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UniProtKB/Swiss-Prot P51787: Variant p.Asp317Asn

Potassium voltage-gated channel subfamily KQT member 1
Gene: KCNQ1
Variant information

Variant position:  317
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Aspartate (D) to Asparagine (N) at position 317 (D317N, p.Asp317Asn).
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 medium size and acidic (D) to medium size and polar (N)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  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

Involvement in disease:  Long QT syndrome 1 (LQT1) [MIM:192500]: A heart disorder characterized by a prolonged QT interval on the ECG and polymorphic ventricular arrhythmias. They cause syncope and sudden death in response to exercise or emotional stress, and can present with a sentinel event of sudden cardiac death in infancy. {ECO:0000269|PubMed:10024302, ECO:0000269|PubMed:10220144, ECO:0000269|PubMed:10220146, ECO:0000269|PubMed:10367071, ECO:0000269|PubMed:10409658, ECO:0000269|PubMed:10482963, ECO:0000269|PubMed:10728423, ECO:0000269|PubMed:10973849, ECO:0000269|PubMed:11799244, ECO:0000269|PubMed:12442276, ECO:0000269|PubMed:15840476, ECO:0000269|PubMed:16414944, ECO:0000269|PubMed:16922724, ECO:0000269|PubMed:18165683, ECO:0000269|PubMed:18400097, ECO:0000269|PubMed:19540844, ECO:0000269|PubMed:19716085, ECO:0000269|PubMed:19808498, ECO:0000269|PubMed:21241800, ECO:0000269|PubMed:24184248, ECO:0000269|PubMed:24269949, ECO:0000269|PubMed:24713462, ECO:0000269|PubMed:25037568, ECO:0000269|PubMed:25139741, ECO:0000269|PubMed:25705178, ECO:0000269|PubMed:8528244, ECO:0000269|PubMed:8818942, ECO:0000269|PubMed:8872472, ECO:0000269|PubMed:9024139, ECO:0000269|PubMed:9272155, ECO:0000269|PubMed:9302275, ECO:0000269|PubMed:9312006, ECO:0000269|PubMed:9323054, ECO:0000269|PubMed:9386136, ECO:0000269|PubMed:9482580, ECO:0000269|PubMed:9570196, ECO:0000269|PubMed:9641694, ECO:0000269|PubMed:9693036, ECO:0000269|PubMed:9702906, ECO:0000269|PubMed:9799083, ECO:0000269|PubMed:9927399, ECO:0000269|Ref.31}. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In LQT1; complete loss of outward potassium current when expressed alone and even in the presence of the wild type at variable ratios; decreases plasma membrane localization.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  317
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  676
The length of the canonical sequence.

Location on the sequence:   GSYADALWWGVVTVTTIGYG  D KVPQTWVGKTIASCFSVFAI
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                         GSYADALWWGVVTVTTIGYGDKVPQTWVGKTIASCFSVFAI

Mouse                         GSYADALWWGVVTVTTIGYGDKVPQTWVGKTIASCFSVFAI

Rat                           GSYADALWWGVVTVTTIGYGDKVPQTWVGKTIASCFSVFAI

Rabbit                        GSYADALWWGVVTVTTIGYGDKVPQTWVGKTIASCFSVFAI

Xenopus laevis                GSYADALWWGVVTVTTIGYGDKVPQTWIGKTIASCFSVFAI

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.

TypePositionsDescription
Chain 1 – 676 Potassium voltage-gated channel subfamily KQT member 1
Intramembrane 300 – 320 Pore-forming; Name=Segment H5
Motif 312 – 317 Selectivity filter
Mutagenesis 324 – 324 V -> L. Has a voltage-gated potassium channel activity. Inhibition of voltage-gated potassium channel activity by KCNE4.
Mutagenesis 326 – 326 K -> R. Has a voltage-gated potassium channel activity. Disrupts KCNE4-mediated voltage-gated potassium channel activity inhibition.
Mutagenesis 327 – 327 T -> V. Has a voltage-gated potassium channel activity. Disrupts KCNE4-mediated voltage-gated potassium channel activity inhibition.
Mutagenesis 328 – 328 I -> L. Has a voltage-gated potassium channel activity. Inhibition of voltage-gated potassium channel activity by KCNE4.
Beta strand 316 – 318


Literature citations

Pathophysiological mechanisms of dominant and recessive KVLQT1 K+ channel mutations found in inherited cardiac arrhythmias.
Wollnik B.; Schroeder B.C.; Kubisch C.; Esperer H.D.; Wieacker P.; Jentsch T.J.;
Hum. Mol. Genet. 6:1943-1949(1997)
Cited for: VARIANT LQT1 ASN-317;

Molecular genetics of the long QT syndrome: two novel mutations of the KVLQT1 gene and phenotypic expression of the mutant gene in a large kindred.
Saarinen K.; Swan H.; Kainulainen K.; Toivonen L.; Viitasalo M.; Kontula K.;
Hum. Mutat. 11:158-165(1998)
Cited for: VARIANTS LQT1 ILE-311 AND ASN-317;

Cellular mechanisms of mutations in Kv7.1: auditory functions in Jervell and Lange-Nielsen syndrome vs. Romano-Ward syndrome.
Mousavi Nik A.; Gharaie S.; Jeong Kim H.;
Front. Cell. Neurosci. 9:32-32(2015)
Cited for: CHARACTERIZATION OF VARIANTS LQT1 ASN-242; PRO-243; HIS-250; VAL-306; ASN-317; ASP-586 AND MET-619; CHARACTERIZATION OF VARIANTS JLNS1 PHE-248; ILE-311; MET-322 AND ASP-589;

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.