BMP6

Chr 6AD

bone morphogenetic protein 6

Also known as: IO, VGR, VGR1

NCBI Gene: 654ENSG00000153162UniProt: P22004

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. This protein regulates a wide range of biological processes including iron homeostasis, fat and bone development, and ovulation. Differential expression of this gene may be associated with progression of breast and prostate cancer. Mutations in this gene may be associated with iron overload in human patients. [provided by RefSeq, Jul 2016]

Primary Disease Associations & Inheritance

{Iron overload, susceptibility to}MIM #620121
AD
159
ClinVar variants
31
Pathogenic / LP
0.76
pLI score
0
Active trials
Clinical Summary— BMP6
🧬
Gene-Disease Validity (ClinGen)
iron overload, susceptibility to · ADLimited

Limited evidence — not for standalone diagnostic reporting

⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.76) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
31 Pathogenic / Likely Pathogenic· 96 VUS of 159 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.41LOEUF
pLI 0.759
Z-score 3.59
OE 0.18 (0.09–0.41)
Moderately constrained

More LoF-intolerant than ~75% of genes

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.
-1.03Z-score
OE missense 1.18 (1.07–1.29)
315 obs / 267.5 exp
Tolerant

Tolerant to missense variation

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.0.18 (0.09–0.41)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.18 (1.07–1.29)
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.1.08
0≤1.21.6
LoF obs/exp: 4 / 22.3Missense obs/exp: 315 / 267.5Syn Z: -0.66

ClinVar Variant Classifications

159 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic27
Likely Pathogenic4
VUS96
Likely Benign20
Benign11
Conflicting1
27
Pathogenic
4
Likely Pathogenic
96
VUS
20
Likely Benign
11
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
27
0
27
Likely Pathogenic
0
1
3
0
4
VUS
0
91
5
0
96
Likely Benign
0
7
3
10
20
Benign
0
3
1
7
11
Conflicting
—1
Total01023917159

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

View in ClinVar →

Protein Context — Lollipop Plot

BMP6 · 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

{Iron overload, susceptibility to}

MIM #620121

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Landscape of pathogenic mutations in premature ovarian insufficiency.
Ke H et al.·Nat Med
2023
H3K27me3-modulated Hofbauer cell BMP2 signalling enhancement compensates for shallow trophoblast invasion in preeclampsia.
Deng J et al.·EBioMedicine
2023
Osteokines in Nonalcoholic Fatty Liver Disease.
Vachliotis ID et al.·Curr Obes Rep
2024Review
Role of the BMP6 protein in breast cancer and other types of cancer.
García Muro AM et al.·Growth Factors
2021Review
Hepcidin in hepatocellular carcinoma.
Joachim JH et al.·Br J Cancer
2022Review
Bone morphogenetic proteins.
Wozney JM·Prog Growth Factor Res
1989Review
Cellular crosstalk in organotypic vasculature: mechanisms of diabetic cardiorenal complications and SGLT2i responses.
Wang W et al.·Cardiovasc Diabetol
2025Functional
Genetic Abnormalities of Oocyte Maturation: Mechanisms and Clinical Implications.
Baldini GM et al.·Int J Mol Sci
2024Review
Bone morphogenic proteins in iron homeostasis.
Xiao X et al.·Bone
2020Review
FAM20A mutations and transcriptome analyses of dental pulp tissues of enamel renal syndrome.
Wang SK et al.·Int Endod J
2023
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