ArticleHuman molecular genetics2019
EAP1 regulation of GnRH promoter activity is important for human pubertal timing.
Article in Human molecular genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
19 citing papers in PubMed, 39 citations in OpenAlex.
- Genetics of Idiopathic Hypogonadotropic HypogonadismJournal of clinical research in pediatric endocrinology · 2026Review
- NEDAMSS syndrome-related truncating and missense mutations are associated with aberrant liquid-liquid phase separation of IRF2BPL.Nature communications · 2026Article
- Deleterious variants in intolerant genes reveal new candidates for self-limited delayed puberty.European journal of endocrinology · 2025Article
- Contributions of Common Genetic Variants to Constitutional Delay of Puberty and Idiopathic Hypogonadotropic Hypogonadism.The Journal of clinical endocrinology and metabolism · 2024Article
- Disorders of puberty and neurodevelopment: A shared etiology?Annals of the New York Academy of Sciences · 2024Review
- Molecular basis of normal and pathological puberty: from basic mechanisms to clinical implications.The lancet. Diabetes & endocrinology · 2023Review
- Genetics of pubertal delay.Clinical endocrinology · 2022Review
- Genetic, epigenetic and enviromental influencing factors on the regulation of precocious and delayed puberty.Frontiers in endocrinology · 2022Review
- Genetics of pubertal timing.Best practice & research. Clinical endocrinology & metabolism · 2022Review
- Genetic architecture of self-limited delayed puberty and congenital hypogonadotropic hypogonadism.Frontiers in endocrinology · 2022Review
- Whole exome sequencing identifies deleterious rare variants in CCDC141 in familial self-limited delayed puberty.NPJ genomic medicine · 2021Article
- Genetic evaluation supports differential diagnosis in adolescent patients with delayed puberty.European journal of endocrinology · 2021Article
- Molecular genetic diagnostics of hypogonadotropic hypogonadism: from panel design towards result interpretation in clinical practice.Human genetics · 2021Review
- MKRN3 inhibits the reproductive axis through actions in kisspeptin-expressing neurons.The Journal of clinical investigation · 2020Article
- DLG2 variants in patients with pubertal disorders.Genetics in medicine : official journal of the American College of Medical Genetics · 2020Article
- LGR4 deficiency results in delayed puberty through impaired Wnt/β-catenin signaling.JCI insight · 2020Article
- Genetic Evaluation of Patients With Delayed Puberty and Congenital Hypogonadotropic Hypogonadism: Is it Worthy of Consideration?Frontiers in endocrinology · 2020Review
- Delayed Puberty-Phenotypic Diversity, Molecular Genetic Mechanisms, and Recent Discoveries.Endocrine reviews · 2019Review
- The Genetic Basis of Delayed Puberty.Frontiers in endocrinology · 2019Review
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 4 countries.
Funding
Abstract
The initiation of puberty is orchestrated by an augmentation of gonadotropin-releasing hormone (GnRH) secretion from a few thousand hypothalamic neurons. Recent findings have indicated that the neuroendocrine control of puberty may be regulated by a hierarchically organized network of transcriptional factors acting upstream of GnRH. These include enhanced at puberty 1 (EAP1), which contributes to the initiation of female puberty through transactivation of the GnRH promoter. However, no EAP1 mutations have been found in humans with disorders of pubertal timing. We performed whole-exome sequencing in 67 probands and 93 relatives from a large cohort of familial self-limited delayed puberty (DP). Variants were analyzed for rare, potentially pathogenic variants enriched in case versus controls and relevant to the biological control of puberty. We identified one in-frame deletion (Ala221del) and one rare missense variant (Asn770His) in EAP1 in two unrelated families; these variants were highly conserved and potentially pathogenic. Expression studies revealed Eap1 mRNA abundance in peri-pubertal mouse hypothalamus. EAP1 binding to the GnRH1 promoter increased in monkey hypothalamus at the onset of puberty as determined by chromatin immunoprecipitation. Using a luciferase reporter assay, EAP1 mutants showed a reduced ability to trans-activate the GnRH promoter compared to wild-type EAP1, due to reduced protein levels caused by the Ala221del mutation and subcellular mislocation caused by the Asn770His mutation, as revealed by western blot and immunofluorescence, respectively. In conclusion, we have identified the first EAP1 mutations leading to reduced GnRH transcriptional activity resulting in a phenotype of self-limited DP.
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