{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Hanna P"],"funding":["NIDDK NIH HHS"],"pagination":["e2208047120"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9974466"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["120(8)"],"pubmed_abstract":["Like other secreted peptides, nascent parathyroid hormone (PTH) is synthesized with a pre- and a pro-sequence (25 and 6 amino acids, respectively). These precursor segments are sequentially removed in parathyroid cells before packaging into secretory granules. Three patients from two unrelated families who presented during infancy with symptomatic hypocalcemia were found to have a homozygous serine (S) to proline (P) change affecting the first amino acid of the mature PTH. Unexpectedly, biological activity of synthetic [P1]PTH(1-34) was indistinguishable from that of unmodified [S1]PTH(1-34). However, in contrast to conditioned medium from COS-7 cells expressing prepro[S1]PTH(1-84), medium from cells expressing prepro[P1]PTH(1-84) failed to stimulate cAMP production despite similar PTH lev"],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pubmed_title":["Homozygous Ser-1 to Pro-1 mutation in parathyroid hormone identified in hypocalcemic patients results in secretion of a biologically inactive pro-hormone."],"pmcid":["PMC9974466"],"funding_grant_id":["R37 DK046718","R01 DK046718","R56 DK046718","P01 DK011794"],"pubmed_authors":["Gardella TJ","Gild ML","Brabant S","Francou B","Clifton-Bligh RJ","Potts JT","Hanna P","Choi S","Linglart A","Khatri A","Prie D","Piketty ML","Juppner H"],"additional_accession":[]},"is_claimable":false,"name":"Homozygous Ser-1 to Pro-1 mutation in parathyroid hormone identified in hypocalcemic patients results in secretion of a biologically inactive pro-hormone.","description":"Like other secreted peptides, nascent parathyroid hormone (PTH) is synthesized with a pre- and a pro-sequence (25 and 6 amino acids, respectively). These precursor segments are sequentially removed in parathyroid cells before packaging into secretory granules. Three patients from two unrelated families who presented during infancy with symptomatic hypocalcemia were found to have a homozygous serine (S) to proline (P) change affecting the first amino acid of the mature PTH. Unexpectedly, biological activity of synthetic [P1]PTH(1-34) was indistinguishable from that of unmodified [S1]PTH(1-34). However, in contrast to conditioned medium from COS-7 cells expressing prepro[S1]PTH(1-84), medium from cells expressing prepro[P1]PTH(1-84) failed to stimulate cAMP production despite similar PTH lev","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Feb","modification":"2026-05-28T08:08:40.132Z","creation":"2025-04-25T17:08:57.269Z"},"accession":"S-EPMC9974466","cross_references":{"pubmed":["36795755"],"doi":["10.1073/pnas.2208047120"]}}