Investigating the potential genetic association between RANBP9 polymorphisms and the risk of schizophrenia

Abstract

Schizophrenia is a serious mental disorder that is affected by genetic and environmental factors. As the disease has a high heritability rate, genetic studies identifying candidate genes for schizophrenia have been conducted in various populations. The gene for human Ran‑binding protein 9 (RANBP9) is a newly discovered candidate gene for schizophrenia. As RANBP9 is a small guanosine‑5'‑triphosphate‑binding protein that interacts with the disrupted in schizophrenia 1 protein, it is considered to be an important molecule in the pathogenesis of schizophrenia. However, to date, no study has examined the possible association between the genetic variations of RANBP9 and the risk of schizophrenia. In the present study, it was hypothesized that RANBP9 variations may influence the risk of schizophrenia. In order to investigate the association between RANBP9 polymorphisms and the risk of schizophrenia and smooth pursuit eye movement (SPEM) abnormalities, a case‑control association analysis was performed. Using a TaqMan assay, five single‑nucleotide polymorphisms and an insertion/deletion variation within the start codon region of RANBP9 were genotyped. Five major haplotypes were identified in 449 patients with schizophrenia and 393 unrelated healthy individuals as controls (total, n=842). However, the association analyses revealed no associations between all genetic variants and schizophrenia and SPEM abnormality. To the best of our knowledge, this is the first study to investigate an association between RANBP9 polymorphisms and schizophrenia and SPEM abnormality. The findings of allele frequencies and association results in this study may aid in further genetic etiological studies in schizophrenia in various populations.

The human GID complex engages two independent modules for substrate recruitment

“…Several subunits of the hGID complex, namely RanBP9, RanBP10, WDR26, and MKLN1, have been linked to neurodegeneration and amyloid β (Aβ) pathologies (Woo et al , 2015; Her et al , 2017), intellectual disability (Skraban et al , 2017), and early‐onset bipolar diseases and schizophrenia (Bae et al , 2015; Nassan et al , 2017). Moreover, suppression of RMND5a in Xenopus laevis leads to malformations in the fore and midbrain (Pfirrmann et al , 2015), suggesting that the GID complex may regulate brain development and neuronal functions.…”

The human GID complex engages two independent modules for substrate recruitment

“…However, little is known about the ARMC8 subunit and its role in the function and regulation of the hGID E3 ligase complex. Several subunits of the hGID complex, namely RanBP9, RanBP10, WDR26 and MKLN1, have been linked to neurodegeneration and amyloid β (Aβ) pathologies (Her et al, 2017;Woo et al, 2015), intellectual disability (Skraban et al, 2017), and early onset bipolar diseases and schizophrenia (Nassan et al, 2017;BAE et al, 2015). Moreover, suppression of RMND5a in Xenopus laevis leads to malformations in the fore and midbrain (Pfirrmann et al, 2015), suggesting that the GID complex may regulate brain development and neuronal functions.…”

Mind Bomb-Binding Partner RanBP9 Plays a Contributory Role in Retinal Development

“…It has also been shown to simultaneously inhibit cell-adhesive processes and enhance amyloid β generation by accelerating APP, LRP, and β1-integrin endocytosis (Woo et al, 2012); and inhibit agonist-induced Mu opioid receptor internalization (Talbot et al, 2009). Reports have demonstrated through genetic epistasis experiments the interaction of RanBP9 with fragile-X mental retardation protein (Menon et al, 2004), as well as disrupted in schizophrenia 1 (DISC1) which is associated with autism, schizophrenia and bipolar disorder (Bae et al, 2015). However, previous study with neo-natal RanBP9 null mice showed suckling problems caused by defects in brain development and subsequent premature death (Palavicini et al, 2013).…”