PTH1R

parathyroid hormone 1 receptor, the group of Parathyroid hormone receptors

Basic information

Region (hg38): 3:46877721-46903799

Previous symbols: [ "PTHR", "PTHR1" ]

Links

ENSG00000160801 ∙ NCBI:5745 ∙ OMIM:168468 ∙ HGNC:9608 ∙ Uniprot:Q03431 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• primary failure of tooth eruption (Definitive), mode of inheritance: AD
• metaphyseal chondrodysplasia, Jansen type (Definitive), mode of inheritance: AD
• chondrodysplasia Blomstrand type (Definitive), mode of inheritance: AR
• chondrodysplasia Blomstrand type (Strong), mode of inheritance: AR
• Eiken syndrome (Limited), mode of inheritance: AR
• metaphyseal chondrodysplasia, Jansen type (Supportive), mode of inheritance: AD
• chondrodysplasia Blomstrand type (Supportive), mode of inheritance: AR
• Eiken syndrome (Supportive), mode of inheritance: AR
• primary failure of tooth eruption (Supportive), mode of inheritance: AD
• chondrodysplasia Blomstrand type (Strong), mode of inheritance: AR
• Eiken syndrome (Strong), mode of inheritance: AR
• metaphyseal chondrodysplasia, Jansen type (Strong), mode of inheritance: AD
• primary failure of tooth eruption (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Eiken syndrome; Chondrodysplasia, Blomstrand type; Metaphyseal chondrodysplasia, Jansen type; Failure of tooth eruption, primary	AD/AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal	3975110; 6734674; 8276022; 7701349; 9268097; 9178745; 9649554; 9745456; 10664159; 12357475; 15525660; 17164305; 19061984; 20135246; 29987841

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PTH1R gene.

• Metaphyseal chondrodysplasia, Jansen type (2 variants)
• Chondrodysplasia Blomstrand type (2 variants)
• not provided (2 variants)
• Primary failure of tooth eruption (2 variants)
• Metaphyseal chondrodysplasia, Jansen type;Eiken syndrome;Chondrodysplasia Blomstrand type;Primary failure of tooth eruption (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PTH1R 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	47	3	53
missense	4	2	140	4		150
nonsense	1	1				2
start loss						0
frameshift						0
inframe indel			1			1
splice donor/acceptor (+/-2bp)	1					1
splice region			9	8		17
non coding			4	35	13	52
Total	6	3	148	86	16

Highest pathogenic variant AF is 0.00000657

Variants in PTH1R

This is a list of pathogenic ClinVar variants found in the PTH1R region.

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

Position	Type	Phenotype	Significance	ClinVar
3-46877783-G-A		Metaphyseal chondrodysplasia, Jansen type • Chondrodysplasia Blomstrand type	Uncertain significance (Jan 12, 2018)
3-46881103-C-A		Metaphyseal chondrodysplasia, Jansen type • Chondrodysplasia Blomstrand type	Uncertain significance (Jan 12, 2018)
3-46883225-C-T			Likely benign (Feb 16, 2019)
3-46883523-G-A		Chondrodysplasia Blomstrand type • Metaphyseal chondrodysplasia, Jansen type	Benign/Likely benign (Jan 13, 2018)
3-46883572-C-G			Uncertain significance (Nov 08, 2021)
3-46883582-C-G			Uncertain significance (Oct 05, 2023)
3-46883584-G-A		Inborn genetic diseases	Uncertain significance (Apr 11, 2023)
3-46883585-GC-TT			Uncertain significance (Sep 04, 2021)
3-46883593-C-T		Inborn genetic diseases	Uncertain significance (May 30, 2022)
3-46883609-C-T			Uncertain significance (May 29, 2023)
3-46883610-C-G			Benign (Jun 02, 2023)
3-46883616-C-G		Chondrodysplasia Blomstrand type • Metaphyseal chondrodysplasia, Jansen type	Uncertain significance (Jan 13, 2018)
3-46883624-C-T			Uncertain significance (Aug 15, 2022)
3-46883641-C-T			Likely benign (Nov 21, 2022)
3-46883643-C-T		Metaphyseal chondrodysplasia, Jansen type • Chondrodysplasia Blomstrand type • Connective tissue disorder	Conflicting classifications of pathogenicity (Jan 18, 2024)
3-46883646-G-A		Chondrodysplasia Blomstrand type • Metaphyseal chondrodysplasia, Jansen type • Primary failure of tooth eruption;Eiken syndrome;Chondrodysplasia Blomstrand type;Metaphyseal chondrodysplasia, Jansen type	Benign/Likely benign (Jan 29, 2024)
3-46893895-T-C			Likely benign (Dec 22, 2022)
3-46893896-C-T			Likely benign (Sep 29, 2022)
3-46893934-G-A		Eiken syndrome	Uncertain significance (Jan 16, 2018)
3-46893940-C-A			Uncertain significance (Apr 08, 2015)
3-46893948-C-T			Likely benign (Apr 18, 2022)
3-46893955-C-T			Uncertain significance (-)
3-46893959-G-A		Chondrodysplasia Blomstrand type • Metaphyseal chondrodysplasia, Jansen type • Primary failure of tooth eruption;Eiken syndrome;Chondrodysplasia Blomstrand type;Metaphyseal chondrodysplasia, Jansen type • PTH1R-related disorder	Benign/Likely benign (Jan 05, 2024)
3-46893965-A-G			Uncertain significance (Jun 15, 2022)
3-46893967-G-A			Uncertain significance (Dec 23, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PTH1R	protein_coding	protein_coding	ENST00000313049	14	26052

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.573	0.427	125740	0	8	125748	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.65	272	360	0.755	0.0000232	3801
Missense in Polyphen		104	152.63	0.68137		1682
Synonymous	0.0638	152	153	0.993	0.0000103	1201
Loss of Function	3.94	6	28.8	0.208	0.00000144	326

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000910	0.0000905
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000545	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000265	0.0000264
Middle Eastern	0.0000545	0.0000544
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Receptor for parathyroid hormone and for parathyroid hormone-related peptide. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase and also a phosphatidylinositol-calcium second messenger system. {ECO:0000269|PubMed:20172855, ECO:0000269|PubMed:27160269, ECO:0000269|PubMed:8397094}.
• Disease: DISEASE: Jansen metaphyseal chondrodysplasia (JMC) [MIM:156400]: Rare autosomal dominant disorder characterized by a short-limbed dwarfism associated with hypercalcemia and normal or low serum concentrations of the two parathyroid hormones. {ECO:0000269|PubMed:10487664, ECO:0000269|PubMed:15240651, ECO:0000269|PubMed:27160269, ECO:0000269|PubMed:7701349, ECO:0000269|PubMed:8703170, ECO:0000269|PubMed:9178745}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Chondrodysplasia Blomstrand type (BOCD) [MIM:215045]: Severe skeletal dysplasia. {ECO:0000269|PubMed:9745456}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Enchondromatosis multiple (ENCHOM) [MIM:166000]: A condition characterized by multiple formation of enchondromas, benign neoplasms derived from mesodermal cells that form cartilage. Enchondromas remain within the substance of a cartilage or bone. Clinical problems caused by enchondromas include skeletal deformity and the potential for malignant change to osteosarcoma. {ECO:0000269|PubMed:11850620}. Note=The disease may be caused by mutations affecting the gene represented in this entry.; DISEASE: Eiken skeletal dysplasia (EISD) [MIM:600002]: A rare skeletal dysplasia characterized by severely retarded ossification, principally of the epiphyses, pelvis, hands and feet, as well as by abnormal modeling of the bones in hands and feet, abnormal persistence of cartilage in the pelvis and mild growth retardation. {ECO:0000269|PubMed:15525660}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Primary failure of tooth eruption (PFE) [MIM:125350]: Rare condition that has high penetrance and variable expressivity and in which tooth retention occurs without evidence of any obvious mechanical interference. Instead, malfunction of the eruptive mechanism itself appears to cause nonankylosed permanent teeth to fail to erupt, although the eruption pathway has been cleared by bone resorption. {ECO:0000269|PubMed:19061984}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Endocrine and other factor-regulated calcium reabsorption - Homo sapiens (human);Neuroactive ligand-receptor interaction - Homo sapiens (human);Osteoblast Signaling;GPCRs, Class B Secretin-like;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)

Intolerance Scores

• loftool: 0.528
• rvis_EVS: 0.07
• rvis_percentile_EVS: 58.96

Haploinsufficiency Scores

• pHI: 0.460
• hipred: Y
• hipred_score: 0.850

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.305

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Pth1r
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; liver/biliary system phenotype; embryo phenotype; neoplasm; 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); hematopoietic system phenotype; 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); vision/eye phenotype; digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; skeleton phenotype; homeostasis/metabolism phenotype; immune system phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; craniofacial phenotype

Zebrafish Information Network

• Gene name: pth1ra
• Affected structure: hypochord
• Phenotype tag: abnormal
• Phenotype quality: decreased process quality

Gene ontology

• Biological process: skeletal system development;chondrocyte differentiation;osteoblast development;cellular calcium ion homeostasis;cell surface receptor signaling pathway;G protein-coupled receptor signaling pathway;G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger;adenylate cyclase-modulating G protein-coupled receptor signaling pathway;adenylate cyclase-activating G protein-coupled receptor signaling pathway;phospholipase C-activating G protein-coupled receptor signaling pathway;positive regulation of cytosolic calcium ion concentration;aging;positive regulation of cell population proliferation;negative regulation of cell population proliferation;bone mineralization;bone resorption;cell maturation;positive regulation of inositol phosphate biosynthetic process
• Cellular component: nucleus;cytoplasm;plasma membrane;integral component of plasma membrane;basolateral plasma membrane;apical plasma membrane;brush border membrane;receptor complex
• Molecular function: parathyroid hormone receptor activity;protein binding;G protein-coupled peptide receptor activity;peptide hormone binding;protein homodimerization activity;protein self-association