Clinical Translationality of KCNJ5 Mutation in Aldosterone Producing Adenoma

Int J Mol Sci. 2022 Aug 12;23(16):9042. doi: 10.3390/ijms23169042.


Hypertension due to primary aldosteronism poses a risk of severe cardiovascular complications compared to essential hypertension. The discovery of the KCNJ5 somatic mutation in aldosteroene producing adenoma (APA) in 2011 and the development of specific CYP11B2 antibodies in 2012 have greatly advanced our understanding of the pathophysiology of primary aldosteronism. In particular, the presence of CYP11B2-positive aldosterone-producing micronodules (APMs) in the adrenal glands of normotensive individuals and the presence of renin-independent aldosterone excess in normotensive subjects demonstrated the continuum of the pathogenesis of PA. Furthermore, among the aldosterone driver mutations which incur excessive aldosterone secretion, KCNJ5 was a major somatic mutation in APA, while CACNA1D is a leading somatic mutation in APMs and idiopathic hyperaldosteronism (IHA), suggesting a distinctive pathogenesis between APA and IHA. Although the functional detail of APMs has not been still uncovered, its impact on the pathogenesis of PA is gradually being revealed. In this review, we summarize the integrated findings regarding APA, APM or diffuse hyperplasia defined by novel CYP11B2, and aldosterone driver mutations. Following this, we discuss the clinical implications of KCNJ5 mutations to support better cardiovascular outcomes of primary aldosteronism.

Keywords: KCNJ5; aldosterone producing adenoma; genetic abnormality; primary aldosteronism.

Publication types

  • Review

MeSH terms

  • Adenoma* / genetics
  • Adenoma* / pathology
  • Adrenocortical Adenoma* / complications
  • Adrenocortical Adenoma* / genetics
  • Aldosterone / genetics
  • Cytochrome P-450 CYP11B2 / genetics
  • Cytochrome P-450 CYP11B2 / metabolism
  • G Protein-Coupled Inwardly-Rectifying Potassium Channels* / genetics
  • Humans
  • Hyperaldosteronism* / etiology
  • Mutation


  • G Protein-Coupled Inwardly-Rectifying Potassium Channels
  • KCNJ5 protein, human
  • Aldosterone
  • Cytochrome P-450 CYP11B2

Grants and funding

Grant for Research on Intractable Diseases provided by the Japanese Ministry of Health, Labour and Welfare.