ArticleMolecular psychiatry2022
The schizophrenia-associated variant in SLC39A8 alters protein glycosylation in the mouse brain.
Article in Molecular psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- The genetic architecture of brainstem structures.Nature communications · 2025Pooled it
- Functional characterization of a novel ZIP8 variant causing impaired manganese homeostasis and congenital disorders of glycosylation.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026Article
- Schizophrenia: from mechanism to therapy.Science China. Life sciences · 2026Review
- Functional screening of ZIP8 naturally occurring variants identifies pathogenic mutations and trafficking defects.bioRxiv : the preprint server for biology · 2026Article
- Blood ATX(N) Biomarkers and Cognitive Dysfunction in Severe Mental Illnesses.International journal of molecular sciences · 2026Review
- Disrupted O-GalNAc glycosylation as a mechanism and biomarker ofbioRxiv : the preprint server for biology · 2026Article
- Metabolic Mechanisms in Electroconvulsive Therapy for Schizophrenia: Role, Potential and Future Directions.International journal of molecular sciences · 2026Review
- Identifying drug targets for schizophrenia through gene prioritization.Translational psychiatry · 2026Article
- A homology-based 3D model and structure-function studies reveal key elements for divalent metal ion transporter ZIP8 (SLC39A8) function.The Journal of biological chemistry · 2025Article
- Review
- Review
- The emerging landscape of brain glycosylation: from molecular complexity to therapeutic potential.Experimental & molecular medicine · 2025Review
- The Role of SLC39A8.p.(Ala391Thr) in Schizophrenia Symptom Severity and Cognitive Ability: Cross-Sectional Studies of Schizophrenia and the General UK Population.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2025Article
- The SLC-ome of membrane transport: From molecular discovery to physiology and clinical applications.Physiological reviews · 2025Review
- Investigating the shared genetic architecture between schizophrenia and sex hormone traits.Translational psychiatry · 2025Article
- O-GalNAc glycans are enriched in neuronal tracts and regulate nodes of Ranvier.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- C1GALT1C1-Associated Mosaic Disorder of Glycosylation in a Female.Journal of inherited metabolic disease · 2025Article
- Role of Glial Cells and Receptors in Schizophrenia Pathogenesis.Neurochemical research · 2025Review
- Distinct impact modes of polygenic disposition to dyslexia in the adult brain.Science advances · 2024Article
- Unique Glycans in Synaptic Glycoproteins in Mouse Brain.ACS chemical neuroscience · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
A missense mutation (A391T) in SLC39A8 is strongly associated with schizophrenia in genomic studies, though the molecular connection to the brain is unknown. Human carriers of A391T have reduced serum manganese, altered plasma glycosylation, and brain MRI changes consistent with altered metal transport. Here, using a knock-in mouse model homozygous for A391T, we show that the schizophrenia-associated variant changes protein glycosylation in the brain. Glycosylation of Asn residues in glycoproteins (N-glycosylation) was most significantly impaired, with effects differing between regions. RNAseq analysis showed negligible regional variation, consistent with changes in the activity of glycosylation enzymes rather than gene expression. Finally, nearly one-third of detected glycoproteins were differentially N-glycosylated in the cortex, including members of several pathways previously implicated in schizophrenia, such as cell adhesion molecules and neurotransmitter receptors that are expressed across all cell types. These findings provide a mechanistic link between a risk allele and potentially reversible biochemical changes in the brain, furthering our molecular understanding of the pathophysiology of schizophrenia and a novel opportunity for therapeutic development.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.