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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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KLHL10
kelch like family member 10
Chromosome 17 · 17q21.2
NCBI Gene: 317719Ensembl: ENSG00000161594.8HGNC: HGNC:18829UniProt: A0A140VJM8
17PubMed Papers
21Diseases
0Drugs
1Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingubiquitin-like ligase-substrate adaptor activityproteasome-mediated ubiquitin-dependent protein catabolic processcytoplasmspermatogenic failure 11male infertility with azoospermia or oligozoospermia due to single gene mutationazoospermiaAbnormality of the skeletal system
✦AI Summary

KLHL10 (kelch like family member 10) is a testis-specific protein that functions as a substrate-specific adapter in CUL3-based E3 ubiquitin ligase complexes, mediating protein ubiquitination and proteasomal degradation during spermatogenesis 1. The protein contains a BTB/POZ domain and six kelch repeats, showing 98.7% amino acid identity between mouse and human orthologs 1. KLHL10 is exclusively expressed in the cytoplasm of elongating and elongated spermatids (steps 9-16) and is essential for proper spermiogenesis 1. Mechanistically, KLHL10 functions through the ubiquitin-proteasome pathway to regulate spermatid maturation, with both alleles required for male fertility 1. Haploinsufficiency causes complete infertility in male mice due to disrupted spermiogenesis, characterized by asynchronous spermatid maturation, degeneration of late spermatids, and sloughing of postmeiotic germ cells 1. The protein can form homodimers and heterodimers through its POZ domain 2. Clinically, KLHL10 is associated with spermatogenic failure, though some reported mutations may not be pathogenic 3. KLHL10 is regulated by BNC1/TAF7L transcriptional complexes and is frequently mutated in patients with idiopathic spermatogenic failure 45.

Sources cited
1
KLHL10 structure, testis-specific expression, evolutionary conservation, and requirement for male fertility
PMID: 15136734
2
Investigation of I510V mutation in oligoasthenoteratozoospermia patients
PMID: 34433733
3
POZ domain-mediated homodimer and heterodimer formation
PMID: 17982253
4
Regulation by BNC1/TAF7L transcriptional complexes
PMID: 31065688
5
Frequent mutations in patients with idiopathic spermatogenic failure
PMID: 32655042
Disease Associationsⓘ21
spermatogenic failure 11Open Targets
0.62Moderate
male infertility with azoospermia or oligozoospermia due to single gene mutationOpen Targets
0.38Weak
azoospermiaOpen Targets
0.17Weak
Abnormality of the skeletal systemOpen Targets
0.10Weak
partial chromosome Y deletionOpen Targets
0.08Suggestive
Male infertility with spermatogenesis disorder due to single gene mutationOpen Targets
0.08Suggestive
spermatogenic failure 57Open Targets
0.07Suggestive
spermatogenic failure 50Open Targets
0.07Suggestive
spermatogenic failure 25Open Targets
0.07Suggestive
Female infertility due to fertilization defectOpen Targets
0.07Suggestive
spermatogenic failure 71Open Targets
0.07Suggestive
spermatogenic failure, X-linked, 2Open Targets
0.07Suggestive
spermatogenic failure 61Open Targets
0.07Suggestive
spermatogenic failure 62Open Targets
0.07Suggestive
spermatogenic failure 88Open Targets
0.07Suggestive
spermatogenic failure 59Open Targets
0.07Suggestive
spermatogenic failure 60Open Targets
0.07Suggestive
spermatogenic failure 73Open Targets
0.07Suggestive
spermatogenic failure 74Open Targets
0.07Suggestive
spermatogenic failure 31Open Targets
0.07Suggestive
Spermatogenic failure 11UniProt
Pathogenic Variants1
NM_152467.5(KLHL10):c.985C>T (p.Arg329Cys)Pathogenic
Spermatogenic failure 11
☆☆☆☆2021→ Residue 329
View on ClinVar ↗
Related Genes
IPPShared pathway100%SH3BGRLShared pathway100%ARMC8Shared pathway100%UBXN7Shared pathway100%KLHL5Shared pathway100%KLHL28Shared pathway100%
Tissue Expression6 tissues
Ovary
100%
Heart
50%
Lung
35%
Liver
30%
Brain
20%
Bone Marrow
5%
Gene Interaction Network
Click a node to explore
KLHL10IPPSH3BGRLARMC8UBXN7KLHL5KLHL28
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q6JEL2
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.37Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.22 [0.14–0.37]
RankingsWhere KLHL10 stands among ~20K protein-coding genes
  • #15,032of 20,598
    Most Researched17
  • #5,411of 5,498
    Most Pathogenic Variants1
  • #1,726of 17,882
    Most Constrained (LOEUF)0.37 · top 10%
Genes detectedKLHL10
Sources retrieved10 papers
Response time—
📄 Sources
10â–¼
1
Haploinsufficiency of kelch-like protein homolog 10 causes infertility in male mice.
PMID: 15136734
Proc Natl Acad Sci U S A · 2004
1.00
2
The I510V mutation in KLHL10 in a patient with oligoasthenoteratozoospermia.
PMID: 34433733
J Reprod Dev · 2021
0.90
3
Male infertility and its genetic causes.
PMID: 26178295
J Obstet Gynaecol Res · 2015
0.80
4
Utilizing
PMID: 39982357
J Dev Biol · 2025
0.70
5
Role of bioactive xenobiotics towards reproductive potential of Odontotermes longignathus through in silico study: An amalgamation of ecoinformatics and ecotechnological insights of termite mounds from a tropical forest, India.
PMID: 35131584
Ecotoxicol Environ Saf · 2022
0.60