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Update on the Kelch-like (KLHL) gene family

Bajinder S Dhanoa1, Tiziana Cogliati2, Akhila G Satish2, Elspeth A Bruford3 and James S Friedman1*

Author Affiliations

1 Department of Ophthalmology, University of Colorado School of Medicine, Aurora, CO 80045, USA

2 Neurobiology-Neurodegeneration and Repair Laboratory (N-NRL), National Eye Institute, National Institutes of Health, Building 6/302, MSC 0610, 6 Center Drive, Bethesda, MD 20892, USA

3 HUGO Gene Nomenclature Committee (HGNC), EMBL-EBI, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SD, UK

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Human Genomics 2013, 7:13  doi:10.1186/1479-7364-7-13

Published: 15 May 2013


The Kelch-like (KLHL) gene family encodes a group of proteins that generally possess a BTB/POZ domain, a BACK domain, and five to six Kelch motifs. BTB domains facilitate protein binding and dimerization. The BACK domain has no known function yet is of functional importance since mutations in this domain are associated with disease. Kelch domains form a tertiary structure of β-propellers that have a role in extracellular functions, morphology, and binding to other proteins. Presently, 42 KLHL genes have been classified by the HUGO Gene Nomenclature Committee (HGNC), and they are found across multiple human chromosomes. The KLHL family is conserved throughout evolution. Phylogenetic analysis of KLHL family members suggests that it can be subdivided into three subgroups with KLHL11 as the oldest member and KLHL9 as the youngest. Several KLHL proteins bind to the E3 ligase cullin 3 and are known to be involved in ubiquitination. KLHL genes are responsible for several Mendelian diseases and have been associated with cancer. Further investigation of this family of proteins will likely provide valuable insights into basic biology and human disease.

KLHL; Kelch domain; BTB domain; Ubiquitination; Gene family; Evolution; Mendelian disease; Gene nomenclature; Cancer