BMP1
Chr 8ARbone morphogenetic protein 1
Also known as: OI13, PCOLC, PCP, PCP2, TLD
This metalloprotease processes extracellular matrix precursor proteins including procollagens I, II, and III and activates lysyl oxidase, which is essential for collagen cross-linking and proper bone and cartilage formation. Biallelic mutations cause autosomal recessive osteogenesis imperfecta type XIII, characterized by bone fragility and skeletal deformities. The gene is highly constrained against loss-of-function variation (LOEUF 0.456), indicating that complete loss of protein function is likely not tolerated.
Primary Disease Associations & Inheritance
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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
600 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 | 4 | 2 | 33 | 0 | 39 |
Likely Pathogenic | 7 | 0 | 5 | 0 | 12 |
VUS | 1 | 107 | 16 | 2 | 126 |
Likely Benign | 0 | 10 | 124 | 236 | 370 |
Benign | 0 | 0 | 21 | 4 | 25 |
Conflicting | — | 11 | |||
| Total | 12 | 119 | 199 | 242 | 583 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
BMP1 · 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