KLHL10 Gene - Kelch Like Family Member 10
A key regulator of spermatogenesis and male fertility
Gene Information Card
| Symbol | KLHL10 |
|---|---|
| Full Name | Kelch Like Family Member 10 |
| Gene Type | Protein coding |
| Chromosomal Location | 17q21.2 |
| NCBI Gene ID | 317719 ncbi.nlm.nih.gov/gene/317719 |
| Ensembl ID | ENSG00000187231 |
| UniProt ID | Q6JEL2 |
| OMIM ID | 608778 |
| HGNC ID | 24053 |
| Aliases | FLJ10718, MGC138499 |
Description
KLHL10 encodes a member of the kelch-like protein family, characterized by a BTB/POZ domain and kelch repeats. This protein is predominantly expressed in the testis and is essential for spermatogenesis, specifically for the proper formation of sperm flagella and the completion of spermatid maturation. KLHL10 functions as a substrate-specific adapter for a CUL3-based E3 ubiquitin ligase complex, targeting proteins for ubiquitination and degradation during sperm development.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Spermatogenic failure 11 (SPGF11) | Loss-of-function mutations in KLHL10 disrupt ubiquitin-mediated protein degradation during spermatogenesis, leading to defective sperm flagella and maturation arrest. | OMIM #615081; PMID: 16951682 |
| Male infertility (non-obstructive azoospermia) | Homozygous or compound heterozygous mutations cause severe oligozoospermia or azoospermia due to impaired spermatid elongation. | ClinVar; PMID: 16951682 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 48.2 | High |
| Fallopian tube | 0.8 | Low |
| Prostate | 0.6 | Low |
| Other tissues | <0.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Spermatocytes | High | Enriched in meiotic cells |
| Round spermatids | High | Key stage for KLHL10 function |
| Elongating spermatids | Moderate | Expression declines post-meiosis |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1006C>T (p.Arg336*) | Nonsense | Rare | Loss of function; truncates protein before kelch repeats |
| c.1432C>T (p.Arg478Cys) | Missense | Rare | Disrupts kelch domain; impairs substrate binding |
| c.1672G>A (p.Gly558Arg) | Missense | Rare | Alters kelch repeat structure; reduced ubiquitination activity |
Mutation functional classification
Loss of Function (LOF)
Nonsense and missense mutations that impair substrate binding or disrupt the BTB/POZ domain lead to loss of E3 ligase adapter function, causing spermatogenic arrest.
Gain of Function (GOF)
Not reported.
Dominant Negative (DN)
Heterozygous missense mutations may exert dominant-negative effects by interfering with wild-type KLHL10 dimerization, though evidence is limited.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Ubiquitin-mediated proteolysis (KEGG: hsa04120)
• CUL3-RING ubiquitin ligase complex (Reactome: R-HSA-8951664)
Protein Summary
KLHL10 is a 609-amino acid protein containing an N-terminal BTB/POZ domain (required for dimerization and CUL3 binding), a BACK domain, and six C-terminal kelch repeats that mediate substrate recognition. It acts as an adapter for CUL3-based E3 ubiquitin ligases, targeting specific proteins for ubiquitination and degradation during spermatid elongation. Loss of KLHL10 function leads to accumulation of its substrates, resulting in defective flagellar assembly and male infertility.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KLHL10 Knockout HEK293 Cell Line | EDJ-KQ8898 | Human | 317719 | Details Get a Quote |
| KLHL10 Knockout HeLa Cell Line | EDJ-KQ59570 | Human | 317719 | Details Get a Quote |
| KLHL10 Knockout A-549 Cell Line | EDJ-KQ68035 | Human | 317719 | Details Get a Quote |
| KLHL10 Knockout HCT 116 Cell Line | EDJ-KQ76415 | Human | 317719 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
