KLHL8 Gene - Kelch Like Family Member 8
Comprehensive genomic and functional overview of KLHL8, a substrate-specific adaptor for CUL3 ubiquitin ligase complexes.
Gene Information Card
| Symbol | KLHL8 |
|---|---|
| Full Name | Kelch Like Family Member 8 |
| Gene Type | Protein coding |
| Chromosomal Location | 4q31.3 |
| NCBI Gene ID | 57563 ncbi.nlm.nih.gov/gene/57563 |
| Ensembl ID | ENSG00000138614 |
| UniProt ID | Q9P2J8 |
| OMIM ID | 611967 |
| HGNC ID | 28997 |
| Aliases | KIAA1378, MGC138290 |
Description
KLHL8 encodes a member of the kelch-like protein family that functions as a substrate-specific adaptor for CUL3-based E3 ubiquitin ligase complexes. The protein contains an N-terminal BTB/POZ domain and a C-terminal kelch repeat domain, mediating protein-protein interactions and ubiquitination of target substrates. KLHL8 is involved in cellular processes including protein degradation, cell cycle regulation, and neuronal development.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Intellectual disability | KLHL8 mutations may disrupt CUL3-mediated ubiquitination of synaptic proteins, impairing neuronal function. | ClinVar; PMID: 25439727 |
| Autism spectrum disorder | Rare variants in KLHL8 have been identified in ASD cohorts, suggesting a role in neurodevelopmental pathways. | COSMIC; ClinVar |
| Cancer (pan-cancer) | Altered KLHL8 expression and copy number changes observed in various tumors; potential impact on ubiquitin-proteasome system. | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Testis | 8.3 | Medium |
| Lung | 4.1 | Low |
| Liver | 2.9 | Low |
| Kidney | 3.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 10.2 | High expression in embryonic kidney cells |
| SH-SY5Y | 8.7 | Neuroblastoma cell line; relevant for neuronal studies |
| HeLa | 6.4 | Cervical carcinoma; moderate expression |
| HepG2 | 3.1 | Hepatocellular carcinoma; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1015C>T (p.Arg339Cys) | Missense | <0.01% | Likely damaging; alters kelch repeat domain |
| c.1243G>A (p.Gly415Ser) | Missense | <0.01% | Uncertain significance; reported in ClinVar |
| c.1687delC (p.Leu563Trpfs*12) | Frameshift | <0.01% | Loss of function; truncation of C-terminal domain |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations predicted to cause loss of adaptor function, impairing ubiquitination of substrates.
Gain of Function (GOF)
No gain-of-function mutations reported in KLHL8.
Dominant Negative (DN)
Missense mutations in BTB domain may interfere with CUL3 binding, acting in a dominant-negative manner.
View complete mutation data：
Gene Ontology (GO)
| • protein binding (GO:0005515) | • ubiquitin protein ligase binding (GO:0031625) |
| • ubiquitin protein ligase activity (GO:0061630) | • cytoplasm (GO:0005737) |
| • nucleus (GO:0005634) |
Pathways
• CUL3-RING ubiquitin ligase complex (Reactome: R-HSA-8951664)
• Ubiquitin-mediated proteolysis (KEGG: hsa04120)
Protein Summary
KLHL8 is a 627-amino acid protein with a BTB/POZ domain (residues 38-140) and six kelch repeats (residues 280-600). It acts as a substrate adaptor for CUL3, targeting proteins for ubiquitination and proteasomal degradation. The protein is predominantly cytoplasmic and expressed in brain and testis. Structural integrity of the kelch repeats is critical for substrate recognition.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KLHL8 Knockout HEK293 Cell Line | EDJ-KQ13952 | Human | 57563 | Details Get a Quote |
| KLHL8 Knockout A-549 Cell Line | EDJ-KQ43870 | Human | 57563 | Details Get a Quote |
| KLHL8 Knockout HCT 116 Cell Line | EDJ-KQ43871 | Human | 57563 | Details Get a Quote |
| KLHL8 Knockout HeLa Cell Line | EDJ-KQ43872 | Human | 57563 | Details Get a Quote |
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