HGNC Approved Gene Symbol: DGCR6
Cytogenetic location: 22q11.21 Genomic coordinates (GRCh38): 22:18,906,223-18,912,088 (from NCBI)
Demczuk et al. (1996) described the cloning of a gene, which they referred to as DGCR6, from the DiGeorge syndrome critical region (188400) on chromosome 22q11. This gene detects a 1.1-kb transcript in many human tissues. The putative protein encoded by this gene shows homology with Drosophila melanogaster gonadal protein (gdl) and with the gamma-1 chain of human laminin (150290), which maps to chromosome 1q31. Although the DGCR6 gene was not interrupted by the translocation breakpoint in a family with a balanced translocation and DiGeorge phenotype, and although no rearrangements had been elucidated in DGS patients who do not bear a large deletion of the DiGeorge critical region, Demczuk et al. (1996) noted that the DGCR6 gene could still be a candidate gene involved in the pathology of the syndrome.
By examining the flanking regions of a low-copy repeat on chromosome 22 deleted in most people with velocardiofacial syndrome (192430)/DiGeorge syndrome, Edelmann et al. (2001) identified DGCR6L (609459), a copy of the DGCR6 gene. They cloned DGCR6 and DGCR6L by PCR of a fetal spleen cDNA library. The 2 cDNAs share 97% identity, and both deduced 220-amino acid proteins share 97% identity. There are 7 amino acid differences between them, 2 of which are conservative changes. PCR analysis using transcript-specific primers revealed DGCR6 expression in all adult and fetal tissues examined, whereas DGCR6L was expressed in all tissues tested except adult skeletal muscle and small intestine.
Pfuhl et al. (2005) cloned DGCR6 and DGCR6L from a brain cDNA library. Western blot analysis detected the endogenous proteins as a double band of about 25 kD in a human mammary carcinoma cell line and in all human tissues examined except heart, which had only 1 band. Protein levels were highest in liver, heart, and skeletal muscle, intermediate in pancreas and placenta, and low in brain. Western blot analysis showed that most human tumor cell lines tested expressed elevated levels of 1 or both proteins. Immunofluorescence localization of epitope-tagged proteins detected both predominantly in the nuclei of transfected cells, with low cytoplasmic reactivity. There was a weak nuclear signal in nontransfected HeLa cells. Immunoprecipitation of radiolabeled proteins expressed by transfected HeLa cells indicated that both proteins were phosphorylated, and both had half-lives of about 2.5 hours.
Edelmann et al. (2001) determined that both DGCR6 and DGCR6L contain 5 exons of equal length, with conserved intron/exon structure.
Demczuk et al. (1996) mapped the DGCR6 gene to chromosome 22q11. By sequencing genomic clones, Edelmann et al. (2001) mapped the DGCR6 gene to a low-copy repeat region of chromosome 22q11 that also contains the DGCR6L gene. The 2 genes are in an inverted orientation with respect to one another.
Edelmann et al. (2001) performed evolutionary studies using FISH in several different species of ape combined with sequence analysis of DGCR6 in a number of different primate species. They determined that the duplication of the DGCR6 gene is at least 12 million years old and may date to before the divergence of Catarrhines from Platyrrhines, 35 million years ago. A full-length HERV-K provirus integrated into the low-copy repeat region containing DGCR6, but not to the region containing DGCR6L, after the divergence of chimpanzees and humans. Edelmann et al. (2001) concluded that there has been selective evolutionary pressure toward the functional maintenance of both paralogs.
Demczuk, S., Thomas, G., Aurias, A. Isolation of a novel gene from the DiGeorge syndrome critical region with homology to Drosophila gdl and to human LAMC1 genes. Hum. Molec. Genet. 5: 633-638, 1996. [PubMed: 8733130] [Full Text: https://doi.org/10.1093/hmg/5.5.633]
Edelmann, L., Stankiewicz, P., Spiteri, E., Pandita, R. K., Shaffer, L., Lupski, J. R., Morrow, B. E. Two functional copies of the DGCR6 gene are present on human chromosome 22q11 due to a duplication of an ancestral locus. Genome Res. 11: 208-217, 2001. Note: Erratum: Genome Res. 11: 503 only, 2001. [PubMed: 11157784] [Full Text: https://doi.org/10.1101/gr.gr-1431r]
Pfuhl, T., Durr, M., Spurk, A., Schwalbert, B., Nord, R., Mysliwietz, J., Kremmer, E., Grasser, F. A. Biochemical characterisation of the proteins encoded by the DiGeorge critical region 6 (DGCR6) genes. Hum. Genet. 117: 70-80, 2005. [PubMed: 15821931] [Full Text: https://doi.org/10.1007/s00439-005-1267-2]