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.

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 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
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