KLHL24 Gene - Kelch Like Family Member 24
KLHL24: A Key Regulator of Intermediate Filament Organization and Associated with Skin Fragility and Cardiomyopathy
Gene Information Card
| Symbol | KLHL24 |
|---|---|
| Full Name | Kelch Like Family Member 24 |
| Gene Type | Protein coding |
| Chromosomal Location | 3q27.1 |
| NCBI Gene ID | 54800 ncbi.nlm.nih.gov/gene/54800 |
| Ensembl ID | ENSG00000114771 |
| UniProt ID | Q6TFL4 |
| OMIM ID | 611295 |
| HGNC ID | 29347 |
| Aliases | DRE1, FLJ20071, MGC131851 |
Description
KLHL24 (Kelch Like Family Member 24) encodes a protein belonging to the kelch-like family, characterized by a BTB/POZ domain and kelch repeats. The protein acts as a substrate-specific adapter for a CUL3-based E3 ubiquitin ligase complex, targeting keratin intermediate filaments for ubiquitination and degradation. KLHL24 is essential for maintaining skin integrity and cardiac function. Mutations in KLHL24 cause autosomal dominant epidermolysis bullosa simplex and are associated with dilated cardiomyopathy.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Epidermolysis bullosa simplex, generalized, with scarring and hair loss | Gain-of-function mutations in the start codon lead to N-terminal truncation of KLHL24, increasing its stability and enhancing ubiquitination and degradation of keratin 14, weakening the intermediate filament network in basal keratinocytes. | OMIM #617294; ClinVar; multiple case reports |
| Dilated cardiomyopathy 1KK | Heterozygous missense and truncating mutations in KLHL24 impair cardiac intermediate filament homeostasis, leading to myocyte fragility and dilated cardiomyopathy. | OMIM #618774; ClinVar; PMID: 31079849 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skin | 35.2 | High |
| Heart | 18.7 | Medium |
| Esophagus | 15.3 | Medium |
| Skeletal Muscle | 12.1 | Medium |
| Lung | 8.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HaCaT (keratinocyte) | 42.5 | High expression in keratinocytes |
| HEK 293 | 22.3 | Moderate expression |
| HeLa | 15.6 | Moderate expression |
| H9c2 (cardiomyocyte) | 19.8 | Relevant for cardiac studies |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1Val) | Missense (start codon) | Pathogenic in families | Gain-of-function; N-terminal truncation, increased protein stability, enhanced keratin degradation |
| c.2T>C (p.Met1Thr) | Missense (start codon) | Pathogenic in families | Gain-of-function; same mechanism as p.Met1Val |
| c.73C>T (p.Arg25Ter) | Nonsense | Rare | Loss-of-function; associated with dilated cardiomyopathy |
| c.1525C>T (p.Arg509Cys) | Missense | Rare | Uncertain significance; possibly loss-of-function |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg25Ter) that lead to premature termination and nonsense-mediated decay, resulting in haploinsufficiency. Associated with dilated cardiomyopathy.
Gain of Function (GOF)
Start codon mutations (e.g., p.Met1Val, p.Met1Thr) that cause N-terminal truncation, increased protein stability, and enhanced ubiquitination of keratin 14. Associated with epidermolysis bullosa simplex.
Dominant Negative (DN)
Not clearly established for KLHL24; current evidence supports gain-of-function for skin disease and loss-of-function for cardiac disease.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Ubiquitin mediated proteolysis (KEGG: hsa04120)
• CUL3-RING ubiquitin ligase complex (Reactome: R-HSA-8951664)
• Keratinization (Reactome: R-HSA-6805567)
Protein Summary
The KLHL24 protein (UniProt Q6TFL4) is a 604-amino acid substrate adapter for CUL3-based E3 ubiquitin ligase complexes. It contains an N-terminal BTB/POZ domain (required for dimerization and CUL3 binding) and six C-terminal kelch repeats that mediate substrate recognition, particularly keratin intermediate filaments. KLHL24 targets keratin 14 (KRT14) for ubiquitination and proteasomal degradation, thereby regulating the turnover of intermediate filaments in skin and heart. Gain-of-function mutations that remove the N-terminal 23 amino acids increase protein stability and enhance keratin degradation, leading to skin fragility. Loss-of-function mutations impair cardiac intermediate filament homeostasis, causing dilated cardiomyopathy.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KLHL24 Knockout HEK293 Cell Line | EDJ-KQ13226 | Human | 54800 | Details Get a Quote |
| KLHL24 Knockout A-549 Cell Line | EDJ-KQ43879 | Human | 54800 | Details Get a Quote |
| KLHL24 Knockout HCT 116 Cell Line | EDJ-KQ43880 | Human | 54800 | Details Get a Quote |
| KLHL24 Knockout HeLa Cell Line | EDJ-KQ43881 | Human | 54800 | Details Get a Quote |
