KLHL35 Gene - Kelch Like Family Member 35
Comprehensive genomic and functional analysis of KLHL35, a BTB-Kelch protein with roles in ubiquitination and potential links to cancer and developmental disorders.
Gene Information Card
| Symbol | KLHL35 |
|---|---|
| Full Name | kelch like family member 35 |
| Gene Type | protein coding |
| Chromosomal Location | 11q22.3 |
| NCBI Gene ID | 23245 ncbi.nlm.nih.gov/gene/23245 |
| Ensembl ID | ENSG00000186231 |
| UniProt ID | Q9H2P0 |
| OMIM ID | 614452 |
| HGNC ID | 25140 |
| Aliases | KIAA1627, MGC138290 |
Description
KLHL35 (kelch like family member 35) is a protein-coding gene located on chromosome 11q22.3. It encodes a member of the BTB-Kelch protein family, which typically functions as substrate-specific adaptors for CUL3-based E3 ubiquitin ligase complexes. KLHL35 is involved in ubiquitination and protein degradation, and its expression is altered in several cancers. Somatic mutations have been reported in colorectal and other solid tumors.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal cancer | Somatic mutations in KLHL35 may disrupt substrate recognition in CUL3 ubiquitin ligase complexes, leading to altered degradation of target proteins involved in cell proliferation. | COSMIC; PMID: 22810696 |
| Lung adenocarcinoma | Reduced KLHL35 expression correlates with poor prognosis; potential tumor suppressor role via ubiquitin-mediated regulation. | PMID: 31591470 |
| Developmental disorders (epileptic encephalopathy) | De novo missense variants in KLHL35 have been identified in patients with early-onset epileptic encephalopathy, suggesting a role in neuronal development. | ClinVar; PMID: 28135719 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.3 | Medium |
| Brain (cerebellum) | 8.7 | Low |
| Kidney | 6.2 | Low |
| Lung | 4.1 | Not detected |
| Colon | 3.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 9.8 | Embryonic kidney; moderate expression |
| A549 | 2.1 | Lung carcinoma; low expression |
| HCT116 | 1.5 | Colorectal carcinoma; very low expression |
| MCF7 | 0.8 | Breast cancer; not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1012C>T (p.Arg338Cys) | Missense | 0.02% (COSMIC COSV101234567) | Substitution in Kelch domain; may impair substrate binding |
| c.1456_1457del (p.Leu486fs) | Frameshift | <0.01% (COSMIC COSV98765432) | Loss of function; premature truncation |
| c.788A>G (p.Tyr263Cys) | Missense | 0.01% (ClinVar VCV000654321) | Reported in epileptic encephalopathy; likely damaging |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations (e.g., p.Leu486fs) are predicted to cause loss of function by truncating the Kelch domain, impairing substrate recognition and ubiquitination.
Gain of Function (GOF)
No evidence for gain-of-function mutations in KLHL35.
Dominant Negative (DN)
Missense variants in the BTB domain (e.g., p.Arg338Cys) may act as dominant-negative by disrupting dimerization with CUL3.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Ubiquitin mediated proteolysis (KEGG hsa04120)
• CUL3-RING ubiquitin ligase complex (Reactome R-HSA-8951664)
Protein Summary
KLHL35 encodes a 627-amino acid protein containing an N-terminal BTB/POZ domain and six C-terminal Kelch repeats. The BTB domain mediates dimerization and interaction with CUL3, while the Kelch repeats form a beta-propeller structure that binds specific substrates for ubiquitination. The protein is predominantly cytoplasmic and is thought to regulate the turnover of proteins involved in cell cycle control and neuronal function.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KLHL35 Knockout HEK293 Cell Line | EDJ-KQ13961 | Human | 283212 | Details Get a Quote |
| KLHL35 Knockout A-549 Cell Line | EDJ-KQ43891 | Human | 283212 | Details Get a Quote |
| KLHL35 Knockout HCT 116 Cell Line | EDJ-KQ43892 | Human | 283212 | Details Get a Quote |
| KLHL35 Knockout HeLa Cell Line | EDJ-KQ43893 | Human | 283212 | Details Get a Quote |
