Kelch-Like 24

Alternative Names

  • KLHL24
  • Kainate Receptor-Interacting Protein for GluR6
  • KRIP6
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OMIM Number

611295

Gene Map Locus
3q27.1

Description

KLHL24 encodes Kelch like 24, a protein known to interact with GluR6, a kainate receptor located at synapses in the central nervous system. KLHL24 reduces endogenous kainate receptor-mediated currents evoked in hippocampal neurons, speculatively by modulating channel properties. It is predicted that by inhibiting peak current mediated by kainate receptors, KLHL24 protects neurons during the high frequency release of glutamate. The protein is also involved in protein ubiquitination and forms a part of the Cul3-RING ubiquitin ligase complex.

The gene is associated with Epidermolysis Bullosa Simplex, Generalized, with Scarring and Hair Loss (EBSSH), an autosomal dominant disorder characterized by skin abnormalities such as denudation, blisters, hypopigmentation, mild atrophy and diffuse palmoplantar keratoderma. 

Molecular Genetics

The KLHL24 gene is located on the long arm of chromosome 3 at position 3q27.1. The gene spans a length of 49.5 kb and its coding sequence is spread across 12 exons. The protein product encoded by KLHL24 has a molecular mass of 68.3 kDa and consists of 600 amino acids. Alternative splicing results in an additional isoform made up of 537 amino acids. While the gene is ubiquitously expressed in the body, overexpression is seen in skeletal muscles. Most mutations in the KLHL24 gene associated with EBSSH are heterozygous transitions or transversions in the first few nucleotides that result in the abolition of translation initiation.

Epidemiology in the Arab World

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Other Reports

Saudi Arabia

Anazi et al. (2016) observed the diagnostic yield of genomic tools to be much higher than standard clinical evaluations in a cohort of 337 Intellectual Disability (ID) cases. In a 5 year old girl suffering from global developmental delay, hypotonia, joint hypermobility, myopathic facies, nystagmus and malar hypoplasia, exome sequencing helped uncover a homozygous c.1609T>A (p.Cys537Ser) mutation in the KLHL24 gene. The gene has been noted in rat studies to be expressed in the cortex and hippocampus and is responsible for glutamate receptor regulation. Further, the amino acid change occurred in the 5th KELCH domain and was predicted to increase the tendency of misfolding or loss of structural stability.  

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