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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P35499: Variant p.Arg225Trp

Sodium channel protein type 4 subunit alpha
Gene: SCN4A
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Variant information Variant position: help 225 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 Arginine (R) to Tryptophan (W) at position 225 (R225W, p.Arg225Trp). 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 large size and basic (R) to large size and aromatic (W) 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 MYOSCN4A and CMYP22A; impaired sodium ion transmembrane transport. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 225 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 1836 The length of the canonical sequence.
Location on the sequence: help YLTEFVDLGNISALRTFRVL R ALKTITVIPGLKTIVGALIQ 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                         YLTEFVDLGNISALRTFRVLRALKTITVIPGLKTIVGALIQ

Mouse                         YVTEFVDLGNISALRTFRVLRALKTITVIPGLKTIVGALIQ

Rat                           YVTEFVDLGNISALRTFRVLRALKTITVIPGLKTIVGALIQ

Horse                         YLTEFVDLGNISALRTFRVLRALKTITVIPGLKTIVGALIQ
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 – 1836 Sodium channel protein type 4 subunit alpha
Transmembrane 217 – 233 Helical; Name=S4 of repeat I
Repeat 113 – 454 I
Glycosylation 214 – 214 N-linked (GlcNAc...) asparagine
Helix 219 – 227



Literature citations
Clinical diversity of SCN4A-mutation-associated skeletal muscle sodium channelopathy.
Lee S.C.; Kim H.S.; Park Y.E.; Choi Y.C.; Park K.H.; Kim D.S.;
J. Clin. Neurol. 5:186-191(2009)
Cited for: VARIANTS MYOSCN4A TRP-225; THR-1156 AND GLU-1306; VARIANT PMC THR-693; VARIANT HYPP THR-1156; Loss-of-function mutations in SCN4A cause severe foetal hypokinesia or 'classical' congenital myopathy.
Zaharieva I.T.; Thor M.G.; Oates E.C.; van Karnebeek C.; Hendson G.; Blom E.; Witting N.; Rasmussen M.; Gabbett M.T.; Ravenscroft G.; Sframeli M.; Suetterlin K.; Sarkozy A.; D'Argenzio L.; Hartley L.; Matthews E.; Pitt M.; Vissing J.; Ballegaard M.; Krarup C.; Sloerdahl A.; Halvorsen H.; Ye X.C.; Zhang L.H.; Loekken N.; Werlauff U.; Abdelsayed M.; Davis M.R.; Feng L.; Phadke R.; Sewry C.A.; Morgan J.E.; Laing N.G.; Vallance H.; Ruben P.; Hanna M.G.; Lewis S.; Kamsteeg E.J.; Maennikkoe R.; Muntoni F.;
Brain 139:674-691(2016)
Cited for: VARIANTS CMYP22A HIS-104; TRP-225; ASN-1069; CYS-1135 AND PHE-1209; VARIANTS CMYP22B LYS-203; THR-382 AND 1593-TYR--VAL-1836 DEL; CHARACTERIZATION OF VARIANTS CMYP22A HIS-104; TRP-225; ASN-1069 AND PHE-1209; CHARACTERIZATION OF VARIANTS CMYP22B LYS-203 AND THR-382; INVOLVEMENT IN CMYP22A; INVOLVEMENT IN CMYP22B; FUNCTION; SUBCELLULAR LOCATION;
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.