PTH2R

protein-coding

parathyroid hormone 2 receptor, the group of Parathyroid hormone receptors

Gene summary

The protein encoded by this gene is a member of the G-protein coupled receptor 2 family. This protein is a receptor for parathyroid hormone (PTH). This receptor is more selective in ligand recognition and has a more specific tissue distribution compared to parathyroid hormone receptor 1 (PTHR1). It is activated only by PTH and not by parathyroid hormone-like hormone (PTHLH) and is particularly abundant in brain and pancreas. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2013]

Previous symbols:

PTHR2

MANE transcript

NM_005048.4

Inheritance

—

ClinVar variants

P:1U:105B:14

Top phenotype

PTH2R-related disorder

gnomAD constraint

pLI —, LoF o/e 1.03

Max pathogenic AF

—

Genomic locus

chr2:208,359,714-208,854,503

External References & Databases

Ensembl (ENSG00000144407)

Transcript & Mutation Effects

hg38 • Region Span ~494.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PTH2R variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 102

PTH2R-related disorderTotal: 12

not providedTotal: 8

Syndromic intellectual disabilityTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005048.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	4 clinvar	2 clinvar	7
missense		1 clinvar	102 clinvar	6 clinvar		109
nonsense				2 clinvar		2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	1	105	12	2	120

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 10 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005048.4	RefSeq	NP_005039.1	13	MANE Select
ENST00000272847.7	Ensembl	ENSP00000272847.2	13	MANE Select
NM_001309516.2	RefSeq	NP_001296445.1	10	Standard
NM_001371905.1	RefSeq	NP_001358834.1	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Neuroactive ligand-receptor interaction - Homo sapiens (human)
GPCRs, Class B Secretin-like
Signaling by GPCR
Signal Transduction
G alpha (s) signalling events

Biological Process

cell surface receptor signaling pathway
G protein-coupled receptor signaling pathway
positive regulation of cold-induced thermogenesis

Molecular Function

parathyroid hormone receptor activity
protein binding
G protein-coupled peptide receptor activity
peptide hormone binding

Cellular Component

plasma membrane
integral component of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000272847
Coding exons: 13
Length: 494790
Individuals with no LoFs: 122560
Homozygous LoFs: 30
Heterozygous LoFs: 3158
Defined: 125748
p: 0.0128

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.774	333	296	1.13	0.0000151	3604
Missense (PolyPhen)		128	112.77	1.135		1437
Synonymous	0.282	105	109	0.966	0.00000587	1038
Loss of Function	-0.133	30	29.2	1.03	0.00000151	324

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0039	0.0039	notable
Latino/Admixed American	0.0091	0.0091	notable
Ashkenazi Jewish	0.0087	0.0086	notable
East Asian	0.00071	0.00071	rare
Finnish	0.0058	0.0058	notable
European (Non-Finnish)	0.021	0.021	notable
South Asian	0.0037	0.0036	notable
Other	0.013	0.013	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: This is a specific receptor for parathyroid hormone. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase. PTH2R may be responsible for PTH effects in a number of physiological systems. It may play a significant role in pancreatic function. PTH2R presence in neurons indicates that it may function as a neurotransmitter receptor (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.178

Intolerance Scores

LoFtool: 0.928
RVIS EVS: -0.66
RVIS percentile EVS: 15.91

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.517

Gene Damage Prediction

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