Evidence mapPaperPMID 42271209Full record

ArticleBasic and clinical andrology2026

Gene set enrichment analysis of curated monogenic loci highlights key pathways and multisystem involvement in male infertility.

Matthew Yang, Katreya Lovrenert, Nannan Thirumavalavan, Michael L Eisenberg, Fredrick R Schumacher, Chen-Han Wilfred Wu

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In one paragraph

Article in Basic and clinical andrology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Matthew YangDepartment of Genetics, Heersink School of Medicine, Hugh Kaul Precision Medicine Institute, University of Alabama, Birmingham, AL, USA.
Katreya LovrenertDepartment of Genetics and Genome Sciences, Case Western Reserve University School of Medicine and University Hospitals, Cleveland, OH, USA.
Nannan ThirumavalavanDepartment of Urology, Case Western Reserve University School of Medicine and University Hospitals, Cleveland, OH, USA.
Michael L EisenbergDepartment of Urology, School of Medicine, Stanford University, Stanford, CA, USA.
Fredrick R SchumacherDepartment of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Chen-Han Wilfred WuDepartment of Genetics, Heersink School of Medicine, Hugh Kaul Precision Medicine Institute, University of Alabama, Birmingham, AL, USA. cwwu@uabmc.edu.

Funding

Impaired fecundity and future health: a prospective investigation of pregnancy planners in North America and DenmarkR01HD115096 · STANFORD UNIVERSITY · 2025 to 2025
$630k
NIH HHS DK135933NIH HHS R01HD115096
6 · The paper itself

Abstract

backgroundMale infertility affects approximately 10% of men globally, yet approximately 70% of cases lack a definitive genetic diagnosis. Next-generation sequencing has identified numerous monogenic causes, many of which are linked to broader systemic conditions. We curated a list of 596 candidate genes associated with male infertility from the literature and clinical genetics panels. Gene set enrichment analyses were performed on the strong-evidence genes using g: Profiler, REVIGO, and PANTHER to identify overrepresented Gene Ontology (GO) terms, and Reactome pathways. Gene-tissue expression profiles were assessed using GTExv8. Among the 178 strong-evidence genes, enrichment analyses revealed significant overrepresentation of terms related to ciliary and flagellar function (e.g., cilium movement, dynein complex), endocrine signaling (e.g., hormone receptor binding, steroid biosynthesis), and DNA repair mechanisms, particularly the Fanconi anemia nuclear complex. Reactome pathway analysis identified overrepresentation of androgen, glucocorticoid, and mineralocorticoid biosynthesis, BBSome-mediated ciliary transport, and meiosis. Tissue expression clustering identified extra-gonadal expression patterns, implicating adrenal, hypothalamic, and systemic involvement in genetic forms of male infertility.

conclusionsOur gene set enrichment and tissue expression analyses suggest that monogenic causes of male infertility are enriched in pathways in ciliary motility, endocrine regulation, and DNA repair which also have roles in extra-gonadal organ systems. These findings are consistent with epidemiological observations linking male infertility to broader health conditions and support multidisciplinary evaluation and care for affected individuals.

Indexed as

Gene ontologyGene set enrichment analysisGeneticsMale infertilityOverall health

Identifiers

PMID42271209
PMCPMC13251197

What Socratic holds

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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 Socratic graph.