KLHL7 Gene - Kelch Like Family Member 7
KLHL7: A BTB-Kelch Protein Involved in Ubiquitination and Retinal Degeneration
Gene Information Card
| Symbol | KLHL7 |
|---|---|
| Full Name | Kelch Like Family Member 7 |
| Gene Type | Protein coding |
| Chromosomal Location | 7p15.3 |
| NCBI Gene ID | 55975 ncbi.nlm.nih.gov/gene/55975 |
| Ensembl ID | ENSG00000122550 |
| UniProt ID | Q8IXQ5 |
| OMIM ID | 611119 |
| HGNC ID | 21336 |
| Aliases | KLHL7A, FLJ10656, MGC138499 |
Description
KLHL7 (Kelch Like Family Member 7) encodes a protein belonging to the BTB-Kelch family, which functions as a substrate-specific adapter for CUL3-based E3 ubiquitin ligase complexes. The protein is involved in ubiquitination and proteasomal degradation of target proteins, playing roles in cellular homeostasis, ciliogenesis, and retinal photoreceptor survival. Mutations in KLHL7 are associated with autosomal dominant retinitis pigmentosa (adRP) and other retinal dystrophies.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Retinitis pigmentosa (autosomal dominant) | Missense mutations in KLHL7 impair substrate recognition or ubiquitin ligase activity, leading to accumulation of toxic proteins in retinal photoreceptors | ClinVar, OMIM #611119 |
| Cone-rod dystrophy | Loss-of-function variants disrupt ciliary protein turnover, affecting photoreceptor outer segment maintenance | ClinVar, OMIM #611119 |
| Cancer (various) | Somatic mutations and copy number alterations in KLHL7 may alter ubiquitination of oncoproteins or tumor suppressors | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Retina | 10.2 | Medium |
| Brain (cerebellum) | 8.1 | Medium |
| Heart | 6.3 | Low |
| Liver | 4.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.3 | High expression |
| HeLa | 9.8 | Medium expression |
| K562 | 7.1 | Low expression |
| SH-SY5Y | 11.4 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.458C>T (p.Ala153Val) | Missense | 0.001% (gnomAD) | Associated with retinitis pigmentosa; disrupts BTB domain dimerization |
| c.1132G>A (p.Glu378Lys) | Missense | 0.0005% (gnomAD) | Pathogenic in adRP; alters Kelch domain substrate binding |
| c.1495C>T (p.Arg499Trp) | Missense | 0.0002% (gnomAD) | Likely pathogenic; impairs CUL3 interaction |
| c.1720_1722del (p.Lys574del) | In-frame deletion | Rare | Loss of function; reduced protein stability |
Mutation functional classification
Loss of Function (LOF)
Deletions and nonsense mutations that reduce KLHL7 protein levels or disrupt CUL3 binding lead to impaired ubiquitination and accumulation of target proteins.
Gain of Function (GOF)
Not clearly established; some missense mutations may alter substrate specificity without complete loss of function.
Dominant Negative (DN)
Missense mutations in the BTB domain (e.g., p.Ala153Val) can form nonfunctional dimers that sequester CUL3, reducing overall ubiquitin ligase activity.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Ubiquitin mediated proteolysis (KEGG: hsa04120)
• CUL3-based E3 ubiquitin ligase complex (Reactome: R-HSA-8951664)
• Cilium assembly and maintenance (Reactome: R-HSA-5620920)
Protein Summary
The KLHL7 protein (UniProt Q8IXQ5) is a 587-amino acid polypeptide containing an N-terminal BTB/POZ domain, a central BACK domain, and six C-terminal Kelch repeats. It functions as a substrate adapter for CUL3-RING E3 ubiquitin ligase complexes, targeting proteins for ubiquitination and proteasomal degradation. KLHL7 is highly expressed in testis and retina, where it regulates ciliary protein turnover and photoreceptor survival. Structural integrity of the BTB and Kelch domains is critical for proper function; mutations in these regions cause retinal degeneration.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KLHL7 Knockout HEK293 Cell Line | EDJ-KQ11531 | Human | 55975 | Details Get a Quote |
| KLHL7 Knockout A-549 Cell Line | EDJ-KQ39844 | Human | 55975 | Details Get a Quote |
| KLHL7 Knockout HCT 116 Cell Line | EDJ-KQ39845 | Human | 55975 | Details Get a Quote |
| KLHL7 Knockout HeLa Cell Line | EDJ-KQ39846 | Human | 55975 | Details Get a Quote |
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