KLHL22 Kelch Like Family Member 22
A BTB-Kelch protein involved in ubiquitination and cell cycle regulation
Gene Information Card
| Symbol | KLHL22 |
|---|---|
| Full Name | Kelch Like Family Member 22 |
| Gene Type | Protein coding |
| Chromosomal Location | 22q11.21 |
| NCBI Gene ID | 100130894 ncbi.nlm.nih.gov/gene/100130894 |
| Ensembl ID | ENSG00000205755 |
| UniProt ID | Q53G59 |
| OMIM ID | 618204 |
| HGNC ID | 28333 |
| Aliases | FLJ32743, MGC138499 |
Description
KLHL22 encodes a member of the Kelch-like family of proteins, characterized by a BTB/POZ domain and Kelch repeats. The protein functions as a substrate-specific adapter for CUL3-based E3 ubiquitin ligase complexes, targeting proteins for ubiquitination and proteasomal degradation. It is involved in cell cycle progression, particularly in mitotic exit and cytokinesis, and has been implicated in cancer and developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | KLHL22 overexpression promotes cell proliferation via ubiquitination of DEPTOR, activating mTOR signaling | COSMIC, PubMed |
| Colorectal cancer | KLHL22 mutations and copy number alterations linked to tumor progression | COSMIC, ClinVar |
| Developmental delay | De novo missense variants in KLHL22 associated with neurodevelopmental phenotypes | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Brain | 8.3 | Low |
| Breast | 6.1 | Low |
| Colon | 5.4 | Low |
| Lung | 4.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | 15.2 | High expression |
| HCT116 (colorectal) | 12.8 | Moderate expression |
| HEK293 (embryonic kidney) | 10.1 | Moderate expression |
| A549 (lung cancer) | 7.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1015C>T (p.Arg339Cys) | Missense | <0.1% | Alters Kelch domain, potential loss of function |
| c.1246G>A (p.Gly416Arg) | Missense | <0.1% | Unknown functional effect |
| c.1573_1574insA (p.Thr525Asnfs*2) | Frameshift | <0.1% | Predicted loss of function |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations predicted to truncate the protein, impairing ubiquitin ligase adapter function.
Gain of Function (GOF)
Not well characterized; overexpression in breast cancer may confer gain-of-function via mTOR activation.
Dominant Negative (DN)
Not reported.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Ubiquitin mediated proteolysis (KEGG: hsa04120)
• mTOR signaling pathway (Reactome: R-HSA-165159)
Protein Summary
KLHL22 is a 648-amino acid protein containing an N-terminal BTB/POZ domain and six C-terminal Kelch repeats. It acts as a substrate adapter for CUL3-RING ubiquitin ligases, targeting proteins such as DEPTOR for degradation. The protein localizes to the cytoplasm and centrosome, and is essential for proper mitotic progression. Structural studies indicate that the Kelch domain forms a beta-propeller structure that mediates substrate recognition.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KLHL22 Knockout HEK293 Cell Line | EDJ-KQ10223 | Human | 84861 | Details Get a Quote |
| KLHL22 Knockout A-549 Cell Line | EDJ-KQ37390 | Human | 84861 | Details Get a Quote |
| KLHL22 Knockout HCT 116 Cell Line | EDJ-KQ37391 | Human | 84861 | Details Get a Quote |
| KLHL22 Knockout HeLa Cell Line | EDJ-KQ37392 | Human | 84861 | Details Get a Quote |
