De novo non-synonymous TBL1XR1 mutation alters Wnt signaling activity

Akira Nishi, Shusuke Numata, Atsushi Tajima, Xiaolei Zhu, Koki Ito, Atsushi Saito, Yusuke Kato, Makoto Kinoshita, Shinji Shimodera, Shinji Ono, Shinichiro Ochi, Akira Imamura, Naohiro Kurotaki, Shu Ichi Ueno, Nakao Iwata, Kiyoshi Fukui, Issei Imoto, Atsushi Kamiya, Tetsuro Ohmori

Research output: Contribution to journalArticle

Abstract

Here we report de novo non-synonymous single-nucleotide variants (SNVs) by conducting whole exome sequencing of 18 trios consisting of Japanese patients with sporadic schizophrenia and their parents. Among nine SNVs, we explored the functional impact of the de novo mutation in TBL1XR1 [c.30 C > G (p.Phe10Leu)], a gene previously found to be associated with autism spectrum disorder and epilepsy. Protein structural analysis revealed that Phe10Leu mutation may decrease the structural stability of the TBL1XR1 protein. We demonstrate that Phe10Leu mutation alters the interaction of TBL1XR1 with N-CoR and β-catenin, which play critical roles in regulation of Wnt-mediated transcriptional activity. Consistently, TBL1XR1-mediated activation of Wnt signaling was up-regulated by Phe10Leu mutation. These results suggest that a de novo TBL1XR1 point mutation could alter Wnt/β-catenin signaling activity. Further studies are required to clarify the involvement of TBL1XR1 mutations in neuropsychiatric conditions.

Original languageEnglish
Article number2887
JournalScientific reports
Volume7
Issue number1
DOIs
Publication statusPublished - 01-12-2017

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Mutation
Catenins
Nucleotides
Exome
Protein Stability
Point Mutation
Epilepsy
Schizophrenia
Parents
Genes
Proteins

All Science Journal Classification (ASJC) codes

  • General

Cite this

Nishi, A., Numata, S., Tajima, A., Zhu, X., Ito, K., Saito, A., ... Ohmori, T. (2017). De novo non-synonymous TBL1XR1 mutation alters Wnt signaling activity. Scientific reports, 7(1), [2887]. https://doi.org/10.1038/s41598-017-02792-z
Nishi, Akira ; Numata, Shusuke ; Tajima, Atsushi ; Zhu, Xiaolei ; Ito, Koki ; Saito, Atsushi ; Kato, Yusuke ; Kinoshita, Makoto ; Shimodera, Shinji ; Ono, Shinji ; Ochi, Shinichiro ; Imamura, Akira ; Kurotaki, Naohiro ; Ueno, Shu Ichi ; Iwata, Nakao ; Fukui, Kiyoshi ; Imoto, Issei ; Kamiya, Atsushi ; Ohmori, Tetsuro. / De novo non-synonymous TBL1XR1 mutation alters Wnt signaling activity. In: Scientific reports. 2017 ; Vol. 7, No. 1.
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abstract = "Here we report de novo non-synonymous single-nucleotide variants (SNVs) by conducting whole exome sequencing of 18 trios consisting of Japanese patients with sporadic schizophrenia and their parents. Among nine SNVs, we explored the functional impact of the de novo mutation in TBL1XR1 [c.30 C > G (p.Phe10Leu)], a gene previously found to be associated with autism spectrum disorder and epilepsy. Protein structural analysis revealed that Phe10Leu mutation may decrease the structural stability of the TBL1XR1 protein. We demonstrate that Phe10Leu mutation alters the interaction of TBL1XR1 with N-CoR and β-catenin, which play critical roles in regulation of Wnt-mediated transcriptional activity. Consistently, TBL1XR1-mediated activation of Wnt signaling was up-regulated by Phe10Leu mutation. These results suggest that a de novo TBL1XR1 point mutation could alter Wnt/β-catenin signaling activity. Further studies are required to clarify the involvement of TBL1XR1 mutations in neuropsychiatric conditions.",
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Nishi, A, Numata, S, Tajima, A, Zhu, X, Ito, K, Saito, A, Kato, Y, Kinoshita, M, Shimodera, S, Ono, S, Ochi, S, Imamura, A, Kurotaki, N, Ueno, SI, Iwata, N, Fukui, K, Imoto, I, Kamiya, A & Ohmori, T 2017, 'De novo non-synonymous TBL1XR1 mutation alters Wnt signaling activity', Scientific reports, vol. 7, no. 1, 2887. https://doi.org/10.1038/s41598-017-02792-z

De novo non-synonymous TBL1XR1 mutation alters Wnt signaling activity. / Nishi, Akira; Numata, Shusuke; Tajima, Atsushi; Zhu, Xiaolei; Ito, Koki; Saito, Atsushi; Kato, Yusuke; Kinoshita, Makoto; Shimodera, Shinji; Ono, Shinji; Ochi, Shinichiro; Imamura, Akira; Kurotaki, Naohiro; Ueno, Shu Ichi; Iwata, Nakao; Fukui, Kiyoshi; Imoto, Issei; Kamiya, Atsushi; Ohmori, Tetsuro.

In: Scientific reports, Vol. 7, No. 1, 2887, 01.12.2017.

Research output: Contribution to journalArticle

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T1 - De novo non-synonymous TBL1XR1 mutation alters Wnt signaling activity

AU - Nishi, Akira

AU - Numata, Shusuke

AU - Tajima, Atsushi

AU - Zhu, Xiaolei

AU - Ito, Koki

AU - Saito, Atsushi

AU - Kato, Yusuke

AU - Kinoshita, Makoto

AU - Shimodera, Shinji

AU - Ono, Shinji

AU - Ochi, Shinichiro

AU - Imamura, Akira

AU - Kurotaki, Naohiro

AU - Ueno, Shu Ichi

AU - Iwata, Nakao

AU - Fukui, Kiyoshi

AU - Imoto, Issei

AU - Kamiya, Atsushi

AU - Ohmori, Tetsuro

PY - 2017/12/1

Y1 - 2017/12/1

N2 - Here we report de novo non-synonymous single-nucleotide variants (SNVs) by conducting whole exome sequencing of 18 trios consisting of Japanese patients with sporadic schizophrenia and their parents. Among nine SNVs, we explored the functional impact of the de novo mutation in TBL1XR1 [c.30 C > G (p.Phe10Leu)], a gene previously found to be associated with autism spectrum disorder and epilepsy. Protein structural analysis revealed that Phe10Leu mutation may decrease the structural stability of the TBL1XR1 protein. We demonstrate that Phe10Leu mutation alters the interaction of TBL1XR1 with N-CoR and β-catenin, which play critical roles in regulation of Wnt-mediated transcriptional activity. Consistently, TBL1XR1-mediated activation of Wnt signaling was up-regulated by Phe10Leu mutation. These results suggest that a de novo TBL1XR1 point mutation could alter Wnt/β-catenin signaling activity. Further studies are required to clarify the involvement of TBL1XR1 mutations in neuropsychiatric conditions.

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