UniProtKB/Swiss-Prot O15269: Variant p.Ala20Ser

Serine palmitoyltransferase 1
Gene: SPTLC1
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Variant information Variant position:

20 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

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:

From Alanine (A) to Serine (S) at position 20 (A20S, p.Ala20Ser). 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 small size and hydrophobic (A) to small size and polar (S) 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 ALS27; the underlying nucleotide substitution predominantly results in exon 2 skipping; in patient's whole blood sample, only exon 2 deletion was observed, but not the missense variant per se; when exon 2 deletion variant is expressed in induced pluripotent stem cells (iPSC) differentiated into motor neuron-like cells, increased production of sphinganine and ceramides is observed; when exon 2 deletion variant is transfected into HEK293 cells, decreased response to inhibition mediated by ORMDL3 or ceramide is observed. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs879254294 [ dbSNP | Ensembl ]

Sequence information Variant position:

20 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

473 The length of the canonical sequence.
Location on the sequence:

MATATEQWVLVEMVQALYE A PAYHLILEGILILWIIRLLF 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                         MATATE------------------QWVLVEMVQ---------------------ALYEAPAYHLILE-GILILWIIRLLF-

Mouse                         MATVAE------------------QWVLVEMVQ-------

Rat                           MATVAE------------------QWVLVEMVQ-------

Bovine                        MATVAE------------------QWVLVEMVQ-------

Caenorhabditis elegans        MGFLPD------------------SWHFY-----------

Slime mold                    -MFLFDIYNN--------------ILYYTKEFI-------

Baker's yeast                 MAHIPEVLPKSIPIPAFIVTTSSYLWYYFNLVL-------

Fission yeast                 MSYSYPFFDD--------------VYAYYNQTVTFFGKAL

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.

Type	Positions	Description
Chain	1 – 473	Serine palmitoyltransferase 1
Transmembrane	16 – 36	Helical
Region	1 – 66	Interaction with SPTLC2

Literature citations
Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis.
Johnson J.O.; Chia R.; Miller D.E.; Li R.; Kumaran R.; Abramzon Y.; Alahmady N.; Renton A.E.; Topp S.D.; Gibbs J.R.; Cookson M.R.; Sabir M.S.; Dalgard C.L.; Troakes C.; Jones A.R.; Shatunov A.; Iacoangeli A.; Al Khleifat A.; Ticozzi N.; Silani V.; Gellera C.; Blair I.P.; Dobson-Stone C.; Kwok J.B.; Bonkowski E.S.; Palvadeau R.; Tienari P.J.; Morrison K.E.; Shaw P.J.; Al-Chalabi A.; Brown R.H. Jr.; Calvo A.; Mora G.; Al-Saif H.; Gotkine M.; Leigh F.; Chang I.J.; Perlman S.J.; Glass I.; Scott A.I.; Shaw C.E.; Basak A.N.; Landers J.E.; Chio A.; Crawford T.O.; Smith B.N.; Traynor B.J.; Smith B.N.; Ticozzi N.; Fallini C.; Gkazi A.S.; Topp S.D.; Scotter E.L.; Kenna K.P.; Keagle P.; Tiloca C.; Vance C.; Troakes C.; Colombrita C.; King A.; Pensato V.; Castellotti B.; Baas F.; Ten Asbroek A.L.M.A.; McKenna-Yasek D.; McLaughlin R.L.; Polak M.; Asress S.; Esteban-Perez J.; Stevic Z.; D'Alfonso S.; Mazzini L.; Comi G.P.; Del Bo R.; Ceroni M.; Gagliardi S.; Querin G.; Bertolin C.; van Rheenen W.; Rademakers R.; van Blitterswijk M.; Lauria G.; Duga S.; Corti S.; Cereda C.; Corrado L.; Soraru G.; Williams K.L.; Nicholson G.A.; Blair I.P.; Leblond-Manry C.; Rouleau G.A.; Hardiman O.; Morrison K.E.; Veldink J.H.; van den Berg L.H.; Al-Chalabi A.; Pall H.; Shaw P.J.; Turner M.R.; Talbot K.; Taroni F.; Garcia-Redondo A.; Wu Z.; Glass J.D.; Gellera C.; Ratti A.; Brown R.H. Jr.; Silani V.; Shaw C.E.; Landers J.E.; Dalgard C.L.; Adeleye A.; Soltis A.R.; Alba C.; Viollet C.; Bacikova D.; Hupalo D.N.; Sukumar G.; Pollard H.B.; Wilkerson M.D.; Martinez E.M.; Abramzon Y.; Ahmed S.; Arepalli S.; Baloh R.H.; Bowser R.; Brady C.B.; Brice A.; Broach J.; Campbell R.H.; Camu W.; Chia R.; Cooper-Knock J.; Ding J.; Drepper C.; Drory V.E.; Dunckley T.L.; Eicher J.D.; England B.K.; Faghri F.; Feldman E.; Floeter M.K.; Fratta P.; Geiger J.T.; Gerhard G.; Gibbs J.R.; Gibson S.B.; Glass J.D.; Hardy J.; Harms M.B.; Heiman-Patterson T.D.; Hernandez D.G.; Jansson L.; Kirby J.; Kowall N.W.; Laaksovirta H.; Landeck N.; Landi F.; Le Ber I.; Lumbroso S.; MacGowan D.J.L.; Maragakis N.J.; Mora G.; Mouzat K.; Murphy N.A.; Myllykangas L.; Nalls M.A.; Orrell R.W.; Ostrow L.W.; Pamphlett R.; Pickering-Brown S.; Pioro E.P.; Pletnikova O.; Pliner H.A.; Pulst S.M.; Ravits J.M.; Renton A.E.; Rivera A.; Robberecht W.; Rogaeva E.; Rollinson S.; Rothstein J.D.; Scholz S.W.; Sendtner M.; Shaw P.J.; Sidle K.C.; Simmons Z.; Singleton A.B.; Smith N.; Stone D.J.; Tienari P.J.; Troncoso J.C.; Valori M.; Van Damme P.; Van Deerlin V.M.; Van Den Bosch L.; Zinman L.; Landers J.E.; Chio A.; Traynor B.J.; Angelocola S.M.; Ausiello F.P.; Barberis M.; Bartolomei I.; Battistini S.; Bersano E.; Bisogni G.; Borghero G.; Brunetti M.; Cabona C.; Calvo A.; Canale F.; Canosa A.; Cantisani T.A.; Capasso M.; Caponnetto C.; Cardinali P.; Carrera P.; Casale F.; Chio A.; Colletti T.; Conforti F.L.; Conte A.; Conti E.; Corbo M.; Cuccu S.; Dalla Bella E.; D'Errico E.; DeMarco G.; Dubbioso R.; Ferrarese C.; Ferraro P.M.; Filippi M.; Fini N.; Floris G.; Fuda G.; Gallone S.; Gianferrari G.; Giannini F.; Grassano M.; Greco L.; Iazzolino B.; Introna A.; La Bella V.; Lattante S.; Lauria G.; Liguori R.; Logroscino G.; Logullo F.O.; Lunetta C.; Mandich P.; Mandrioli J.; Manera U.; Manganelli F.; Marangi G.; Marinou K.; Marrosu M.G.; Martinelli I.; Messina S.; Moglia C.; Mora G.; Mosca L.; Murru M.R.; Origone P.; Passaniti C.; Petrelli C.; Petrucci A.; Pozzi S.; Pugliatti M.; Quattrini A.; Ricci C.; Riolo G.; Riva N.; Russo M.; Sabatelli M.; Salamone P.; Salivetto M.; Salvi F.; Santarelli M.; Sbaiz L.; Sideri R.; Simone I.; Simonini C.; Spataro R.; Tanel R.; Tedeschi G.; Ticca A.; Torriello A.; Tranquilli S.; Tremolizzo L.; Trojsi F.; Vasta R.; Vacchiano V.; Vita G.; Volanti P.; Zollino M.; Zucchi E.;
JAMA Neurol. 78:1236-1248(2021)
Cited for: INVOLVEMENT IN ALS27; VARIANTS ALS27 SER-20; LEU-39 DEL AND TYR-331;
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.