<i>SLC9A9</i> Co‐expression modules in autism‐associated brain regions

Patak, Jameson; Hess, Jonathan; Zhang-James, Yanli; Glatt, Stephen J.; Faraone, Stephen V.

doi:10.1002/aur.1670

Cited by 12 publications

(9 citation statements)

References 95 publications

(127 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In a single family, a pericentric inversion of chromosome 3 co-segregating with ADHD symptoms [115,116] implicated SLC9A9. Mutations of that gene lead to an animal model of ADHD [117,118] and have been associated with both autism [119,120] and ADHD [121].…”

Section: The Search For Rare Genetic Variantsmentioning

confidence: 99%

Genetics of attention deficit hyperactivity disorder

2018

Self Cite

View full text Add to dashboard Cite

Decades of research show that genes play an vital role in the etiology of attention deficit hyperactivity disorder (ADHD) and its comorbidity with other disorders. Family, twin, and adoption studies show that ADHD runs in families. ADHD's high heritability of 74% motivated the search for ADHD susceptibility genes. Genetic linkage studies show that the effects of DNA risk variants on ADHD must, individually, be very small. Genome-wide association studies (GWAS) have implicated several genetic loci at the genome-wide level of statistical significance. These studies also show that about a third of ADHD's heritability is due to a polygenic component comprising many common variants each having small effects. From studies of copy number variants we have also learned that the rare insertions or deletions account for part of ADHD's heritability. These findings have implicated new biological pathways that may eventually have implications for treatment development.Attention deficit hyperactivity disorder (ADHD) is a childhood-onset condition with impairing symptoms of inattention, impulsivity, and hyperactivity. Decades of research have documented and replicated key facts about the disorder (for a review, see ref.[1]). It occurs in about 5% of children with little geographic or cross-cultural variation in prevalence and often co-occurs with other conditions, including mood, anxiety, conduct, learning, and substance use disorders. Longitudinal studies show that two-thirds of ADHD youth will continue to have impairing symptoms of ADHD in adulthood. People with ADHD are at risk for a wide range of functional impairments: school failure, peer rejection, injuries due to accidents, criminal behavior, occupational failure, divorce, suicide, and premature death. Although many details of ADHD's pathophysiology are unknown, neuropsychological and neuroimaging studies implicate brain circuits regulating executive functioning, reward processing, timing, and temporal information processing.This article reviews data about the role that genes play in the etiology of ADHD from two perspectives. Family, twin, and adoption studies provide a firm foundation for asserting that genes are involved in the etiology of ADHD. The view from molecular genetics provides a basis for understanding mechanisms whereby genes affect biological pathways that lead to ADHD. Family, twin and adoption studies of ADHDEvidence for heritability from family, adoption, and twin studies A study of 894 ADHD probands and 1135 of their siblings aged 5-17 years old found a ninefold increased risk of ADHD in siblings of ADHD probands compared with siblings of controls [2]. Adoption studies suggest that the familial factors of ADHD are attributable to genetic factors rather than shared environmental factors [3,4] with the most recent one reporting rates of ADHD to be greater among biological relatives of non-adopted ADHD children than adoptive relatives of adopted ADHD children. The adoptive relatives had a risk for ADHD like the risk in relatives of control childr...

show abstract

Section: The Search For Rare Genetic Variantsmentioning

confidence: 99%

Genetics of attention deficit hyperactivity disorder

2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…SLC9A9 upregulation was also observed in immortalized hypothalamic neurons and primary cortex cells subjected to amino acid starvation (Hellsten, Lekholm, Ahmad, & Fredriksson, 2017). The role of SLC9A9 in the regulation of cellular nutrients and metabolism is further supported by a weighted gene network co‐expression analysis that found significant enrichment of metabolism genes in SLC9A9 co‐expression modules (Patak, Hess, Zhang‐James, Glatt, & Faraone, 2016).…”

Section: Nhe9 Cellular Functionsmentioning

confidence: 87%

“…Although the role of SLC9A9 in autophagy regulation has not been directly studied, it has been implicated in the signal transduction cascades for autophagy such as the AKT pathway and Bcl‐2 expression (J. Chen, Yang, et al, 2015; Kondapalli et al, 2015; Nakamura et al, 2005). Furthermore, SLC9A9 was found to co‐express with autophagic intermediates gene (Patak, Hess, et al, 2016). What is more, starvation of hypothalamic neurons, conditions known to induce autophagy, significantly upregulate SLC9A9 expression (Hellsten et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

“…microRNA 135a downregulates SLC9A9 expression in U87 cells and this consequently acidifies sorting endosomes, which limits EGFR trafficking to the cell membrane and dampens oncogenic signaling (Gomez Zubieta, Hamood, Beydoun, Pall, & Kondapalli, 2017). Furthermore, co‐expression analysis found that SLC9A9 was co‐regulated with genes within the Bcl‐2 and PI3K‐AKT signaling pathways (Patak, Hess, et al, 2016). Furthermore, the C‐terminal interaction of NHE9 with RACK1 was found to drive Src/Akt/beta‐catenin signaling pathway and Bcl‐2 expression, which increased cell survival (J. Chen, Yang, et al, 2015).…”

Section: Nhe9 Cellular Functionsmentioning

confidence: 99%

“…Abnormally increased expression of SLC9A9 in astrocytes is associated with oncogenic properties in glioblastoma (Gomez Zubieta et al, 2017; Kondapalli et al, 2015). Co‐expression analysis revealed astrocytes, neurons, and oligodendrocytes markers for the SLC9A9 module (Patak, Hess, et al, 2016). The RNA‐seq based cell‐type specific profile from the DropViz database (Saunders et al, 2018) showed the highest expression in microglia from various brain regions, followed by oligodendrocytes and astrocytes, with consistently lower expression in neurons.…”

Section: Cellular Slc9a9 Expression and Tissue Distributionmentioning

confidence: 99%

See 2 more Smart Citations

Sodium hydrogen exchanger 9 NHE9 (SLC9A9) and its emerging roles in neuropsychiatric comorbidity

Patak

Faraone

Zhang‐James

2020

American J of Med Genetics Pt B

Self Cite

View full text Add to dashboard Cite

Variations in SLC9A9 gene expression and protein function are associated with multiple human diseases, which range from Attention-deficit/hyperactivity disorder (ADHD) to glioblastoma multiforme. In an effort to determine the full spectrum of human disease associations with SLC9A9, we performed a systematic review of the literature. We also review SLC9A9's biochemistry, protein structure, and function, as well as its interacting partners with the goal of identifying mechanisms of disease and druggable targets. We report gaps in the literature regarding the genes function along with consistent trends in disease associations that can be used to further research into treating the respective diseases. We report that SLC9A9 has strong associations with neuropsychiatric diseases and various cancers. Interestingly, we find strong overlap in SLC9A9 disease associations and propose a novel role for SLC9A9 in neuropsychiatric comorbidity. In conclusion, SLC9A9 is a multifunctional protein that, through both its endosome regulatory function and its protein-protein interaction network, has the ability to modulate signaling axes, such as the PI3K pathway, among others.

show abstract

SLC gene mutations and pediatric neurological disorders: diverse clinical phenotypes in a Saudi Arabian population

et al. 2021

View full text Add to dashboard Cite

The uptake and efflux of solutes across a plasma membrane is controlled by transporters. There are two main superfamilies of transporters, adenosine 5′-triphosphate (ATP) binding cassettes (ABCs) and solute carriers (SLCs). In the brain, SLC transporters are involved in transporting various solutes across the blood-brain barrier, blood-cerebrospinal fluid barrier, astrocytes, neurons, and other brain cell types including oligodendrocytes and microglial cells. SLCs play an important role in maintaining normal brain function. Hence, mutations in the genes that encode SLC transporters can cause a variety of neurological disorders. We identified the following SLC gene variants in 25 patients in our cohort: SLC1A2,

show abstract

SLC9A9 Co‐expression modules in autism‐associated brain regions

Cited by 12 publications

References 95 publications

Genetics of attention deficit hyperactivity disorder

Genetics of attention deficit hyperactivity disorder

Sodium hydrogen exchanger 9 NHE9 (SLC9A9) and its emerging roles in neuropsychiatric comorbidity

SLC gene mutations and pediatric neurological disorders: diverse clinical phenotypes in a Saudi Arabian population

Contact Info

Product

Resources

About