GREM1

This gene encodes a member of the BMP (bone morphogenic protein) antagonist family. Like BMPs, BMP antagonists contain cystine knots and typically form homo- and heterodimers. The CAN (cerberus and dan) subfamily of BMP antagonists, to which this gene belongs, is characterized by a C-terminal cystine knot with an eight-membered ring. The antagonistic effect of the secreted glycosylated protein encoded by this gene is likely due to its direct binding to BMP proteins. As an antagonist of BMP, this gene may play a role in regulating organogenesis, body patterning, and tissue differentiation. In mouse, this protein has been shown to relay the sonic hedgehog (SHH) signal from the polarizing region to the apical ectodermal ridge during limb bud outgrowth. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2010]

Gremlin 1, DAN Family BMP Antagonist

Cytokine that may play an important role during carcinogenesis and metanephric kidney organogenesis, as a BMP antagonist required for early limb outgrowth and patterning in maintaining the FGF4-SHH feedback loop. Down-regulates the BMP4 signaling in a dose-dependent manner (By similarity).

Antagonist of BMP2; inhibits BMP2-mediated differentiation of osteoblasts (in vitro) (PubMed:27036124).

Acts as inhibitor of monocyte chemotaxis. Can inhibit the growth or viability of normal cells but not transformed cells when is overexpressed (By similarity).

Animal organ morphogenesis Source: GO_Central
Apoptotic process Source: Ensembl
Cell-cell signaling Source: Ensembl
Cell migration involved in sprouting angiogenesis Source: BHF-UCL
Cell morphogenesis Source: BHF-UCL
Collagen fibril organization Source: BHF-UCL
Determination of dorsal identity Source: BHF-UCL
Embryonic limb morphogenesis Source: Ensembl
Limb development Source: AgBase
Mesenchymal to epithelial transition involved in metanephros morphogenesis Source: Ensembl
Negative regulation of apoptotic process Source: AgBase
Negative regulation of BMP signaling pathway Source: BHF-UCL
Negative regulation of bone mineralization Source: BHF-UCL
Negative regulation of bone mineralization involved in bone maturation Source: BHF-UCL
Negative regulation of bone remodeling Source: BHF-UCL
Negative regulation of bone trabecula formation Source: BHF-UCL
Negative regulation of canonical Wnt signaling pathway Source: BHF-UCL
Negative regulation of cell growth Source: Ensembl
Negative regulation of chondrocyte differentiation Source: AgBase
Negative regulation of monocyte chemotaxis Source: BHF-UCL
Negative regulation of osteoblast differentiation Source: UniProtKB
Negative regulation of osteoblast proliferation Source: BHF-UCL
Negative regulation of osteoclast proliferation Source: BHF-UCL
Negative regulation of pathway-restricted SMAD protein phosphorylation Source: BHF-UCL
Negative regulation of transcription, DNA-templated Source: Ensembl
Positive regulation of angiogenesis Source: Ensembl
Positive regulation of branching involved in ureteric bud morphogenesis Source: Ensembl
Positive regulation of cardiac muscle cell differentiation Source: BHF-UCL
Positive regulation of cell population proliferation Source: BHF-UCL
Positive regulation of NF-kappaB transcription factor activity Source: Ensembl
Positive regulation of NIK/NF-kappaB signaling Source: Ensembl
Positive regulation of peptidyl-tyrosine autophosphorylation Source: BHF-UCL
Positive regulation of receptor internalization Source: BHF-UCL
Positive regulation of signaling receptor activity Source: BHF-UCL
Positive regulation of telomerase activity Source: BHF-UCL
Positive regulation of transcription by RNA polymerase II Source: BHF-UCL
Positive regulation of transcription from RNA polymerase II promoter involved in myocardial precursor cell differentiation Source: BHF-UCL
Proximal/distal pattern formation Source: Ensembl
Regulation of epithelial to mesenchymal transition Source: UniProtKB
Regulation of focal adhesion assembly Source: Ensembl
Requestering of BMP from receptor via BMP binding Source: GO_Central
Rignal transduction Source: BHF-UCL
Ureteric bud formation Source: Ensembl

Secreted

Polyposis syndrome, mixed hereditary 1 (HMPS1):
The disease is caused by variants affecting the gene represented in this entry. HMPS1 is caused by a duplication spanning the 3' end of the SCG5 gene and a region upstream of the GREM1 locus. This duplication is associated with increased allele-specific GREM1 expression that may cause reduced bone morphogenetic protein (BMP) pathway activity. This mechanism also underlies tumorigenesis in juvenile polyposis of the large bowel (PubMed:22561515). A disease characterized by apparent autosomal dominant inheritance of multiple types of colorectal polyp, with colorectal carcinoma occurring in a high proportion of affected individuals. Patients can develop polyps of multiple and mixed morphologies, including serrated lesions, Peutz-Jeghers polyps, juvenile polyps, conventional adenomas and colorectal carcinoma in the absence of any identifiable extra-colonic features.