Manganese Transporter Genes and Environmental Exposure in Neurodevelopmental Disorders: Integrating Genetic, Epidemiological, and Experimental Evidence
- 1Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou 730000, China
Abstract
Manganese (Mn) is an essential trace element, but both insufficient cellular availability and excessive accumulation can disrupt neurological function. This narrative review integrates evidence from inherited Mn transporter disorders, common genetic variation, environmental epidemiology, and experimental models to examine potential links at the gene-environment interface. Biallelic pathogenic variants in SLC39A8, SLC30A10, and SLC39A14 provide direct human evidence that impaired Mn uptake, utilization, or clearance can cause distinct neurological and neurodevelopmental phenotypes. Environmental Mn studies in children mainly report associations with cognitive, motor, attentional, and behavioral outcomes, but findings vary according to exposure timing, biomarker, sex, nutritional status, co-exposure, and outcome definition. Evidence linking environmental Mn specifically to attention deficit hyperactivity disorder or autism spectrum disorder remains heterogeneous and observational. Experimental data suggest that Mn deficiency and excess involve partly distinct mechanisms, including altered glycosylation, mitochondrial and cellular dysfunction, iron-redox imbalance, ferroptosis-related responses, glial activation, and epigenetic or transcriptional changes. However, a causal Mn-epigenetic-neurodevelopmental pathway and a generalizable gene–environment interaction have not been established in humans. Advancing this field will require studies that integrate time-resolved exposure assessment, genetic and nutritional stratification, multi-omics, neuroimaging, and functional models.
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BibTeX
@article{wang2026manganese,
title = {{Manganese Transporter Genes and Environmental Exposure in Neurodevelopmental Disorders: Integrating Genetic, Epidemiological, and Experimental Evidence}},
author = {Xuanfang Wang and Jierong Li and Mingfang Wang and Yingqi Zhang and Xiaomeng Yang and Qianxing Liu and Xuhong Chang and Hui Wang},
journal = {Biomolecules},
year = {2026},
month = nov,
doi = {10.3390/biom16111617},
url = {https://www.mdpi.com/2218-273X/16/11/1617},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Manganese Transporter Genes and Environmental Exposure in Neurodevelopmental Disorders: Integrating Genetic, Epidemiological, and Experimental Evidence
AU - Xuanfang Wang
AU - Jierong Li
AU - Mingfang Wang
AU - Yingqi Zhang
AU - Xiaomeng Yang
AU - Qianxing Liu
AU - Xuhong Chang
AU - Hui Wang
PY - 2026
DA - 2026/11/06
JO - Biomolecules
DO - 10.3390/biom16111617
UR - https://www.mdpi.com/2218-273X/16/11/1617
AB - Manganese (Mn) is an essential trace element, but both insufficient cellular availability and excessive accumulation can disrupt neurological function. This narrative review integrates evidence from inherited Mn transporter disorders, common genetic variation, environmental epidemiology, and experimental models to examine potential links at the gene-environment interface. Biallelic pathogenic variants in SLC39A8, SLC30A10, and SLC39A14 provide direct human evidence that impaired Mn uptake, utilization, or clearance can cause distinct neurological and neurodevelopmental phenotypes. Environmental Mn studies in children mainly report associations with cognitive, motor, attentional, and behavioral outcomes, but findings vary according to exposure timing, biomarker, sex, nutritional status, co-exposure, and outcome definition. Evidence linking environmental Mn specifically to attention deficit hyperactivity disorder or autism spectrum disorder remains heterogeneous and observational. Experimental data suggest that Mn deficiency and excess involve partly distinct mechanisms, including altered glycosylation, mitochondrial and cellular dysfunction, iron-redox imbalance, ferroptosis-related responses, glial activation, and epigenetic or transcriptional changes. However, a causal Mn-epigenetic-neurodevelopmental pathway and a generalizable gene–environment interaction have not been established in humans. Advancing this field will require studies that integrate time-resolved exposure assessment, genetic and nutritional stratification, multi-omics, neuroimaging, and functional models.
SN - 2218-273X
ER -