PTH
parathyroid hormone, the group of Receptor ligands
Basic information
Region (hg38): 11:13492054-13496181
Links
Phenotypes
GenCC
Source:
- hypoparathyroidism, familial isolated 1 (Strong), mode of inheritance: AR
- familial isolated hypoparathyroidism due to impaired PTH secretion (Supportive), mode of inheritance: AD
- hypoparathyroidism, familial isolated 1 (Strong), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Hypoparathyroidism, familial isolated 1 | AD/AR | Endocrine | Early recognition of electrolyte abnormalitities (eg, hypocalcemia) can allow prompt treatment in order to avoid severe sequelae | Endocrine | 3005800; 2212001; 1302009; 10523031 |
ClinVar
This is a list of variants' phenotypes submitted to
- not_provided (16 variants)
- not_specified (10 variants)
- Hypoparathyroidism,_familial_isolated_1 (8 variants)
- Familial_hypoparathyroidism (7 variants)
- Primary_hyperparathyroidism (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the PTH gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000315.4. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 5 | |||||
| missense | 18 | 24 | ||||
| nonsense | 1 | |||||
| start loss | 0 | |||||
| frameshift | 1 | |||||
| splice donor/acceptor (+/-2bp) | 1 | |||||
| Total | 3 | 4 | 18 | 5 | 2 |
Highest pathogenic variant AF is 0.000008058358
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| PTH | protein_coding | protein_coding | ENST00000282091 | 2 | 4127 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.0121 | 0.661 | 125738 | 0 | 5 | 125743 | 0.0000199 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.549 | 50 | 62.2 | 0.804 | 0.00000302 | 761 |
| Missense in Polyphen | 20 | 18.608 | 1.0748 | 255 | ||
| Synonymous | -0.0435 | 22 | 21.7 | 1.01 | 0.00000108 | 217 |
| Loss of Function | 0.496 | 3 | 4.08 | 0.735 | 2.57e-7 | 46 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000123 | 0.000123 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000544 | 0.0000544 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000176 | 0.0000176 |
| Middle Eastern | 0.0000544 | 0.0000544 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: PTH elevates calcium level by dissolving the salts in bone and preventing their renal excretion. Stimulates [1-14C]-2- deoxy-D-glucose (2DG) transport and glycogen synthesis in osteoblastic cells. {ECO:0000269|PubMed:21076856}.;
- Disease
- DISEASE: Hypoparathyroidism, familial isolated (FIH) [MIM:146200]: A disorder characterized by hypocalcemia and hyperphosphatemia due to inadequate secretion of parathyroid hormone. Clinical features include seizures, tetany and cramps. {ECO:0000269|PubMed:10523031, ECO:0000269|PubMed:18056632, ECO:0000269|PubMed:2212001}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Vitamin D Metabolism;Vitamin D Receptor Pathway;Osteoblast Signaling;Endochondral Ossification;Signaling by GPCR;Signal Transduction;G alpha (s) signalling events;Class B/2 (Secretin family receptors);GPCR ligand binding;GPCR downstream signalling
(Consensus)
Recessive Scores
- pRec
- 0.954
Intolerance Scores
- loftool
- 0.475
- rvis_EVS
- -0.08
- rvis_percentile_EVS
- 47.79
Haploinsufficiency Scores
- pHI
- 0.144
- hipred
- N
- hipred_score
- 0.146
- ghis
- 0.457
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.534
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Low | Low | Low |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Low | Low | Low |
Mouse Genome Informatics
- Gene name
- Pth
- Phenotype
- hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); immune system phenotype; skeleton phenotype; limbs/digits/tail phenotype; craniofacial phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype; cellular phenotype;
Zebrafish Information Network
- Gene name
- pth1a
- Affected structure
- ceratohyal cartilage
- Phenotype tag
- abnormal
- Phenotype quality
- morphology
Gene ontology
- Biological process
- negative regulation of transcription by RNA polymerase II;skeletal system development;calcium ion transport;cellular calcium ion homeostasis;G protein-coupled receptor signaling pathway;adenylate cyclase-activating G protein-coupled receptor signaling pathway;activation of phospholipase C activity;Rho protein signal transduction;cell-cell signaling;hormone-mediated apoptotic signaling pathway;positive regulation of signal transduction;response to lead ion;regulation of gene expression;regulation of signaling receptor activity;magnesium ion homeostasis;bone mineralization;positive regulation of bone mineralization;negative regulation of chondrocyte differentiation;response to vitamin D;cellular macromolecule biosynthetic process;bone resorption;response to ethanol;positive regulation of glycogen biosynthetic process;positive regulation of transcription by RNA polymerase II;cAMP metabolic process;positive regulation of glucose import;response to cadmium ion;homeostasis of number of cells within a tissue;phosphate ion homeostasis;positive regulation of inositol phosphate biosynthetic process;response to parathyroid hormone;response to fibroblast growth factor;positive regulation of cell proliferation in bone marrow;negative regulation of apoptotic process in bone marrow cell;positive regulation of osteoclast proliferation;negative regulation of bone mineralization involved in bone maturation
- Cellular component
- extracellular region;extracellular space;cell
- Molecular function
- DNA-binding transcription factor activity, RNA polymerase II-specific;hormone activity;parathyroid hormone receptor binding;type 1 parathyroid hormone receptor binding;protein N-terminus binding;receptor ligand activity;peptide hormone receptor binding