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| Mendeliome v1.3063 | ZNF319 | Zornitza Stark Marked gene: ZNF319 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3063 | ZNF319 | Zornitza Stark Gene: znf319 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3063 | ZNF319 |
Zornitza Stark gene: ZNF319 was added gene: ZNF319 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ZNF319 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ZNF319 were set to 40820230 Phenotypes for gene: ZNF319 were set to Leukodystrophy, MONDO:0019046, ZNF319-related Review for gene: ZNF319 was set to RED Added comment: Single individual with homozygous missense variant reported, p.Phe267Ser. 18-year-old male presenting with spasticity, ataxia, cognitive decline, and white matter abnormalities on MRI. Molecular dynamics simulations revealed that F267 is a stabilizing residue within a β-strand of the zinc finger domain, forming π-stacking and hydrophobic interactions that are lost upon substitution with serine, leading to structural instability, increased flexibility, and protein unfolding. Despite normal transcript and protein expression, ZNF319-F267S mislocalized to the cytoplasm due to disruption of its bipartite nuclear localization signal (NLS), resulting in impaired interaction with importin α1 (KPNA1). Functional analysis confirmed that the variant disrupts nuclear transport and prevents transcriptional activation of genes involved in myelination. Protein interaction network and gene ontology analysis highlighted ZNF319's role in transcriptional regulation and its localization in the CHOP-C/EBP transcriptional complex. Expression profiling demonstrated ZNF319 enrichment in oligodendrocytes and white matter regions, correlating with the observed leukoencephalopathy. Sources: Literature |
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