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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P51787: Variant p.Ala590Thr

Potassium voltage-gated channel subfamily KQT member 1
Gene: KCNQ1
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Variant information Variant position: help 590 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 Threonine (T) at position 590 (A590T, p.Ala590Thr). 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 polar (T) 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 LQT1; reduces IKs density and causes a right-shift of the current?voltage relation of channel activation; reduces cell surface expression; no effect on interaction with AKAP9; does not affect the cAMP-dependent IKs up-regulation. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 590 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 676 The length of the canonical sequence.
Location on the sequence: help PSLFISVSEKSKDRGSNTIG A RLNRVEDKVTQLDQRLALIT 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                         PSLFISVSEKSKDRGSNTIGARLNRVEDKVTQLDQRLALIT

Mouse                         PSLFIPISEKSKDRGSNTIGARLNRVEDKVTQLDQRLVIIT

Rat                           PSLFIPISEKSKDRGSNTIGARLNRVEDKVTQLDQRLVIIT

Pig                           PALFISSSEKVKDRGSNTIGARLNRVEDKVTQLDQRLELIT

Rabbit                        PSLFVPISEKSKDRGSNSIGARLNRVEDKVTQLDQRLVLIA

Xenopus laevis                PSLFLSVSDKVKDKGINTIGSRLNRVEDKVTQMDHKLNLIT
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 – 676 Potassium voltage-gated channel subfamily KQT member 1
Topological domain 349 – 676 Cytoplasmic
Region 588 – 616 Interaction with AKAP9
Region 589 – 620 C-terminal assembly domain
Coiled coil 585 – 621
Mutagenesis 589 – 589 G -> M. No effect.
Mutagenesis 590 – 590 A -> W. Reduced cell surface expression and strongly reduced potassium current.
Mutagenesis 593 – 593 N -> G. Reduced cell surface expression and moderately reduced potassium current.
Mutagenesis 602 – 602 L -> A. Does not interact with AKAP9 and the targeting protein kinase A (PKA) catalytic subunit and protein phosphatase 1 (PP1); when associated with I-609.
Mutagenesis 609 – 609 I -> A. Does not interact with AKAP9 and the kinase A (PKA) catalytic subunit and protein phosphatase 1 (PP1); when associated with L-602.
Helix 588 – 609



Literature citations
Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing.
Tester D.J.; Will M.L.; Haglund C.M.; Ackerman M.J.;
Heart Rhythm 2:507-517(2005)
Cited for: VARIANTS LQT1 71-ALA--PRO-73 DEL; THR-73; GLY-115; TYR-122; ILE-133; PHE-136; LYS-160; ARG-168; CYS-174; GLN-190; PHE-204; LEU-225; ASN-235; ASN-242; CYS-243; MET-254; 254-VAL--PHE-256 DEL; CYS-259; LEU-259; ASP-261; PRO-266; SER-269; ASP-269; PHE-273; ARG-273; SER-276 DEL; LEU-277; HIS-278; LYS-290; ASP-292; CYS-293; VAL-302; ARG-304; SER-305; ILE-312; SER-314; ARG-314; ASP-314; CYS-315; ARG-316; ALA-322; PHE-339 DEL; VAL-341; SER-343; GLU-344; VAL-344; GLU-345; TRP-349; PRO-353; ARG-362; TRP-366; HIS-374; SER-380; TYR-389; TRP-452; GLY-524; GLU-526; TRP-539; LEU-546; CYS-555; HIS-555; TYR-566; SER-567; ARG-568; MET-587; THR-590; HIS-591; GLN-594; MET-619 AND SER-626; A590T mutation in KCNQ1 C-terminal helix D decreases IKs channel trafficking and function but not Yotiao interaction.
Kinoshita K.; Komatsu T.; Nishide K.; Hata Y.; Hisajima N.; Takahashi H.; Kimoto K.; Aonuma K.; Tsushima E.; Tabata T.; Yoshida T.; Mori H.; Nishida K.; Yamaguchi Y.; Ichida F.; Fukurotani K.; Inoue H.; Nishida N.;
J. Mol. Cell. Cardiol. 72:273-280(2014)
Cited for: VARIANT LQT1 THR-590; CHARACTERIZATION OF VARIANT LQT1 THR-590;
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.