R150S mutation in the human oxytocin receptor: Gain-of-function effects and implication in autism spectrum disorder

IF 2.8 4区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Xiaoxi Liu , Stanislav Cherepanov , Mehdi Abouzari , Amila Zuko , Shu Yang , Jamasb Sayadi , Xiaoyuan Jia , Chikashi Terao , Tsukasa Sasaki , Shigeru Yokoyama
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引用次数: 0

Abstract

This study investigates the rs547238576 (R150S) missense variant in the oxytocin receptor (OXTR) gene, previously observed through screening of rare variants in Japanese individuals with autism spectrum disorders (ASD). Contrary to the anticipated loss-of-function, R150S exhibits gain-of-function effects, enhancing oxytocin (OXT) sensitivity, ligand-binding affinity, and OXT-induced Ca2+ mobilization in vitro. This suggests R150S may alter OXT signaling, potentially contributing to the excitatory/inhibitory imbalance seen in ASD and other psychiatric disorders. Our findings underscore the significance of genetic variations in OXTR on functional activity and highlight the necessity for population-specific genetic study and in vitro analysis to elucidate genetic susceptibilities to neuropsychiatric conditions.
人类催产素受体的 R150S 突变:功能增益效应及其对自闭症谱系障碍的影响
本研究调查了催产素受体(OXTR)基因中的rs547238576(R150S)错义变异,该变异先前是通过筛查日本自闭症谱系障碍(ASD)患者中的罕见变异而发现的。与预期的功能缺失相反,R150S 表现出功能增益效应,在体外增强了催产素(OXT)的敏感性、配体结合亲和力和 OXT 诱导的 Ca2+ 调动。这表明 R150S 可能会改变 OXT 信号转导,从而可能导致 ASD 和其他精神疾病中出现的兴奋/抑制失衡。我们的研究结果强调了 OXTR 基因变异对功能活动的重要影响,并突出了进行特定人群基因研究和体外分析以阐明神经精神疾病遗传易感性的必要性。
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来源期刊
Peptides
Peptides 医学-生化与分子生物学
CiteScore
6.40
自引率
6.70%
发文量
130
审稿时长
28 days
期刊介绍: Peptides is an international journal presenting original contributions on the biochemistry, physiology and pharmacology of biological active peptides, as well as their functions that relate to gastroenterology, endocrinology, and behavioral effects. Peptides emphasizes all aspects of high profile peptide research in mammals and non-mammalian vertebrates. Special consideration can be given to plants and invertebrates. Submission of articles with clinical relevance is particularly encouraged.
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