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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O95470: Variant p.Ser346Ile

Sphingosine-1-phosphate lyase 1
Gene: SGPL1
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Variant information Variant position: help 346 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 Serine (S) to Isoleucine (I) at position 346 (S346I, p.Ser346Ile). 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 Change from small size and polar (S) to medium size and hydrophobic (I) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -2 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 RENI; decreased protein abundance in cells of patients homozygous for the mutation; increased aggregation; decreased sphinganine-1-phosphate aldolase activity. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 346 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 568 The length of the canonical sequence.
Location on the sequence: help MEKAGYPLEHPFDFRVKGVT S ISADTHKYGYAPKGSSLVLY 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                         MEKAGYPLEHPFDFRVKGVTSISADTHKYGYAPKGSSLVLY

Mouse                         MEKAGYPLEKPFDFRVKGVTSISADTHKYGYAPKGSSVVMY

Rat                           MEKAGYPLEKPFDFRVKGVTSISADTHKYGYAPKGSSVVMY
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 – 568 Sphingosine-1-phosphate lyase 1
Topological domain 62 – 568 Cytoplasmic
Modified residue 353 – 353 N6-(pyridoxal phosphate)lysine; alternate
Modified residue 353 – 353 N6-acetyllysine; alternate
Modified residue 356 – 356 3'-nitrotyrosine
Modified residue 366 – 366 3'-nitrotyrosine
Mutagenesis 353 – 353 K -> L. Loss of sphinganine-1-phosphate aldolase activity.
Beta strand 344 – 349



Literature citations
Mutations in sphingosine-1-phosphate lyase cause nephrosis with ichthyosis and adrenal insufficiency.
Lovric S.; Goncalves S.; Gee H.Y.; Oskouian B.; Srinivas H.; Choi W.I.; Shril S.; Ashraf S.; Tan W.; Rao J.; Airik M.; Schapiro D.; Braun D.A.; Sadowski C.E.; Widmeier E.; Jobst-Schwan T.; Schmidt J.M.; Girik V.; Capitani G.; Suh J.H.; Lachaussee N.; Arrondel C.; Patat J.; Gribouval O.; Furlano M.; Boyer O.; Schmitt A.; Vuiblet V.; Hashmi S.; Wilcken R.; Bernier F.P.; Innes A.M.; Parboosingh J.S.; Lamont R.E.; Midgley J.P.; Wright N.; Majewski J.; Zenker M.; Schaefer F.; Kuss N.; Greil J.; Giese T.; Schwarz K.; Catheline V.; Schanze D.; Franke I.; Sznajer Y.; Truant A.S.; Adams B.; Desir J.; Biemann R.; Pei Y.; Ars E.; Lloberas N.; Madrid A.; Dharnidharka V.R.; Connolly A.M.; Willing M.C.; Cooper M.A.; Lifton R.P.; Simons M.; Riezman H.; Antignac C.; Saba J.D.; Hildebrandt F.;
J. Clin. Invest. 127:912-928(2017)
Cited for: INVOLVEMENT IN RENI; VARIANTS RENI GLN-222; TRP-222; ILE-346 AND CYS-416; CHARACTERIZATION OF VARIANTS RENI GLN-222 AND ILE-346; FUNCTION; CATALYTIC ACTIVITY; PATHWAY; MUTAGENESIS OF GLU-132;
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.