BMP5

Chr 6

bone morphogenetic protein 5

NCBI Gene: 653ENSG00000112175UniProt: P22003

This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer, which plays a role in bone and cartilage development. Polymorphisms in this gene may be associated with osteoarthritis in human patients. This gene is differentially regulated in multiple human cancers. This gene encodes distinct protein isoforms that may be similarly proteolytically processed. [provided by RefSeq, Jul 2016]

97
ClinVar variants
9
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— BMP5
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
9 Pathogenic / Likely Pathogenic· 71 VUS of 97 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.70LOEUF
pLI 0.001
Z-score 2.64
OE 0.40 (0.24–0.70)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.63Z-score
OE missense 0.89 (0.80–0.99)
228 obs / 256.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.40 (0.24–0.70)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.89 (0.80–0.99)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.00
0≤1.21.6
LoF obs/exp: 9 / 22.5Missense obs/exp: 228 / 256.2Syn Z: 0.02

ClinVar Variant Classifications

97 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6
Likely Pathogenic3
VUS71
Likely Benign9
Benign8
6
Pathogenic
3
Likely Pathogenic
71
VUS
9
Likely Benign
8
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
6
0
6
Likely Pathogenic
2
0
1
0
3
VUS
0
65
6
0
71
Likely Benign
0
2
4
3
9
Benign
0
3
1
4
8
Total27018797

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

BMP5 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Bone morphogenetic proteins.
Wozney JM·Prog Growth Factor Res
1989Review
Erythroferrone inhibits the induction of hepcidin by BMP6.
Arezes J et al.·Blood
2018
MiR-32 promotes tumorigenesis of colorectal cancer by targeting BMP5.
Chen E et al.·Biomed Pharmacother
2018
TRP-related gene signatures predict survival and the immune microenvironment in rectal cancer: a comprehensive bioinformatics study.
Wang X et al.·Front Immunol
2025
Establishing and Characterizing the Molecular Profiles, Cellular Features, and Clinical Utility of a Patient-Derived Xenograft Model Using Benign Prostatic Tissues.
Polasko AL et al.·Lab Invest
2024Functional
Hemochromatosis Proteins Hemojuvelin and Homeostatic Iron Regulator in Bone Morphogenetic Protein-Mediated Hepcidin Regulation and Iron Homeostasis.
Xiao X et al.·Am J Hematol
2025
The concept of onychodermis containing onychofibroblasts has histological (microanatomical), immunohistochemical as well as molecular basis.
Shim J et al.·J Cutan Pathol
2024Review
Compound heterozygosity for two variants in BMP5 in human skeletal dysostosis with atrioventricular septal defect.
Gregersen PA et al.·Clin Genet
2025Case report
Upregulated bone morphogenetic protein 5 enhances proliferation and epithelial-mesenchymal transition process in benign prostatic hyperplasia via BMP/Smad signaling pathway.
Liu D et al.·Prostate
2021
Genomic analysis of benign prostatic hyperplasia implicates cellular re-landscaping in disease pathogenesis.
Middleton LW et al.·JCI Insight
2019
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools