Alternative titles; symbols
HGNC Approved Gene Symbol: CMKLR2
Cytogenetic location: 2q33.3 Genomic coordinates (GRCh38): 2:206,175,316-206,217,912 (from NCBI)
Members of the G protein-coupled receptor family share a common motif of 7 transmembrane domains and likely mediate the actions of endogenous peptides in the brain. In a search for genes responsible for mediating brain reward that may have a role in drug addiction, Marchese et al. (1994) cloned several G protein-coupled receptors. One of these, GPR1, encoded a receptor protein that is intronless in the coding region and shared 43% identity in the transmembrane regions with the opioid receptors (see, e.g., OPRD1; 165195). Northern blot analysis revealed that GPR1 transcripts were expressed in a human hippocampus.
By FISH analysis, Marchese et al. (1994) mapped the CMKLR2 gene to chromosome 15q21.6. However, Gross (2023) mapped the CMKLR2 gene to chromosome 2q33.3 based on an alignment of the CMKLR2 sequence (GenBank BC067833) with the genomic sequence (GRCh38).
Spiegel (1996) reviewed mutations that affect various G protein-coupled receptors and cause endocrine diseases. The diseases associated with loss of G protein-coupled receptor function include nephrogenic diabetes insipidus (V2 vasopressin receptor), familial ACTH resistance (ACTH receptor), familial GH deficiency (GHRH receptor), hypergonadotropic ovarian dysgenesis (FSH receptor), male pseudohermaphroditism (LH receptor), familial hypothyroidism (TSH receptor), and familial hypocalcemia (CASR; 601199). The endocrine diseases associated with gain of G protein-coupled receptor function include familial male precocious puberty (LH receptor), sporadic hyperfunctional thyroid nodules (TSH receptor), familial nonautoimmune hyperthyroidism (TSH receptor), familial hypocalciuric hypercalcemia, and Jansen metaphyseal chondrodysplasia (PTH/PTHrP receptor). Endocrine diseases caused by G protein alpha-subunit mutations include pseudohypoparathyroidism (PHP) type Ia (G-alpha-s, loss of function), PHP Ia with precocious puberty (G-alpha-s, loss or gain of function), acromegaly, hyperfunctional thyroid nodules, McCune-Albright syndrome (G-alpha-s, gain of function), and ovarian and adrenocortical tumors (G-alpha-i2, gain of function).
Vassilatis et al. (2003) determined that there are 367 GPRs in humans and 392 in mice, with a high level of orthology between GPRs of the 2 species. Expression profiling of 100 mouse GPRs demonstrated that most are expressed in multiple murine tissues and that individual tissues express multiple GPRs. The profiles of most GPRs are unique, yielding thousands of tissue- and cell-specific receptor combinations for the modulation of physiologic processes.
Gross, M. B. Personal Communication. Baltimore, Md. 5/1/2023.
Marchese, A., Docherty, J. M., Nguyen, T., Heiber, M., Cheng, R., Heng, H. H. Q., Tsui, L.-C., Shi, X., George, S. R., O'Dowd, B. F. Cloning of human genes encoding novel G protein-coupled receptors. Genomics 23: 609-618, 1994. [PubMed: 7851889] [Full Text: https://doi.org/10.1006/geno.1994.1549]
Spiegel, A. M. Genetic basis of endocrine disease: mutations in G proteins and G protein-coupled receptors in endocrine disease. J. Clin. Endocr. Metab. 81: 2434-2442, 1996. [PubMed: 8675557] [Full Text: https://doi.org/10.1210/jcem.81.7.8675557]
Vassilatis, D. K., Hohmann, J. G., Zeng, H., Li, F., Ranchalis, J. E., Mortrud, M. T., Brown, A., Rodriguez, S. S., Weller, J. R., Wright, A. C., Bergmann, J. E., Gaitanaris, G. A. The G protein-coupled receptor repertoires of human and mouse. Proc. Nat. Acad. Sci. 100: 4903-4908, 2003. [PubMed: 12679517] [Full Text: https://doi.org/10.1073/pnas.0230374100]