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UniProtKB/Swiss-Prot O15554: Variant p.Val282Met

Intermediate conductance calcium-activated potassium channel protein 4
Gene: KCNN4
Chromosomal location: 19q13.2
Variant information

Variant position:  282
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 Valine (V) to Methionine (M) at position 282 (V282M, p.Val282Met).
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

Involvement in disease:  Dehydrated hereditary stomatocytosis 2 (DHS2) [MIM:616689]: An autosomal dominant hemolytic anemia characterized by primary erythrocyte dehydration. Erythrocytes exhibit decreased total cation and potassium content that are not accompanied by a proportional net gain of sodium and water. Affected individuals typically manifest mild to moderate compensated hemolytic anemia, with an increased erythrocyte mean corpuscular hemoglobin concentration and a decreased osmotic fragility, both of which reflect cellular dehydration. Their red cells exhibit a panel of various shape abnormalities such as elliptocytes, hemighosts, schizocytes, and very rare stomatocytic cells. Complications such as splenomegaly and cholelithiasis, resulting from increased red cell trapping in the spleen and elevated bilirubin levels, respectively, may occur. {ECO:0000269|PubMed:26148990, ECO:0000269|PubMed:26178367, ECO:0000269|PubMed:26198474}. 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 DHS2.
Any additional useful information about the variant.

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



Sequence information

Variant position:  282
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  427
The length of the canonical sequence.

Location on the sequence:   WGKIVCLCTGVMGVCCTALL  V AVVARKLEFNKAEKHVHNFM
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                         WGKIVCLCTGVMGVCCTALLVAVVARKLEFNKAEKHVHNFM

Mouse                         WGKIVCLCTGVMGVCCTALLVAVVARKLEFNKAEKHVHNFM

Rat                           WGKIVCLCTGVMGVCCTALLVAVVARKLEFNKAEKHVHNFM

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 – 427 Intermediate conductance calcium-activated potassium channel protein 4
Transmembrane 265 – 285 Helical; Name=Segment S6
Mutagenesis 275 – 275 V -> A. Loss of sensitivity to triarylmethanes.
Helix 261 – 287


Literature citations

Novel Gardos channel mutations linked to dehydrated hereditary stomatocytosis (xerocytosis).
Andolfo I.; Russo R.; Manna F.; Shmukler B.E.; Gambale A.; Vitiello G.; De Rosa G.; Brugnara C.; Alper S.L.; Snyder L.M.; Iolascon A.;
Am. J. Hematol. 90:921-926(2015)
Cited for: VARIANTS DHS2 MET-282 AND HIS-352;

Mutations in the Gardos channel (KCNN4) are associated with hereditary xerocytosis.
Glogowska E.; Lezon-Geyda K.; Maksimova Y.; Schulz V.P.; Gallagher P.G.;
Blood 126:1281-1284(2015)
Cited for: VARIANTS DHS2 GLU-282 AND MET-282;

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.