ArticlePLoS biology2019
KHDC3L mutation causes recurrent pregnancy loss by inducing genomic instability of human early embryonic cells.
Article in PLoS biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- Molecular Drivers of Developmental Arrest in the Human Preimplantation Embryo: A Systematic Review and Critical Analysis Leading to Mapping Future Research.International journal of molecular sciences · 2021Pooled it
- Tcf15 promotes an open nucleolar chromatin state to safeguard ribosome biogenesis and genome stability in mouse embryonic stem cells.PLoS biology · 2026Article
- Construction of a DNA Methylation Map of Argali Hybrid Sheep During Mo Infection.Microorganisms · 2026Article
- The retrospective data analysis of NLRP7 and KHDC3L mutations in Turkish patients with recurrent hydatidiform mole.Turkish journal of obstetrics and gynecology · 2025Article
- LINE-1 Methylation sustains telomere length in pregnant women: effects on pregnancy failure.Clinical epigenetics · 2025Article
- Hyperthyroidism Associated with Gestational Trophoblastic Neoplasia: Systematic Literature Review and Pathways Analysis.Cancers · 2025Review
- NLRP7 maintains the genomic stability during early human embryogenesis via mediating alternative splicing.Communications biology · 2025Article
- Subcortical Maternal Complex in Female Infertility: A Transition from Animal Models to Human Studies.Molecular biology reports · 2025Review
- Gestational trophoblastic disease: understanding the molecular mechanisms of placental tumours.Disease models & mechanisms · 2025Review
- Whole-Exome Sequencing in Recurrent Pregnancy Loss: Current Evidence and Future Directions in Saudi Arabia.Medical archives (Sarajevo, Bosnia and Herzegovina) · 2025Review
- A Maternal Loss-of-Function Variant in KHDC3L Gene Causes a Range of Adverse Pregnancy Outcomes: A Case Report.Molecular genetics & genomic medicine · 2025Article
- Advances in the genetic etiology of female infertility.Journal of assisted reproduction and genetics · 2024Review
- Proteomic Analysis of Domestic Cat Blastocysts and Their Secretome Produced in an In Vitro Culture System without the Presence of the Zona Pellucida.International journal of molecular sciences · 2024Article
- Identification of chromosomal abnormalities in miscarriages by CNV-Seq.Molecular cytogenetics · 2024Article
- Whole exome sequencing identifies a novel mutation inFrontiers in medicine · 2024Article
- Long noncoding RNA Lnc530 localizes on R-loops and regulates R-loop formation and genomic stability in mouse embryonic stem cells.Stem cell reports · 2023Article
- Revealing the expression profile of genes that encode the Subcortical Maternal Complex in human reproductive failures.Genetics and molecular biology · 2023Article
- A novel homozygous C-terminal deletion in BTG4 causes zygotic cleavage failure and female infertility.Journal of assisted reproduction and genetics · 2023Article
- Expression profiles of meiotic genes in male vs. female gonads and gametes: Insights into fertility issues.Frontiers in genetics · 2023Article
- Understanding recurrent pregnancy loss: recent advances on its etiology, clinical diagnosis, and management.Medical review (2021) · 2022Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recurrent pregnancy loss (RPL) is an important complication in reproductive health. About 50% of RPL cases are unexplained, and understanding the genetic basis is essential for its diagnosis and prognosis. Herein, we report causal KH domain containing 3 like (KHDC3L) mutations in RPL. KHDC3L is expressed in human epiblast cells and ensures their genome stability and viability. Mechanistically, KHDC3L binds to poly(ADP-ribose) polymerase 1 (PARP1) to stimulate its activity. In response to DNA damage, KHDC3L also localizes to DNA damage sites and facilitates homologous recombination (HR)-mediated DNA repair. KHDC3L dysfunction causes PARP1 inhibition and HR repair deficiency, which is synthetically lethal. Notably, we identified two critical residues, Thr145 and Thr156, whose phosphorylation by Ataxia-telangiectasia mutated (ATM) is essential for KHDC3L's functions. Importantly, two deletions of KHDC3L (p.E150_V160del and p.E150_V172del) were detected in female RPL patients, both of which harbor a common loss of Thr156 and are impaired in PARP1 activation and HR repair. In summary, our study reveals both KHDC3L as a new RPL risk gene and its critical function in DNA damage repair pathways.
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