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Review
. 2025 May 29:27:e17.
doi: 10.1017/erm.2025.12.

Retinoic Acid-Induced 1 Gene and Neuropsychiatric Diseases: A Systematic Review

Tianmi Yang  1   2 , Dejiang Pang  1   2   3 , Chunyu Li  1   2   3 , Huifang Shang  1   2   3
Affiliations
Review

Retinoic Acid-Induced 1 Gene and Neuropsychiatric Diseases: A Systematic Review

Tianmi Yang et al. Expert Rev Mol Med. .

Abstract

Background: Retinoic acid-induced 1 (RAI1) is a dosage-sensitive gene implicated in a range of rare neuropsychiatric diseases.

Methods: This review provides a comprehensive overview of RAI1's role, integrating both clinical and basic research on Smith-Magenis syndrome (SMS) and Potocki-Lupski syndrome (PTLS) while also summarising research progress on its involvement in spinocerebellar ataxia (SCA), autism spectrum disorder (ASD), schizophrenia, bipolar disorder and major depression. A systematic review of the literature was conducted using PubMed and EMBASE, following the PRISMA guidelines, with the protocol registered in PROSPERO (CRD42023474165).

Results: A total of 99 eligible studies on RAI1 were included. We presented detailed characterisations of SMS and PTLS patients, emphasising the crucial role of RAI1 haploinsufficiency and overexpression in their pathogenesis. Additionally, we summarised research progress on RAI1 in SCA, ASD, schizophrenia, bipolar disorder and major depression. Integrating findings from animal studies, particularly those examining the regulatory mechanisms of RAI1 in critical phenotypes, such as body weight, sleep and epilepsy, underscores the precise regulation of RAI1 expression in maintaining various nervous system functions.

Conclusions: Overall, this review contributes to the identification of RAI1-related neuropsychiatric diseases, with a particular emphasis on enhancing clinical diagnosis of SMS and PTLS in developing countries.

Keywords: Potocki–Lupski syndrome; RAI1; Smith–Magenis syndrome; neuropsychiatric diseases; retinoic acid-induced 1; systematic review.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1.
Figure 1.
Flowchart of study selection. ASD: autism spectrum disorder; PTLS: Potocki–Lupski syndrome; SCA: spinocerebellar ataxia; SMS: Smith–Magenis syndrome.
Figure 2.
Figure 2.
RAI1 point mutations in Smith–Magenis syndrome. A. RAI1 gene structure. B. RAI1 protein structure with the distribution of point mutations. C–E. Classification of RAI1 point mutations.
See this image and copyright information in PMC

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