PTH

parathyroid hormone, the group of Receptor ligands

Basic information

Region (hg38): 11:13492053-13496181

Links

ENSG00000152266 ∙ NCBI:5741 ∙ OMIM:168450 ∙ HGNC:9606 ∙ Uniprot:P01270 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 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: CGD

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 ClinVar and linked to the PTH gene.

• Familial hypoparathyroidism (14 variants)
• not provided (14 variants)
• Inborn genetic diseases (5 variants)
• Hypoparathyroidism, familial isolated 1 (4 variants)
• not specified (2 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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				3	3	6
missense		2	7	2		11
nonsense		1				1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			2			2
non coding			4		7	11
Total	0	3	11	5	10

Highest pathogenic variant AF is 0.00000660

Variants in PTH

This is a list of pathogenic ClinVar variants found in the PTH region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-13492086-T-C		Familial hypoparathyroidism	Benign (Nov 12, 2018)
11-13492216-CAA-C			Benign (Nov 12, 2018)
11-13492308-T-C		Familial hypoparathyroidism	Uncertain significance (Apr 27, 2017)
11-13492350-G-A		Familial hypoparathyroidism	Uncertain significance (Jan 13, 2018)
11-13492354-T-C		Familial hypoparathyroidism	Benign (Jan 13, 2018)
11-13492449-C-T		not specified	Uncertain significance (Jun 18, 2021)
11-13492453-C-A			Uncertain significance (-)
11-13492468-T-A		not specified	Uncertain significance (Jul 05, 2023)
11-13492477-C-T		Familial hypoparathyroidism	Benign (Dec 12, 2023)
11-13492506-G-A		Primary hyperparathyroidism • Familial hypoparathyroidism	Likely pathogenic (Apr 10, 2022)
11-13492506-G-T		not specified • Familial hypoparathyroidism • Hypoparathyroidism, familial isolated 1	Benign (Jan 29, 2024)
11-13492523-G-T		not specified	Uncertain significance (Jan 30, 2023)
11-13492542-G-A		not specified	Likely benign (Sep 22, 2022)
11-13492557-C-T		not specified	Likely benign (Apr 13, 2022)
11-13492562-T-C		Familial hypoparathyroidism	Uncertain significance (Jan 13, 2018)
11-13492576-C-T			Likely benign (Dec 31, 2019)
11-13492587-G-A			Likely pathogenic (Aug 31, 2016)
11-13492629-G-A			Likely benign (Nov 29, 2017)
11-13492630-G-T		Familial hypoparathyroidism	Uncertain significance (Jan 12, 2018)
11-13492631-T-C			Uncertain significance (-)
11-13492633-A-G			Likely benign (Dec 31, 2019)
11-13492655-A-T		Hypoparathyroidism, familial isolated 1	Uncertain significance (-)
11-13492716-C-T			Benign (Nov 12, 2018)
11-13492761-A-C		Familial hypoparathyroidism	Benign (Dec 12, 2023)
11-13492762-GTACT-G		Hypoparathyroidism, familial isolated 1	Uncertain significance (Feb 18, 2022)

GnomAD

Source: gnomAD

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: dbNSFP

• 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