KLHL40 Gene
Kelch Like Family Member 40
Gene Information Card
| Symbol | KLHL40 |
|---|---|
| Full Name | Kelch Like Family Member 40 |
| Gene Type | Protein coding |
| Chromosomal Location | 3p21.31 |
| NCBI Gene ID | 131377 ncbi.nlm.nih.gov/gene/131377 |
| Ensembl ID | ENSG00000188910 |
| UniProt ID | Q2TBA0 |
| OMIM ID | 615340 |
| HGNC ID | 30372 |
| Aliases | KBTBD5, MGC16384, nemaline myopathy 8 |
Description
KLHL40 encodes a member of the kelch-like protein family, characterized by a BTB/POZ domain and a kelch repeat domain. The protein is predominantly expressed in skeletal muscle and is involved in the stabilization of thin filament proteins, including nebulin and tropomyosin. Mutations in KLHL40 cause autosomal recessive nemaline myopathy 8, a severe congenital muscle disorder.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Nemaline Myopathy 8 | Loss-of-function mutations in KLHL40 disrupt thin filament assembly, leading to nemaline rod formation and muscle weakness. | ClinVar, OMIM #615348 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal Muscle | 48.2 | High |
| Heart | 3.1 | Low |
| Other Tissues | <1.0 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| LHCN-M2 (myotubes) | 52.0 | Differentiated skeletal muscle cells |
| HSMM (skeletal muscle myoblasts) | 12.5 | Undifferentiated myoblasts |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1516C>T (p.Arg506*) | Nonsense | Rare | Loss of function; truncation of protein |
| c.1225C>T (p.Arg409Trp) | Missense | Rare | Loss of function; impaired protein stability |
| c.1A>G (p.Met1Val) | Start loss | Rare | Loss of function; no translation initiation |
Mutation functional classification
Loss of Function (LOF)
Most KLHL40 mutations are loss-of-function, leading to reduced or absent protein, causing nemaline myopathy 8.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
| • actin binding | • protein homodimerization activity |
| • ubiquitin protein ligase activity | • skeletal muscle thin filament assembly |
| • sarcomere organization |
Pathways
• Thin filament assembly
• Ubiquitin-proteasome pathway
Protein Summary
KLHL40 is a 621-amino acid protein containing an N-terminal BTB/POZ domain and six C-terminal kelch repeats. It acts as a substrate adaptor for a CUL3-based E3 ubiquitin ligase complex, targeting proteins for degradation. In skeletal muscle, it stabilizes nebulin and tropomyosin, essential for sarcomere integrity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KLHL40 Knockout HEK293 Cell Line | EDJ-KQ9266 | Human | 131377 | Details Get a Quote |
| KLHL40 Knockout HeLa Cell Line | EDJ-KQ58295 | Human | 131377 | Details Get a Quote |
| KLHL40 Knockout A-549 Cell Line | EDJ-KQ66783 | Human | 131377 | Details Get a Quote |
| KLHL40 Knockout HCT 116 Cell Line | EDJ-KQ75186 | Human | 131377 | Details Get a Quote |
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