HGNC Approved Gene Symbol: ZNF219
Cytogenetic location: 14q11.2 Genomic coordinates (GRCh38) : 14:21,090,077-21,104,722 (from NCBI)
By screening a testis cDNA library, Sakai et al. (2000) isolated a cDNA encoding ZNF219. The deduced 723-amino acid ZNF219 protein contains 9 sets of Kruppel-related zinc finger structures and several proline-rich regions. Northern blot analysis detected ZNF219 expression in all fetal and adult tissues tested. The ZNF219 transcript was 5.5 kb in adult tissues, whereas a predominant 3.5-kb transcript as well as the 5.5-kb transcript was detected in fetal tissues. When a plasmid cloned with green fluorescent protein-tagged ZNF219 was expressed in HeLa and COS-7 cells, strong fluorescence intensities were observed only in the nucleus of both types of cells by confocal microscopy. These data suggested that ZNF219 may be related to the regulation of transcription and developmental regulation.
By random oligonucleotide selection assay and electromobility gel shift assay, Sakai et al. (2003) determined that ZNF219 recognized 2 copies of CCCCCA. The DNA binding core element was CCCCC, and the 3-prime flanking A residue enhanced ZNF219 binding. Using truncation mutants, Sakai et al. (2003) found that zinc fingers 1 to 3 or 5 and 6 were sufficient for DNA binding, and both domains independently recognized the same CCCCCA consensus sequence. ZNF219 bound to potential ZNF219-binding sites in the HMGN1 (163920) promoter and repressed transcription from the HMGN1 promoter in a reporter assay. A proline-rich sequence (amino acids 226 to 272; 49% proline content) was responsible for part of the repression activity.
Sakai et al. (2000) identified an STS mapping between markers D14S72 and D14S990 in an intron region of ZNF219, mapping the gene to 14q11.
Associations Pending Confirmation
Patel et al. (2018) studied a cohort of 147 patients from 93 families from highly consanguineous populations (Saudi Arabian, Egyptian, and Lebanese) with a diagnosis of microphthalmia, anophthalmia, colobomatous microphthalmia (66 families), Warburg Micro syndrome (4 families) and posterior microphthalmia (23 families). In each family, authors analyzed a panel of 322 genes associated with eye diseases, followed by whole-exome sequencing if the panel did not yield a likely causal mutation. They identified a brother (12DG0568) and sister (12DG0569) from a consanguineous family (F57-M) who had colobomatous microphthalmia (see MCOPCB1, 300345) and were homozygous for a nonsense mutation in the ZNF219 gene (c.817G-T; E273X). Their first-cousin parents were heterozygous for the mutation, which was not found in an unaffected sister, in an in-house database of 2,369 patients, or in the gnomAD database.
Patel, N., Khan, A. O., Alsahli, S., Abdel-Salam, G., Nowilaty, S. R., Mansour, A. M., Nabil, A., Al-Owain, M., Sogati, S., Salih, M. A., Kamal, A. M., Alsharif, H., and 14 others. Genetic investigation of 93 families with microphthalmia or posterior microphthalmos. Clin. Genet. 93: 1210-1222, 2018. [PubMed: 29450879] [Full Text: https://doi.org/10.1111/cge.13239]
Sakai, T., Hino, K., Wada, S., Maeda, H. Identification of the DNA binding specificity of the human ZNF219 protein and its function as a transcriptional repressor. DNA Res. 10: 155-165, 2003. [PubMed: 14621294] [Full Text: https://doi.org/10.1093/dnares/10.4.155]
Sakai, T., Toyoda, A., Hashimoto, K., Maeda, H. Isolation and characterization of a novel zinc finger gene, ZNF219, and mapping to the human chromosome 14q11 region. DNA Res. 7: 137-141, 2000. [PubMed: 10819330] [Full Text: https://doi.org/10.1093/dnares/7.2.137]