GREM1 Gene: Gremlin 1, DAN Family BMP Antagonist
Key regulator of bone morphogenetic protein signaling in development and disease
Gene Information Card
| Symbol | GREM1 |
|---|---|
| Full Name | Gremlin 1, DAN Family BMP Antagonist |
| Gene Type | Protein-coding |
| Chromosomal Location | 15q13.3 |
| NCBI Gene ID | 26585 ncbi.nlm.nih.gov/gene/26585 |
| Ensembl ID | ENSG00000166923 |
| UniProt ID | O60565 |
| OMIM ID | 603054 |
| HGNC ID | 4499 |
| Aliases | CKTSF1B1, DAND2, DRM, GREM1, gremlin 1 |
Description
GREM1 encodes gremlin 1, a secreted antagonist of bone morphogenetic proteins (BMPs). It belongs to the DAN family of BMP antagonists and plays critical roles in embryonic development, tissue patterning, and organogenesis. GREM1 inhibits BMP2, BMP4, and BMP7 by binding directly and preventing receptor interaction. Dysregulation of GREM1 is implicated in hereditary mixed polyposis syndrome, fibrosis, and various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary Mixed Polyposis Syndrome (HMPS) | GREM1 duplication or overexpression leads to BMP signaling inhibition, causing aberrant crypt proliferation and polyp formation | OMIM #601228; ClinVar |
| Colorectal Cancer | Increased GREM1 expression promotes tumor growth by suppressing BMP-mediated differentiation | COSMIC; NCBI PubMed |
| Pulmonary Fibrosis | GREM1 upregulation in lung fibroblasts enhances TGF-β signaling and extracellular matrix deposition | UniProt; NCBI PubMed |
| Renal Fibrosis | Overexpression of GREM1 in kidney tubules contributes to epithelial-mesenchymal transition and fibrosis | OMIM; NCBI PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 12.5 | Medium |
| Lung | 8.3 | Medium |
| Placenta | 6.1 | Low |
| Small Intestine | 4.2 | Low |
| Colon | 3.8 | Low |
| Brain | 1.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.0 | Embryonic kidney cell line |
| A549 | 9.5 | Lung carcinoma cell line |
| HCT 116 | 6.2 | Colorectal carcinoma cell line |
| MCF7 | 2.1 | Breast cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.−126_−124dupGGC | Promoter duplication | Rare (HMPS families) | Increased GREM1 expression |
| c.1A>G (p.Met1?) | Start loss | <0.01% | Loss of protein function |
| c.103C>T (p.Arg35Cys) | Missense | <0.01% | Unknown effect |
Mutation functional classification
Loss of Function (LOF)
Start loss mutations (e.g., p.Met1?) abolish protein translation, leading to reduced BMP antagonism.
Gain of Function (GOF)
Promoter duplications (e.g., c.−126_−124dupGGC) increase GREM1 expression, enhancing BMP inhibition and contributing to polyposis.
Dominant Negative (DN)
No confirmed dominant-negative mutations reported in GREM1.
View complete mutation data：
Gene Ontology (GO)
Pathways
• BMP signaling pathway (Reactome: R-HSA-201451)
• TGF-beta signaling pathway (KEGG: hsa04350)
• Signaling by BMP (Reactome: R-HSA-201451)
Protein Summary
Gremlin 1 is a 184-amino-acid secreted glycoprotein containing a cysteine-knot domain characteristic of the DAN family. It forms homodimers and binds BMP2, BMP4, and BMP7 with high affinity, preventing their interaction with type I and type II BMP receptors. The protein is involved in limb development, kidney morphogenesis, and lung branching. Post-translational modifications include N-glycosylation at Asn42. Altered gremlin 1 levels are associated with fibrotic diseases and tumor progression.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GREM1 Knockout HEK293 Cell Line | EDJ-KQ381 | Human | 26585 | Details Get a Quote |
| GREM1 Knockout A-549 Cell Line | EDJ-KQ18586 | Human | 26585 | Details Get a Quote |
| GREM1 Knockout HeLa Cell Line | EDJ-KQ18587 | Human | 26585 | Details Get a Quote |
| GREM1 Knockout HCT 116 Cell Line | EDJ-KQ72897 | Human | 26585 | Details Get a Quote |
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