UniProtKB/Swiss-Prot Q14003 : Variant p.Arg420His
Voltage-gated potassium channel KCNC3
Gene: KCNC3
Feedback ?
Variant information
Variant position:
420
The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:
LP/P [Disclaimer : Variants classification is intended for research purposes only, not for clinical and diagnostic use . The label disease variant is assigned according to literature reports on probable disease-association that can be based on theoretical reasons. This label must not be considered as a definitive proof for the pathogenic role of a variant. ]
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 Arginine (R) to Histidine (H) at position 420 (R420H, p.Arg420His).
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 large size and basic (R) to medium size and polar (H)
The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:
0
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 SCA13; dominant negative that induces loss of channel activity; decreases protein abundance; decreases protein stability; decreases localization to the plasma membrane and alters the localization of the wild-type protein; impairs N-glycosylation; no effect on tetramerization.
Any additional useful information about the variant.
Other resources:
Links to websites of interest for the variant.
Sequence information
Variant position:
420
The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:
757
The length of the canonical sequence.
Location on the sequence:
GLSSKAAKDVLGFLRVVRFV
R ILRIFKLTRHFVGLRVLGHT
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 GLSSKAAKDVLGFLRVVRFVR ILRIFKLTRHFVGLRVLGHT
Mouse GLSSKAAKDVLGFLRVVRFVR ILRIFKLTRHFVGLRVLGHT
Rat GLSSKAAKDVLGFLRVVRFVR ILRIFKLTRHFVGLRVLGHT
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 – 757
Voltage-gated potassium channel KCNC3
Transmembrane
412 – 434
Helical; Voltage-sensor; Name=Segment S4
Mutagenesis
420 – 420
R -> KA. Decreases protein abundance.
Mutagenesis
423 – 423
R -> KA. Decreases protein abundance.
Literature citations
Altered Kv3.3 channel gating in early-onset spinocerebellar ataxia type 13.
Minassian N.A.; Lin M.C.; Papazian D.M.;
J. Physiol. (Lond.) 590:1599-1614(2012)
Cited for: CHARACTERIZATION OF VARIANTS SCA13 HIS-420; HIS-423 AND LEU-448; FUNCTION; TRANSPORTER ACTIVITY; SUBCELLULAR LOCATION;
Spinocerebellar ataxia-13 Kv3.3 potassium channels: arginine-to-histidine mutations affect both functional and protein expression on the cell surface.
Zhao J.; Zhu J.; Thornhill W.B.;
Biochem. J. 454:259-265(2013)
Cited for: CHARACTERIZATION OF VARIANTS SCA13 HIS-366; HIS-420; HIS-423 AND LEU-448; FUNCTION; TRANSPORTER ACTIVITY; SUBCELLULAR LOCATION; SUBUNIT; INTERACTION WITH KCNC1; MUTAGENESIS OF ARG-366; ARG-420 AND ARG-423;
KCNC3(R420H), a K(+) channel mutation causative in spinocerebellar ataxia 13 displays aberrant intracellular trafficking.
Gallego-Iradi C.; Bickford J.S.; Khare S.; Hall A.; Nick J.A.; Salmasinia D.; Wawrowsky K.; Bannykh S.; Huynh D.P.; Rincon-Limas D.E.; Pulst S.M.; Nick H.S.; Fernandez-Funez P.; Waters M.F.;
Neurobiol. Dis. 71:270-279(2014)
Cited for: CHARACTERIZATION OF VARIANTS SCA13 HIS-420 AND LEU-448; SUBCELLULAR LOCATION; GLYCOSYLATION;
Mutations in voltage-gated potassium channel KCNC3 cause degenerative and developmental nervous system phenotypes.
Waters M.F.; Minassian N.A.; Stevanin G.; Figueroa K.P.; Bannister J.P.A.; Nolte D.; Mock A.F.; Evidente V.G.H.; Fee D.B.; Mueller U.; Duerr A.; Brice A.; Papazian D.M.; Pulst S.M.;
Nat. Genet. 38:447-451(2006)
Cited for: VARIANTS SCA13 HIS-420 AND LEU-448; CHARACTERIZATION OF VARIANTS SCA13 HIS-420 AND LEU-448; FUNCTION; TRANSPORTER ACTIVITY; SUBCELLULAR LOCATION;
KCNC3: phenotype, mutations, channel biophysics-a study of 260 familial ataxia patients.
Figueroa K.P.; Minassian N.A.; Stevanin G.; Waters M.; Garibyan V.; Forlani S.; Strzelczyk A.; Buerk K.; Brice A.; Duerr A.; Papazian D.M.; Pulst S.M.;
Hum. Mutat. 31:191-196(2010)
Cited for: VARIANTS SCA13 HIS-366; HIS-420 AND HIS-423; CHARACTERIZATION OF VARIANTS SCA13 HIS-366 AND HIS-423; FUNCTION; TRANSPORTER ACTIVITY; SUBCELLULAR LOCATION;
Functional analysis helps to define KCNC3 mutational spectrum in dutch ataxia cases.
Duarri A.; Nibbeling E.A.; Fokkens M.R.; Meijer M.; Boerrigter M.; Verschuuren-Bemelmans C.C.; Kremer B.P.; van de Warrenburg B.P.; Dooijes D.; Boddeke E.; Sinke R.J.; Verbeek D.S.;
PLoS ONE 10:E0116599-E0116599(2015)
Cited for: VARIANTS SCA13 ASN-129; HIS-420; HIS-423; ASN-477; MET-535; GLY-591; SER-643; ARG-645 AND ASN-746; VARIANTS HIS-41 AND GLY-63; CHARACTERIZATION OF VARIANTS SCA13 ASN-129; HIS-420; HIS-423; ASN-477; MET-535; GLY-591; SER-643; ARG-645 AND ASN-746; FUNCTION; TRANSPORTER ACTIVITY; 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.