更新于：2024-11-01

SEL1L2

更新于：2024-11-01

基本信息

别名

C20orf50、DKFZp434C1826、Protein sel-1 homolog 2

+ [4]

简介-

关联

靶点

SEL1L2

作用机制

SEL1L2 modulators

在研机构

AnHorn Medicines Co., Ltd.初创企业

原研机构

AnHorn Medicines Co., Ltd.初创企业

在研适应症

肿瘤

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期1800-01-20

novel E3 ligase (Plexium)

靶点

SEL1L2

作用机制

SEL1L2抑制剂

在研机构-

原研机构

Plexium, Inc.初创企业

在研适应症-

非在研适应症

肿瘤

最高研发阶段终止

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 SEL1L2 相关的临床结果

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100 项与 SEL1L2 相关的转化医学

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0 项与 SEL1L2 相关的专利（医药）

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项与 SEL1L2 相关的文献（医药）

2023-03-23·Nutrients

Crosstalk between Gut Microbiota and Epigenetic Markers in Obesity Development: Relationship between Ruminococcus, BMI, and MACROD2/SEL1L2 Methylation.

Article

作者: Milagro, Fermín I ; Salas-Perez, Francisca ; Assmann, Taís Silveira ; Riezu-Boj, Jose Ignacio ; Ramos-Lopez, Omar ; Martínez, J Alfredo

Changes in gut microbiota composition and in epigenetic mechanisms have been proposed to play important roles in energy homeostasis, and the onset and development of obesity. However, the crosstalk between epigenetic markers and the gut microbiome in obesity remains unclear. The main objective of this study was to establish a link between the gut microbiota and DNA methylation patterns in subjects with obesity by identifying differentially methylated DNA regions (DMRs) that could be potentially regulated by the gut microbiota. DNA methylation and bacterial DNA sequencing analysis were performed on 342 subjects with a BMI between 18 and 40 kg/m². DNA methylation analyses identified a total of 2648 DMRs associated with BMI, while ten bacterial genera were associated with BMI. Interestingly, only the abundance of Ruminococcus was associated with one BMI-related DMR, which is located between the MACROD2/SEL1L2 genes. The Ruminococcus abundance negatively correlated with BMI, while the hypermethylated DMR was associated with reduced MACROD2 protein levels in serum. Additionally, the mediation test showed that 19% of the effect of Ruminococcus abundance on BMI is mediated by the methylation of the MACROD2/SEL1L2 DMR. These findings support the hypothesis that a crosstalk between gut microbiota and epigenetic markers may be contributing to obesity development.

2020-07-01·Annals of Clinical and Translational Neurology2区 · 医学

A recurrent PJA1 variant in trigonocephaly and neurodevelopmental disorders

2区 · 医学

ArticleOA

作者: Watanabe, Ken ; Raveau, Matthieu ; Shimoji, Takeyoshi ; Nakaoka, Kentaro ; Kushima, Itaru ; Yoshikawa, Takeo ; Shimohata, Atsushi ; Sasaki, Aya ; Ohmori, Iori ; Kaneko, Sunao ; Suzuki, Toshimitsu ; Sudo, Genki ; Tsurusaki, Yoshinori ; Inoue, Yushi ; Ozaki, Norio ; Suzuki, Toshifumi ; Watanabe, Takaki ; Toyota, Tomoko ; Miyake, Noriko ; Shiino, Tomoko ; Kano, Masanobu ; Mazaki, Emi ; Sugaya, Yuki ; Iwayama, Yoshimi ; Tatsukawa, Tetsuya ; Matsumoto, Naomichi ; Aleksic, Branko ; Yamakawa, Kazuhiro ; Hirose, Shinichi

AbstractObjectiveNeurodevelopmental disorders (NDDs) often associate with epilepsy or craniofacial malformations. Recent large‐scale DNA analyses identified hundreds of candidate genes for NDDs, but a large portion of the cases still remain unexplained. We aimed to identify novel candidate genes for NDDs.MethodsWe performed exome sequencing of 95 patients with NDDs including 51 with trigonocephaly and subsequent targeted sequencing of additional 463 NDD patients, functional analyses of variant in vitro, and evaluations of autism spectrum disorder (ASD)‐like phenotypes and seizure‐related phenotypes in vivo.ResultsWe identified de novo truncation variants in nine novel genes; CYP1A1, C14orf119, FLI1, CYB5R4, SEL1L2, RAB11FIP2, ZMYND8, ZNF143, and MSX2. MSX2 variants have been described in patients with cranial malformations, and our present patient with the MSX2 de novo truncation variant showed cranial meningocele and partial epilepsy. MSX2 protein is known to be ubiquitinated by an E3 ubiquitin ligase PJA1, and interestingly we found a PJA1 hemizygous p.Arg376Cys variant recurrently in seven Japanese NDD patients; five with trigonocephaly and one with partial epilepsy, and the variant was absent in 886 Japanese control individuals. Pja1 knock‐in mice carrying p.Arg365Cys, which is equivalent to p.Arg376Cys in human, showed a significant decrease in PJA1 protein amount, suggesting a loss‐of‐function effect of the variant. Pja1 knockout mice displayed moderate deficits in isolation‐induced ultrasonic vocalizations and increased seizure susceptibility to pentylenetetrazole.InterpretationThese findings propose novel candidate genes including PJA1 and MSX2 for NDDs associated with craniofacial abnormalities and/or epilepsy.