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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P35499: Variant p.Arg1135Cys

Sodium channel protein type 4 subunit alpha
Gene: SCN4A
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Variant information Variant position: help 1135 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 Cysteine (C) at position 1135 (R1135C, p.Arg1135Cys). 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 medium size and polar (C) 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 HOKPP2 and CMYP22A; increased depolarization tendency at normal and reduced extracellular potassium and reduced amplitude and rise time of action potentials. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 1135 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 NWLGYSELGPIKSLRTLRAL R PLRALSRFEGMRVVVNALLG 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                         NWLGYSELGPIKSLRTLRALRPLRALSRFEGMRVVVNALLG

Mouse                         NWLGYSELGPIKSLRTLRALRPLRALSRFEGMRVVVNALLG

Rat                           NWLGYSELGPIKSLRTLRALRPLRALSRFEGMRVVVNALLG

Horse                         NWLGYSELGPIKSLRTLRALRPLRALSRFEGMRVVVNALLG
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 1124 – 1142 Helical; Name=S4 of repeat III
Repeat 1013 – 1326 III
Helix 1130 – 1141



Literature citations
NaV1.4 mutations cause hypokalaemic periodic paralysis by disrupting IIIS4 movement during recovery.
Groome J.R.; Lehmann-Horn F.; Fan C.; Wolf M.; Winston V.; Merlini L.; Jurkat-Rott K.;
Brain 137:998-1008(2014)
Cited for: VARIANTS HOKPP2 CYS-1135 AND HIS-1135; CHARACTERIZATION OF VARIANTS HOKPP2 CYS-1135 AND HIS-1135; 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.