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UniProtKB/Swiss-Prot O95470: Variant p.Arg222Gln

Sphingosine-1-phosphate lyase 1
Gene: SGPL1
Variant information

Variant position:  222
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Arginine (R) to Glutamine (Q) at position 222 (R222Q, p.Arg222Gln).
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:  Change from large size and basic (R) to medium size and polar (Q)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  1
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:  In NPHS14; probable disease-associated mutation also found in a patient with isolated primary adrenal insufficiency; decreased protein abundance; increased aggregation; decreased sphinganine-1-phosphate aldolase activity.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  222
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  568
The length of the canonical sequence.

Location on the sequence:   SCGCVTSGGTESILMACKAY  R DLAFEKGIKTPEIVAPQSAH
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: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         SCGCVTSGGTESILMACKAYRDLAFEKGIKTPEIVAPQSAH

Mouse                         SCGCVTSGGTESILMACKAYRDLALEKGIKTPEIVAPESAH

Rat                           SCGCVTSGGTESILMACKAYRDLALEKGIKTPEIVAPESAH

Sequence annotation in neighborhood:  
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
Mutagenesis 218 – 218 C -> G. Loss of sphinganine-1-phosphate aldolase activity.
Helix 210 – 227


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 NPHS14; VARIANTS NPHS14 GLN-222; TRP-222; ILE-346 AND CYS-416; CHARACTERIZATION OF VARIANTS NPHS14 GLN-222 AND ILE-346; FUNCTION; CATALYTIC ACTIVITY; PATHWAY; MUTAGENESIS OF GLU-132;

Sphingosine-1-phosphate lyase mutations cause primary adrenal insufficiency and steroid-resistant nephrotic syndrome.
Prasad R.; Hadjidemetriou I.; Maharaj A.; Meimaridou E.; Buonocore F.; Saleem M.; Hurcombe J.; Bierzynska A.; Barbagelata E.; Bergada I.; Cassinelli H.; Das U.; Krone R.; Hacihamdioglu B.; Sari E.; Yesilkaya E.; Storr H.L.; Clemente M.; Fernandez-Cancio M.; Camats N.; Ram N.; Achermann J.C.; Van Veldhoven P.P.; Guasti L.; Braslavsky D.; Guran T.; Metherell L.A.;
J. Clin. Invest. 127:942-953(2017)
Cited for: INVOLVEMENT IN NPHS14; VARIANTS NPHS14 GLN-222 AND PHE-545 DEL; CHARACTERIZATION OF VARIANTS NPHS14 GLN-222 AND PHE-545 DEL; TISSUE SPECIFICITY;

SGPL1 Deficiency: A Rare Cause of Primary Adrenal Insufficiency.
Settas N.; Persky R.; Faucz F.R.; Sheanon N.; Voutetakis A.; Lodish M.; Metherell L.A.; Stratakis C.A.;
J. Clin. Endocrinol. Metab. 104:1484-1490(2019)
Cited for: VARIANTS LEU-21 AND GLN-222;

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.