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25 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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PTH
parathyroid hormone
Chromosome 11 Β· 11p15.3
NCBI Gene: 5741Ensembl: ENSG00000152266.7HGNC: HGNC:9606UniProt: P01270
341PubMed Papers
21Diseases
0Drugs
8Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
RESEARCH IMPACT
Highly Studied
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
type 1 parathyroid hormone receptor bindingpeptide hormone receptor bindingregulation of gene expressionGO:0005615hypoparathyroidism, familial isolated 1Familial isolated hypoparathyroidismneurodegenerative diseasefamilial isolated hypoparathyroidism due to impaired PTH secretion
✦AI Summary

PTH (parathyroid hormone) is an 84-amino acid peptide hormone secreted by the parathyroid gland that serves as the primary regulator of calcium homeostasis 1. The hormone elevates serum calcium by stimulating bone resorption and reducing renal calcium excretion through binding to PTH1R, a G protein-coupled receptor that activates dual signaling cascades 12. PTH engages both adenylyl cyclase/PKA and phospholipase C/PKC pathways, enabling context-dependent anabolic or catabolic effects on bone 2. In bone tissue, PTH acts directly on osteoblasts and osteocytes while indirectly regulating osteoclasts through RANKL/RANK/OPG and Wnt signaling pathways; intermittent administration promotes bone formation while continuous exposure drives resorption 1. Beyond skeletal regulation, PTH influences adrenocortical steroid secretion and modulates immediate-early gene transcription in renal cells 34. PTH secretion is regulated by extracellular calcium sensing through CASR and modulated by magnesium levels 56. Loss-of-function mutations cause familial isolated hypoparathyroidism 7. Recombinant human PTH(1-84) replacement therapy, FDA-approved in 2015, effectively treats hypoparathyroidism with sustained efficacy over 6+ years 7.

Sources cited
1
PTH is an 84-amino acid peptide hormone that regulates bone metabolism through PTH1R binding, promoting bone formation with intermittent administration and bone resorption with continuous administration
PMID: 34224692
2
PTH activates dual signaling pathways through PTH1R, stimulating both adenylyl cyclase and phospholipase C with different receptor density requirements
PMID: 9893061
3
Parathyroid glands sense extracellular calcium through CASR and release PTH to maintain calcium homeostasis
PMID: 27816765
4
PTH enhances steroid secretion from adrenocortical cells through cAMP/PKA and PLC/PKC signaling pathways
PMID: 11158922
5
PTH 1-84 regulates immediate-early gene promoter activation in renal tubular cells
PMID: 18279669
6
Intracellular magnesium depletion impairs PTH secretion from the parathyroid gland
PMID: 17660616
7
Recombinant human PTH(1-84) was FDA-approved in 2015 for hypoparathyroidism treatment with demonstrated efficacy up to 6 years
PMID: 30390821
Disease Associationsβ“˜21
hypoparathyroidism, familial isolated 1Open Targets
0.71Strong
Familial isolated hypoparathyroidismOpen Targets
0.71Strong
neurodegenerative diseaseOpen Targets
0.40Weak
familial isolated hypoparathyroidism due to impaired PTH secretionOpen Targets
0.37Weak
Alzheimer diseaseOpen Targets
0.35Weak
primary hyperparathyroidismOpen Targets
0.35Weak
Parkinson diseaseOpen Targets
0.34Weak
multiple sclerosisOpen Targets
0.34Weak
lysosomal storage diseaseOpen Targets
0.33Weak
familial hypoparathyroidismOpen Targets
0.33Weak
joint diseaseOpen Targets
0.32Weak
enteritisOpen Targets
0.27Weak
metabolic diseaseOpen Targets
0.24Weak
myocardial infarctionOpen Targets
0.19Weak
chronic kidney diseaseOpen Targets
0.12Weak
HypocalcemiaOpen Targets
0.12Weak
neoplasmOpen Targets
0.11Weak
diabetes mellitusOpen Targets
0.11Weak
cardiovascular diseaseOpen Targets
0.11Weak
HypercalcemiaOpen Targets
0.10Weak
Hypoparathyroidism, familial isolated, 1UniProt
Pathogenic Variants8
NM_000315.4(PTH):c.86+4A>TPathogenic
not provided
β˜…β˜†β˜†β˜†2026
NM_000315.4(PTH):c.1_2insGCAT (p.Met1fs)Likely pathogenic
Hypoparathyroidism, familial isolated 1
β˜…β˜†β˜†β˜†2025β†’ Residue 1
NM_000315.4(PTH):c.247C>T (p.Arg83Ter)Likely pathogenic
Primary hyperparathyroidism|Familial hypoparathyroidism
β˜…β˜†β˜†β˜†2022β†’ Residue 83
NM_000315.4(PTH):c.46_47delinsAA (p.Ala16Lys)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2017β†’ Residue 16
NM_000315.4(PTH):c.166C>T (p.Arg56Cys)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2016β†’ Residue 56
NM_000315.4(PTH):c.52T>C (p.Cys18Arg)Pathogenic
Hypoparathyroidism, familial isolated 1
β˜†β˜†β˜†β˜†2007β†’ Residue 18
NM_000315.4(PTH):c.67T>C (p.Ser23Pro)Pathogenic
Hypoparathyroidism, familial isolated 1
β˜†β˜†β˜†β˜†1999β†’ Residue 23
NM_000315.4(PTH):c.86+1G>CPathogenic
Hypoparathyroidism, familial isolated 1
β˜†β˜†β˜†β˜†1992
View on ClinVar β†—
Related Genes
SCTProtein interaction100%PTH2RProtein interaction100%CASRProtein interaction98%DMP1Protein interaction98%EMP1Protein interaction98%GALNT3Protein interaction98%
Tissue Expression6 tissues
Ovary
0%
Liver
0%
Brain
0%
Heart
0%
Lung
0%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
PTHSCTPTH2RCASRDMP1EMP1GALNT3
PROTEIN STRUCTURE
Preparing viewer…
PDB1ET1 Β· 0.90 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.32LoF Tolerant
pLIβ“˜
0.05Tolerant
Observed/Expected LoF0.63 [0.33–1.32]
RankingsWhere PTH stands among ~20K protein-coding genes
  • #942of 20,598
    Most Researched341 Β· top 5%
  • #3,018of 5,498
    Most Pathogenic Variants8
  • #13,864of 17,882
    Most Constrained (LOEUF)1.32
Genes detectedPTH
Sources retrieved25 papers
Response timeβ€”
πŸ“„ Sources
25β–Ό
1
Parathyroid hormone and its related peptides in bone metabolism.
PMID: 34224692
Biochem Pharmacol Β· 2021
1.00
2
MicroRNAs in parathyroid physiopathology.
PMID: 27816765
Mol Cell Endocrinol Β· 2017
0.90
3
Post-traumatic headache: epidemiology and pathophysiological insights.
PMID: 31527806
Nat Rev Neurol Β· 2019
0.80
4
Cultured human fibroblasts and not cultured human keratinocytes express a PTH/PTHrP receptor mRNA.
PMID: 7615967
J Invest Dermatol Β· 1995
0.80
5
New Directions in Treatment of Hypoparathyroidism.
PMID: 30390821
Endocrinol Metab Clin North Am Β· 2018
0.70