* 601469

PARATHYROID HORMONE 2 RECEPTOR; PTH2R


Alternative titles; symbols

PARATHYROID HORMONE RECEPTOR 2; PTHR2


HGNC Approved Gene Symbol: PTH2R

Cytogenetic location: 2q34     Genomic coordinates (GRCh38): 2:208,359,692-208,494,506 (from NCBI)


TEXT

Cloning and Expression

Usdin et al. (1995) identified a 7-transmembrane-domain G protein-coupled receptor that selectively recognizes parathyroid hormone (PTH; 168450). The receptor, which they designated PTHR2, is a member of the secretin receptor family of G protein-coupled receptors (see 182098). There is 30 to 70% amino acid sequence identity between receptors within the secretin receptor family, but these receptors have essentially no sequence identity with most known G protein-coupled receptors of the rhodopsin family (see 180380) or with the metabotropic glutamate receptor family (see 601115). PTHR2 is most similar (51% overall amino acid identity) to the PTH/PTHRP receptor (168468). The PTHR2 gene was most abundantly expressed in brain, pancreas, testis, and placenta.


Gene Function

Although both PTH and PTH-related peptide (PTHRP; 168470) bind to the PTH/PTHRP receptor and stimulate cAMP accumulation with similar efficacy, only PTH activates PTHR2. To determine the structural basis for this selectivity, Clark et al. (1998) analyzed receptor chimeras in which the amino terminus and third extracellular domains of the 2 receptors were interchanged. Simultaneous interchange of wildtype amino termini and third extracellular loops eliminated agonist activation but not binding for both receptors. These results suggested that the amino terminus and third extracellular loop of the PTH2 and PTH/PTHRP receptors interact similarly with PTH, and that both domains contribute to differential interaction with PTHRP.


Mapping

By FISH analysis, Usdin et al. (1996) mapped the PTHR2 gene to chromosome 2q33.


Cytogenetics

In a 15-month-old boy with nonsyndromic sagittal and metopic craniosynostosis (see 123100), Kim et al. (2015) identified a complex paracentric inversion involving chromosome 2q14.3 and 2q34; whole genome sequencing demonstrated an intronic break of the PTH2R gene, and fluorescence in situ hybridization analysis confirmed disruption of PTH2R.


Molecular Genetics

Meulenbelt et al. (2006) performed linkage analysis in 6 multigenerational families with early-onset osteoarthritis and found significant linkage on chromosome 2q33.3 with a maximum 2-point lod score of 6.05 at marker D2S155 (theta = 0.0). Haplotype analysis of affected family members defined a minimum candidate gene region of 4.6 Mb between D2S1384 and D2S2178, which includes the PTHR2 gene. Meulenbelt et al. (2006) identified a missense variant in PTHR2 that cosegregated with disease in 1 family, but stated that it was unlikely to be the major disease gene for the observed linkage to the osteoarthritis phenotype.


REFERENCES

  1. Clark, J. A., Bonner, T. I., Kim, A. S., Usdin, T. B. Multiple regions of ligand discrimination revealed by analysis of chimeric parathyroid hormone 2 (PTH2) and PTH/PTH-related peptide (PTHrP) receptors. Molec. Endocr. 12: 193-206, 1998. [PubMed: 9482662, related citations] [Full Text]

  2. Kim, J., Won, H.-H., Kim, Y., Choi, J. R., Yu, N., Lee, K.-A. Breakpoint mapping by whole genome sequencing identifies PTH2R gene disruption in a patient with midline craniosynostosis and a de novo balanced chromosomal rearrangement. J. Med. Genet. 52: 706-709, 2015. [PubMed: 26044810, related citations] [Full Text]

  3. Meulenbelt, I., Min, J. L., van Duijn, C. M., Kloppenburg, M., Breedveld, F. C., Slagboom, P. E. Strong linkage on 2q33.3 to familial early-onset generalized osteoarthritis and a consideration of two positional candidate genes. Europ. J. Hum. Genet. 14: 1280-1287, 2006. [PubMed: 16912703, related citations] [Full Text]

  4. Usdin, T. B., Gruber, C., Bonner, T. I. Identification and functional expression of a receptor selectively recognizing parathyroid hormone, the PTH2 receptor. J. Biol. Chem. 270: 15455-15458, 1995. [PubMed: 7797535, related citations] [Full Text]

  5. Usdin, T. B., Modi, W., Bonner, T. I. Assignment of the human PTH2 receptor gene (PTHR2) to chromosome 2q33 by fluorescence in situ hybridization. Genomics 37: 140-141, 1996. [PubMed: 8921382, related citations] [Full Text]


Marla J. F. O'Neill - updated : 01/15/2016
Marla J. F. O'Neill - updated : 3/2/2007
John A. Phillips, III - updated : 4/14/1999
Creation Date:
Victor A. McKusick : 10/16/1996
carol : 01/15/2016
carol : 3/25/2014
wwang : 3/8/2007
terry : 3/2/2007
carol : 5/30/2001
kayiaros : 7/27/1999
mgross : 4/14/1999
mark : 10/17/1996
mark : 10/17/1996

* 601469

PARATHYROID HORMONE 2 RECEPTOR; PTH2R


Alternative titles; symbols

PARATHYROID HORMONE RECEPTOR 2; PTHR2


HGNC Approved Gene Symbol: PTH2R

Cytogenetic location: 2q34     Genomic coordinates (GRCh38): 2:208,359,692-208,494,506 (from NCBI)


TEXT

Cloning and Expression

Usdin et al. (1995) identified a 7-transmembrane-domain G protein-coupled receptor that selectively recognizes parathyroid hormone (PTH; 168450). The receptor, which they designated PTHR2, is a member of the secretin receptor family of G protein-coupled receptors (see 182098). There is 30 to 70% amino acid sequence identity between receptors within the secretin receptor family, but these receptors have essentially no sequence identity with most known G protein-coupled receptors of the rhodopsin family (see 180380) or with the metabotropic glutamate receptor family (see 601115). PTHR2 is most similar (51% overall amino acid identity) to the PTH/PTHRP receptor (168468). The PTHR2 gene was most abundantly expressed in brain, pancreas, testis, and placenta.


Gene Function

Although both PTH and PTH-related peptide (PTHRP; 168470) bind to the PTH/PTHRP receptor and stimulate cAMP accumulation with similar efficacy, only PTH activates PTHR2. To determine the structural basis for this selectivity, Clark et al. (1998) analyzed receptor chimeras in which the amino terminus and third extracellular domains of the 2 receptors were interchanged. Simultaneous interchange of wildtype amino termini and third extracellular loops eliminated agonist activation but not binding for both receptors. These results suggested that the amino terminus and third extracellular loop of the PTH2 and PTH/PTHRP receptors interact similarly with PTH, and that both domains contribute to differential interaction with PTHRP.


Mapping

By FISH analysis, Usdin et al. (1996) mapped the PTHR2 gene to chromosome 2q33.


Cytogenetics

In a 15-month-old boy with nonsyndromic sagittal and metopic craniosynostosis (see 123100), Kim et al. (2015) identified a complex paracentric inversion involving chromosome 2q14.3 and 2q34; whole genome sequencing demonstrated an intronic break of the PTH2R gene, and fluorescence in situ hybridization analysis confirmed disruption of PTH2R.


Molecular Genetics

Meulenbelt et al. (2006) performed linkage analysis in 6 multigenerational families with early-onset osteoarthritis and found significant linkage on chromosome 2q33.3 with a maximum 2-point lod score of 6.05 at marker D2S155 (theta = 0.0). Haplotype analysis of affected family members defined a minimum candidate gene region of 4.6 Mb between D2S1384 and D2S2178, which includes the PTHR2 gene. Meulenbelt et al. (2006) identified a missense variant in PTHR2 that cosegregated with disease in 1 family, but stated that it was unlikely to be the major disease gene for the observed linkage to the osteoarthritis phenotype.


REFERENCES

  1. Clark, J. A., Bonner, T. I., Kim, A. S., Usdin, T. B. Multiple regions of ligand discrimination revealed by analysis of chimeric parathyroid hormone 2 (PTH2) and PTH/PTH-related peptide (PTHrP) receptors. Molec. Endocr. 12: 193-206, 1998. [PubMed: 9482662] [Full Text: https://doi.org/10.1210/mend.12.2.0063]

  2. Kim, J., Won, H.-H., Kim, Y., Choi, J. R., Yu, N., Lee, K.-A. Breakpoint mapping by whole genome sequencing identifies PTH2R gene disruption in a patient with midline craniosynostosis and a de novo balanced chromosomal rearrangement. J. Med. Genet. 52: 706-709, 2015. [PubMed: 26044810] [Full Text: https://doi.org/10.1136/jmedgenet-2015-103001]

  3. Meulenbelt, I., Min, J. L., van Duijn, C. M., Kloppenburg, M., Breedveld, F. C., Slagboom, P. E. Strong linkage on 2q33.3 to familial early-onset generalized osteoarthritis and a consideration of two positional candidate genes. Europ. J. Hum. Genet. 14: 1280-1287, 2006. [PubMed: 16912703] [Full Text: https://doi.org/10.1038/sj.ejhg.5201704]

  4. Usdin, T. B., Gruber, C., Bonner, T. I. Identification and functional expression of a receptor selectively recognizing parathyroid hormone, the PTH2 receptor. J. Biol. Chem. 270: 15455-15458, 1995. [PubMed: 7797535] [Full Text: https://doi.org/10.1074/jbc.270.26.15455]

  5. Usdin, T. B., Modi, W., Bonner, T. I. Assignment of the human PTH2 receptor gene (PTHR2) to chromosome 2q33 by fluorescence in situ hybridization. Genomics 37: 140-141, 1996. [PubMed: 8921382] [Full Text: https://doi.org/10.1006/geno.1996.0532]


Contributors:
Marla J. F. O'Neill - updated : 01/15/2016
Marla J. F. O'Neill - updated : 3/2/2007
John A. Phillips, III - updated : 4/14/1999

Creation Date:
Victor A. McKusick : 10/16/1996

Edit History:
carol : 01/15/2016
carol : 3/25/2014
wwang : 3/8/2007
terry : 3/2/2007
carol : 5/30/2001
kayiaros : 7/27/1999
mgross : 4/14/1999
mark : 10/17/1996
mark : 10/17/1996