Alternative titles; symbols
HGNC Approved Gene Symbol: VEZF1
Cytogenetic location: 17q22 Genomic coordinates (GRCh38) : 17:57,971,552-57,988,254 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 17q22 | ?Cardiomyopathy, dilated, 1OO | 620247 | Autosomal dominant | 3 |
Transcriptional regulatory proteins containing tandemly repeated zinc finger domains are thought to be involved in both normal and abnormal cellular proliferation and differentiation. ZNF161 is a C2H2-type zinc finger protein (Koyano-Nakagawa et al., 1994). See 603971 for general information on zinc finger proteins.
Koyano-Nakagawa et al. (1994) cloned ZNF161 from a human Jurkat T-cell cDNA library using a CT/GC-rich sequence as probe. ZNF161 encodes a deduced 516-amino acid protein with a calculated molecular mass of about 56 kD. The predicted sequence contains 4 potential N-glycosylation sites and 6 C2H2-type zinc finger motifs. ZNF161 shares 48% sequence homology with the zinc finger protein MAZ (600999). Northern blot analysis and RT-PCR demonstrated ubiquitous expression of 4.0- and 4.8-kb ZNF161 transcripts in all human tissues and cell lines tested.
Shi et al. (2023) stated that the VEZF1 gene maps to chromosome 7q22.
Using electrophoretic mobility shift assays, Koyano-Nakagawa et al. (1994) showed that recombinant ZNF161 bound to the CT/GC-rich transcriptional regulatory region of interleukin-3 (IL3; 147740). They found that ZNF161 augmented Tax-dependent IL3 transcriptional activity approximately 3-fold.
In a large 4-generation Chinese family segregating autosomal dominant dilated cardiomyopathy (CMD1OO; 620247), Shi et al. (2023) identified heterozygosity for a nonsense mutation in the VEZF1 gene (K164X; 606747.0001) that segregated fully with disease and was not found in 400 control individuals or in public variant databases. Functional analysis demonstrated that the mutant protein failed to transactivate the promoters of MYH7 (160760) and ET1 (EDN1; 131240), which wildtype VEZF1 activated by 15-fold and 48-fold, respectively. Noting that atrial septal defect was present in 2 affected family members, the authors suggested that VEZF1 loss-of-function mutations might confer enhanced susceptibility to congenital heart disease in a subset of patients.
Gowher et al. (2008) stated that Vezf1 knockout in mice is embryonic lethal (Kuhnert et al., 2005), and that embryoid bodies derived from in vitro-differentiated Vezf1 -/- embryonic stem cells fail to form a well-organized vascular network and display vascular sprouting defects. They found that Vezf1 -/- embryonic stem cells lacked genomic methylation at specific sites, including certain repeat elements, some imprinted loci, and many CpG islands. Loss of methylation was associated with decreased abundance of DNA methyltransferase-3B (DNMT3B; 602900). Gowher et al. (2008) identified a functional GC-rich Vezf1-binding site in Dnmt3b intron 3, near the 3-prime end of the gene.
In a large 4-generation Chinese family segregating autosomal dominant dilated cardiomyopathy (CMD1OO; 620247), Shi et al. (2023) identified heterozygosity for a c.490A-T transversion (c.490A-T, NM_007146.3) in the VEZF1 gene, resulting in a lys164-to-ter (K164X) substitution. Sanger sequencing validated the mutation, which segregated fully with disease in the family and was not found in 200 additional patients with CMD, 400 healthy controls, or in the dbSNP or gnomAD databases. Functional analysis demonstrated that the mutant protein failed to transactivate the promoters of MYH7 (160760) and ET1 (EDN1; 131240), which wildtype VEZF1 activated by 15-fold and 48-fold, respectively.
Gowher, H., Stuhlmann, H., Felsenfeld, G. Vezf1 regulates genomic DNA methylation through its effects on expression of DNA methyltransferase Dnmt3b. Genes Dev. 22: 2075-2084, 2008. [PubMed: 18676812] [Full Text: https://doi.org/10.1101/gad.1658408]
Koyano-Nakagawa, N., Nishida, J., Baldwin, D., Arai, K., Yokota, T. Molecular cloning of a novel human cDNA encoding a zinc finger protein that binds to the interleukin-3 promoter. Molec. Cell. Biol. 14: 5099-5107, 1994. [PubMed: 8035792] [Full Text: https://doi.org/10.1128/mcb.14.8.5099-5107.1994]
Kuhnert, F., Campagnolo, L., Xiong, J.-W., Lemons, D., Fitch, M. J., Zou, Z., Kiosses, W. B., Gardner, H., Stuhlmann, H. Dosage-dependent requirement for mouse Vezf1 in vascular system development. Dev. Biol. 283: 140-156, 2005. [PubMed: 15882861] [Full Text: https://doi.org/10.1016/j.ydbio.2005.04.003]
Shi, H.-Y., Xie, M.-S., Guo, Y.-H., Yang, C.-X., Gu, J.-N., Qiao, Q., Di, R.-M., Qiu, X.-B., Xu, Y.-J., Yang, Y.-Q. VEZF1 loss-of-function mutation underlying familial dilated cardiomyopathy. Europ. J. Med. Genet. 66: 104705, 2023. [PubMed: 36657711] [Full Text: https://doi.org/10.1016/j.ejmg.2023.104705]