KLHL32 Gene - Kelch Like Family Member 32
Comprehensive genomic and functional overview of KLHL32, a BTB-Kelch protein implicated in cellular signaling and disease.
Gene Information Card
| Symbol | KLHL32 |
|---|---|
| Full Name | Kelch Like Family Member 32 |
| Gene Type | Protein coding |
| Chromosomal Location | 6q21 |
| NCBI Gene ID | 114792 ncbi.nlm.nih.gov/gene/114792 |
| Ensembl ID | ENSG00000186103 |
| UniProt ID | Q8N2M8 |
| OMIM ID | 614523 |
| HGNC ID | 29334 |
| Aliases | KIAA1627, MGC138290 |
Description
KLHL32 (Kelch Like Family Member 32) is a protein-coding gene located on chromosome 6q21. It encodes a member of the BTB-Kelch protein family, characterized by an N-terminal BTB/POZ domain and C-terminal Kelch repeats. These proteins typically function as substrate-specific adaptors for CUL3-based E3 ubiquitin ligases, targeting proteins for ubiquitination and proteasomal degradation. KLHL32 is involved in cellular processes including cytoskeletal organization, cell cycle regulation, and signal transduction. Expression is observed in multiple tissues, with notable levels in the brain and testis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Schizophrenia | Potential involvement in synaptic signaling and neurodevelopment; genetic association studies suggest risk variants. | PMID: 26198764 |
| Autism Spectrum Disorder | Rare variants in KLHL32 have been identified in ASD cohorts, implicating ubiquitin pathway dysregulation. | PMID: 25363760 |
| Cancer (general) | Altered expression in various tumors; potential role in cell proliferation via CUL3-mediated degradation. | COSMIC v99 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | 8.5 | Medium |
| Testis | 6.2 | Medium |
| Heart | 3.1 | Low |
| Liver | 1.8 | Low |
| Kidney | 2.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 7.0 | Neuronal model |
| HEK293 (embryonic kidney) | 4.5 | Common expression |
| HeLa (cervical carcinoma) | 3.2 | Low expression |
| K562 (leukemia) | 1.0 | Very low |
Data source:Human Protein Atlas(proteinatlas.org)
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412Cys) | Missense | 0.01% (gnomAD) | Substitution in Kelch domain; may alter substrate binding |
| c.567delA (p.Lys189fs) | Frameshift | <0.001% | Loss-of-function; premature stop |
| c.890G>A (p.Arg297His) | Missense | 0.005% | Located in BTB domain; potential impact on CUL3 interaction |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense variants leading to truncated protein or nonsense-mediated decay are classified as loss-of-function.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported for KLHL32.
Dominant Negative (DN)
Missense variants in the BTB domain may act in a dominant-negative manner by disrupting CUL3 complex assembly.
View complete mutation data:
Gene Ontology (GO)
| • protein binding (GO:0005515) | • ubiquitin protein ligase binding (GO:0031625) |
| • cytosol (GO:0005829) | • nucleus (GO:0005634) |
| • ubiquitin-dependent protein catabolic process (GO:0006511) |
Pathways
• Ubiquitin mediated proteolysis (KEGG: hsa04120)
• CUL3-RING ubiquitin ligase complex
Protein Summary
KLHL32 is a 627-amino acid protein containing an N-terminal BTB/POZ domain (residues 40-140) and six C-terminal Kelch repeats (residues 280-620). The BTB domain mediates homodimerization and interaction with CUL3, while the Kelch repeats form a beta-propeller structure that recognizes specific substrates. KLHL32 is predicted to function as a substrate adaptor for CUL3-based E3 ubiquitin ligases, targeting proteins for ubiquitination. Structural modeling suggests the Kelch domain forms a conserved binding pocket for substrate recognition. Post-translational modifications include phosphorylation sites (e.g., Ser200, Thr450) that may regulate activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KLHL32 Knockout HEK293 Cell Line | EDJ-KQ7463 | Human | 114792 | Details Get a Quote |
| KLHL32 Knockout HCT 116 Cell Line | EDJ-KQ32682 | Human | 114792 | Details Get a Quote |
| KLHL32 Knockout HeLa Cell Line | EDJ-KQ57930 | Human | 114792 | Details Get a Quote |
| KLHL32 Knockout A-549 Cell Line | EDJ-KQ66420 | Human | 114792 | Details Get a Quote |