• Gene id: 26585

Gene Summary

• Gene Symbol: GREM1   Gene   UCSC   Ensembl
• Aliases: C15DUPq, CKTSF1B1, CRAC1, CRCS4, DAND2, DRM, DUP15q, GREMLIN, HMPS, HMPS1, IHG-2, MPSH, PIG2
• Gene name: gremlin 1, DAN family BMP antagonist
• Alternate names: gremlin-1, DAN domain family member 2, cell proliferation-inducing gene 2 protein, colorectal adenoma and carcinoma 1, cysteine knot superfamily 1, BMP antagonist 1, down-regulated in Mos-transformed cells protein, gremlin 1, cysteine knot superfamily, homolog, ,
• Gene location: 15q13.3 (32718003: 32745105)     Exons: 3     NC_000015.10
• Gene summary(Entrez): 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 bel
• OMIM: 606092

SNPs

rs3743104

Strand:    Allele origin:   Allele change:   Mutation type: snv

NC_000015.10   g.32731784A>C
NC_000015.10   g.32731784A>G
NC_000015.10   g.32731784A>T
NC_000015.9   g.33023985A>C
NC_000015.9   g.33023985A>G
NC_000015.9   g.33023985A>T
NG_033791.1   g.18781A>C
NG_033791.1   g.18781A>G
NG_033791.1   g.18781A>T
NG_033791.2   g.18781A>C

Protein Summary

• Protein general information: O60565  
  • Name: Gremlin 1 (Cell proliferation inducing gene 2 protein) (Cysteine knot superfamily 1, BMP antagonist 1) (DAN domain family member 2) (Down regulated in Mos transformed cells protein) (Increased in high glucose protein 2) (IHG 2)
  • Length: 184  
  • Mass: 20697
  • Tissue specificity: Highly expressed in small intestine, fetal brain and colon. Expression is restricted to intestinal subepithelial myofibroblasts (ISEMFs) at the crypt base. In subjects with HMPS1, by contrast, GREM1 is expressed, not only in basal ISEM
• Sequence:

  MSRTAYTVGALLLLLGTLLPAAEGKKKGSQGAIPPPDKAQHNDSEQTQSPQQPGSRNRGRGQGRGTAMPGEEVLE
  SSQEALHVTERKYLKRDWCKTQPLKQTIHEEGCNSRTIINRFCYGQCNSFYIPRHIRKEEGSFQSCSFCKPKKFT
  TMMVTLNCPELQPPTKKKRVTRVKQCRCISIDLD

• Structural information:
  • Protein Domains: (94..18-)
    (/note="CTCK"-)
  • Interpro: IPR006207  IPR029034  IPR004133  IPR017159  
  • PDB: 5AEJ
  • PDBsum: 5AEJ
  • STRING: ENSP00000478319
• Other Databases: GeneCards:  GREM1  Malacards:  GREM1

Gene ontology

GO accession	Term name	Evidence code	Go category
GO:0038098	sequestering of BMP from receptor via BMP binding	IBA	biological process
GO:0036122	BMP binding	IBA	molecular function
GO:0009887	animal organ morphogenesis	IBA	biological process
GO:0005615	extracellular space	IBA	cellular component
GO:0048018	receptor ligand activity	IBA	molecular function
GO:0036122	BMP binding	IDA	molecular function
GO:0042803	protein homodimerization activity	IPI	molecular function
GO:0045668	negative regulation of osteoblast differentiation	IMP	biological process
GO:0005515	protein binding	IPI	molecular function
GO:0030514	negative regulation of BMP signaling pathway	IMP	biological process
GO:0005615	extracellular space	IEA	cellular component
GO:0005125	cytokine activity	IEA	molecular function
GO:0005576	extracellular region	IEA	cellular component
GO:0043066	negative regulation of apoptotic process	IMP	biological process
GO:0032331	negative regulation of chondrocyte differentiation	IMP	biological process
GO:0060173	limb development	IMP	biological process
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005615	extracellular space	IEA	cellular component
GO:0030308	negative regulation of cell growth	IEA	biological process
GO:0090027	negative regulation of monocyte chemotaxis	IEA	biological process
GO:0001525	angiogenesis	IEA	biological process
GO:0003257	positive regulation of transcription from RNA polymerase II promoter involved in myocardial precursor cell differentiation	IEA	biological process
GO:0005615	extracellular space	IEA	cellular component
GO:0007165	signal transduction	IEA	biological process
GO:0007267	cell-cell signaling	IEA	biological process
GO:0009887	animal organ morphogenesis	IEA	biological process
GO:0030297	transmembrane receptor protein tyrosine kinase activator activity	IEA	molecular function
GO:0030326	embryonic limb morphogenesis	IEA	biological process
GO:0043542	endothelial cell migration	IEA	biological process
GO:0045892	negative regulation of transcription, DNA-templated	IEA	biological process
GO:0045893	positive regulation of transcription, DNA-templated	IEA	biological process
GO:0051092	positive regulation of NF-kappaB transcription factor activity	IEA	biological process
GO:2000727	positive regulation of cardiac muscle cell differentiation	IEA	biological process
GO:0002689	negative regulation of leukocyte chemotaxis	IEA	biological process
GO:0006915	apoptotic process	IEA	biological process
GO:0009986	cell surface	IEA	cellular component
GO:0045766	positive regulation of angiogenesis	IEA	biological process
GO:0002042	cell migration involved in sprouting angiogenesis	IEA	biological process
GO:0002092	positive regulation of receptor internalization	IEA	biological process
GO:0003337	mesenchymal to epithelial transition involved in metanephros morphogenesis	IEA	biological process
GO:0009954	proximal/distal pattern formation	IEA	biological process
GO:0009986	cell surface	IEA	cellular component
GO:0030514	negative regulation of BMP signaling pathway	IEA	biological process
GO:0043184	vascular endothelial growth factor receptor 2 binding	IEA	molecular function
GO:0045766	positive regulation of angiogenesis	IEA	biological process
GO:0045944	positive regulation of transcription by RNA polymerase II	IEA	biological process
GO:0048018	receptor ligand activity	IEA	molecular function
GO:0051893	regulation of focal adhesion assembly	IEA	biological process
GO:0060676	ureteric bud formation	IEA	biological process
GO:0061098	positive regulation of protein tyrosine kinase activity	IEA	biological process
GO:0090190	positive regulation of branching involved in ureteric bud morphogenesis	IEA	biological process
GO:1900086	positive regulation of peptidyl-tyrosine autophosphorylation	IEA	biological process
GO:1901224	positive regulation of NIK/NF-kappaB signaling	IEA	biological process
GO:2000273	positive regulation of signaling receptor activity	IEA	biological process
GO:0062023	collagen-containing extracellular matrix	HDA	cellular component
GO:0016015	morphogen activity	ISS	molecular function
GO:0030297	transmembrane receptor protein tyrosine kinase activator activity	ISS	molecular function
GO:0036122	BMP binding	ISS	molecular function
GO:0043184	vascular endothelial growth factor receptor 2 binding	ISS	molecular function
GO:0048018	receptor ligand activity	ISS	molecular function
GO:0000902	cell morphogenesis	IDA	biological process
GO:0008284	positive regulation of cell population proliferation	IDA	biological process
GO:0060394	negative regulation of pathway-restricted SMAD protein phosphorylation	IDA	biological process
GO:0003257	positive regulation of transcription from RNA polymerase II promoter involved in myocardial precursor cell differentiation	ISS	biological process
GO:0005615	extracellular space	NAS	cellular component
GO:0007165	signal transduction	ISS	biological process
GO:0030502	negative regulation of bone mineralization	IMP	biological process
GO:0032872	regulation of stress-activated MAPK cascade	ISS	NOT|biological process
GO:0033689	negative regulation of osteoblast proliferation	IMP	biological process
GO:0046851	negative regulation of bone remodeling	IMP	biological process
GO:0072331	signal transduction by p53 class mediator	ISS	NOT|biological process
GO:0090027	negative regulation of monocyte chemotaxis	ISS	biological process
GO:1900158	negative regulation of bone mineralization involved in bone maturation	IMP	biological process
GO:2000727	positive regulation of cardiac muscle cell differentiation	ISS	biological process
GO:0030514	negative regulation of BMP signaling pathway	IDA	biological process
GO:0051973	positive regulation of telomerase activity	IDA	biological process
GO:0090090	negative regulation of canonical Wnt signaling pathway	IDA	biological process
GO:0002042	cell migration involved in sprouting angiogenesis	ISS	biological process
GO:0002092	positive regulation of receptor internalization	ISS	biological process
GO:0030199	collagen fibril organization	IMP	biological process
GO:0045944	positive regulation of transcription by RNA polymerase II	ISS	biological process
GO:0048263	determination of dorsal identity	IMP	biological process
GO:0090291	negative regulation of osteoclast proliferation	IMP	biological process
GO:1900086	positive regulation of peptidyl-tyrosine autophosphorylation	ISS	biological process
GO:1900155	negative regulation of bone trabecula formation	IMP	biological process
GO:2000273	positive regulation of signaling receptor activity	ISS	biological process
GO:0062023	collagen-containing extracellular matrix	HDA	colocalizes with
GO:0005576	extracellular region	IEA	cellular component
GO:0007171	activation of transmembrane receptor protein tyrosine kinase activity	IEA	biological process
GO:0007171	activation of transmembrane receptor protein tyrosine kinase activity	IEA	biological process
GO:0010717	regulation of epithelial to mesenchymal transition	IMP	biological process
GO:0030514	negative regulation of BMP signaling pathway	IMP	biological process

KEGG pathways

Pathway id	Pathway name
hsa04350	TGF-beta signaling pathway

Diseases

Associated diseases	References
Hypospadias	MIK: 25108383
Spermatogenic defects	MIK: 31037746

PubMed references

PMID	Condition	Mutation	Ethnicity	Population details	Infertility_type	Associated_genes
31037746	Spermatogenic defects			16 (1 control, 15 cases)	Male infertility	GSE6023 analyzed using GEO2R
25108383	Hypospadias	rs3743104		1,006 boys who underwent surgery for hypospadias and 5,486 individuals (2,390 males and 3,096 females)	Male infertility	GWAS