KLHDC10 Kelch Domain Containing 10
A substrate adaptor for the CUL2-RING E3 ubiquitin ligase complex involved in oxidative stress response and protein quality control.
Gene Information Card
| Symbol | KLHDC10 |
|---|---|
| Full Name | Kelch Domain Containing 10 |
| Gene Type | Protein coding |
| Chromosomal Location | 7q32.3 |
| NCBI Gene ID | 23008 ncbi.nlm.nih.gov/gene/23008 |
| Ensembl ID | ENSG00000106333 |
| UniProt ID | Q6PJP8 |
| OMIM ID | 617924 |
| HGNC ID | 25128 |
| Aliases | FLJ10707, dJ1033B10.2, KLHDC10 |
Description
KLHDC10 encodes a kelch domain-containing protein that functions as a substrate recognition subunit of the CUL2-RING (CRL2) E3 ubiquitin ligase complex. It mediates ubiquitination and degradation of specific target proteins, playing a role in cellular responses to oxidative stress, protein homeostasis, and cell cycle regulation. The kelch repeats form a beta-propeller structure that binds substrates, while the N-terminal BTB/POZ domain mediates interaction with CUL2.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | Dysregulation of KLHDC10 expression may alter ubiquitination of tumor suppressors or oncoproteins, affecting cell proliferation and survival. | NCBI Gene, COSMIC |
| Neurodegenerative disorders | Impaired protein quality control via KLHDC10-mediated ubiquitination could contribute to accumulation of misfolded proteins. | UniProt, literature |
| Oxidative stress-related pathologies | KLHDC10 is induced by oxidative stress and regulates antioxidant responses; altered function may exacerbate cellular damage. | NCBI Gene, UniProt |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Brain (cerebellum) | 8.2 | Medium |
| Heart | 6.8 | Low |
| Liver | 4.1 | Low |
| Kidney | 5.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 10.1 | Embryonic kidney cells |
| HeLa | 7.4 | Cervical cancer cells |
| K562 | 6.2 | Leukemia cells |
| A549 | 5.8 | Lung cancer cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412Cys) | Missense | <0.1% (gnomAD) | Unknown functional impact; located in kelch repeat domain |
| c.567_568insA (p.Glu190Argfs*12) | Frameshift | <0.01% (COSMIC) | Predicted loss of function; truncation before BTB domain |
| c.890A>G (p.Asn297Ser) | Missense | <0.05% (ClinVar) | Uncertain significance; may affect substrate binding |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations that truncate the protein before or within the BTB/POZ domain are predicted to abolish CUL2 interaction and ubiquitin ligase activity.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported; missense variants in kelch repeats could potentially alter substrate specificity.
Dominant Negative (DN)
Mutations that disrupt substrate binding but retain CUL2 interaction may act as dominant negatives by sequestering the ligase complex.
View complete mutation data：
Gene Ontology (GO)
| • ubiquitin-protein transferase activity | • protein ubiquitination |
| • response to oxidative stress | • kelch repeat domain binding |
| • BTB domain binding | • cytosol |
| • nucleus |
Pathways
• Ubiquitin mediated proteolysis (KEGG: hsa04120)
• CRL2 ubiquitin ligase complex
• Oxidative stress response
Protein Summary
KLHDC10 is a 597-amino acid protein containing an N-terminal BTB/POZ domain and six C-terminal kelch repeats. It serves as a substrate adaptor for the CUL2-RING E3 ubiquitin ligase, targeting proteins for proteasomal degradation. The protein is localized in the cytosol and nucleus, and its expression is induced under oxidative stress conditions. Structural studies indicate the kelch domain forms a beta-propeller that recognizes specific degron motifs in substrates.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KLHDC10 Knockout HEK293 Cell Line | EDJ-KQ7771 | Human | 23008 | Details Get a Quote |
| KLHDC10 Knockout A-549 Cell Line | EDJ-KQ33244 | Human | 23008 | Details Get a Quote |
| KLHDC10 Knockout HCT 116 Cell Line | EDJ-KQ33245 | Human | 23008 | Details Get a Quote |
| KLHDC10 Knockout HeLa Cell Line | EDJ-KQ33246 | Human | 23008 | Details Get a Quote |
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