UniProtKB/Swiss-Prot Q9UGI6: Variant p.Val450Leu

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 450 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: US 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 Leucine (L) at position 450 (V450L, p.Val450Leu). 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: Found in a family with non-cirrhotic portal hypertension; uncertain significance; gain-of-function variant leading to constitutive activity with very low calcium levels; does not affect interaction with CALM1. Any additional useful information about the variant.

Sequence information

Variant position: 450 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 731 The length of the canonical sequence.
Location on the sequence: TDASSRSIGALNKINFNTRF V MKTLMTICPGTVLLVFSISL 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.
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.

Type	Positions	Description
Chain	1 – 731	Small conductance calcium-activated potassium channel protein 3

Literature citations

Gain-of-function mutations in KCNN3 encoding the small-conductance Ca2+-activated K+ channel SK3 cause Zimmermann-Laband syndrome.
Bauer C.K.; Schneeberger P.E.; Kortuem F.; Altmueller J.; Santos-Simarro F.; Baker L.; Keller-Ramey J.; White S.M.; Campeau P.M.; Gripp K.W.; Kutsche K.;
Am. J. Hum. Genet. 104:1139-1157(2019)
Cited for: FUNCTION; ACTIVITY REGULATION; INTERACTION WITH CALM1; INVOLVEMENT IN ZLS3; VARIANTS ZLS3 GLU-269; ASP-350 AND CYS-436; CHARACTERIZATION OF VARIANTS ZLS3 GLU-269; ASP-350 AND CYS-436; CHARACTERIZATION OF VARIANT LEU-450; A de novo mutation in KCNN3 associated with autosomal dominant idiopathic non-cirrhotic portal hypertension.
Koot B.G.; Alders M.; Verheij J.; Beuers U.; Cobben J.M.;
J. Hepatol. 64:974-977(2016)
Cited for: VARIANT LEU-450;