Alternative titles; symbols
HGNC Approved Gene Symbol: CDR1
Cytogenetic location: Xq27.1 Genomic coordinates (GRCh38): X:140,772,083-140,793,212 (from NCBI)
Autoantibodies directed against neuronal proteins have been identified in some patients with paraneoplastic cerebellar degeneration (PCD), which occurs in association with small cell carcinoma of the lung, neoplasms of the breast and ovary, and Hodgkin disease. The corresponding antigen is designated cerebellar degeneration protein (CDR). Using IgG from a PCD patient to screen a human cerebellum cDNA library, then rescreening the library with the resultant cDNA fragment, Dropcho et al. (1987) cloned CDR. The deduced 223-amino acid protein has a calculated molecular mass of 27.0 kD. Over 90% of CDR is made up of 34 inexact tandem repeats of 6 amino acids that feature a nearly invariant core of glutamine and aspartic acid residues. Possible splice variants encoding variants that differ at the C-terminal end, outside of the hexapeptide repeat region, were also identified. Northern blot analysis detected 3 transcripts between 1.3 and 1.5 kb, with the 1.5-kb transcript predominating, in cerebellum and SMS-KAN neuroblastoma cells. RNA dot blot revealed high CDR expression in cerebellum and cerebrum, but little expression in heart, lung, and kidney, and none in liver. Among cancer cells lines, CDR expression was detected in all 10 neuroblastoma cell lines examined, as well as in a majority of renal cell carcinoma cell lines and in some astrocytoma, melanoma, and lung carcinoma cell lines.
Furneaux et al. (1990) demonstrated the selective expression of Purkinje cell antigens in tumor tissue from PCD patients. The origins of the cancers were breast (5 patients), ovary (3), endometrium (1), and fallopian tube (1). These patients had a high titer of anti-Purkinje cell autoantibody, called anti-Yo. Anti-Yo serum recognized 2 Purkinje cell antigens, of 62 and 34 kD, known as CDR62 and CDR34. All samples of anti-Yo serum seemed to recognize both antigens. CDR62 was the major antigen; reactivity against CDR34 was typically an order of magnitude less. Furneaux et al. (1990) suggested that this reaction be called anti-onconeural. The fact that brain cells do not express major histocompatibility antigens suggests that proteins specifically expressed in neuronal cells, e.g., CDR34 and CDR62, may not have been present in the immune system during the establishment of immune tolerance. Thus, neuronal-specific proteins, although obviously 'self,' may be regarded as 'foreign' by the immune system. In normal persons, these 'foreign' neuronal proteins are not recognized by the immune system, since they are expressed only in cells without MHC. Expression of the neuronal-specific proteins in a tumor tissue that expresses MHC is accompanied by a profound immune reaction.
Chen et al. (1990) cloned the human CDR34 gene. Examination of corresponding mouse cDNA clones revealed similar hexapeptide repeating units and a highly conserved glu-asp core in each repetitive unit.
Hansen et al. (2011) found that expression of endogenous CDR1 in HEK293 cells was controlled by its antisense transcript, CDR1AS (CIRS7; 300898), and microRNA-671 (MIR671; 615245). CDR1AS was spliced into a circular noncoding RNA that appeared to stabilize the CDR1 transcript. MIR671 destabilized both CDR1 and CDR1AS by directing ARGO2 (EIF2C2; 606229)-dependent degradation of CDR1AS.
Chen et al. (1990) determined that the CDR1 gene is intronless.
Rettig et al. (1987) used Southern blot analysis of DNA extracted from rodent-human somatic cell hybrids to assign the CDR gene to chromosome Xq. By in situ hybridization, the CDR gene was located to region Xq24-q27. Siniscalco et al. (1989) confirmed and refined the regional localization of the CDR gene by linkage studies. They concluded that the gene is located in the region Xq26-q27.2, the region of a cytogenetically detectable deletion associated also with factor IX deficiency (306900).
Using somatic cell hybrid analysis, Chen et al. (1990) mapped CDR34 to both human and mouse X chromosomes. Regional localization of the human gene to Xq24-q27 was accomplished by in situ hybridization. Hirst et al. (1991) localized the CDR gene to a region proximal to the fragile site close to DXS98 and DXS105. Siniscalco et al. (1991) reported similar results.
Chen, Y.-T., Rettig, W. J., Yenamandra, A. K., Kozak, C. A., Chaganti, R. S. K., Posner, J. B., Old, L. J. Cerebellar degeneration-related antigen: a highly conserved neuroectodermal marker mapped to chromosomes X in human and mouse. Proc. Nat. Acad. Sci. 87: 3077-3081, 1990. [PubMed: 2326268] [Full Text: https://doi.org/10.1073/pnas.87.8.3077]
Dropcho, E. J., Chen, Y. T., Posner, J. B., Old, L. J. Cloning of a brain protein identified by autoantibodies from a patient with paraneoplastic cerebellar degeneration. Proc. Nat. Acad. Sci. 84: 4552-4556, 1987. [PubMed: 3474619] [Full Text: https://doi.org/10.1073/pnas.84.13.4552]
Furneaux, H. M., Rosenblum, M. K., Dalmau, J., Wong, E., Woodruff, P., Graus, F., Posner, J. B. Selective expression of Purkinje-cell antigens in tumor tissue from patients with paraneoplastic cerebellar degeneration. New Eng. J. Med. 322: 1844-1851, 1990. [PubMed: 2348838] [Full Text: https://doi.org/10.1056/NEJM199006283222604]
Furneaux, H. M., Wong, E., Posner, J. B. Isolation of cDNA clones encoding the major Yo paraneoplastic antigen. (Abstract) Neurology 40 (suppl. 1): 166 only, 1990.
Hansen, T. B., Wiklund, E. D., Bramsen, J. B., Villadsen, S. B., Statham, A. L., Clark, S. J., Kjems, J. miRNA-dependent gene silencing involving Ago2-mediated cleavage of a circular antisense RNA. EMBO J. 30: 4414-4422, 2011. [PubMed: 21964070] [Full Text: https://doi.org/10.1038/emboj.2011.359]
Hirst, M. C., Bell, M. V., MacKinnon, R. N., Watson, J. E. V., Callen, D., Sutherland, G., Dahl, N., Patterson, M. N., Schwartz, C., Ledbetter, D., Ledbetter, S., Davies, K. E. Mapping of a cerebellar degeneration related protein and DXS304 around the fragile site. Am. J. Med. Genet. 38: 354-356, 1991. [PubMed: 1673311] [Full Text: https://doi.org/10.1002/ajmg.1320380238]
Rettig, W. J., Chen, Y. T., Yenamandra, A. K., Chaganti, R. S. K., Dropcho, E. J., Posner, J. B., Old, L. J. Assignment of the cerebellar degeneration-related autoantigen CDR to human chromosome X. (Abstract) Cytogenet. Cell Genet. 46: 681 only, 1987.
Siniscalco, M., Alhadeff, B., Kekish, O., Melis, P., Maltioni, T., Filippi, G., Murray, J. C., Oberle, I., Chen, Y. T., Old, L. J., Posner, J. B. The CDR gene, located at the upper boundary of the FRAXA, is tightly linked to DXS98 and DXS105 RFLPs, moderately to the FRA(X)-syndrome and loosely to the cluster of DXS15-DXS52 RFLPs. (Abstract) Cytogenet. Cell Genet. 51: 1081 only, 1989.
Siniscalco, M., Oberle, I., Melis, P., Alhadeff, B., Murray, J., Filippi, G., Mattioni, T., Chen, Y.-T., Furneaux, H., Old, L. J., Posner, J. B. Physical and genetic mapping of the CDR gene with particular reference to its position with respect to the FRAXA site. Am. J. Med. Genet. 38: 357-362, 1991. [PubMed: 1708201] [Full Text: https://doi.org/10.1002/ajmg.1320380239]