PTH2R

Chr 2

parathyroid hormone 2 receptor

This G-protein coupled receptor specifically binds parathyroid hormone and activates adenylyl cyclase, with abundant expression in brain and pancreas where it may function in neurotransmission and pancreatic regulation. Mutations cause primary failure of tooth eruption, an autosomal recessive disorder characterized by failure of teeth to erupt despite normal tooth and root development. The gene shows very low constraint against loss-of-function variants.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.39
Clinical SummaryPTH2R
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.39LOEUF
pLI 0.000
Z-score -0.13
OE 1.03 (0.771.39)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.77Z-score
OE missense 1.13 (1.031.23)
333 obs / 295.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.03 (0.771.39)
00.351.4
Missense OE1.13 (1.031.23)
00.61.4
Synonymous OE0.97
01.21.6
LoF obs/exp: 30 / 29.2Missense obs/exp: 333 / 295.5Syn Z: 0.28
DN
0.74top 25%
GOF
0.81top 10%
LOF
0.2968th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PTH2R · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →