KCNJ1 Gene
The KCNJ1 gene encodes the ROMK potassium channel, a key regulator of kidney salt reabsorption and blood pressure. Mutations in this gene can lead to Bartter syndrome type II and influence individual blood‑pressure variation.
Normal Function
The KCNJ1 gene belongs to a large family of genes that produce potassium channels. These channels transport positively charged potassium ions into and out of cells, enabling cells to generate and transmit electrical signals.
Channels made with the KCNJ1 protein, also known as ROMK, are predominantly found in the kidneys. ROMK works with other proteins to regulate the movement of ions into and out of kidney cells. In particular, ROMK’s transport of potassium ions is necessary for the normal function of the NKCC2 transporter (encoded by the SLC12A1 gene). NKCC2 reabsorbs salt (sodium chloride, NaCl) from the urine back into the bloodstream, a process that maintains fluid levels and blood pressure.
Health Conditions Related to Genetic Changes
Bartter syndrome
Several dozen mutations in the KCNJ1 gene have been identified in people with Bartter syndrome type II. This severe form of the disorder presents before or soon after birth and can be life‑threatening.
Some mutations alter single amino acids in the ROMK protein, preventing it from reaching the cell membrane or impairing its ability to transport potassium ions. Other mutations delete amino acids or produce an abnormally short, nonfunctional ROMK.
A loss of functional ROMK disrupts NKCC2 activity, preventing ion transport into kidney cells. Consequently, the kidneys cannot reabsorb salt normally, leading to salt wasting. The resulting imbalance of sodium, potassium, and other ions underlies the major features of Bartter syndrome.
Other disorders
Normal variants (polymorphisms) in the KCNJ1 gene may explain variations in blood pressure among individuals. Certain rare polymorphisms appear to protect against hypertension, while others may increase risk. These genetic changes likely affect the kidneys’ ability to reabsorb salt into the bloodstream.
Other Names for This Gene
- ATP‑regulated potassium channel ROM‑K
- ATP‑sensitive inward rectifier potassium channel 1
- Inward rectifier K(+) channel Kir1.1
- Inward rectifying K+ channel
- IRK1_HUMAN
- KIR1.1
- Potassium channel, inwardly rectifying subfamily J member 1
- Potassium channel, inwardly rectifying subfamily J, member 1
- Potassium inwardly‑rectifying channel, subfamily J, member 1
- ROMK
- ROMK1
Additional Information & Resources
Genomic Location
The KCNJ1 gene is located on chromosome 11.
Tests Listed in the Genetic Testing Registry
- Tests of KCNJ1
Scientific Articles on PubMed
- Derst C, Konrad M, Kockerling A, Karolyi L, Deschenes G, Daut J, Karschin A, Seyberth HW. Mutations in the ROMK gene in antenatal Bartter syndrome are associated with impaired K+ channel function. Biochem Biophys Res Commun. 1997 Jan 23;230(3):641-5. doi: 10.1006/bbrc.1996.6024.
- Jeck N, Derst C, Wischmeyer E, Ott H, Weber S, Rudin C, Seyberth HW, Daut J, Karschin A, Konrad M. Functional heterogeneity of ROMK mutations linked to hyperprostaglandin E syndrome. Kidney Int. 2001 May;59(5):1803-11. doi: 10.1046/j.1523-1755.2001.0590051803.x.
- Ji W, Foo JN, O'Roak BJ, Zhao H, Larson MG, Simon DB, Newton-Cheh C, State MW, Levy D, Lifton RP. Rare independent mutations in renal salt handling genes contribute to blood pressure variation. Nat Genet. 2008 May;40(5):592-599. doi: 10.1038/ng.118.
- Peters M, Ermert S, Jeck N, Derst C, Pechmann U, Weber S, Schlingmann KP, Seyberth HW, Waldegger S, Konrad M. Classification and rescue of ROMK mutations underlying hyperprostaglandin E syndrome/antenatal Bartter syndrome. Kidney Int. 2003 Sep;64(3):923-32. doi: 10.1046/j.1523-1755.2003.00153.x.
- Simon DB, Karet FE, Rodriguez‑Soriano J, Hamdan JH, DiPietro A, Trachtman H, Sanjad SA, Lifton RP. Genetic heterogeneity of Bartter's syndrome revealed by mutations in the K+ channel, ROMK. Nat Genet. 1996 Oct;14(2):152-6. doi: 10.1038/ng1096-152.
- Tobin MD, Tomaszewski M, Braund PS, Hajat C, Raleigh SM, Palmer TM, Caulfield M, Burton PR, Samani NJ. Common variants in genes underlying monogenic hypertension and hypotension and blood pressure in the general population. Hypertension. 2008 Jun;51(6):1658-64. doi: 10.1161/HYPERTENSIONAHA.108.112664.
- Welling PA, Ho K. A comprehensive guide to the ROMK potassium channel: form and function in health and disease. Am J Physiol Renal Physiol. 2009 Oct;297(4):F849-63. doi: 10.1152/ajprenal.00181.2009.
Gene and Variant Databases
- NCBI Gene
- ClinVar