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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P48544: Variant p.Thr158Ala

G protein-activated inward rectifier potassium channel 4
Gene: KCNJ5
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Variant information Variant position: help 158 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help 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: help From Threonine (T) to Alanine (A) at position 158 (T158A, p.Thr158Ala). 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: help Change from medium size and polar (T) to small size and hydrophobic (A) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help 0 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: help In HALD3; also found in aldosterone-producing adrenal adenoma samples; results in loss of channel selectivity and membrane depolarization; increases expression of CYP11B2 and its transcriptional regulators NR4A2 and ATF2; increases aldosterone and hybrid steroids 18-oxocortisol and 18-hydroxycortisol synthesis; increases STAR expression and phosphorylation. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 158 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 419 The length of the canonical sequence.
Location on the sequence: help SAFLFSIETETTIGYGFRVI T EKCPEGIILLLVQAILGSIV 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         SAFLFSIETETTIGYGFRVITEKCPEGIILLLVQAILGSIV

Mouse                         SAFLFSIETETTIGYGFRVITEKCPEGIILLLVQAILGSIV

Rat                           SAFLFSIETETTIGYGFRVITEKCPEGIILLLVQAILGSIV

Pig                           SAFLFSIETETTIGYGFRVITEKCPEGIVLLLVQAILGSIV

Bovine                        SAFLFSIETETTIGYGFRVITEKCPEGIVLLLVQAILGSIV
Sequence annotation in neighborhood: help 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 – 419 G protein-activated inward rectifier potassium channel 4
Topological domain 155 – 163 Extracellular



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; Potassium channel mutant KCNJ5 T158A expression in HAC-15 cells increases aldosterone synthesis.
Oki K.; Plonczynski M.W.; Luis Lam M.; Gomez-Sanchez E.P.; Gomez-Sanchez C.E.;
Endocrinology 153:1774-1782(2012)
Cited for: CHARACTERIZATION OF VARIANT HALD3 ALA-158; FUNCTION; SUBCELLULAR LOCATION; 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; 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; Mutated KCNJ5 activates the acute and chronic regulatory steps in aldosterone production.
Hattangady N.G.; Karashima S.; Yuan L.; Ponce-Balbuena D.; Jalife J.; Gomez-Sanchez C.E.; Auchus R.J.; Rainey W.E.; Else T.;
J. Mol. Endocrinol. 57:1-11(2016)
Cited for: CHARACTERIZATION OF VARIANT HALD3 ALA-158; FUNCTION;
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.