ArticleEMBO molecular medicine2022
IQCN disruption causes fertilization failure and male infertility due to manchette assembly defect.
Article in EMBO molecular medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed, 32 citations in OpenAlex.
- Characterization and therapy of fertilization failure in murine and human models with HNRNPR mutations.EMBO molecular medicine · 2026Article
- Identification of nonfunctional CABS1 causing fertilization failure and male infertility in humans: a case report.Journal of assisted reproduction and genetics · 2025Article
- Sperm-Derived Dysfunction of Human Embryos: Molecular Mechanisms and Clinical Resolution.International journal of molecular sciences · 2025Review
- Function of manchette and intra-manchette transport in spermatogenesis and male fertility.Cell communication and signaling : CCS · 2025Review
- Loss of Cep135 causes oligoasthenoteratozoospermia and male infertility in mice.Cellular and molecular life sciences : CMLS · 2025Article
- IQ motif family genes in male infertility: pathogenesis, mechanisms, and clinical perspectives.Frontiers in reproductive health · 2025Review
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- Conserved genes regulating human sex differentiation, gametogenesis and fertilization.Journal of translational medicine · 2024Review
- High rate of detected variants in maleHuman reproduction open · 2024Article
- Advances in the study of genetic factors and clinical interventions for fertilization failure.Journal of assisted reproduction and genetics · 2023Review
- IQCN disruption causes fertilization failure and male infertility due to manchette assembly defect.EMBO molecular medicine · 2022Article
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
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Abstract
Total fertilization failure (TFF) is an important cause of infertility; however, the genetic basis of TFF caused by male factors remains to be clarified. In this study, whole-exome sequencing was firstly used to screen for genetic causes of TFF after intracytoplasmic sperm injection (ICSI), and homozygous variants in the novel gene IQ motif-containing N (IQCN) were identified in two affected individuals with abnormal acrosome structures. Then, Iqcn-knockout mice were generated by CRISPR-Cas9 technology and showed that the knockout male mice resembled the human phenotypes. Additionally, we found that IQCN regulates microtubule nucleation during manchette assembly via calmodulin and related calmodulin-binding proteins, which resulted in head deformity with aberrant oocyte activation factor PLCζ. Fortunately, ICSI with assisted oocyte activation can overcome IQCN-associate TFF and male infertility. Thus, our study firstly identified the function of IQCN, highlights the relationship between the manchette assembly and fertilization, and provides a genetic marker and a therapeutic option for male-source TFF.
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