KLHL6 Gene - Kelch Like Family Member 6
KLHL6: A BTB-Kelch Protein Involved in B-Cell Development and Lymphoid Malignancies
Gene Information Card
| Symbol | KLHL6 |
|---|---|
| Full Name | Kelch Like Family Member 6 |
| Gene Type | Protein coding |
| Chromosomal Location | 3q27.3 |
| NCBI Gene ID | 89857 ncbi.nlm.nih.gov/gene/89857 |
| Ensembl ID | ENSG00000172531 |
| UniProt ID | Q8WZ60 |
| OMIM ID | 611381 |
| HGNC ID | 18683 |
| Aliases | FLJ20032, MGC131944 |
Description
KLHL6 encodes a member of the Kelch-like protein family characterized by an N-terminal BTB/POZ domain and C-terminal Kelch repeats. The protein is predominantly expressed in lymphoid tissues, particularly in germinal center B-cells, and is involved in B-cell receptor signaling and germinal center formation. Mutations in KLHL6 have been identified in chronic lymphocytic leukemia (CLL) and diffuse large B-cell lymphoma (DLBCL), suggesting a tumor suppressor role.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Chronic lymphocytic leukemia (CLL) | Somatic mutations in KLHL6 disrupt BTB domain function, impairing protein-protein interactions and potentially altering B-cell receptor signaling. | COSMIC, ClinVar, PMID: 22237106 |
| Diffuse large B-cell lymphoma (DLBCL) | Recurrent missense and nonsense mutations in KLHL6 are observed, with loss of function contributing to lymphomagenesis. | COSMIC, PMID: 22237106 |
| B-cell non-Hodgkin lymphoma | KLHL6 mutations are enriched in germinal center B-cell subtypes, suggesting a role in germinal center exit or differentiation. | COSMIC, PMID: 22237106 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.5 | Medium |
| Spleen | 10.2 | Medium |
| Bone marrow | 8.7 | Medium |
| Tonsil | 15.3 | High |
| Appendix | 6.1 | Low |
| Whole blood | 0.8 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Raji (Burkitt lymphoma) | 14.2 | High expression |
| Daudi (Burkitt lymphoma) | 12.8 | High expression |
| K562 (leukemia) | 1.5 | Low expression |
| HEK293 (embryonic kidney) | 0.3 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.101C>T (p.Pro34Leu) | Missense | <1% | Located in BTB domain; may disrupt dimerization |
| c.200_201del (p.Glu67fs) | Frameshift | <1% | Loss of function; truncation |
| c.421G>A (p.Glu141Lys) | Missense | <1% | Observed in CLL; potential gain-of-function? |
| c.1123C>T (p.Arg375*) | Nonsense | <1% | Premature stop; loss of function |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations (e.g., p.Glu67fs, p.Arg375*) lead to truncated protein lacking Kelch repeats, impairing substrate binding and ubiquitination.
Gain of Function (GOF)
No clear gain-of-function mutations reported; some missense variants (e.g., p.Glu141Lys) require functional validation.
Dominant Negative (DN)
Missense mutations in the BTB domain (e.g., p.Pro34Leu) may interfere with dimerization of wild-type KLHL6, potentially acting in a dominant-negative manner.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Ubiquitin mediated proteolysis (KEGG: hsa04120)
• B cell receptor signaling pathway (Reactome: R-HSA-983705)
Protein Summary
KLHL6 is a 619-amino acid protein with a BTB/POZ domain (residues 33–130) and six Kelch repeats (residues 280–600). It functions as a substrate-specific adapter for CUL3-based E3 ubiquitin ligase complexes, targeting proteins for proteasomal degradation. In B-cells, KLHL6 is essential for germinal center formation and B-cell receptor signaling. Loss of function due to mutation is associated with lymphoid malignancies.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KLHL6 Knockout HEK293 Cell Line | EDJ-KQ10528 | Human | 89857 | Details Get a Quote |
| KLHL6 Knockout HeLa Cell Line | EDJ-KQ57742 | Human | 89857 | Details Get a Quote |
| KLHL6 Knockout A-549 Cell Line | EDJ-KQ66238 | Human | 89857 | Details Get a Quote |
| KLHL6 Knockout HCT 116 Cell Line | EDJ-KQ74659 | Human | 89857 | Details Get a Quote |
