PTHLH
Chr 12ADparathyroid hormone like hormone
Also known as: BDE2, HHM, PLP, PTHR, PTHRP
The protein encoded by this gene is a neuroendocrine peptide that regulates cellular growth, development, and survival, and specifically controls endochondral bone development and epithelial-mesenchymal interactions during formation of mammary glands and teeth through its receptor PTH1R. Mutations cause brachydactyly type E2, characterized by shortened digits, and follow an autosomal dominant inheritance pattern. This gene is highly constrained against loss-of-function variants, indicating that such mutations are likely to have significant clinical consequences.
Primary Disease Associations & Inheritance
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
165 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 3 | 3 | 40 | 0 | 46 |
Likely Pathogenic | 3 | 4 | 3 | 0 | 10 |
VUS | 2 | 62 | 6 | 1 | 71 |
Likely Benign | 0 | 1 | 6 | 20 | 27 |
Benign | 0 | 0 | 4 | 0 | 4 |
Conflicting | — | 1 | |||
| Total | 8 | 70 | 59 | 21 | 159 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
PTHLH · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools