BMP4 Gene: Bone Morphogenetic Protein 4 - Function, Disease Associations, and Expression
A comprehensive overview of the BMP4 gene, including its genomic context, protein function, associated diseases, tissue expression, and mutation landscape.
Gene Information Card
| Symbol | BMP4 |
|---|---|
| Full Name | Bone Morphogenetic Protein 4 |
| Gene Type | Protein Coding |
| Chromosomal Location | 14q22.2 |
| NCBI Gene ID | 652 ncbi.nlm.nih.gov/gene/652 |
| Ensembl ID | ENSG00000125378 |
| UniProt ID | P12644 |
| OMIM ID | 112262 |
| HGNC ID | 1071 |
| Aliases | BMP2B, BMP2B1, ZYME |
Description
The BMP4 gene encodes bone morphogenetic protein 4, a secreted ligand of the transforming growth factor-beta (TGF-beta) superfamily. BMP4 plays a critical role in embryonic development, particularly in mesoderm formation, limb development, neural crest cell differentiation, and bone and cartilage formation. It functions by binding to serine/threonine kinase receptors (BMPR1A, BMPR1B, BMPR2), leading to the phosphorylation of SMAD proteins (SMAD1/5/8) which then translocate to the nucleus to regulate gene transcription. BMP4 is also involved in postnatal processes such as bone remodeling, wound healing, and the regulation of stem cell fate.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Microphthalmia, Syndromic 6 (MCOPS6) | Heterozygous mutations in BMP4, including missense and frameshift variants, are associated with this condition. The mechanism is often haploinsufficiency or dominant-negative effects, leading to reduced BMP4 signaling during eye development. | OMIM: 607932; ClinVar |
| Polydactyly, Postaxial, Type A1 (PDA1) | Specific missense mutations in BMP4 have been linked to postaxial polydactyly. The mechanism is thought to involve altered BMP4 signaling during limb bud development, affecting digit formation. | OMIM: 617527; ClinVar |
| Orofacial Clefts | Variants in BMP4 have been associated with non-syndromic cleft lip with or without cleft palate. Disruption of BMP4 signaling in the developing facial processes can impair fusion and growth. | ClinVar; Literature (e.g., Suzuki et al., 2009) |
| Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) | BMP4 mutations are implicated in CAKUT, including renal hypodysplasia. BMP4 is crucial for ureteric bud development and nephrogenesis; loss of function disrupts these processes. | OMIM: 112262; ClinVar |
| Colorectal Cancer | BMP4 is often hypermethylated and silenced in colorectal cancer. Loss of BMP4 expression can lead to increased Wnt signaling and tumor progression, acting as a tumor suppressor in this context. | COSMIC; Literature (e.g., Kim et al., 2002) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 24.5 | High |
| Kidney | 18.2 | High |
| Small Intestine | 15.1 | Medium |
| Stomach | 12.8 | Medium |
| Colon | 11.9 | Medium |
| Liver | 8.5 | Low |
| Brain | 6.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (Lung Carcinoma) | 22.3 | High expression observed in this cell line. |
| HepG2 (Hepatocellular Carcinoma) | 15.7 | Moderate expression detected. |
| MCF7 (Breast Adenocarcinoma) | 9.8 | Low to moderate expression. |
| HeLa (Cervical Carcinoma) | 7.1 | Low expression. |
| K562 (Chronic Myelogenous Leukemia) | 3.2 | Very low expression. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.542C>T (p.Pro181Leu) | Missense | Rare | Associated with Microphthalmia; likely disrupts protein folding or receptor binding. |
| c.823C>T (p.Arg275Trp) | Missense | Rare | Linked to Polydactyly; may alter signaling specificity or affinity. |
| c.1040delC (p.Pro347LeufsTer5) | Frameshift | Rare | Causes premature truncation, leading to loss of function and haploinsufficiency. |
| c.361G>A (p.Gly121Ser) | Missense | Rare | Reported in CAKUT; likely affects ligand-receptor interaction. |
| Promoter Hypermethylation | Epigenetic | Frequent in Colorectal Cancer | Silences BMP4 expression, contributing to tumorigenesis. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations, including frameshift, nonsense, and some missense variants, reduce BMP4 protein levels or activity. This leads to haploinsufficiency, which is a primary mechanism for developmental disorders like Microphthalmia and CAKUT. In cancer, epigenetic silencing also results in loss of function.
Gain of Function (GOF)
Gain-of-function mutations in BMP4 are less common but have been suggested in certain contexts. Some missense mutations might increase receptor binding affinity or alter the duration of signaling, potentially contributing to ectopic bone formation or other hyperactive signaling phenotypes.
Dominant Negative (DN)
Certain missense mutations can exert a dominant-negative effect. The mutant BMP4 protein can dimerize with wild-type BMP4 or compete for receptor binding, thereby inhibiting the function of the normal protein. This mechanism is particularly relevant for Microphthalmia, where a single mutant allele can disrupt the signaling of the wild-type allele.
View complete mutation data：
Gene Ontology (GO)
| • BMP receptor binding | • Cytokine activity |
| • Growth factor activity | • Protein heterodimerization activity |
| • Transforming growth factor beta receptor binding | • Extracellular space |
| • Extracellular region | • Regulation of DNA-templated transcription |
| • SMAD protein signal transduction | • BMP signaling pathway |
| • Cell differentiation | • Bone mineralization |
| • Embryonic skeletal system morphogenesis | • Positive regulation of cell proliferation |
| • Negative regulation of cell proliferation |
Pathways
• BMP signaling pathway
• TGF-beta signaling pathway
• Cytokine-cytokine receptor interaction
• Signaling pathways regulating pluripotency of stem cells
• Hedgehog signaling pathway (cross-talk)
Protein Summary
BMP4 is synthesized as a large precursor protein that undergoes proteolytic cleavage to form a mature, biologically active C-terminal domain. The mature protein forms disulfide-linked homodimers or heterodimers with other BMPs (e.g., BMP2, BMP7). It binds to a complex of type I (BMPR1A/ALK3, BMPR1B/ALK6) and type II (BMPR2, ACVR2A, ACVR2B) serine/threonine kinase receptors. Upon ligand binding, the type II receptor phosphorylates the type I receptor, which then phosphorylates receptor-regulated SMADs (R-SMADs: SMAD1, SMAD5, SMAD8). Phosphorylated R-SMADs complex with SMAD4 and translocate to the nucleus to regulate target gene expression. BMP4 activity is tightly regulated by secreted antagonists such as Noggin, Chordin, and Follistatin, which bind to BMP4 and prevent receptor interaction.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| BMP4 Knockout HEK293 Cell Line | EDJ-KQ368 | Human | 652 | Details Get a Quote |
| BMP4 Knockout A-549 Cell Line | EDJ-KQ18559 | Human | 652 | Details Get a Quote |
| BMP4 Knockout HCT 116 Cell Line | EDJ-KQ18560 | Human | 652 | Details Get a Quote |
| BMP4 Knockout HeLa Cell Line | EDJ-KQ18561 | Human | 652 | Details Get a Quote |
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