distinct disease outcomes remain to be determined.
  • No cryo-EM or crystal structure of mammalian SPT holoenzyme with ORMDL bound
  • Mechanism of 1-deoxysphingolipid neurotoxicity at the cellular level unresolved
  • Whether pharmacological correction of substrate specificity or ORMDL binding is therapeutically feasible is untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 7 GO:0098772 molecular function regulator activity 3
Localization
GO:0005783 endoplasmic reticulum 2
Pathway
R-HSA-1430728 Metabolism 6 R-HSA-1643685 Disease 5
Partners
ABCA1ABL1ORMDL3PARD3SPTLC2
Complex memberships
SPT (serine palmitoyltransferase heterodimer: SPTLC1-SPTLC2)SPT-ORMDL regulatory complex

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 LCB1 (yeast ortholog of SPTLC1) encodes serine palmitoyltransferase or a subunit thereof, as demonstrated by molecular cloning and complementation of lcb1-defective yeast strains that lack serine palmitoyltransferase activity. The protein has predicted transmembrane helices and homology to pyridoxal 5'-phosphate-dependent alpha-oxoamine synthases. Molecular cloning, yeast complementation assay, sequence analysis Journal of bacteriology High 2066332
1994 Yeast LCB1 and LCB2 (orthologs of SPTLC1 and SPTLC2) both encode subunits of serine palmitoyltransferase; overproduction of both together is required for increased SPT activity, establishing a heterodimeric complex. Yeast genetics, overexpression, enzyme activity assay Proceedings of the National Academy of Sciences of the United States of America High 8058731
1997 Mammalian LCB1 (SPTLC1) is a component of serine palmitoyltransferase; transfection of SPT-defective CHO cells (LY-B) with CHO LCB1 cDNA restored both SPT activity and de novo sphingolipid synthesis; SPT activity co-purified with His6-tagged LCB1 on Ni2+ resin. CHO cell complementation, affinity purification, enzyme activity assay The Journal of biological chemistry High 9405408
1998 SPTLC1 (LCB1) and LCB2 form a heterodimeric SPT complex in mammalian cells; anti-LCB2 antibody co-immunoprecipitated both SPT activity and LCB1; affinity-tagged LCB1 pulled down endogenous LCB2, demonstrating direct physical interaction. Co-immunoprecipitation, affinity pulldown, enzyme activity assay The Journal of biological chemistry High 9837968
2001 Missense mutations in SPTLC1 (C133Y, C133W, V144D) cause hereditary sensory neuropathy type I (HSN1) and are associated with increased de novo glucosyl ceramide synthesis in lymphoblast cell lines, suggesting altered SPT enzyme activity. Mutation screening, lipid biosynthesis assay in patient lymphoblasts Nature genetics High 11242106 11242114
2002 HSN1-corresponding mutations in yeast LCB1 (equivalent to SPTLC1) dominantly reduce SPT activity by ~50% when co-expressed with wild-type, establishing a dominant-negative mechanism. The mutant Lcb1p retains interaction with Lcb2p. Modeling indicates SPT has a single active site at the LCB1-LCB2 interface, and the mutations reside near the PLP-binding lysine in LCB2. Yeast genetics, enzyme activity assay, co-expression dominance test, structural modeling, co-immunoprecipitation The Journal of biological chemistry High 11781309
2002 SPTLC1 is an integral ER membrane protein with a single transmembrane domain near the N-terminus, with its N-terminus oriented to the ER lumen and C-terminus to the cytosol. SPTLC1 is required for maintenance of LCB2 protein levels; LY-B cells lacking SPTLC1 have drastically reduced LCB2, which is restored by SPTLC1 transfection. Indirect immunofluorescence with N- and C-terminal epitope tags, subcellular fractionation, Western blotting, stable transfection of LY-B cells The Journal of biological chemistry High 12464627
2005 Transgenic mice overexpressing mutant SPTLC1 (C133W) dominantly inhibit SPT activity in vivo and develop age-dependent peripheral neuropathy with loss of myelinated axons and myelin thinning, confirming the dominant inhibition mechanism in a mammalian model. Transgenic mouse model, SPT activity assay, neuropathological analysis, axon counting Human molecular genetics High 16210380
2008 SPTLC1 (but not SPTLC2) physically interacts with ABCA1 and negatively regulates ABCA1's cholesterol efflux activity by blocking ABCA1 exit from the ER. This interaction was confirmed by co-immunoprecipitation in THP-1 macrophages and mouse liver. siRNA knockdown of SPTLC1 and pharmacologic inhibition with myriocin both increased ABCA1 efflux activity ~60%. Affinity purification/mass spectrometry, co-immunoprecipitation, siRNA knockdown, dominant-negative SPTLC1 mutants, ABCA1 trafficking assay Biochemistry High 18484747
2009 SPTLC1 HSN1 mutations (C133W) alter the amino acid substrate selectivity of SPT such that palmitate is condensed with alanine and glycine in addition to serine, generating neurotoxic deoxysphingoid bases (1-deoxy-sphingolipids). Overexpression of wild-type SPTLC1 rescues the neuropathy phenotype and reduces deoxysphingolipid levels in a mouse model. Transgenic mouse genetics (double transgenic rescue), lipid mass spectrometry, SPT activity assay The Journal of neuroscience High 19923297
2009 Crystal structures and kinetic analysis of bacterial SPT (Sphingomonas paucimobilis) mimicking HSN1 mutations (N100Y, N100W equivalent to SPTLC1 C133Y/W) reveal structural changes around the active site that impair movement of catalytic Arg378, alter PLP chemistry, and destabilize a quinonoid intermediate, providing mechanistic insight into how disease mutations perturb enzyme activity. X-ray crystallography, kinetic assays, spectroscopic analysis, site-directed mutagenesis The Journal of biological chemistry High 19376777
2009 SPTLC1 interacts with the PDZ protein Par3 via a conserved C-terminal type II PDZ-binding motif. Par3 associates with the SPTLC1/2 holoenzyme, and Par3 knockdown by siRNA reduces SPT activity and de novo ceramide synthesis by ~40% in THP-1 monocytes, and also reduces MCP-1-induced chemotaxis in a manner dependent on SPT activity. PDZ domain protein array screen, co-immunoprecipitation, siRNA knockdown, enzyme activity assay, chemotaxis assay The Journal of biological chemistry High 19592499
2011 SPTLC1 mutations p.S331F and p.A352V reduce SPT activity in vitro and increase deoxysphingoid base (1-deoxy-sphinganine, 1-deoxymethyl-sphinganine) levels in patients' plasma and in stably expressing HEK293T cells, confirming the substrate shift to L-alanine as a shared pathogenic mechanism across HSAN1 mutations. In vitro SPT activity assay, stable cell expression, plasma lipid mass spectrometry Human mutation High 21618344
2013 SPTLC1 is phosphorylated at Tyr164 by the tyrosine kinase ABL, which inhibits SPT enzyme activity. Phosphoproteomic identification in ER microsomes, validated by in vitro kinase assay. Y164F mutation of SPTLC1 increased SPT activity, increased ceramide-driven apoptosis, and sensitized BCR-ABL-expressing cells to imatinib-induced cell death. Phosphoproteomic analysis, in vitro ABL kinase assay, site-directed mutagenesis (Y164F), SPT activity assay, apoptosis assay The Journal of biological chemistry High 23629659
2015 Systematic enzymatic profiling of 11 SPTLC1 and 6 SPTLC2 HSAN1 mutants using isotope-labelling revealed that HSAN1 mutations cause increased 1-deoxysphingolipid synthesis without reducing canonical serine activity. A homology model based on prokaryotic SPT structure grouped mutations into structural clusters that predict clinical severity. Stable isotope labelling SPT activity assay, homology structural modeling, plasma sphingoid base profiling Human molecular genetics High 26681808
2015 SPTLC2 Ser384 is a phosphorylation site (confirmed by isoelectric focusing); phosphomimetic S384D mutation increased 1-deoxysphingolipid formation, suggesting that phosphorylation at this position regulates SPT substrate specificity in wild-type enzyme. Isoelectric focusing, site-directed mutagenesis, SPT activity assay in HEK293 cells Neuromolecular medicine Medium 25567748
2018 The first transmembrane domain (TMD1) of Lcb1 (yeast SPTLC1 ortholog) is required for ORM protein binding to SPT. Loss of ORM binding abolishes ORM-dependent SPT oligomerization and partially alters SPT redistribution within the ER, establishing TMD1 as the ORM interaction interface that mediates homeostatic regulation. Co-immunoprecipitation, in vivo fluorescence imaging, yeast genetics, deletion/replacement mutagenesis of TMD1 Biochimica et biophysica acta. Molecular and cell biology of lipids High 30529276
2019 Sptlc1 deletion in adult bone marrow cells causes defective myeloid differentiation, expansion of multipotent progenitors, and ER stress due to accumulation of fatty acid substrate. ER stress (also induced by thapsigargin or palmitate) independently compromises myeloid differentiation, establishing that sphingolipid biosynthesis via SPTLC1 is required for normal myeloid cell development. Conditional bone marrow knockout, chimeric mouse transplant assay, ER stress marker analysis, pharmacological ER stress induction Blood advances High 31751474
2021 SPTLC1 ALS-linked variants (p.Ala20Ser, p.Ser331Tyr, p.Leu39del) are de novo mutations that disrupt the sphingolipid synthesis pathway, broadening the pathogenic mechanism of SPTLC1 mutations beyond sensory neuropathy to include motor neuron disease. Trio whole-exome sequencing, genetic analysis of de novo variants JAMA neurology Medium 34459874
2022 Endothelial-specific knockout of SPTLC1 in mice reduces EC sphingolipid de novo synthesis, impairs lipid raft formation, decreases VEGF signaling efficiency, reduces EC proliferation and tip/stalk cell differentiation, causing delayed retinal vascular development and reduced neovascularization. Postnatal EC-specific deletion also rapidly reduces sphingolipid metabolites in plasma and peripheral organs but not CNS. Endothelial-specific conditional knockout (Cre-lox), retinal vascular imaging, VEGF signaling assay, lipid raft analysis, lipidomics eLife High 36197001
2023 Novel SPTLC1 p.L38R mutation (in the first transmembrane domain/exon 2) impedes interaction with the regulatory ORMDL subunit, releasing homeostatic suppression of SPT activity. This results in globally increased sphingolipid levels and particularly elevated dihydrosphingolipids in patient plasma and p.L38R-expressing HEK293 cells. Plasma lipidomics, HEK293 cell expression, SPT activity assay, clinical/genetic characterization Biochimica et biophysica acta. Molecular and cell biology of lipids Medium 37348646
2025 ATF4, induced by cocaine-triggered ER stress in D1-MSNs, directly targets the SPTLC1 promoter and upregulates SPTLC1 expression, remodeling sphingolipid metabolism. D1-MSN-specific knockdown of SPTLC1 markedly reduced cocaine-induced behavioral and neuroplastic changes, establishing an ATF4-SPTLC1 signaling axis in ER stress-driven neuroadaptation. Promoter analysis, functional validation, D1-MSN-specific viral knockdown, behavioral assays, sphingolipid synthesis assay Frontiers in pharmacology Medium 41378204

Source papers

Stage 0 corpus · 64 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Mutations in SPTLC1, encoding serine palmitoyltransferase, long chain base subunit-1, cause hereditary sensory neuropathy type I. Nature genetics 330 11242114
2001 SPTLC1 is mutated in hereditary sensory neuropathy, type 1. Nature genetics 233 11242106
1994 The LCB2 gene of Saccharomyces and the related LCB1 gene encode subunits of serine palmitoyltransferase, the initial enzyme in sphingolipid synthesis. Proceedings of the National Academy of Sciences of the United States of America 187 8058731
1991 Cloning and characterization of LCB1, a Saccharomyces gene required for biosynthesis of the long-chain base component of sphingolipids. Journal of bacteriology 175 2066332
1998 Mammalian cell mutants resistant to a sphingomyelin-directed cytolysin. Genetic and biochemical evidence for complex formation of the LCB1 protein with the LCB2 protein for serine palmitoyltransferase. The Journal of biological chemistry 165 9837968
2006 The essential nature of sphingolipids in plants as revealed by the functional identification and characterization of the Arabidopsis LCB1 subunit of serine palmitoyltransferase. The Plant cell 133 17194770
1997 A mammalian homolog of the yeast LCB1 encodes a component of serine palmitoyltransferase, the enzyme catalyzing the first step in sphingolipid synthesis. The Journal of biological chemistry 121 9405408
2002 Mutations in the yeast LCB1 and LCB2 genes, including those corresponding to the hereditary sensory neuropathy type I mutations, dominantly inactivate serine palmitoyltransferase. The Journal of biological chemistry 92 11781309
2009 Overexpression of the wild-type SPT1 subunit lowers desoxysphingolipid levels and rescues the phenotype of HSAN1. The Journal of neuroscience : the official journal of the Society for Neuroscience 89 19923297
2002 Localization, topology, and function of the LCB1 subunit of serine palmitoyltransferase in mammalian cells. The Journal of biological chemistry 71 12464627
2021 Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis. JAMA neurology 70 34459874
2015 HSAN1 mutations in serine palmitoyltransferase reveal a close structure-function-phenotype relationship. Human molecular genetics 69 26681808
2009 The external aldimine form of serine palmitoyltransferase: structural, kinetic, and spectroscopic analysis of the wild-type enzyme and HSAN1 mutant mimics. The Journal of biological chemistry 62 19376777
2005 Mutant SPTLC1 dominantly inhibits serine palmitoyltransferase activity in vivo and confers an age-dependent neuropathy. Human molecular genetics 61 16210380
2013 DNMT1 mutation hot spot causes varied phenotypes of HSAN1 with dementia and hearing loss. Neurology 56 23365052
2011 Characterization of two mutations in the SPTLC1 subunit of serine palmitoyltransferase associated with hereditary sensory and autonomic neuropathy type I. Human mutation 36 21618344
2013 Mutations at Ser331 in the HSN type I gene SPTLC1 are associated with a distinct syndromic phenotype. European journal of medical genetics 35 23454272
2004 Activity of partially inhibited serine palmitoyltransferase is sufficient for normal sphingolipid metabolism and viability of HSN1 patient cells. Biochimica et biophysica acta 35 14990347
2008 SPTLC1 binds ABCA1 to negatively regulate trafficking and cholesterol efflux activity of the transporter. Biochemistry 34 18484747
2018 The ORMs interact with transmembrane domain 1 of Lcb1 and regulate serine palmitoyltransferase oligomerization, activity and localization. Biochimica et biophysica acta. Molecular and cell biology of lipids 30 30529276
2004 SPTLC1 mutation in twin sisters with hereditary sensory neuropathy type I. Neurology 30 15037712
2015 Novel HSAN1 mutation in serine palmitoyltransferase resides at a putative phosphorylation site that is involved in regulating substrate specificity. Neuromolecular medicine 25 25567748
2019 Decreased SPTLC1 expression predicts worse outcomes in ccRCC patients. Journal of cellular biochemistry 23 31512789
2014 Mutations in the SPTLC1 protein cause mitochondrial structural abnormalities and endoplasmic reticulum stress in lymphoblasts. DNA and cell biology 22 24673574
2013 Phosphorylation of serine palmitoyltransferase long chain-1 (SPTLC1) on tyrosine 164 inhibits its activity and promotes cell survival. The Journal of biological chemistry 21 23629659
2005 SPTLC1 and RAB7 mutation analysis in dominantly inherited and idiopathic sensory neuropathies. Journal of neurology, neurosurgery, and psychiatry 21 15965219
2013 Early-onset severe hereditary sensory and autonomic neuropathy type 1 with S331F SPTLC1 mutation. Molecular medicine reports 20 24247255
2022 Murine endothelial serine palmitoyltransferase 1 (SPTLC1) is required for vascular development and systemic sphingolipid homeostasis. eLife 17 36197001
2021 Precision mouse models of Yars/dominant intermediate Charcot-Marie-Tooth disease type C and Sptlc1/hereditary sensory and autonomic neuropathy type 1. Journal of anatomy 17 34875719
2009 Cell polarity factor Par3 binds SPTLC1 and modulates monocyte serine palmitoyltransferase activity and chemotaxis. The Journal of biological chemistry 17 19592499
2021 Metabolism of HSAN1- and T2DM-associated 1-deoxy-sphingolipids inhibits the migration of fibroblasts. Journal of lipid research 14 34563520
2005 Late-onset hereditary sensory neuropathy type I due to SPTLC1 mutation: autopsy findings. Clinical neurology and neurosurgery 12 16271825
2023 SPTLC1 p.Leu38Arg, a novel mutation associated with childhood ALS. Biochimica et biophysica acta. Molecular and cell biology of lipids 11 37348646
2022 The SPTLC1 p.S331 mutation bridges sensory neuropathy and motor neuron disease and has implications for treatment. Neuropathology and applied neurobiology 11 35904184
2019 Sptlc1 is essential for myeloid differentiation and hematopoietic homeostasis. Blood advances 11 31751474
2013 The pyridoxal 5'-phosphate (PLP)-dependent enzyme serine palmitoyltransferase (SPT): effects of the small subunits and insights from bacterial mimics of human hLCB2a HSAN1 mutations. BioMed research international 11 24175284
2023 Mutation screening of SPTLC1 and SPTLC2 in amyotrophic lateral sclerosis. Human genomics 10 36966328
2022 Resistance profile and mechanism of severe acute respiratory syndrome coronavirus-2 variants to LCB1 inhibitor targeting the spike receptor-binding motif. Frontiers in microbiology 9 36304946
2008 [The first break-through of the genotype 2.3.2 of high-virulence influenza A virus A/HSN1, which is new for Russia, in the Far East]. Voprosy virusologii 9 19069785
2023 Pathogenic variants in the SPTLC1 gene cause hyperkeratosis lenticularis perstans. The British journal of dermatology 8 36689507
2022 Description of a patient cohort with Hereditary Sensory Neuropathy type 1 without retinal disease Macular Telangiectasia type 2 - implications for retinal screening in HSN1. Journal of the peripheral nervous system : JPNS 7 35837722
2019 SPTLC1 inhibits cell growth via modulating Akt/FOXO1 pathway in renal cell carcinoma cells. Biochemical and biophysical research communications 7 31554600
2018 V144D Mutation of SPTLC1 Can Present with Both Painful and Painless Phenotypes in Hereditary Sensory and Autonomic Neuropathies Type I. Case reports in genetics 7 30420926
2014 Mitochondrial protein alterations in a familial peripheral neuropathy caused by the V144D amino acid mutation in the sphingolipid protein, SPTLC1. Journal of chemical biology 7 25584079
2022 New Insights into the Neuromyogenic Spectrum of a Gain of Function Mutation in SPTLC1. Genes 6 35627278
2022 A de novo c.113 T > C: p.L38R mutation of SPTLC1: case report of a girl with sporadic juvenile amyotrophic lateral sclerosis. Amyotrophic lateral sclerosis & frontotemporal degeneration 6 36204986
2023 Development of highly effective LCB1-based lipopeptides targeting the spike receptor-binding motif of SARS-CoV-2. Antiviral research 5 36682464
2023 Phosphorylation of the LCB1 subunit of Arabidopsis serine palmitoyltransferase stimulates its activity and modulates sphingolipid biosynthesis. Journal of integrative plant biology 5 36738228
2020 Expanding the spectrum of SPTLC1-related disorders beyond hereditary sensory and autonomic neuropathies: A novel case of the distinct "S331 syndrome". Journal of the peripheral nervous system : JPNS 5 32470188
2023 Clinical feature difference between juvenile amyotrophic lateral sclerosis with SPTLC1 and FUS mutations. Chinese medical journal 4 36801857
2013 Enhanced stability of newly isolated trimeric l-methionine-N-carbamoylase from Brevibacillus reuszeri HSN1 by covalent immobilization. Biotechnology and applied biochemistry 4 23682726
2023 Spectrum of SPTLC1-related disorders: a novel case of 'Ser331 syndrome' that expand the phenotype of hereditary sensory and autonomic neuropathy type 1A and motor neuron diseases. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 3 36964315
2023 Specific Deoxyceramide Species Correlate with Expression of Macular Telangiectasia Type 2 (MacTel2) in a SPTLC2 Carrier HSAN1 Family. Genes 3 37107689
2022 Calcium-Mediated Calpain Activation and Microtubule Dissociation in Cell Model of Hereditary Sensory Neuropathy Type-1 Expressing V144D SPTLC1 Mutation. DNA and cell biology 3 34986032
2013 Trimeric l-N-carbamoylase from newly isolated Brevibacillus reuszeri HSN1: a potential biocatalyst for production of l-α-amino acids. Biotechnology and applied biochemistry 3 23586522
2023 Susceptibility and Resistance of SARS-CoV-2 Variants to LCB1 and Its Multivalent Derivatives. Viruses 2 38257736
2025 Effect of SPTLC1 on type 2 diabetes mellitus. World journal of diabetes 1 39959268
2025 Lack of motor defects and ALS-like neuropathology in heterozygous Sptlc1 Exon 2 deletion mice. bioRxiv : the preprint server for biology 0 40027730
2025 Fusion of SARS-CoV-2 neutralizing LCB1 peptide with Bacillus amyloliquefaciens RNase improves antiviral efficacy. Scientific reports 0 40744985
2025 Effects of sphingolipid metabolism related genes-SPTLC1, ORMDL3, SPHK1 and S1PR3 polymorphisms on susceptibility to hashimoto's thyroiditis. Journal of endocrinological investigation 0 40782218
2025 The Contradictory Effects of SPTLC1 on Clear Cell Renal Carcinoma Sensitivity to Sunitinib Mediated by Androgen Receptor. Molecular carcinogenesis 0 40793989
2025 Antisense oligonucleotides reverse SPTLC1-related hereditary sensory neuropathy in a mouse model. Brain : a journal of neurology 0 41124364
2025 ER stress in D1-MSNs mediates cocaine-induced behavioral plasticity via the ATF4-SPTLC1 axis. Frontiers in pharmacology 0 41378204
2019 Comprehensive Computational Analysis of Protein Phenotype Changes Due to Plausible Deleterious Variants of Human SPTLC1 Gene. International journal of molecular and cellular medicine 0 32195206