KCNJ5

Chr 11AD

potassium inwardly rectifying channel subfamily J member 5

Also known as: CIR, GIRK4, KATP1, KIR3.4, LQT13

NCBI Gene: 3762 ENSG00000120457 UniProt: P48544 OMIM: 600734

This gene encodes an inward-rectifier potassium channel subunit that preferentially allows potassium influx and is regulated by G-proteins and extracellular potassium concentrations. Mutations cause autosomal dominant familial hyperaldosteronism type III and long QT syndrome 13, affecting adrenal hormone regulation and cardiac electrophysiology. The gene shows low constraint to loss-of-function variants (pLI 0.0003), suggesting that complete protein loss may be tolerated.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes an integral membrane protein which belongs to one of seven subfamilies of inward-rectifier potassium channel proteins called potassium channel subfamily J. The encoded protein is a subunit of the potassium channel which is homotetrameric. It is controlled by G-proteins and has a greater tendency to allow potassium to flow into a cell rather than out of a cell. Naturally occurring mutations in this gene are associated with aldosterone-producing adenomas. [provided by RefSeq, Aug 2017]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Hyperaldosteronism, familial, type IIIMIM #613677

Long QT syndrome 13MIM #613485

Clinical highlights

Gene-disease validity (ClinGen)

long QT syndrome · ADDisputedevidence questions this relationship2 gene-disease associations curated in total

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.14

LOEUF

Multiple*

Mechanism· predicted

📖

GeneReview available — KCNJ5

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.14LOEUF

pLI 0.000

Z-score 1.23

OE 0.61 (0.34–1.14)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.33Z-score

OE missense 0.76 (0.68–0.86)

190 obs / 249.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.61 (0.34–1.14)

0≤0.351.4

Missense OE?0.76 (0.68–0.86)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 7 / 11.5Missense obs/exp: 190 / 249.0Syn Z: -0.39

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

KCNJ5 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

📖

GeneReview available — KCNJ5

Authoritative clinical overview · NCBI Bookshelf · Recommended first read

Open GeneReview ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Primary Aldosteronism

Pathological Type，Gene Mutation and Clinical Characteristics of Unilateral Primary Aldosteronism

RECRUITING

NCT06597630Qifu LiStarted 2023-12-01

Tissue specimens were stained by histopathology of hematoxylin-eosin

Clinical Literature

Open Research Assistant →

Landmark / reviewRecent case evidence

Full-Text Mentions

NLP-detected gene mentions in article bodies · via PubTator3

PubTator3

Identification of KCNJ5 gene an adverse prognosis associated novel onco-ionchannel in Indian pancreatic cancer cohort

Bararia A et al.·Discov Oncol

2025Cohort

Identifying KCNJ5 Mutation in Aldosterone-Producing Adenoma Patients With Baseline Characteristics Using Machine Learning Technology

Chen LC et al.·JACC Asia

2023Cohort

Pathophysiological and Pharmacological Characteristics of KCNJ5 157-159delITE Somatic Mutation in Aldosterone-Producing Adenomas

Peng KY et al.·Biomedicines

2021

Clinical Translationality of KCNJ5 Mutation in Aldosterone Producing Adenoma

Kitamoto T et al.·Int J Mol Sci

2022

KCNJ5 Somatic Mutations in Aldosterone-Producing Adenoma Are Associated with a Greater Recovery of Arterial Stiffness

Chang YY et al.·Cancers (Basel)

2021

Top 5 full-text resultsSearch PubTator3 ↗

Key Publications

Landmark & review papers · by relevance

PubMed

18-Oxocortisol: A journey.

Gomez-Sanchez CE et al.·J Steroid Biochem Mol Biol

2023

An International, Multicentered, Evidence-Based Reappraisal of Genes Reported to Cause Congenital Long QT Syndrome.

Adler A et al.·Circulation

2020

Clinical implications of aldosterone responsiveness to adrenocorticotropic hormone stimulation in two major subtypes of primary aldosteronism.

Watanabe D et al.·Clin Exp Hypertens

2026

Genomics of benign adrenocortical tumors.

Jouinot A et al.·J Steroid Biochem Mol Biol

2019Review

Diagnostics in skeletal muscle channelopathies.

Vicino A et al.·Expert Rev Mol Diagn

2023Review

Top 5 results · since 2015Search PubMed ↗

Recent Gene-Specific Literature

Gene in title · MEDLINE · newest first

Europe PMC

Tumor-specific KCNJ5 mutation in an aldosterone-producing adenoma not detected in adrenal venous plasma cell-free DNA.

Aono D et al.·JCEM Case Rep

2026Open Access

Selective Cell Death of Adrenocortical Cells by Pharmacological Activation of Mutant KCNJ5.

Mir-Bashiri S et al.·Hypertension

2026

Macrolide-induced aldosterone suppression as a functional marker of KCNJ5-mutated aldosterone-producing adenoma: a proof-of-concept clinical and experimental study (MAPA study).

Rossi GP et al.·Eur J Endocrinol

2026Functional

KCNJ5-Dependent 68Ga-Pentixafor PET/CT in Primary Aldosteronism Surgery.

Wang Z et al.·J Clin Endocrinol Metab

2026

Case Report: A novel MYBPC3 gene variant in a Chinese patient with hypertrophic cardiomyopathy and apical ventricular aneurysm, with a concurrent novel KCNJ5 gene variant.

Han S et al.·Front Cardiovasc Med

2026Open AccessCase report

Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

KCNJ5

Primary Disease Associations & Inheritance

Clinical highlights

Population Genetics & Constraint

ClinVar Variant Classifications

Protein Context — Lollipop Plot

Mechanism of Pathogenicity

Tissue Expression

Transcripts & Isoforms

Transcript architecture

DECIPHER · Gene2Phenotype

OMIM — Genotype-Phenotype Relationships

Gene Overview

ClinGen Curation

Disease Associations

External Resources

Clinical Trials

Drug Interactions

External Resources

Drug Interactions

Transcripts & Isoforms

Mechanism of Pathogenicity