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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q9BYP7: Variant p.Leu300Ser

Serine/threonine-protein kinase WNK3
Gene: WNK3
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Variant information Variant position: help 300 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 Leucine (L) to Serine (S) at position 300 (L300S, p.Leu300Ser). 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 medium size and hydrophobic (L) to small size and polar (S) 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 PRS; likely pathogenic; results in decreased SLC12A5/KCC2 phosphorylation. Any additional useful information about the variant.


Sequence information Variant position: help 300 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 1800 The length of the canonical sequence.
Location on the sequence: help NIFITGPTGSVKIGDLGLAT L MRTSFAKSVIGTPEFMAPEM 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                         NIFITGPTGSVKIGDLGLATLMRTSFAKSVIGTPEFMAPEM

Mouse                         NIFITGPTGSVKIGDLGLATLMRTSFAKSVIGTPEFMAPEM
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 – 1800 Serine/threonine-protein kinase WNK3
Domain 147 – 405 Protein kinase
Active site 294 – 294 Proton acceptor
Modified residue 304 – 304 Phosphoserine; by autocatalysis
Modified residue 308 – 308 Phosphoserine; by autocatalysis
Mutagenesis 294 – 294 D -> A. Catalytically inactive form. Inhibits sodium-coupled chloride cotransporters and activates potassium-coupled chloride cotransporters.
Helix 297 – 301



Literature citations
Rare pathogenic variants in WNK3 cause X-linked intellectual disability.
Kuery S.; Zhang J.; Besnard T.; Caro-Llopis A.; Zeng X.; Robert S.M.; Josiah S.S.; Kiziltug E.; Denomme-Pichon A.S.; Cogne B.; Kundishora A.J.; Hao L.T.; Li H.; Stevenson R.E.; Louie R.J.; Deb W.; Torti E.; Vignard V.; McWalter K.; Raymond F.L.; Rajabi F.; Ranza E.; Grozeva D.; Coury S.A.; Blanc X.; Brischoux-Boucher E.; Keren B.; Ounap K.; Reinson K.; Ilves P.; Wentzensen I.M.; Barr E.E.; Guihard S.H.; Charles P.; Seaby E.G.; Monaghan K.G.; Rio M.; van Bever Y.; van Slegtenhorst M.; Chung W.K.; Wilson A.; Quinquis D.; Breheret F.; Retterer K.; Lindenbaum P.; Scalais E.; Rhodes L.; Stouffs K.; Pereira E.M.; Berger S.M.; Milla S.S.; Jaykumar A.B.; Cobb M.H.; Panchagnula S.; Duy P.Q.; Vincent M.; Mercier S.; Gilbert-Dussardier B.; Le Guillou X.; Audebert-Bellanger S.; Odent S.; Schmitt S.; Boisseau P.; Bonneau D.; Toutain A.; Colin E.; Pasquier L.; Redon R.; Bouman A.; Rosenfeld J.A.; Friez M.J.; Perez-Pena H.; Akhtar Rizvi S.R.; Haider S.; Antonarakis S.E.; Schwartz C.E.; Martinez F.; Bezieau S.; Kahle K.T.; Isidor B.;
Genet. Med. 24:1941-1951(2022)
Cited for: VARIANTS PRS ARG-204; 241-ARG--LYS-1800 DEL; SER-300 AND VAL-607; CHARACTERIZATION OF VARIANTS PRS ARG-204; SER-300 AND VAL-607; INVOLVEMENT IN PRS;
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.