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UniProtKB/Swiss-Prot Q9NZV8: Variant p.Val404Met

Potassium voltage-gated channel subfamily D member 2
Gene: KCND2
Variant information

Variant position:  404
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  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:  From Valine (V) to Methionine (M) at position 404 (V404M, p.Val404Met).
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:  Similar physico-chemical property. Both residues are medium size and hydrophobic.
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

Variant description:  Probable disease-associated variant found in a family with atypical autism and severe epilepsy; disrupts potassium current inactivation.
Any additional useful information about the variant.

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



Sequence information

Variant position:  404
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  630
The length of the canonical sequence.

Location on the sequence:   KIFGSICSLSGVLVIALPVP  V IVSNFSRIYHQNQRADKRRA
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                         KIFGSICSLSGVLVIALPVPVIVSNFSRIYHQNQRADKRRA

Mouse                         KIFGSICSLSGVLVIALPVPVIVSNFSRIYHQNQRADKRRA

Rat                           KIFGSICSLSGVLVIALPVPVIVSNFSRIYHQNQRADKRRA

Rabbit                        KIFGSICSLSGVLVIALPVPVIVSNFSRIYHQNQRADKRRA

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 – 630 Potassium voltage-gated channel subfamily D member 2
Transmembrane 385 – 413 Helical; Name=Segment S6
Mutagenesis 397 – 397 V -> A. May impair protein folding.
Mutagenesis 398 – 398 I -> A. Loss of channel activity.
Mutagenesis 399 – 399 A -> V. May impair protein folding.
Mutagenesis 401 – 401 P -> A. May impair protein folding.
Mutagenesis 402 – 404 VPV -> IPI. Increases pak current amplitude and causes a positive shift in the voltage-dependence of activation and steady-state inactivation. May increase the affinity for the closed-inactivated state of the channel.
Mutagenesis 403 – 403 P -> A. Loss of channel activity.
Mutagenesis 405 – 405 I -> A. Loss of channel activity.
Mutagenesis 406 – 406 V -> A. Loss of channel activity.
Mutagenesis 407 – 407 S -> A. Increases peak current amplitude but has no effect on the voltage-dependence of activation. May increase the affinity for the closed-inactivated state of the channel.
Mutagenesis 408 – 408 N -> A. Decreases peak current amplitude and causes a positive shift in the voltage-dependence of activation. May increase the affinity for the closed-inactivated state of the channel.
Mutagenesis 409 – 409 F -> A. May impair protein folding.


Literature citations

Exome sequencing identifies de novo gain of function missense mutation in KCND2 in identical twins with autism and seizures that slows potassium channel inactivation.
Lee H.; Lin M.C.; Kornblum H.I.; Papazian D.M.; Nelson S.F.;
Hum. Mol. Genet. 23:3481-3489(2014)
Cited for: VARIANT MET-404; CHARACTERIZATION OF VARIANT MET-404; FUNCTION; 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.