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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O15269: Variant p.Tyr23Phe

Serine palmitoyltransferase 1
Gene: SPTLC1
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Variant information Variant position: help 23 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help LP/P [Disclaimer] The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance
Residue change: help From Tyrosine (Y) to Phenylalanine (F) at position 23 (Y23F, p.Tyr23Phe). Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.
Physico-chemical properties: help Similar physico-chemical property. Both residues are large size and aromatic. The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help 3 The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page
Variant description: help In ALS27; increased production of sphinganine and ceramides, when expressed in induced pluripotent stem cells (iPSC) differentiated into motor neuron-like cells; decreased response to inhibition mediated by ORMDL3 and ceramide; no effect on the interaction with ORMDL3. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 23 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 473 The length of the canonical sequence.
Location on the sequence: help TATEQWVLVEMVQALYEAPA Y HLILEGILILWIIRLLFSKT The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.
Residue conservation: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         TATE------------------QWVLVEMVQ---------------------ALYEAPAYHLILE-GILILWIIRLLF-SKT

Mouse                         TVAE------------------QWVLVEMVQ----------

Rat                           TVAE------------------QWVLVEMVQ----------

Bovine                        TVAE------------------QWVLVEMVQ----------

Caenorhabditis elegans        FLPD------------------SWHFY--------------

Slime mold                    FLFDIYNN--------------ILYYTKEFI----------

Baker's yeast                 HIPEVLPKSIPIPAFIVTTSSYLWYYFNLVL-------TQI

Fission yeast                 YSYPFFDD--------------VYAYYNQTVTFFGKALDVL
Sequence annotation in neighborhood: help The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.
TypePositionsDescription
Chain 1 – 473 Serine palmitoyltransferase 1
Transmembrane 16 – 36 Helical
Region 1 – 66 Interaction with SPTLC2
Helix 22 – 39



Literature citations
Ceramide sensing by human SPT-ORMDL complex for establishing sphingolipid homeostasis.
Xie T.; Liu P.; Wu X.; Dong F.; Zhang Z.; Yue J.; Mahawar U.; Farooq F.; Vohra H.; Fang Q.; Liu W.; Wattenberg B.W.; Gong X.;
Nat. Commun. 14:3475-3475(2023)
Cited for: STRUCTURE BY ELECTRON MICROSCOPY (2.70 ANGSTROMS) IN COMPLEX WITH SPTLC2; SPTSSA AND ORMDL3; CHARACTERIZATION OF VARIANTS ALS27 PHE-23; LEU-39 DEL AND 40-PHE-SER-41 DEL; ACTIVITY REGULATION;
Childhood amyotrophic lateral sclerosis caused by excess sphingolipid synthesis.
Mohassel P.; Donkervoort S.; Lone M.A.; Nalls M.; Gable K.; Gupta S.D.; Foley A.R.; Hu Y.; Saute J.A.M.; Moreira A.L.; Kok F.; Introna A.; Logroscino G.; Grunseich C.; Nickolls A.R.; Pourshafie N.; Neuhaus S.B.; Saade D.; Gangfuss A.; Koelbel H.; Piccus Z.; Le Pichon C.E.; Fiorillo C.; Ly C.V.; Toepf A.; Brady L.; Specht S.; Zidell A.; Pedro H.; Mittelmann E.; Thomas F.P.; Chao K.R.; Konersman C.G.; Cho M.T.; Brandt T.; Straub V.; Connolly A.M.; Schara U.; Roos A.; Tarnopolsky M.; Hoeke A.; Brown R.H.; Lee C.H.; Hornemann T.; Dunn T.M.; Boennemann C.G.;
Nat. Med. 27:1197-1204(2021)
Cited for: INVOLVEMENT IN ALS27; VARIANTS ALS27 SER-20; PHE-23; LEU-39 DEL AND 40-PHE-SER-41 DEL; CHARACTERIZATION OF VARIANTS ALS27 SER-20; PHE-23; LEU-39 DEL AND 40-PHE-SER-41 DEL; HOMEOSTATIC REGULATION BY ORMDL3 IN THE PRESENCE OF CERAMIDES;
Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.