UniProtKB/Swiss-Prot P48544: Variant p.Leu168Arg

G protein-activated inward rectifier potassium channel 4
Gene: KCNJ5
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Variant information Variant position:

168 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

LB/B 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 Arginine (R) at position 168 (L168R, p.Leu168Arg). 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 hydrophobic (L) to large size and basic (R) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

-2 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 aldosterone-producing adrenal adenoma samples; somatic mutation; results in loss of channel selectivity and membrane depolarization. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs386352318 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

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

TTIGYGFRVITEKCPEGIIL L LVQAILGSIVNAFMVGCMFV 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                         TTIGYGFRVITEKCPEGIILLLVQAILGSIVNAFMVGCMFV

Mouse                         TTIGYGFRVITEKCPEGIILLLVQAILGSIVNAFMVGCMFV

Rat                           TTIGYGFRVITEKCPEGIILLLVQAILGSIVNAFMVGCMFV

Pig                           TTIGYGFRVITEKCPEGIVLLLVQAILGSIVNAFMVGCMFV

Bovine                        TTIGYGFRVITEKCPEGIVLLLVQAILGSIVNAFMVGCMFV

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 – 419	G protein-activated inward rectifier potassium channel 4
Transmembrane	164 – 185	Helical; Name=M2
Site	179 – 179	Role in the control of polyamine-mediated channel gating and in the blocking by intracellular magnesium

Literature citations
K+ channel mutations in adrenal aldosterone-producing adenomas and hereditary hypertension.
Choi M.; Scholl U.I.; Yue P.; Bjorklund P.; Zhao B.; Nelson-Williams C.; Ji W.; Cho Y.; Patel A.; Men C.J.; Lolis E.; Wisgerhof M.V.; Geller D.S.; Mane S.; Hellman P.; Westin G.; Akerstrom G.; Wang W.; Carling T.; Lifton R.P.;
Science 331:768-772(2011)
Cited for: TISSUE SPECIFICITY; VARIANTS HALD3 ARG-151 AND ALA-158; VARIANTS HIS-39; ARG-168 AND ILE-210; CHARACTERIZATION OF VARIANT HALD3 ARG-151; CHARACTERIZATION OF VARIANT ARG-168; INVOLVEMENT IN ALDOSTERONISM ASSOCIATED WITH ADRENAL ADENOMAS; KCNJ5 mutations in European families with nonglucocorticoid remediable familial hyperaldosteronism.
Mulatero P.; Tauber P.; Zennaro M.C.; Monticone S.; Lang K.; Beuschlein F.; Fischer E.; Tizzani D.; Pallauf A.; Viola A.; Amar L.; Williams T.A.; Strom T.M.; Graf E.; Bandulik S.; Penton D.; Plouin P.F.; Warth R.; Allolio B.; Jeunemaitre X.; Veglio F.; Reincke M.;
Hypertension 59:235-240(2012)
Cited for: VARIANT ARG-168; VARIANTS HALD3 ARG-151; GLU-151 AND ALA-158; CHARACTERIZATION OF VARIANT HALD3 GLU-151; INVOLVEMENT IN ALDOSTERONISM ASSOCIATED WITH ADRENAL ADENOMAS; Prevalence, clinical, and molecular correlates of KCNJ5 mutations in primary aldosteronism.
Boulkroun S.; Beuschlein F.; Rossi G.P.; Golib-Dzib J.F.; Fischer E.; Amar L.; Mulatero P.; Samson-Couterie B.; Hahner S.; Quinkler M.; Fallo F.; Letizia C.; Allolio B.; Ceolotto G.; Cicala M.V.; Lang K.; Lefebvre H.; Lenzini L.; Maniero C.; Monticone S.; Perrocheau M.; Pilon C.; Plouin P.F.; Rayes N.; Seccia T.M.; Veglio F.; Williams T.A.; Zinnamosca L.; Mantero F.; Benecke A.; Jeunemaitre X.; Reincke M.; Zennaro M.C.;
Hypertension 59:592-598(2012)
Cited for: VARIANT HALD3 ARG-151; VARIANT ARG-168; INVOLVEMENT IN ALDOSTERONISM ASSOCIATED WITH ADRENAL ADENOMAS; A novel point mutation in the KCNJ5 gene causing primary hyperaldosteronism and early-onset autosomal dominant hypertension.
Charmandari E.; Sertedaki A.; Kino T.; Merakou C.; Hoffman D.A.; Hatch M.M.; Hurt D.E.; Lin L.; Xekouki P.; Stratakis C.A.; Chrousos G.P.;
J. Clin. Endocrinol. Metab. 97:E1532-E1539(2012)
Cited for: VARIANT HALD3 SER-157; CHARACTERIZATION OF VARIANTS HALD3 ARG-151; SER-157 AND ALA-158; CHARACTERIZATION OF VARIANT ARG-168; FUNCTION; Comprehensive re-sequencing of adrenal aldosterone producing lesions reveal three somatic mutations near the KCNJ5 potassium channel selectivity filter.
Akerstrom T.; Crona J.; Delgado Verdugo A.; Starker L.F.; Cupisti K.; Willenberg H.S.; Knoefel W.T.; Saeger W.; Feller A.; Ip J.; Soon P.; Anlauf M.; Alesina P.F.; Schmid K.W.; Decaussin M.; Levillain P.; Wangberg B.; Peix J.L.; Robinson B.; Zedenius J.; Backdahl M.; Caramuta S.; Iwen K.A.; Botling J.; Stalberg P.; Kraimps J.L.; Dralle H.; Hellman P.; Sidhu S.; Westin G.; Lehnert H.; Walz M.K.; Akerstrom G.; Carling T.; Choi M.; Lifton R.P.; Bjorklund P.;
PLoS ONE 7:E41926-E41926(2012)
Cited for: VARIANT HALD3 ARG-151; VARIANTS GLN-145 AND ARG-168; INVOLVEMENT IN ALDOSTERONISM ASSOCIATED WITH ADRENAL ADENOMAS;

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.