Reviewed March 2015
What is the official name of the SPTLC1 gene?
The official name of this gene is “serine palmitoyltransferase, long chain base subunit 1.”
SPTLC1 is the gene's official symbol. The SPTLC1 gene is also known by other names, listed below.
What is the normal function of the SPTLC1 gene?
The SPTLC1 gene provides instructions for making one part (subunit) of an enzyme called serine palmitoyltransferase (SPT). The SPT enzyme is involved in making certain fats called sphingolipids. Sphingolipids are important components of cell membranes that play a role in many cell functions. The SPT enzyme initiates the first step of sphingolipid production, in which the molecules serine and palmitoyl CoA combine to form a molecule called ketodihydrosphingosine. Additional chemical reactions convert ketodihydrosphingosine into various types of sphingolipids. Within the cell, the SPT enzyme is mainly found on the endoplasmic reticulum, which is a structure involved in protein processing and transport.
How are changes in the SPTLC1 gene related to health conditions?
- hereditary sensory neuropathy type IA - caused by mutations in the SPTLC1 gene
At least nine mutations in the SPTLC1 gene have been found to cause hereditary sensory neuropathy type IA. This condition is characterized by nerve abnormalities in the legs and feet (peripheral neuropathy); a reduced ability to feel pain, which can lead to the development of open sores; and muscle weakness that can impair mobility. The SPTLC1 gene mutations change single protein building blocks (amino acids) in the SPTLC1 subunit. One mutation that has been found in multiple affected families worldwide replaces the amino acid cysteine with the amino acid tryptophan at position 133 in the SPTLC1 subunit (written as Cys133Trp or C133W).
SPTLC1 gene mutations reduce the amount of functional SPTLC1 subunit that is produced, which results in an SPT enzyme with altered activity. This altered enzyme makes molecules called deoxysphingoid bases, which it does not normally produce. Because of this new function, the SPT enzyme's production of sphingolipid is reduced. Overall, there does not seem to be a decrease in sphingolipid production because the body is able to compensate for the SPT enzyme's reduced production. When accumulated, deoxysphingoid bases are toxic to neurons. The gradual destruction of nerve cells caused by the buildup of toxic molecules results in loss of sensation and muscle weakness in people with hereditary sensory neuropathy type IA.
Where is the SPTLC1 gene located?
Cytogenetic Location: 9q22.2
Molecular Location on chromosome 9: base pairs 92,031,133 to 92,115,473
The SPTLC1 gene is located on the long (q) arm of chromosome 9 at position 22.2.
More precisely, the SPTLC1 gene is located from base pair 92,031,133 to base pair 92,115,473 on chromosome 9.
See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.
Where can I find additional information about SPTLC1?
You and your healthcare professional may find the following resources about SPTLC1 helpful.
- Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/books/NBK1390)
Genetic Testing Registry - Repository of genetic test information
- GTR: Genetic tests for SPTLC1 (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=10558%5Bgeneid%5D)
You may also be interested in these resources, which are designed for genetics professionals and researchers.
- PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=%28SPTLC1%5BTIAB%5D%29%20AND%20%28%28Genes%5BMH%5D%29%20OR%20%28Genetic%20Phenomena%5BMH%5D%29%29%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%203600%20days%22%5Bdp%5D)
- OMIM - Genetic disorder catalog (http://omim.org/entry/605712)
Research Resources - Tools for researchers
- Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/GC_SPTLC1.html)
- HGNC Gene Symbol Report (http://www.genenames.org/cgi-bin/gene_symbol_report?q=data/hgnc_data.php&hgnc_id=11277)
- Inherited Peripheral Neuropathies Mutation Database: Mutations in SPTLC1 (http://www.molgen.ua.ac.be/CMTMutations/Mutations/Mutations.cfm?Context=13)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/10558)
What other names do people use for the SPTLC1 gene or gene products?
- long chain base biosynthesis protein 1
- serine C-palmitoyltransferase
- serine-palmitoyl-CoA transferase 1
- serine palmitoyltransferase subunit 1
See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
What glossary definitions help with understanding SPTLC1?
amino acid ;
endoplasmic reticulum ;
peripheral neuropathy ;
sensory neuropathy ;
You may find definitions for these and many other terms in the Genetics Home Reference
- Auer-Grumbach M, Bode H, Pieber TR, Schabhüttl M, Fischer D, Seidl R, Graf E, Wieland T, Schuh R, Vacariu G, Grill F, Timmerman V, Strom TM, Hornemann T. Mutations at Ser331 in the HSN type I gene SPTLC1 are associated with a distinct syndromic phenotype. Eur J Med Genet. 2013 May;56(5):266-9. doi: 10.1016/j.ejmg.2013.02.002. Epub 2013 Feb 27. (http://www.ncbi.nlm.nih.gov/pubmed/23454272?dopt=Abstract)
- Bejaoui K, Wu C, Scheffler MD, Haan G, Ashby P, Wu L, de Jong P, Brown RH Jr. SPTLC1 is mutated in hereditary sensory neuropathy, type 1. Nat Genet. 2001 Mar;27(3):261-2. (http://www.ncbi.nlm.nih.gov/pubmed/11242106?dopt=Abstract)
- Dawkins JL, Hulme DJ, Brahmbhatt SB, Auer-Grumbach M, Nicholson GA. Mutations in SPTLC1, encoding serine palmitoyltransferase, long chain base subunit-1, cause hereditary sensory neuropathy type I. Nat Genet. 2001 Mar;27(3):309-12. (http://www.ncbi.nlm.nih.gov/pubmed/11242114?dopt=Abstract)
- Hornemann T, Richard S, Rütti MF, Wei Y, von Eckardstein A. Cloning and initial characterization of a new subunit for mammalian serine-palmitoyltransferase. J Biol Chem. 2006 Dec 8;281(49):37275-81. Epub 2006 Oct 4. (http://www.ncbi.nlm.nih.gov/pubmed/17023427?dopt=Abstract)
- Houlden H, King R, Blake J, Groves M, Love S, Woodward C, Hammans S, Nicoll J, Lennox G, O'Donovan DG, Gabriel C, Thomas PK, Reilly MM. Clinical, pathological and genetic characterization of hereditary sensory and autonomic neuropathy type 1 (HSAN I). Brain. 2006 Feb;129(Pt 2):411-25. Epub 2005 Dec 19. (http://www.ncbi.nlm.nih.gov/pubmed/16364956?dopt=Abstract)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/10558)
- Penno A, Reilly MM, Houlden H, Laurá M, Rentsch K, Niederkofler V, Stoeckli ET, Nicholson G, Eichler F, Brown RH Jr, von Eckardstein A, Hornemann T. Hereditary sensory neuropathy type 1 is caused by the accumulation of two neurotoxic sphingolipids. J Biol Chem. 2010 Apr 9;285(15):11178-87. doi: 10.1074/jbc.M109.092973. Epub 2010 Jan 22. (http://www.ncbi.nlm.nih.gov/pubmed/20097765?dopt=Abstract)
- Rotthier A, Penno A, Rautenstrauss B, Auer-Grumbach M, Stettner GM, Asselbergh B, Van Hoof K, Sticht H, Lévy N, Timmerman V, Hornemann T, Janssens K. Characterization of two mutations in the SPTLC1 subunit of serine palmitoyltransferase associated with hereditary sensory and autonomic neuropathy type I. Hum Mutat. 2011 Jun;32(6):E2211-25. doi: 10.1002/humu.21481. Epub 2011 Feb 24. (http://www.ncbi.nlm.nih.gov/pubmed/21618344?dopt=Abstract)
- OMIM: SERINE PALMITOYLTRANSFERASE, LONG-CHAIN BASE SUBUNIT 1 (http://omim.org/entry/605712)
- Wei J, Yerokun T, Leipelt M, Haynes CA, Radhakrishna H, Momin A, Kelly S, Park H, Wang E, Carton JM, Uhlinger DJ, Merrill AH Jr. Serine palmitoyltransferase subunit 1 is present in the endoplasmic reticulum, nucleus and focal adhesions, and functions in cell morphology. Biochim Biophys Acta. 2009 Aug;1791(8):746-56. doi: 10.1016/j.bbalip.2009.03.016. Epub 2009 Apr 9. (http://www.ncbi.nlm.nih.gov/pubmed/19362163?dopt=Abstract)
The resources on this site should not be used as a substitute for
professional medical care or advice. Users seeking information about
a personal genetic disease, syndrome, or condition should consult with a qualified
See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.