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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q8NCM2: Variant p.Arg327His

Voltage-gated delayed rectifier potassium channel KCNH5
Gene: KCNH5
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Variant information Variant position: help 327 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 Histidine (H) at position 327 (R327H, p.Arg327His). 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 (H) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help 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: help In DEE112; pathogenic; causes a hyperpolarizing shift in the voltage-gated potassium channel activity and an acceleration of activation; weakens the ionic interaction between residue 327 and negatively charged residues of helix S1-S3 thus favoring channel opening. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 327 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 988 The length of the canonical sequence.
Location on the sequence: help NAFENVDEGISSLFSSLKVV R LLRLGRVARKLDHYLEYGAA 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                         NAFENVDEGISSLFSSLKVVRLLRLGRVARKLDHYLEYGAA

Mouse                         NAFENVDEGISSLFSSLKVVRLLRLGRVARKLDHYLEYGAA

Rat                           NAFENVDEGISSLFSSLKVVRLLRLGRVARKLDHYLEYGAA
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 – 988 Voltage-gated delayed rectifier potassium channel KCNH5
Transmembrane 320 – 340 Helical; Voltage-sensor; Name=Segment S4
Mutagenesis 337 – 337 K -> A. Left-shifts the half-activation membrane potential.
Helix 326 – 330



Literature citations
Exome sequencing reveals new causal mutations in children with epileptic encephalopathies.
Veeramah K.R.; Johnstone L.; Karafet T.M.; Wolf D.; Sprissler R.; Salogiannis J.; Barth-Maron A.; Greenberg M.E.; Stuhlmann T.; Weinert S.; Jentsch T.J.; Pazzi M.; Restifo L.L.; Talwar D.; Erickson R.P.; Hammer M.F.;
Epilepsia 54:1270-1281(2013)
Cited for: INVOLVEMENT IN DEE112; VARIANT DEE112 HIS-327;
Multistate structural modeling and voltage-clamp analysis of epilepsy/autism mutation Kv10.2-R327H demonstrate the role of this residue in stabilizing the channel closed state.
Yang Y.; Vasylyev D.V.; Dib-Hajj F.; Veeramah K.R.; Hammer M.F.; Dib-Hajj S.D.; Waxman S.G.;
J. Neurosci. 33:16586-16593(2013)
Cited for: VARIANT DEE112 HIS-327; CHARACTERIZATION OF VARIANT DEE112 HIS-327; FUNCTION; TRANSPORTER ACTIVITY;
Whole-exome sequencing in adult patients with developmental and epileptic encephalopathy: It is never too late.
Minardi R.; Licchetta L.; Baroni M.C.; Pippucci T.; Stipa C.; Mostacci B.; Severi G.; Toni F.; Bergonzini L.; Carelli V.; Seri M.; Tinuper P.; Bisulli F.;
Clin. Genet. 98:477-485(2020)
Cited for: VARIANT DEE112 HIS-327;
Clinical Feature, Treatment, and KCNH5 Mutations in Epilepsy.
Hu X.; Yang J.; Zhang M.; Fang T.; Gao Q.; Liu X.;
Front. Pediatr. 10:858008-858008(2022)
Cited for: VARIANTS DEE112 ASN-321 AND HIS-327;
Neurodevelopmental and Epilepsy Phenotypes in Individuals With Missense Variants in the Voltage-Sensing and Pore Domains of KCNH5.
Happ H.C.; Sadleir L.G.; Zemel M.; de Valles-Ibanez G.; Hildebrand M.S.; McConkie-Rosell A.; McDonald M.; May H.; Sands T.; Aggarwal V.; Elder C.; Feyma T.; Bayat A.; Moeller R.S.; Fenger C.D.; Klint Nielsen J.E.; Datta A.N.; Gorman K.M.; King M.D.; Linhares N.D.; Burton B.K.; Paras A.; Ellard S.; Rankin J.; Shukla A.; Majethia P.; Olson R.J.; Muthusamy K.; Schimmenti L.A.; Starnes K.; Sedlackova L.; Sterbova K.; Vlckova M.; Lassuthova P.; Jahodova A.; Porter B.E.; Couque N.; Colin E.; Prouteau C.; Collet C.; Smol T.; Caumes R.; Vansenne F.; Bisulli F.; Licchetta L.; Person R.; Torti E.; McWalter K.; Webster R.; Gerard E.E.; Lesca G.; Szepetowski P.; Scheffer I.E.; Mefford H.C.; Carvill G.L.;
Neurology 100:e603-e615(2023)
Cited for: VARIANTS DEE112 GLU-324; HIS-327; HIS-333; PRO-468 AND SER-471;
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.