Alternative titles; symbols
HGNC Approved Gene Symbol: ZC3H12D
Cytogenetic location: 6q25.1 Genomic coordinates (GRCh38): 6:149,446,795-149,485,014 (from NCBI)
ZC3H12D is a CCCH-type zinc finger protein, like TTP (ZFP36; 190700), ZAP (ZC3HAV1; 607312), and ROQUIN (RC3H1; 609424), whereas most mammalian zinc finger proteins are CCHH- or CCCC-type proteins. Liang et al. (2008) found that ZC3H12B, also known as MCPIP2, and other MCPIP proteins, MCPIP1 (ZC3H12A; 610562), MCPIP2 (ZC3H12B; 300889), and MCPIP3 (ZC3H12C; 615001), regulate macrophage activation.
Wang et al. (2007) reported frequent loss of heterozygosity (LOH) on chromosome 6q25.1 in sporadic lung tumors (211980) and determined a 2.2-Mb minimum region of LOH. By direct sequencing and SNP genotyping using genomic DNAs from lung cancer pedigrees showing linkage to this region, they identified a novel candidate gene, ZC3H12D, and identified a nonsynonymous A/G SNP at codon 106 that changes a lysine to an arginine. The deduced 321-amino acid protein has a predicted molecular mass of 34 kD and contains a zinc finger CCCH (C-x8-C-x5-C-x3-H) motif. The protein shares significant blocks of conservation with homologs in other mammals and in lower organisms such as zebrafish and Drosophila.
By database searching for genes similar to MCPIP1, Liang et al. (2008) identified MCPIP4, a 527-amino acid protein containing a single central CCCH-type zinc finger and no other identifiable motifs. Mouse macrophages treated with lipopolysaccharide (LPS), but not Ifng (147570), showed some induction of MCPIP4 by Northern blot analysis.
Wang et al. (2007) performed in vitro clonogenic and in vivo nude mouse studies which showed that overexpression of the ZC3H12D 106A allele exerts tumor suppressor function compared with the G allele.
Wang et al. (2007) found that approximately 73% (8/11) of heterozygous lung cancer tissues with LOH and the A/G SNP also exhibited loss of the A allele. Wang et al. (2007) noted that the ZC3H12D gene was located within a region containing a lung cancer susceptibility locus (608935), but association studies of the A/G SNP demonstrated no association between the less frequent 106G (arginine) allele and lung cancer susceptibility in the families studied by Bailey-Wilson et al. (2004).
Wang et al. (2007) determined that the ZC3H12D gene contains 6 coding exons and 2 untranslated exons.
By genomic sequence analysis, Wang et al. (2007) mapped the ZC3H12D gene to chromosome 6q25.1 (build 36.2).
Bailey-Wilson, J. E., Amos, C. I., Pinney, S. M., Petersen, G. M., de Andrade, M., Wiest, J. S., Fain, P., Schwartz, A. G., You, M., Franklin, W., Klein, C., Gazdar, A., and 15 others. A major lung cancer susceptibility locus maps to chromosome 6q23-25. Am. J. Hum. Genet. 75: 460-474, 2004. [PubMed: 15272417] [Full Text: https://doi.org/10.1086/423857]
Liang, J., Wang, J., Azfer, A., Song, W., Tromp, G., Kolattukudy, P. E., Fu, M. A novel CCCH-zinc finger protein family regulates proinflammatory activation of macrophages. J. Biol. Chem. 283: 6337-6346, 2008. [PubMed: 18178554] [Full Text: https://doi.org/10.1074/jbc.M707861200]
Wang, M., Vikis, H. G., Wang, Y., Jia, D., Wang, D., Bierut, L. J., Bailey-Wilson, J. E., Amos, C. I., Pinney, S. M., Petersen, G. M., de Andrade, M., Yang, P., and 15 others. Identification of a novel tumor suppressor gene p34 on human chromosome 6q25.1. Cancer Res. 67: 93-99, 2007. [PubMed: 17210687] [Full Text: https://doi.org/10.1158/0008-5472.CAN-06-2723]