ArticleNature communications2022
A de novo paradigm for male infertility.
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Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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49citing papers in PubMed
18.0field-weighted citation impact, top 1% of its field
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Who cites it
49 citing papers in PubMed, 98 citations in OpenAlex.
- A Western-style diet exacerbates male infertility in M1ap knockout mice.Human reproduction (Oxford, England) · 2026Article
- Application of Whole-Exome Sequencing in Identifying the Molecular Basis of Idiopathic Male Infertility.Journal of clinical medicine · 2026Review
- Review
- A clinical protocol for the detection of comorbidities associated with monogenic causes of male infertility.Human reproduction (Oxford, England) · 2026Article
- The influence and mechanism of gut microbiota on spermatogenesis.Cell biology and toxicology · 2026Review
- A novel loss-of-function mutation in MCMDC2 is associated with male infertility.Human genome variation · 2026Article
- Genetic diversity of infertile males in India.Journal of assisted reproduction and genetics · 2026Article
- Mapping the Non-Canonical Splicing Variants: Decrypting the Hidden Genetic Architecture of Idiopathic Male Infertility.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The Role of Whole Exome Sequencing in the Genetic Evaluation of the Infertile Man.Advances in experimental medicine and biology · 2026Review
- A comparison of spermatogenesis between flies and men-conserved processes of male gamete production.Human reproduction update · 2025Review
- Breathing new life into male fertility: the potential of mitochondrial transplantation.Molecular biology reports · 2025Review
- Genetic Testing for Monogenic Forms of Male Infertility Contributes to the Clinical Diagnosis of Men with Severe Idiopathic Male Infertility.The world journal of men's health · 2025Article
- Genetic and epigenetic landscape of male infertility.Trends in genetics : TIG · 2025Review
- Artificial Gametogenesis and In Vitro Spermatogenesis: Emerging Strategies for the Treatment of Male Infertility.International journal of molecular sciences · 2025Review
- NXT2 is a key component of the RNA nuclear export factor complex in the human testis and essential for spermatogenesis.Nature communications · 2025Article
- Introduction to androgenetics: terminology, approaches, and impactful studies across 60 years.Andrology · 2025Review
- How exome sequencing improves the diagnostics and management of men with non-syndromic infertility.Andrology · 2025Review
- Estimating mutation rate and characterising single nucleotide de novo mutations in pigs.Genetics, selection, evolution : GSE · 2025Article
- Genetic insights into non-obstructive azoospermia: Implications for diagnosis and TESE outcomes.Journal of assisted reproduction and genetics · 2025Article
- Prevalence of HSV-1/HSV-2 and CMV Infections in Infertile Men and Their Impact on Sperm Parameters: A Cross-Sectional Study in Iran.Health science reports · 2025Article
Corrections and comments
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Authors and funding
41 authors at 20 institutions in 13 countries.
M S Oud *Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboudumc, Nijmegen, The Netherlands.ORCID http://orcid.org/0000-0001-9513-3030
R M Smits *Department of Obstetrics and Gynaecology, Radboudumc, Nijmegen, The Netherlands.
H E Smith *Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
F K MastrorosaBiosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.ORCID http://orcid.org/0000-0003-0579-1895
G S HoltBiosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
B J HoustonSchool of BioSciences, Faculty of Science, The University of Melbourne, Parkville, VIC, Australia.
P F de VriesDepartment of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboudumc, Nijmegen, The Netherlands.
B K S AlobaidiBiosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.ORCID http://orcid.org/0000-0003-2718-4826
L E BattyBiosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
H IsmailBiosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
J GreenwoodDepartment of Genetic Medicine, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
H ShethFoundation for Research in Genetics and Endocrinology, Institute of Human Genetics, Ahmedabad, India.ORCID http://orcid.org/0000-0001-9626-0971
A MikulasovaBiosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
G D N AstutiDepartment of Human Genetics, Radboud Institute for Molecular Life Sciences, Radboudumc, Nijmegen, The Netherlands.
C GilissenDepartment of Human Genetics, Radboud Institute for Molecular Life Sciences, Radboudumc, Nijmegen, The Netherlands.ORCID http://orcid.org/0000-0003-1693-9699
K McElenyNewcastle Fertility Centre, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
H TurnerDepartment of Cellular Pathology, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
J CoxheadGenomics Core Facility, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.ORCID http://orcid.org/0000-0002-6128-9560
S CockellBioinformatics Support Unit, Faculty of Medical Sciences New, castle University, Newcastle upon Tyne, UK.
D D M BraatDepartment of Obstetrics and Gynaecology, Radboudumc, Nijmegen, The Netherlands.ORCID http://orcid.org/0000-0002-0847-3684
K FleischerDepartment of Obstetrics and Gynaecology, Radboudumc, Nijmegen, The Netherlands.
K W M D'HauwersDepartment of Urology, Radboudumc, Nijmegen, The Netherlands.
E SchaafsmaDepartment of Pathology, Radboudumc, Nijmegen, The Netherlands.
Genetics of Male Infertility Initiative (GEMINI) consortium
L NagirnajaDivision of Genetics, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR, USA.ORCID http://orcid.org/0000-0003-1948-2495
D F ConradDivision of Genetics, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR, USA.ORCID http://orcid.org/0000-0003-3828-8970
C FriedrichInstitute of Reproductive Genetics, University of Münster, Münster, Germany.
S KlieschCentre of Reproductive Medicine and Andrology, Department of Clinical and Surgical Andrology, University Hospital Münster, Münster, Germany.ORCID http://orcid.org/0000-0002-7561-4870
K I AstonDepartment of Surgery, Division of Urology, University of Utah School of Medicine, Salt Lake City, UT, USA.
A Riera-EscamillaAndrology Department, Fundació Puigvert, Universitat Autònoma de Barcelona, Instituto de Investigaciones Biomédicas Sant Pau (IIB-Sant Pau), Barcelona, Catalonia, Spain.
C KrauszDepartment of Biomedical, Experimental and Clinical Sciences "Mario Serio", University of Florence, Florence, Italy.
C Gonzaga-JaureguiRegeneron Genetics Center, Tarrytown, NY, USA.
M Santibanez-KorefBiosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
D J ElliottBiosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
L E L M VissersDepartment of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboudumc, Nijmegen, The Netherlands.ORCID http://orcid.org/0000-0001-6470-5497
F TüttelmannInstitute of Reproductive Genetics, University of Münster, Münster, Germany.ORCID http://orcid.org/0000-0003-2745-9965
M K O'BryanSchool of BioSciences, Faculty of Science, The University of Melbourne, Parkville, VIC, Australia.ORCID http://orcid.org/0000-0001-7298-4940
L RamosDepartment of Obstetrics and Gynaecology, Radboudumc, Nijmegen, The Netherlands.ORCID http://orcid.org/0000-0002-4269-013X
M J XavierBiosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.ORCID http://orcid.org/0000-0003-0709-7223
G W van der HeijdenDepartment of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboudumc, Nijmegen, The Netherlands.ORCID http://orcid.org/0000-0001-5894-7027
J A VeltmanBiosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK. joris.veltman@newcastle.ac.uk.ORCID http://orcid.org/0000-0002-3218-8250
Newcastle University · GBRadboud University Nijmegen · NLUniversity of Utah · USOregon National Primate Research Center · USNewcastle upon Tyne Hospitals NHS Foundation Trust · GBThe University of Melbourne · AUUniversidade do Porto · PTUniversity of Copenhagen · DKCentro de Genética Clínica · PTi3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto · PTNational Institute of Health Dr. Ricardo Jorge · PTPuigvert Foundation · ESUniversity of Münster · DEWashington University in St. Louis · USCornell University · USDiponegoro University · IDGenomics (United Kingdom) · GBHudson Institute of Medical Research · AUInstitute of Genetics and Hospital for Genetic Diseases · INMedical College of Wisconsin · US
Funding
Project IIIP50HD096723 · NICHD · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Kyle Edwin Orwig · 2019 to 2026
$15.0MGENOMICS OF SPERMATOGENIC IMPAIRMENTR01HD078641 · NICHD · WASHINGTON UNIVERSITY · PI Kenneth Ivan Aston, DONALD F. CONRAD · 2014 to 2026
$6.3MMODELING THE EFFECTS OF STRUCTURAL VARIATION IN GTEX DATA AND MENDELIAN DISEASER01MH101810 · NIMH · WASHINGTON UNIVERSITY · PI CONRAD, DONALD F. · 2013 to 2016
$1.3MBiotechnology and Biological Sciences Research Council BB/S008039/1NICHD NIH HHS P50 HD096723NICHD NIH HHS R01 HD078641NIMH NIH HHS R01 MH101810Wellcome Trust 209451Wellcome Trust 209451/Z/17/Z
Abstract
De novo mutations are known to play a prominent role in sporadic disorders with reduced fitness. We hypothesize that de novo mutations play an important role in severe male infertility and explain a portion of the genetic causes of this understudied disorder. To test this hypothesis, we utilize trio-based exome sequencing in a cohort of 185 infertile males and their unaffected parents. Following a systematic analysis, 29 of 145 rare (MAF < 0.1%) protein-altering de novo mutations are classified as possibly causative of the male infertility phenotype. We observed a significant enrichment of loss-of-function de novo mutations in loss-of-function-intolerant genes (p-value = 1.00 × 10
Indexed as
Genetic Predisposition to DiseaseLoss of Function MutationMutation, MissenseAdultAzoospermiaCase-Control StudiesCell Cycle ProteinsDNA-Binding ProteinsExomeExome SequencingGene ExpressionGene Expression ProfilingHumansMaleOligospermiaRNA-Binding ProteinsCell Cycle ProteinsDNA-Binding ProteinsRBM5 protein, humanRNA-Binding ProteinsTumor Suppressor Proteins
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.