Genetic variants help define the role of the MC4R C-terminus in signaling and cell surface stability

• Published in: Scientific reports Vol. 8; no. 1; pp. 10397 - 8
• Main Authors: Moore, Bryn S., Mirshahi, Tooraj
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 10.07.2018; Nature Publishing Group; Nature Portfolio
• Subjects: 13/106; 13/109; 13/95; 14/19; 14/33; 631/1647/245/2225; 631/208/726/649/2219; 631/443/319/1642/393; 631/80/304; 692/163/2743/393; Adult; Aged; Aged, 80 and over; Binding sites; Body Mass Index; Body weight; C-Terminus; Cell surface; Codon, Nonsense - genetics; Cysteine - genetics; Electronic health records; Exome - genetics; Female; Gene Expression Regulation; Genetic diversity; Genetic variance; Haploinsufficiency; Haploinsufficiency - genetics; HEK293 Cells; Heterozygote; Humanities and Social Sciences; Humans; Lipids - genetics; Loss of Function Mutation - genetics; Male; Melanocortin; Melanocortin MC4 receptors; Middle Aged; multidisciplinary; Obesity; Obesity - genetics; Obesity - pathology; Overweight; Pedigree; Protein transport; Proteins; Receptor, Melanocortin, Type 4 - genetics; Science; Science (multidisciplinary); Signal Transduction - genetics; Software

Screening 92,445 subjects in the Geisinger-Regeneron DiscovEHR cohort, we identified 5 patients heterozygous for nonsense mutations causing early terminations at Glu307 or Leu328 on the C-terminus of melanocortin 4 receptor (MC4R). Two Q307Ter carriers are severely obese (BMI > 40), while one is...