UniProtKB/Swiss-Prot O14649: Variant p.Leu122Val

Potassium channel subfamily K member 3
Gene: KCNK3
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Variant information Variant position:

122 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 Leucine (L) to Valine (V) at position 122 (L122V, p.Leu122Val). 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 patient with DDSA; de novo; gain of function; increases channel open probability; results in increased potassium currents for homo- and heterodimeric KCNK3:KCNK9 channels; impairs G-protein coupled receptor-mediated inhibition; does not affect pH dependence. Any additional useful information about the variant.

Sequence information Variant position:

122 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

394 The length of the canonical sequence.
Location on the sequence:

STDGGKVFCMFYALLGIPLT L VMFQSLGERINTLVRYLLHR 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                         STDGGKVFCMFYALLGIPLTLVMFQSLGERINTLVRYLLHR

Mouse                         STDGGKVFCMFYALLGIPLTLVMFQSLGERINTFVRYLLHR

Rat                           STDGGKVFCMFYALLGIPLTLVMFQSLGERINTFVRYLLHR

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 – 394	Potassium channel subfamily K member 3
Transmembrane	108 – 128	Helical
Mutagenesis	130 – 130	E -> C. No effect on channel basal activity.
Mutagenesis	131 – 131	R -> CDE. Increases potassium current amplitude.
Mutagenesis	132 – 132	I -> C. No effect on channel basal activity.
Mutagenesis	133 – 133	N -> ADFQTV. Increases potassium current.
Mutagenesis	133 – 133	N -> C. Increases potassium current amplitude.
Mutagenesis	134 – 134	T -> C. No effect on channel basal activity.
Helix	104 – 147

Literature citations
Gain-of-function mutations in KCNK3 cause a developmental disorder with sleep apnea.
Soermann J.; Schewe M.; Proks P.; Jouen-Tachoire T.; Rao S.; Riel E.B.; Agre K.E.; Begtrup A.; Dean J.; Descartes M.; Fischer J.; Gardham A.; Lahner C.; Mark P.R.; Muppidi S.; Pichurin P.N.; Porrmann J.; Schallner J.; Smith K.; Straub V.; Vasudevan P.; Willaert R.; Carpenter E.P.; Roedstroem K.E.J.; Hahn M.G.; Mueller T.; Baukrowitz T.; Hurles M.E.; Wright C.F.; Tucker S.J.;
Nat. Genet. 54:1534-1543(2022)
Cited for: INVOLVEMENT IN DDSA; VARIANTS VAL-122; PRO-122; ASP-129; SER-133; GLN-141; PRO-239 AND PHE-241; CHARACTERIZATION OF VARIANTS VAL-122; PRO-122; ASP-129; SER-133; GLN-141; PRO-239 AND PHE-241; FUNCTION; TRANSPORTER ACTIVITY; ACTIVITY REGULATION; MUTAGENESIS OF ASN-133;

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.