PTH2

protein-coding

parathyroid hormone 2, the group of Receptor ligands

Gene summary

This gene encodes the precursor of a peptide hormone that shares sequence similarity with the parathyroid hormone. This gene is expressed in various regions of the brain where it plays a role in the release of pituitary hormones, anxiety and nociception. The encoded precursor protein is proteolytically processed to generate the biologically active neuropeptide. [provided by RefSeq, Jul 2015]

MANE transcript

NM_178449.4

Inheritance

—

ClinVar variants

U:23

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.81

Max pathogenic AF

—

Genomic locus

chr19:49,422,419-49,423,441

External References & Databases

Ensembl (ENSG00000142538)

Transcript & Mutation Effects

hg38 • Region Span ~1.0 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 PTH2 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 23

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_178449.4. 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						0
missense			23 clinvar			23
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	23	0	0	23

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 4 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_178449.4	RefSeq	NP_848544.1	2	MANE Select
ENST00000270631.2	Ensembl	ENSP00000270631.1	2	MANE Select
ENST00000923239.1	Ensembl	ENSP00000593298.1	2	Standard
ENST00000923239.2	Ensembl	ENSP00000593298.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Signaling by GPCR
Signal Transduction
G alpha (s) signalling events
Class B/2 (Secretin family receptors)
GPCR ligand binding

Biological Process

G protein-coupled receptor signaling pathway
neuropeptide signaling pathway

Cellular Component

extracellular region

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000270631
Coding exons: 2
Length: 1028
Individuals with no LoFs: 124780
Homozygous LoFs: 0
Heterozygous LoFs: 27
Defined: 124807
p: 0.000108

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.440	61	52.1	1.17	0.00000237	576
Missense (PolyPhen)		18	15.803	1.139		162
Synonymous	1.37	20	29.4	0.680	0.00000134	253
Loss of Function	-0.963	3	1.66	1.81	7.16e-8	21

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.00026	0.00022	rare
South Asian	0	0.0	absent
Other	0.00019	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays a role as a potent and selective agonist of PTH2R resulting in adenyl cyclase activation and intracellular calcium levels elevation. Induces protein kinase C beta activation, recruitment of beta-arrestin and PTH2R internalization. May inhibit cell proliferation via its action on PTH2R activation. Neuropeptide which may also have a role in spermatogenesis. May activate nociceptors and nociceptive circuits. {ECO:0000269|PubMed:11861531, ECO:0000269|PubMed:12559132, ECO:0000269|PubMed:12754053, ECO:0000269|PubMed:14988434}.;

Recessive Scores

pRec: 0.135

Intolerance Scores

LoFtool: 0.343
RVIS EVS: 0.64
RVIS percentile EVS: 83.63

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0591

Gene Damage Prediction

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