SPTLC1

Protein identityUniProt · HPA

UniProt accession

O15269

Gene

SPTLC1

Ensembl

ENSG00000090054

Chromosome

9

Canonical length

473 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted membrane proteins

Subcellular location

Endoplasmic reticulum

OverviewNCBI Gene

This gene encodes a member of the class-II pyridoxal-phosphate-dependent aminotransferase family. The encoded protein is the long chain base subunit 1 of serine palmitoyltransferase. Serine palmitoyltransferase converts L-serine and palmitoyl-CoA to 3-oxosphinganine with pyridoxal 5'-phosphate and is the key enzyme in sphingolipid biosynthesis. Mutations in this gene were identified in patients with hereditary sensory neuropathy type 1. Alternatively spliced variants encoding different isoforms have been identified. Pseudogenes of this gene have been defined on chromosomes 1, 6, 10, and 13. [provided by RefSeq, Jul 2013]

Canonical amino-acid sequenceUniProt

473 residues, UniProt reviewed canonical sequence.

>O15269|SPTLC1
     1  MATATEQWVL VEMVQALYEA PAYHLILEGI LILWIIRLLF SKTYKLQERS DLTVKEKEEL
    61  IEEWQPEPLV PPVPKDHPAL NYNIVSGPPS HKTVVNGKEC INFASFNFLG LLDNPRVKAA
   121  ALASLKKYGV GTCGPRGFYG TFDVHLDLED RLAKFMKTEE AIIYSYGFAT IASAIPAYSK
   181  RGDIVFVDRA ACFAIQKGLQ ASRSDIKLFK HNDMADLERL LKEQEIEDQK NPRKARVTRR
   241  FIVVEGLYMN TGTICPLPEL VKLKYKYKAR IFLEESLSFG VLGEHGRGVT EHYGINIDDI
   301  DLISANMENA LASIGGFCCG RSFVIDHQRL SGQGYCFSAS LPPLLAAAAI EALNIMEENP
   361  GIFAVLKEKC GQIHKALQGI SGLKVVGESL SPAFHLQLEE STGSREQDVR LLQEIVDQCM
   421  NRSIALTQAR YLEKEEKCLP PPSIRVVVTV EQTEEELERA ASTIKEVAQA VLL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against SPTLC1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Other membrane

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.28

Highest tissue expression

52 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about SPTLC1.

Disease | AllUniProt

Conditions SPTLC1 is implicated in, by any mechanism.

• Amyotrophic lateral sclerosis 27, juvenile (ALS27) MIM:620285
• Neuropathy, hereditary sensory and autonomic, 1A (HSAN1A) MIM:162400

Disease | GeneticClinVar

14 pathogenic / likely-pathogenic of 554 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Hereditary sensory and autonomic neuropathy type 1
• Neuropathy, hereditary sensory and autonomic, type 1A
• Amyotrophic lateral sclerosis 27, juvenile
• Charcot-Marie-Tooth disease
• Inborn genetic diseases

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.98

gnomAD pLI

0

gnomAD missense Z

1.13

DepMap mean gene effect

-0.66

DepMap dependency class

common

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• ceramide biosynthetic process
• positive regulation of lipophagy
• sphinganine biosynthetic process
• sphingolipid biosynthetic process
• sphingolipid metabolic process
• sphingomyelin biosynthetic process
• sphingosine biosynthetic process
• regulation of fat cell apoptotic process

Molecular functions

• pyridoxal phosphate binding
• serine C-palmitoyltransferase activity

Cellular components

• endoplasmic reticulum
• endoplasmic reticulum membrane
• serine palmitoyltransferase complex

Protein domainsUniProt · Pfam · InterPro

• Aminotransferase, class I/classII, large domain
• Pyridoxal phosphate-dependent transferase, major domain
• Pyridoxal phosphate-dependent transferase, small domain
• Pyridoxal phosphate-dependent transferase
• 8-amino-7-oxononanoate synthase class-II
• Aminotransferase class I and II

KeywordsUniProt

• Acyltransferase
• Amyotrophic lateral sclerosis
• Endoplasmic reticulum
• Lipid metabolism
• Membrane
• Neurodegeneration
• Neuropathy
• Phosphoprotein
• Pyridoxal phosphate
• Sphingolipid metabolism
• Transferase
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of SPTLC1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• RTN4
• SERINC1
• ORMDL3
• SPTLC2