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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q15858: Variant p.Ala1643Glu

Sodium channel protein type 9 subunit alpha
Gene: SCN9A
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Variant information Variant position: help 1643 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 Alanine (A) to Glutamate (E) at position 1643 (A1643E, p.Ala1643Glu). 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 small size and hydrophobic (A) to medium size and acidic (E) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -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: help In PERYTHM and PEXPD; hyperpolarizes voltage-dependence of channel activation; depolarizes the voltage-dependence of steady-state fast inactivation; slows channel deactivation; enhances persistent and resurgent current; enhances neuronal hyperexcitability in dorsal root ganglion neurons. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 1643 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 1988 The length of the canonical sequence.
Location on the sequence: help LVKGAKGIRTLLFALMMSLP A LFNIGLLLFLVMFIYAIFGM 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                         LVKGAKGIRTLLFALMMSLPALFNIGLLLFLVMFIYAIFGM

Mouse                         LIKGAKGIRTLLFALMMSLPALFNIGLLLFLVMFIYAIFGM

Rat                           LIKGAKGIRTLLFALMMSLPALFNIGLLLFLVMFIYAIFGM

Rabbit                        LIKGAKGIRTLLFALMMSLPALFNIGLLLFLVMFIYAIFGM
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 – 1988 Sodium channel protein type 9 subunit alpha
Topological domain 1625 – 1643 Cytoplasmic
Repeat 1497 – 1795 IV
Mutagenesis 1643 – 1643 A -> D. Depolarizes the voltage-dependence of steady-state fast inactivation; enhances persistent current.
Mutagenesis 1643 – 1643 A -> K. No effect on voltage-dependence of steady-state fast inactivation.
Mutagenesis 1643 – 1643 A -> V. No effect on voltage-dependence of steady-state fast inactivation.
Helix 1641 – 1665



Literature citations
NaV1.7 gain-of-function mutations as a continuum: A1632E displays physiological changes associated with erythromelalgia and paroxysmal extreme pain disorder mutations and produces symptoms of both disorders.
Estacion M.; Dib-Hajj S.D.; Benke P.J.; Te Morsche R.H.; Eastman E.M.; Macala L.J.; Drenth J.P.; Waxman S.G.;
J. Neurosci. 28:11079-11088(2008)
Cited for: VARIANT PERYTHM GLU-1643; CHARACTERIZATION OF VARIANT PERYTHM GLU-1643; VARIANT PEXPD GLU-1643; CHARACTERIZATION OF VARIANT PEXPD GLU-1643;
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.