Alternative titles; symbols
HGNC Approved Gene Symbol: FOLR2
Cytogenetic location: 11q13.4 Genomic coordinates (GRCh38): 11:72,216,794-72,221,950 (from NCBI)
The FOLR2 gene encodes a placental folate-binding protein. See also folate receptor alpha (FOLR1; 136430).
Ratnam et al. (1989) obtained a full-length cDNA for a placental folate-binding protein and deduced the corresponding protein sequence. It contained a putative 16-residue amino terminal signal peptide that is cleaved, resulting in a 239-residue polypeptide. The mature protein exhibited 2 potential sites for N-linked glycosylation at asn99 and asn179. The protein bore a 68% sequence homology with the adult folate-binding protein.
Ragoussis et al. (1992) found 4 FOLR-related genes within 140 kb. The adult and fetal genes were not more than 23 kb apart, with the 3-prime end of the adult gene facing the 5-prime end of the fetal gene. There appeared to be one or more pseudogenes in the cluster. The analysis of the region was performed by pulsed field gel electrophoresis of YAC DNA isolated using the adult FOLR gene probe. The chromosomal assignment of the FOLR cluster was refined to 11q13.3-q13.5, telomeric of the FGF3 locus (164950), using fluorescence in situ hybridization.
In the absence of clinical folate deficiency, periconceptional supplementation with folic acid reduces a woman's risk of having an infant with a neural tube defect (NTDFS; 601634). Since antiserum to folate receptors induces embryo resorption and malformations in rats, Rothenberg et al. (2004) hypothesized that autoantibodies against folate receptors in women may be associated with pregnancy complicated by a neural tube defect. They found that serum from 9 of 12 women who were or had been pregnant with a fetus with a neural tube defect contained autoantibodies against folate receptors, as compared with 2 of 20 control subjects (P less than 0.001). The autoantibodies blocked the binding of radiolabeled folic acid to folate receptors on placental membranes and on cultured cells incubated at 4 degrees C and blocked the uptake of labeled folic acid by cells incubated at 37 degrees C.
Molloy et al. (2009) found no association between the presence and titer of maternal folate receptor autoantibodies and neural tube defect-affected pregnancies in an Irish population consisting of 103 mothers with a history of pregnancy complicated by a neural tube defect and 103 mothers with a history of pregnancy not complicated by a neural tube defect. Blocking autoantibodies were found in 17% of case mothers, as compared to 13% of control mothers, and binding autoantibodies in 29% and 32% of case and control mothers, respectively.
Molloy, A. M., Quadros, E. V., Sequeira, J. M., Troendle, J. F., Scott, J. M., Kirke, P. N., Mills, J. L. Lack of association between folate-receptor autoantibodies and neural-tube defects. New Eng. J. Med. 361: 152-160, 2009. [PubMed: 19587340] [Full Text: https://doi.org/10.1056/NEJMoa0803783]
Ragoussis, J., Senger, G., Trowsdale, J., Campbell, I. G. Genomic organization of the human folate receptor genes on chromosome 11q13. Genomics 14: 423-430, 1992. [PubMed: 1330883] [Full Text: https://doi.org/10.1016/s0888-7543(05)80236-8]
Ratnam, M., Marquardt, H., Duhring, J. L., Freisheim, J. H. Homologous membrane folate binding proteins in human placenta: cloning and sequence of a cDNA. Biochemistry 28: 8249-8254, 1989. [PubMed: 2605182] [Full Text: https://doi.org/10.1021/bi00446a042]
Rothenberg, S. P., da Costa, M. P., Sequeira, J. M., Cracco, J., Roberts, J. L., Weedon, J., Quadros, E. V. Autoantibodies against folate receptors in women with a pregnancy complicated by a neural-tube defect. New Eng. J. Med. 350: 134-142, 2004. [PubMed: 14711912] [Full Text: https://doi.org/10.1056/NEJMoa031145]