HGNC Approved Gene Symbol: RENBP
Cytogenetic location: Xq28 Genomic coordinates (GRCh38): X:153,935,269-153,944,643 (from NCBI)
Renin-binding protein, originally isolated from porcine kidney, is a proteinaceous renin inhibitor. In inhibiting renin, the protein forms a complex with it, so-called high molecular weight renin (summary by Takahashi et al., 1992).
The nucleotide sequences of cDNAs encoding the porcine, human, and rat renin-binding proteins, the predicted amino acid sequences consist of 402, 417, and 419 amino acids, respectively. Sequences of the three are highly homologous. The leucine zipper motif, which is a key structure for the formation of a heterodimer or a homodimer of several proteins, was also conserved in each RENBP. Northern blot analysis demonstrated expression of RENBP in porcine kidney, liver, and adrenal and pituitary glands (summary by Takahashi et al., 1992).
From studies of the RENBP gene isolated from a human placenta genomic library, Takahashi et al. (1992) found that it spans about 10 kb and contains 11 exons.
Faranda et al. (1995) found that the 3-prime end of HCFC1 (300019) lies 2,763-bp upstream from the 3-prime end of the RENBP gene. Thus both genes are transcribed in the same direction from the telomere to the centromere.
By polymerase chain reaction amplification of hybrid DNAs from human and hamster somatic cells, Takahashi et al. (1992) demonstrated that the RENBP gene is located on the X chromosome.
Using the method by which cDNA libraries are screened with positionally identified genomic clones, van den Ouweland et al. (1994) mapped the RENBP gene to Xq28 between DXS52 and G6PD in the same interval as that for the colorblindness gene, DXS707, and the AVPR2 (300538), L1CAM (308840), and QM (312173) genes. Cosmid clones were selected from a cosmid library derived from the Q1Z cell line, a hamster/human somatic cell hybrid that contains the Xq28 region as its sole human component (Warren et al., 1990). Kidney-expressed genes were sought by screening a kidney cDNA library with cosmid-derived probes.
'Drift Mapping'
In human populations that have remained of small and constant size, high levels of linkage disequilibrium (LD) are generated by genetic drift. Theoretical considerations suggest that such LD can be used to identify chromosomal regions involved in diseases or other traits, by 'drift mapping' (Terwilliger et al., 1998). This concept relies on the assumption that when 'cases' and 'controls' are compared within a population in which extensive LD exists, disequilibrium will be observed between the trait and marker loci close to the gene(s) that contributes to the trait. To evaluate this idea empirically, Laan and Paabo (1998) studied polymorphic loci in and around the RENBP gene. They used particularly the 61T-C polymorphism which was described by Knoll et al. (1997) and which occurs with a frequency of 0.18 in Germans. They scored this polymorphism in males from the Saami and the Finns, 2 populations that differ radically in their demographic history. Whereas the Saami have not expanded during historical times and show no indication of expansion in tests based on DNA sequence variability, the Finns are thought to have expanded drastically during the past few thousand years, on the basis of both epidemiologic and genetic evidence. The frequency of the C allele was found to be 0.21 and 0.19 in the Saami and the Finns, respectively. The fact that the C allele occurs at appreciably higher frequencies in 3 European populations indicates that it is older than these populations. It was therefore a useful model of alleles involved in complex traits, since such alleles are expected to be both frequent in the population and of old age. The findings confirmed the hypothesis that, in principle, LD generated by drift in a small and constant population can be used to localize a gene, whereas it is difficult, if not impossible, in a population that has expanded. Laan and Paabo (1998) expressed the hope that chromosomal regions involved in complex traits could be identified by an approach based on LD in populations such as the Saami.
Faranda, S., Frattini, A., Vezzoni, P. The human genes encoding renin-binding protein and host cell factor are closely linked in Xq28 and transcribed in the same direction. Gene 155: 237-239, 1995. [PubMed: 7721097] [Full Text: https://doi.org/10.1016/0378-1119(94)00810-f]
Knoll, A., Schunkert, H., Reichwald, K., Danser, A. H. J., Bauer, D., Platzer, M., Stein, G., Rosenthal, A. Human renin binding protein: complete genomic sequence and association of an intronic T/C polymorphism with the prorenin level in males. Hum. Molec. Genet. 6: 1527-1534, 1997. [PubMed: 9285790] [Full Text: https://doi.org/10.1093/hmg/6.9.1527]
Laan, M., Paabo, S. Mapping genes by drift-generated linkage disequilibrium. (Letter) Am. J. Hum. Genet. 63: 654-656, 1998. [PubMed: 9683603] [Full Text: https://doi.org/10.1086/301972]
Takahashi, S., Inoue, H., Miyake, Y. The human gene for renin-binding protein. J. Biol. Chem. 267: 13007-13013, 1992. [PubMed: 1618798]
Terwilliger, J. D., Zollner, S., Laan, M., Paabo, S. Mapping genes through the use of linkage disequilibrium generated by genetic drift: 'drift mapping' in small populations with no demographic expansion. Hum. Hered. 48: 138-154, 1998. [PubMed: 9618061] [Full Text: https://doi.org/10.1159/000022794]
van den Ouweland, A. M. W., Verdijk, M., Kiochis, P., Poustka, A., van Oost, B. A. The human renin-binding protein gene (RENBP) maps in Xq28. Genomics 21: 279-281, 1994. [PubMed: 8088804] [Full Text: https://doi.org/10.1006/geno.1994.1259]
Warren, S. T., Knight, S. J. L., Peters, J. F., Stayton, C. L., Consalez, G. G., Zhang, F. Isolation of the human chromosomal band Xq28 within somatic cell hybrids by fragile X site breakage. Proc. Nat. Acad. Sci. 87: 3856-3860, 1990. [PubMed: 2339126] [Full Text: https://doi.org/10.1073/pnas.87.10.3856]