ArticleHuman mutation2018
Insights into the genotype-phenotype correlation and molecular function of SLC25A46.
Article in Human mutation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 36 citations in OpenAlex.
- Molecular machineries shaping the mitochondrial inner membrane.Nature reviews. Molecular cell biology · 2025Review
- Review
- A novel homozygous variant inFrontiers in pediatrics · 2024Article
- Anesthetic Management for a Child With a Newly Identified Mitochondrial Disease SLC25A46 Mutation: A Case Report.Cureus · 2023Article
- The role of the mitochondrial outer membrane protein SLC25A46 in mitochondrial fission and fusion.Life science alliance · 2023Article
- Decoding Diabetes Biomarkers and Related Molecular Mechanisms by Using Machine Learning, Text Mining, and Gene Expression Analysis.International journal of environmental research and public health · 2022Article
- Diagnosis of SLC25A46-related pontocerebellar hypoplasia in two siblings with fulminant neonatal course: role of postmortem CT and whole genomic analysis: a case report.BMC neurology · 2022Article
- Case report: A novel variant inFrontiers in neurology · 2022Article
- Mitochondrial protein dysfunction in pathogenesis of neurological diseases.Frontiers in molecular neuroscience · 2022Review
- Mitochondrial Retinopathies.International journal of molecular sciences · 2021Review
- Reanalysis of Exome Data Identifies NovelJournal of personalized medicine · 2021Article
- Nanoscopic quantification of sub-mitochondrial morphology, mitophagy and mitochondrial dynamics in living cells derived from patients with mitochondrial diseases.Journal of nanobiotechnology · 2021Article
- Review
- Epigenetic Regulation of ALS and CMT: A Lesson fromInternational journal of molecular sciences · 2021Review
- Evaluating systematic reanalysis of clinical genomic data in rare disease from single center experience and literature review.Molecular genetics & genomic medicine · 2020Review
- The SLC25 Carrier Family: Important Transport Proteins in Mitochondrial Physiology and Pathology.Physiology (Bethesda, Md.) · 2020Review
- Article
- Diseases Caused by Mutations in Mitochondrial Carrier GenesBiomolecules · 2020Review
- Article
- Mitochondrial diseases: expanding the diagnosis in the era of genetic testing.Journal of translational genetics and genomics · 2020Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Recessive SLC25A46 mutations cause a spectrum of neurodegenerative disorders with optic atrophy as a core feature. We report a patient with optic atrophy, peripheral neuropathy, ataxia, but not cerebellar atrophy, who is on the mildest end of the phenotypic spectrum. By studying seven different nontruncating mutations, we found that the stability of the SLC25A46 protein inversely correlates with the severity of the disease and the patient's variant does not markedly destabilize the protein. SLC25A46 belongs to the mitochondrial transporter family, but it is not known to have transport function. Apart from this possible function, SLC25A46 forms molecular complexes with proteins involved in mitochondrial dynamics and cristae remodeling. We demonstrate that the patient's mutation directly affects the SLC25A46 interaction with MIC60. Furthermore, we mapped all of the reported substitutions in the protein onto a 3D model and found that half of them fall outside of the signature carrier motifs associated with transport function. We thus suggest that there are two distinct molecular mechanisms in SLC25A46-associated pathogenesis, one that destabilizes the protein while the other alters the molecular interactions of the protein. These results have the potential to inform clinical prognosis of such patients and indicate a pathway to drug target development.
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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.