Gene: KLHL3

Alternate names for this Gene: PHA2D

Gene Summary: This gene is ubiquitously expressed and encodes a full-length protein which has an N-terminal BTB domain followed by a BACK domain and six kelch-like repeats in the C-terminus. These kelch-like repeats promote substrate ubiquitination of bound proteins via interaction of the BTB domain with the CUL3 (cullin 3) component of a cullin-RING E3 ubiquitin ligase (CRL) complex. Muatations in this gene cause pseudohypoaldosteronism type IID (PHA2D); a rare Mendelian syndrome featuring hypertension, hyperkalaemia and metabolic acidosis. Alternative splicing results in multiple transcript variants encoding distinct isoforms.

Gene is located in Chromosome: 5

Location in Chromosome : 5q31.2

Description of this Gene: kelch like family member 3

Type of Gene: protein-coding

rs56289631 in KLHL3 gene and Age at menarche PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs2967790 in KLHL3 gene and Malaria PMID 29381699 2018 Novel genetic polymorphisms associated with severe malaria and under selective pressure in North-eastern Tanzania.

rs200892557 in KLHL3 gene and PSEUDOHYPOALDOSTERONISM, TYPE IID PMID 28052936 2017 KLHL3 Knockout Mice Reveal the Physiological Role of KLHL3 and the Pathophysiology of Pseudohypoaldosteronism Type II Caused by Mutant KLHL3.

PMID 23665031 2013 Disease-causing mutations in KLHL3 impair its effect on WNK4 degradation.

PMID 27780982 2016 A patient with pseudohypoaldosteronism type II complicated by congenital hypopituitarism carrying a KLHL3 mutation.

PMID 26435498 2015 Impaired degradation of WNK by Akt and PKA phosphorylation of KLHL3.

PMID 28511177 2017 Familial Hyperkalemia and Hypertension (FHHt) and KLHL3: Description of a Family with a New Recessive Mutation (S553L) Compared to a Family with a Dominant Mutation, Q309R, with Analysis of Urinary Sodium Chloride Cotransporter.

PMID 23387299 2013 The CUL3-KLHL3 E3 ligase complex mutated in Gordon's hypertension syndrome interacts with and ubiquitylates WNK isoforms: disease-causing mutations in KLHL3 and WNK4 disrupt interaction.

PMID 23453970 2013 Impaired KLHL3-mediated ubiquitination of WNK4 causes human hypertension.

PMID 23576762 2013 Kelch-like 3 and Cullin 3 regulate electrolyte homeostasis via ubiquitination and degradation of WNK4.

PMID 22266938 2012 Mutations in kelch-like 3 and cullin 3 cause hypertension and electrolyte abnormalities.

PMID 22406640 2012 KLHL3 mutations cause familial hyperkalemic hypertension by impairing ion transport in the distal nephron.

PMID 27026694 2016 A novel mutation in KLHL3 gene causes familial hyperkalemic hypertension.