KLHL20: Kelch Like Family Member 20
A BTB-Kelch Protein Involved in Ubiquitination, Autophagy, and Cancer
Gene Information Card
| Symbol | KLHL20 |
|---|---|
| Full Name | kelch like family member 20 |
| Gene Type | protein coding |
| Chromosomal Location | 1q23.3 |
| NCBI Gene ID | 27243 ncbi.nlm.nih.gov/gene/27243 |
| Ensembl ID | ENSG00000143157 |
| UniProt ID | Q9Y2M5 |
| OMIM ID | 617075 |
| HGNC ID | 29199 |
| Aliases | KLEIP, KLHLX, DKFZp686B16170 |
Description
KLHL20 (kelch like family member 20) encodes a protein belonging to the BTB-Kelch family. It functions as a substrate-specific adapter for CUL3-based E3 ubiquitin ligase complexes, targeting proteins for ubiquitination and proteasomal degradation. KLHL20 is involved in diverse cellular processes including autophagy, cell cycle regulation, and response to hypoxia. Dysregulation of KLHL20 has been implicated in cancer progression, particularly prostate cancer, and neurodegenerative diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Prostate cancer | KLHL20 overexpression promotes degradation of the tumor suppressor PML, enhancing cell survival and invasion under hypoxia. | PMID: 25910212 |
| Breast cancer | KLHL20 is upregulated and associated with poor prognosis; promotes cell proliferation and migration. | PMID: 29367603 |
| Neurodegeneration (ALS) | KLHL20 mediates ubiquitination of DCTN1 (dynactin), affecting axonal transport and motor neuron survival. | PMID: 23911931 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 28.5 | High |
| Brain | 15.2 | Medium |
| Prostate | 12.8 | Medium |
| Lung | 8.4 | Low |
| Liver | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 18.3 | Embryonic kidney |
| HeLa | 22.1 | Cervical cancer |
| PC3 | 35.7 | Prostate cancer |
| MCF7 | 14.6 | Breast cancer |
| SH-SY5Y | 11.2 | Neuroblastoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1192C>T (p.Arg398Trp) | Missense | 0.01% (gnomAD) | Unknown functional effect; located in Kelch domain |
| c.1450G>A (p.Glu484Lys) | Missense | 0.005% (gnomAD) | Potential impact on substrate binding |
| c.1723_1724insA (p.Thr575Asnfs*2) | Frameshift | Rare | Predicted loss of function |
Mutation functional classification
Loss of Function (LOF)
Frameshift mutations (e.g., p.Thr575Asnfs*2) are predicted to truncate the protein and abolish its adapter function in ubiquitination.
Gain of Function (GOF)
Not well characterized; overexpression in cancers suggests possible gain-of-function through increased degradation of tumor suppressors.
Dominant Negative (DN)
No dominant-negative mutations reported in KLHL20.
View complete mutation data：
Gene Ontology (GO)
Pathways
• CUL3-RING ubiquitin ligase complex
• Autophagy (regulation of ULK1 stability)
• Hypoxia-inducible factor (HIF) signaling
Protein Summary
KLHL20 is a 609-amino acid protein containing an N-terminal BTB domain and a C-terminal Kelch repeat domain. It acts as a substrate receptor for CUL3-based E3 ubiquitin ligases, targeting proteins such as PML, DCTN1, and ULK1 for ubiquitination. Through these interactions, KLHL20 regulates cell cycle, autophagy, and stress responses. Its expression is elevated in several cancers and correlates with poor prognosis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KLHL20 Knockout HEK293 Cell Line | EDJ-KQ8730 | Human | 27252 | Details Get a Quote |
| KLHL20 Knockout A-549 Cell Line | EDJ-KQ34973 | Human | 27252 | Details Get a Quote |
| KLHL20 Knockout HCT 116 Cell Line | EDJ-KQ34974 | Human | 27252 | Details Get a Quote |
| KLHL20 Knockout HeLa Cell Line | EDJ-KQ34975 | Human | 27252 | Details Get a Quote |
