ZNRF3 in neurodevelopmental disorders: insights into Wnt signaling and therapeutic potential

Affiliations

¹ Department of Genetics, College of Basic Medical Sciences, Jilin University, No. 126 Xinmin Street, Changchun, 130021, Jilin, China.
² Department of Cardiovascular Diseases, The First Hospital of Jilin University, Changchun, 130021, Jilin, China.
³ Department of Genetics, University of Calcutta, Kolkata, 700019, India.
⁴ Department of Zoology, University of Jammu, Jammu and Kashmir, Baba Saheb Ambedkar Road, Jammu, 180006, India.
⁵ Centre for Genetic Disorders, Banaras Hindu University, Varanasi, 221005, Uttar Pradesh, India.
⁶ Department of Human Genetics and Molecular Medicine, Central University of Punjab, Ghudda, Bathinda, 151001, Punjab, India.
⁷ S.N. Pradhan Centre for Neurosciences, University of Calcutta, 35, Ballygunge Circular Road, Kolkata, 700019, India.
⁸ Department of Developmental and Behavioral Pediatrics, The First Hospital of Jilin University, Jilin University, Changchun, 130021, Jilin, China.
⁹ Department of Genetics, College of Basic Medical Sciences, Jilin University, No. 126 Xinmin Street, Changchun, 130021, Jilin, China. wenjp@jlu.edu.cn.
¹⁰ Department of Genetics, College of Basic Medical Sciences, Jilin University, No. 126 Xinmin Street, Changchun, 130021, Jilin, China. santasree.banerjee@yahoo.com.

PMID: 41037104
DOI: 10.1007/s10048-025-00852-5

Review

ZNRF3 in neurodevelopmental disorders: insights into Wnt signaling and therapeutic potential

Yasmin Yusuf Hussein Dinle et al. Neurogenetics. 2025.

. 2025 Oct 2;26(1):72.

doi: 10.1007/s10048-025-00852-5.

Authors

Affiliations

¹ Department of Genetics, College of Basic Medical Sciences, Jilin University, No. 126 Xinmin Street, Changchun, 130021, Jilin, China.
² Department of Cardiovascular Diseases, The First Hospital of Jilin University, Changchun, 130021, Jilin, China.
³ Department of Genetics, University of Calcutta, Kolkata, 700019, India.
⁴ Department of Zoology, University of Jammu, Jammu and Kashmir, Baba Saheb Ambedkar Road, Jammu, 180006, India.
⁵ Centre for Genetic Disorders, Banaras Hindu University, Varanasi, 221005, Uttar Pradesh, India.
⁶ Department of Human Genetics and Molecular Medicine, Central University of Punjab, Ghudda, Bathinda, 151001, Punjab, India.
⁷ S.N. Pradhan Centre for Neurosciences, University of Calcutta, 35, Ballygunge Circular Road, Kolkata, 700019, India.
⁸ Department of Developmental and Behavioral Pediatrics, The First Hospital of Jilin University, Jilin University, Changchun, 130021, Jilin, China.
⁹ Department of Genetics, College of Basic Medical Sciences, Jilin University, No. 126 Xinmin Street, Changchun, 130021, Jilin, China. wenjp@jlu.edu.cn.
¹⁰ Department of Genetics, College of Basic Medical Sciences, Jilin University, No. 126 Xinmin Street, Changchun, 130021, Jilin, China. santasree.banerjee@yahoo.com.

PMID: 41037104
DOI: 10.1007/s10048-025-00852-5

Abstract

Neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD), and intellectual disabilities (ID), have seen an increasing prevalence in recent years. Both genetic and environmental factors have been implicated in the pathogenesis of these conditions. One such gene, ZNRF3, plays a pivotal role in regulating neural cell growth and connectivity, with variations in this gene linked to disruptions in neural differentiation and communication. This review synthesizes genetic, molecular, and clinical research to examine the role of ZNRF3 in brain development. Furthermore, it explores the impact of prenatal environmental exposures and healthcare policies on diagnostic practices and treatment accessibility. The findings highlight the need for improved genetic screening, early intervention strategies, and policy reforms aimed at facilitating personalized care for individuals affected by ZNRF3-related NDDs.

Keywords: Autism spectrum disorder; Intellectual disability; Neurodevelopmental disorders; Wnt/β-Catenin signaling; ZNRF3.

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Conflict of interest statement

Declarations. Consent for publication: Not applicable. Ethics approval and consent to participate: Not applicable. Competing interests: The authors declare no competing interests.

References

1. Gao S et al (2024) Genetic advances in neurodevelopmental disorders. Med Rev 5(2):139–151 - DOI
1. Farnhammer F, Colozza G, Kim J (2023) RNF43 and ZNRF3 in Wnt Signaling - A master regulator at the membrane. Int J Stem Cells 2023(164):376–384 - DOI
1. Hao HX et al (2012) ZNRF3 promotes Wnt receptor turnover in an R-spondin-sensitive manner. Nature 485(7397):195–200 - PubMed - DOI
1. Kim M, Reinhard C, Niehrs C (2021) A MET-PTPRK kinase-phosphatase rheostat controls ZNRF3 and Wnt signaling. eLife 10:e70885 - PubMed - PMC - DOI
1. Kwan V, Unda BK, Singh KK (2016) Wnt signaling networks in autism spectrum disorder and intellectual disability. J Neurodev Disord 8:45 - PubMed - PMC - DOI

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ZNRF3 in neurodevelopmental disorders: insights into Wnt signaling and therapeutic potential

Affiliations

ZNRF3 in neurodevelopmental disorders: insights into Wnt signaling and therapeutic potential

Authors

Affiliations

Abstract

Conflict of interest statement

References

Publication types

MeSH terms

LinkOut - more resources

Full Text Sources