KLHL5 Gene: Kelch-Like Family Member 5 - Function, Disease Associations, and Expression
Comprehensive biomedical overview of KLHL5, a BTB-Kelch protein involved in ubiquitination and potential tumor suppression.
Gene Information Card
| Symbol | KLHL5 |
|---|---|
| Full Name | Kelch-like family member 5 |
| Gene Type | protein coding |
| Chromosomal Location | 4p14 |
| NCBI Gene ID | 51088 ncbi.nlm.nih.gov/gene/51088 |
| Ensembl ID | ENSG00000107815 |
| UniProt ID | Q96PQ7 |
| OMIM ID | 610386 |
| HGNC ID | 6357 |
| Aliases | DKFZp686P16112, FLJ20580, MGC126562 |
Description
KLHL5 encodes a member of the kelch-like family, characterized by a BTB/POZ domain and kelch repeats. The protein is predicted to function as a substrate-specific adaptor for CUL3-based E3 ubiquitin ligases, involved in protein ubiquitination and degradation. KLHL5 is widely expressed and has been implicated in various cancers, though its precise biological roles are still under investigation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | Altered expression; potential tumor suppressor or oncogenic role depending on context | COSMIC lists KLHL5 mutations in various cancers; studies suggest dysregulation in breast, lung, and other tumors |
| Neuroblastoma | Possible involvement in cell proliferation and differentiation | Limited evidence from expression studies |
| Intellectual Disability (candidate) | Rare variants reported in some cohorts | ClinVar has few entries; not firmly established |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 20.1 | Medium |
| Kidney | 15.3 | Medium |
| Liver | 12.8 | Medium |
| Brain | 10.5 | Low |
| Lung | 8.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 18.5 | Cervical cancer cell line; moderate expression |
| A549 | 12.3 | Lung carcinoma; lower expression |
| MCF7 | 9.8 | Breast cancer; low expression |
| HEK293 | 22.1 | Embryonic kidney; high expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234A>G (p.Thr412Ala) | Missense | 0.01% (gnomAD) | Unknown; predicted benign |
| c.567delC (p.Leu190TrpfsTer5) | Frameshift | Rare | Loss of function; may affect protein stability |
| c.890C>T (p.Pro297Leu) | Missense | 0.005% | Possibly damaging; not validated |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense variants likely lead to reduced KLHL5 protein levels, potentially impairing ubiquitin ligase activity and substrate degradation.
Gain of Function (GOF)
No clear gain-of-function mutations reported; some missense variants may alter substrate specificity but evidence is limited.
Dominant Negative (DN)
Not established; if KLHL5 forms dimers, certain mutations could interfere with complex assembly, but no data support this.
View complete mutation data：
Gene Ontology (GO)
| • protein binding | • ubiquitin-protein transferase activity |
| • protein ubiquitination | • cytoskeleton organization |
| • cell cycle |
Pathways
• CUL3-RING ubiquitin ligase complex
• Proteasome-mediated protein degradation
Protein Summary
KLHL5 is a 748-amino acid protein containing an N-terminal BTB/POZ domain and six C-terminal kelch repeats. It is predicted to assemble with CUL3 to form an E3 ubiquitin ligase complex, targeting specific substrates for proteasomal degradation. The protein is localized in the cytoplasm and possibly in actin filaments. Its expression varies across tissues, with highest levels in testis and kidney. KLHL5 has been linked to cancer biology, where altered expression may influence tumor progression.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KLHL5 Knockout HEK293 Cell Line | EDJ-KQ10908 | Human | 51088 | Details Get a Quote |
| KLHL5 Knockout A-549 Cell Line | EDJ-KQ38636 | Human | 51088 | Details Get a Quote |
| KLHL5 Knockout HCT 116 Cell Line | EDJ-KQ38637 | Human | 51088 | Details Get a Quote |
| KLHL5 Knockout HeLa Cell Line | EDJ-KQ38638 | Human | 51088 | Details Get a Quote |
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