ArticleThe Journal of clinical endocrinology and metabolism2023
Prevalence of Deleterious Variants in MC3R in Patients With Constitutional Delay of Growth and Puberty.
Article in The Journal of clinical endocrinology and metabolism, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 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
9 citing papers in PubMed, 13 citations in OpenAlex.
- Dlk1-deficient mice achieve puberty despite low body weight and low levels of leptin and kisspeptin.Journal of neuroendocrinology · 2026Article
- Genetics of Idiopathic Hypogonadotropic HypogonadismJournal of clinical research in pediatric endocrinology · 2026Review
- Sex-differential associations of MC3R p.F45S with human metabolic profile.Journal of neuroendocrinology · 2026Article
- Cross-species studies implicate the melanocortin 3 receptor more strongly in the control of pubertal development than energy balance.Molecular metabolism · 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
- Metabolic control of puberty: 60 years in the footsteps of Kennedy and Mitra's seminal work.Nature reviews. Endocrinology · 2024Review
- Prevalence of Deleterious Variants in MC3R in Patients With Constitutional Delay of Growth and Puberty.The Journal of clinical endocrinology and metabolism · 2023Article
- Dimerization of melanocortin 4 receptor controls puberty onset and body size polymorphism.Frontiers in endocrinology · 2023Article
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Authors and funding
36 authors at 17 institutions in 6 countries.
Funding
Abstract
contextThe melanocortin 3 receptor (MC3R) has recently emerged as a critical regulator of pubertal timing, linear growth, and the acquisition of lean mass in humans and mice. In population-based studies, heterozygous carriers of deleterious variants in MC3R report a later onset of puberty than noncarriers. However, the frequency of such variants in patients who present with clinical disorders of pubertal development is currently unknown.
objectiveThis work aimed to determine whether deleterious MC3R variants are more frequently found in patients clinically presenting with constitutional delay of growth and puberty (CDGP) or normosmic idiopathic hypogonadotropic hypogonadism (nIHH).
methodsWe examined the sequence of MC3R in 362 adolescents with a clinical diagnosis of CDGP and 657 patients with nIHH, experimentally characterized the signaling properties of all nonsynonymous variants found and compared their frequency to that in 5774 controls from a population-based cohort. Additionally, we established the relative frequency of predicted deleterious variants in individuals with self-reported delayed vs normally timed menarche/voice-breaking in the UK Biobank cohort.
resultsMC3R loss-of-function variants were infrequent but overrepresented in patients with CDGP (8/362 [2.2%]; OR = 4.17; P = .001). There was no strong evidence of overrepresentation in patients with nIHH (4/657 [0.6%]; OR = 1.15; P = .779). In 246 328 women from the UK Biobank, predicted deleterious variants were more frequently found in those self-reporting delayed (aged ≥16 years) vs normal age at menarche (OR = 1.66; P = 3.90E-07).
conclusionWe have found evidence that functionally damaging variants in MC3R are overrepresented in individuals with CDGP but are not a common cause of this phenotype.
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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.