Human Gene GREM1 (ENST00000651154.1_4) from GENCODE V47lift37
Description: gremlin 1, DAN family BMP antagonist, transcript variant 1 (from RefSeq NM_013372.7)Gencode Transcript: ENST00000651154.1_4Gencode Gene: ENSG00000166923.12_14Transcript (Including UTRs) Position: hg19 chr15:33,010,205-33,037,307 Size: 27,103 Total Exon Count: 2 Strand: +Coding Region Position: hg19 chr15:33,022,892-33,023,446 Size: 555 Coding Exon Count: 1
Data last updated at UCSC: 2024-08-22 23:36:26
Sequence and Links to Tools and Databases
Comments and Description Text from UniProtKB
ID: GREM1_HUMAN DESCRIPTION: RecName: Full=Gremlin-1; AltName: Full=Cell proliferation-inducing gene 2 protein; AltName: Full=Cysteine knot superfamily 1, BMP antagonist 1; AltName: Full=DAN domain family member 2; AltName: Full=Down-regulated in Mos-transformed cells protein; AltName: Full=Increased in high glucose protein 2; Short=IHG-2; Flags: Precursor;FUNCTION: 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. Acts as inhibitor of monocyte chemotaxis (By similarity).SUBUNIT: Interacts with SLIT1 and SLIT2 in a glycosylation- dependent manner (By similarity).INTERACTION: Q04917:YWHAH; NbExp=5; IntAct=EBI-944395, EBI-306940;SUBCELLULAR LOCATION: Secreted (Probable).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 ISEMFs, but also at very high levels in epithelial cells (predominantly colonocytes), with expression extending most of the way up the sides of the crypt. Weakly expressed in brain, ovary, prostate, pancreas and skeletal muscle. In brain found in the region localized around the internal capsule in the large subcortical nuclei, including caudate, putamen, substantia nigra, thalamus and subthalamus. Predominantly expressed in normal cells including neurons, astrocytes and fibroblasts.INDUCTION: By high glucose through TGFB1-mediated pathways in mesangial cell. Down-regulated in tumor cell lines.DISEASE: Defects in GREM1 are the cause of polyposis syndrome, mixed hereditary type 1 (HMPS1) [MIM:601228] . 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. Note=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).SIMILARITY: Belongs to the DAN family.SIMILARITY: Contains 1 CTCK (C-terminal cystine knot-like) domain.
Primer design for this transcript
MalaCards Disease Associations
MalaCards Gene Search: GREM1
Diseases sorted by gene-association score: hereditary mixed polyposis syndrome * (261), hereditary mixed polyposis syndrome 1 * (71), sclerosteosis (12), pauci-immune glomerulonephritis (10), anisometropia (9), renal hypoplasia (8), loeys-dietz syndrome (8), norrie disease (6), suppression amblyopia (6), idiopathic interstitial pneumonia (5), asphyxiating thoracic dystrophy (5), hereditary colorectal cancer (5), astigmatism (4), synostosis (3)* = Manually curated disease association
Comparative Toxicogenomics Database (CTD)
The following chemicals interact with this gene
D017638
Asbestos, Crocidolite
D001564
Benzo(a)pyrene
D013749
Tetrachlorodibenzodioxin
C032668
1-nitropyrene
C111118
2',3,3',4',5-pentachloro-4-hydroxybiphenyl
C404910
2,2-bis(4-hydroxyphenyl)-1,1,1-trichloroethane
C548651
2-(1'H-indolo-3'-carbonyl)thiazole-4-carboxylic acid methyl ester
C093973
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
C009505
4,4'-diaminodiphenylmethane
C459179
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide
more ... click here to view the complete list
Common Gene Haplotype Alleles
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Microarray Expression Data
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mRNA Secondary Structure of 3' and 5' UTRs
Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
Protein Domain and Structure Information
InterPro Domains: Graphical view of domain structure IPR006207 - Cys_knot_CIPR004133 - DANIPR017159 - Gremlin_precursorPfam Domains: PF03045 - DAN domainModBase Predicted Comparative 3D Structure on O60565 The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.
Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0005125 cytokine activityGO:0005515 protein bindingGO:0016015 morphogen activityGO:0030297 transmembrane receptor protein tyrosine kinase activator activityGO:0036122 BMP bindingGO:0042803 protein homodimerization activityGO:0043184 vascular endothelial growth factor receptor 2 bindingGO:0048018 receptor agonist activityBiological Process: GO:0000902 cell morphogenesisGO:0001525 angiogenesisGO:0001658 branching involved in ureteric bud morphogenesisGO:0002042 cell migration involved in sprouting angiogenesisGO:0002092 positive regulation of receptor internalizationGO:0002689 negative regulation of leukocyte chemotaxisGO:0003257 positive regulation of transcription from RNA polymerase II promoter involved in myocardial precursor cell differentiationGO:0003337 mesenchymal to epithelial transition involved in metanephros morphogenesisGO:0006915 apoptotic processGO:0007165 signal transductionGO:0007171 activation of transmembrane receptor protein tyrosine kinase activityGO:0007267 cell-cell signalingGO:0008284 positive regulation of cell proliferationGO:0009887 animal organ morphogenesisGO:0009954 proximal/distal pattern formationGO:0010717 regulation of epithelial to mesenchymal transitionGO:0030199 collagen fibril organizationGO:0030308 negative regulation of cell growthGO:0030326 embryonic limb morphogenesisGO:0030502 negative regulation of bone mineralizationGO:0030514 negative regulation of BMP signaling pathwayGO:0032331 negative regulation of chondrocyte differentiationGO:0033689 negative regulation of osteoblast proliferationGO:0043066 negative regulation of apoptotic processGO:0043542 endothelial cell migrationGO:0045668 negative regulation of osteoblast differentiationGO:0045766 positive regulation of angiogenesisGO:0045892 negative regulation of transcription, DNA-templatedGO:0045893 positive regulation of transcription, DNA-templatedGO:0045944 positive regulation of transcription from RNA polymerase II promoterGO:0046851 negative regulation of bone remodelingGO:0048263 determination of dorsal identityGO:0051092 positive regulation of NF-kappaB transcription factor activityGO:0051893 regulation of focal adhesion assemblyGO:0051973 positive regulation of telomerase activityGO:0060173 limb developmentGO:0060394 negative regulation of pathway-restricted SMAD protein phosphorylationGO:0060676 ureteric bud formationGO:0061098 positive regulation of protein tyrosine kinase activityGO:0090027 negative regulation of monocyte chemotaxisGO:0090090 negative regulation of canonical Wnt signaling pathwayGO:0090190 positive regulation of branching involved in ureteric bud morphogenesisGO:0090191 negative regulation of branching involved in ureteric bud morphogenesisGO:0090291 negative regulation of osteoclast proliferationGO:1900086 positive regulation of peptidyl-tyrosine autophosphorylationGO:1900155 negative regulation of bone trabecula formationGO:1900158 negative regulation of bone mineralization involved in bone maturationGO:1901224 positive regulation of NIK/NF-kappaB signalingGO:2000273 positive regulation of receptor activityGO:2000727 positive regulation of cardiac muscle cell differentiationGO:0032872 regulation of stress-activated MAPK cascadeGO:0072331 signal transduction by p53 class mediatorCellular Component: GO:0005576 extracellular regionGO:0005615 extracellular spaceGO:0009986 cell surface
Descriptions from all associated GenBank mRNAs
LF211837 - JP 2014500723-A/19340: Polycomb-Associated Non-Coding RNAs.LF205829 - JP 2014500723-A/13332: Polycomb-Associated Non-Coding RNAs.AK095741 - Homo sapiens cDNA FLJ38422 fis, clone FEBRA2011356.AK312265 - Homo sapiens cDNA, FLJ92561, Homo sapiens cysteine knot superfamily 1, BMP antagonist 1 (CKTSF1B1), mRNA.AK095890 - Homo sapiens cDNA FLJ38571 fis, clone HCHON2006770, highly similar to Homo sapiens gremlin mRNA.AK095972 - Homo sapiens cDNA FLJ38653 fis, clone HHDPC2009114, highly similar to Gremlin-1 precursor.AY232290 - Homo sapiens proliferation-inducing gene 2 mRNA, complete cds.AF154054 - Homo sapiens DRM (DRM) mRNA, complete cds.LF348625 - JP 2014500723-A/156128: Polycomb-Associated Non-Coding RNAs.AF110137 - Homo sapiens gremlin mRNA, complete cds.BC093778 - Homo sapiens gremlin 1, cysteine knot superfamily, homolog (Xenopus laevis), mRNA (cDNA clone MGC:120813 IMAGE:7939623), complete cds.BC101611 - Homo sapiens gremlin 1, cysteine knot superfamily, homolog (Xenopus laevis), mRNA (cDNA clone MGC:126660 IMAGE:8069117), complete cds.CU686886 - Synthetic construct Homo sapiens gateway clone IMAGE:100022598 5' read GREM1 mRNA.HQ448400 - Synthetic construct Homo sapiens clone IMAGE:100071827; CCSB013800_01 gremlin 1, cysteine knot superfamily, homolog (Xenopus laevis) (GREM1) gene, encodes complete protein.AF045800 - Homo sapiens gremlin mRNA, complete cds.BC069525 - Homo sapiens gremlin 1, cysteine knot superfamily, homolog (Xenopus laevis), mRNA (cDNA clone MGC:96899 IMAGE:7262108), complete cds.LF348624 - JP 2014500723-A/156127: Polycomb-Associated Non-Coding RNAs.LF348623 - JP 2014500723-A/156126: Polycomb-Associated Non-Coding RNAs.LF348622 - JP 2014500723-A/156125: Polycomb-Associated Non-Coding RNAs.DQ572664 - Homo sapiens piRNA piR-40776, complete sequence.LF348621 - JP 2014500723-A/156124: Polycomb-Associated Non-Coding RNAs.LF348620 - JP 2014500723-A/156123: Polycomb-Associated Non-Coding RNAs.JD320878 - Sequence 301902 from Patent EP1572962.JD090132 - Sequence 71156 from Patent EP1572962.JD535380 - Sequence 516404 from Patent EP1572962.JD371844 - Sequence 352868 from Patent EP1572962.JD144887 - Sequence 125911 from Patent EP1572962.JD036813 - Sequence 17837 from Patent EP1572962.JD432905 - Sequence 413929 from Patent EP1572962.LF348619 - JP 2014500723-A/156122: Polycomb-Associated Non-Coding RNAs.JD173167 - Sequence 154191 from Patent EP1572962.JD503737 - Sequence 484761 from Patent EP1572962.LF348618 - JP 2014500723-A/156121: Polycomb-Associated Non-Coding RNAs.JD495001 - Sequence 476025 from Patent EP1572962.JD182210 - Sequence 163234 from Patent EP1572962.JD328550 - Sequence 309574 from Patent EP1572962.JD167872 - Sequence 148896 from Patent EP1572962.LF348617 - JP 2014500723-A/156120: Polycomb-Associated Non-Coding RNAs.JD304814 - Sequence 285838 from Patent EP1572962.AL359060 - Homo sapiens mRNA full length insert cDNA clone EUROIMAGE 324951.LF348616 - JP 2014500723-A/156119: Polycomb-Associated Non-Coding RNAs.JD381964 - Sequence 362988 from Patent EP1572962.JD147147 - Sequence 128171 from Patent EP1572962.JD244259 - Sequence 225283 from Patent EP1572962.LF348615 - JP 2014500723-A/156118: Polycomb-Associated Non-Coding RNAs.JD154747 - Sequence 135771 from Patent EP1572962.LF348614 - JP 2014500723-A/156117: Polycomb-Associated Non-Coding RNAs.JD488944 - Sequence 469968 from Patent EP1572962.JD492577 - Sequence 473601 from Patent EP1572962.JD324067 - Sequence 305091 from Patent EP1572962.JD308856 - Sequence 289880 from Patent EP1572962.JD193397 - Sequence 174421 from Patent EP1572962.LF348613 - JP 2014500723-A/156116: Polycomb-Associated Non-Coding RNAs.AL359059 - Homo sapiens mRNA full length insert cDNA clone EUROIMAGE 265368.LF348612 - JP 2014500723-A/156115: Polycomb-Associated Non-Coding RNAs.JD499307 - Sequence 480331 from Patent EP1572962.JD442272 - Sequence 423296 from Patent EP1572962.LF348611 - JP 2014500723-A/156114: Polycomb-Associated Non-Coding RNAs.JD237372 - Sequence 218396 from Patent EP1572962.JD323348 - Sequence 304372 from Patent EP1572962.LF348610 - JP 2014500723-A/156113: Polycomb-Associated Non-Coding RNAs.JD046906 - Sequence 27930 from Patent EP1572962.LF348609 - JP 2014500723-A/156112: Polycomb-Associated Non-Coding RNAs.JD271240 - Sequence 252264 from Patent EP1572962.JD053197 - Sequence 34221 from Patent EP1572962.LF348608 - JP 2014500723-A/156111: Polycomb-Associated Non-Coding RNAs.JD315787 - Sequence 296811 from Patent EP1572962.JD291704 - Sequence 272728 from Patent EP1572962.JD078061 - Sequence 59085 from Patent EP1572962.JD220539 - Sequence 201563 from Patent EP1572962.JD442034 - Sequence 423058 from Patent EP1572962.JD202824 - Sequence 183848 from Patent EP1572962.JD343201 - Sequence 324225 from Patent EP1572962.LF348607 - JP 2014500723-A/156110: Polycomb-Associated Non-Coding RNAs.JD048354 - Sequence 29378 from Patent EP1572962.JD339979 - Sequence 321003 from Patent EP1572962.LF348606 - JP 2014500723-A/156109: Polycomb-Associated Non-Coding RNAs.JD106507 - Sequence 87531 from Patent EP1572962.JD224892 - Sequence 205916 from Patent EP1572962.LF348605 - JP 2014500723-A/156108: Polycomb-Associated Non-Coding RNAs.JD499176 - Sequence 480200 from Patent EP1572962.JD540766 - Sequence 521790 from Patent EP1572962.LF348604 - JP 2014500723-A/156107: Polycomb-Associated Non-Coding RNAs.JD286282 - Sequence 267306 from Patent EP1572962.JD300526 - Sequence 281550 from Patent EP1572962.LF348603 - JP 2014500723-A/156106: Polycomb-Associated Non-Coding RNAs.JD299212 - Sequence 280236 from Patent EP1572962.LF348602 - JP 2014500723-A/156105: Polycomb-Associated Non-Coding RNAs.JD269075 - Sequence 250099 from Patent EP1572962.JD323906 - Sequence 304930 from Patent EP1572962.JD404107 - Sequence 385131 from Patent EP1572962.JD563704 - Sequence 544728 from Patent EP1572962.LF348601 - JP 2014500723-A/156104: Polycomb-Associated Non-Coding RNAs.JD312856 - Sequence 293880 from Patent EP1572962.JD417616 - Sequence 398640 from Patent EP1572962.JD258406 - Sequence 239430 from Patent EP1572962.JD411851 - Sequence 392875 from Patent EP1572962.JD294128 - Sequence 275152 from Patent EP1572962.JD472420 - Sequence 453444 from Patent EP1572962.JD472421 - Sequence 453445 from Patent EP1572962.MA584202 - JP 2018138019-A/156128: Polycomb-Associated Non-Coding RNAs.MA584201 - JP 2018138019-A/156127: Polycomb-Associated Non-Coding RNAs.MA584200 - JP 2018138019-A/156126: Polycomb-Associated Non-Coding RNAs.MA584199 - JP 2018138019-A/156125: Polycomb-Associated Non-Coding RNAs.MA584198 - JP 2018138019-A/156124: Polycomb-Associated Non-Coding RNAs.MA584197 - JP 2018138019-A/156123: Polycomb-Associated Non-Coding RNAs.MA584196 - JP 2018138019-A/156122: Polycomb-Associated Non-Coding RNAs.MA584195 - JP 2018138019-A/156121: Polycomb-Associated Non-Coding RNAs.MA584194 - JP 2018138019-A/156120: Polycomb-Associated Non-Coding RNAs.MA584193 - JP 2018138019-A/156119: Polycomb-Associated Non-Coding RNAs.MA584192 - JP 2018138019-A/156118: Polycomb-Associated Non-Coding RNAs.MA584191 - JP 2018138019-A/156117: Polycomb-Associated Non-Coding RNAs.MA584190 - JP 2018138019-A/156116: Polycomb-Associated Non-Coding RNAs.MA584189 - JP 2018138019-A/156115: Polycomb-Associated Non-Coding RNAs.MA584188 - JP 2018138019-A/156114: Polycomb-Associated Non-Coding RNAs.MA584187 - JP 2018138019-A/156113: Polycomb-Associated Non-Coding RNAs.MA584186 - JP 2018138019-A/156112: Polycomb-Associated Non-Coding RNAs.MA584185 - JP 2018138019-A/156111: Polycomb-Associated Non-Coding RNAs.MA584184 - JP 2018138019-A/156110: Polycomb-Associated Non-Coding RNAs.MA584183 - JP 2018138019-A/156109: Polycomb-Associated Non-Coding RNAs.MA584182 - JP 2018138019-A/156108: Polycomb-Associated Non-Coding RNAs.MA584181 - JP 2018138019-A/156107: Polycomb-Associated Non-Coding RNAs.MA584180 - JP 2018138019-A/156106: Polycomb-Associated Non-Coding RNAs.MA584179 - JP 2018138019-A/156105: Polycomb-Associated Non-Coding RNAs.MA584178 - JP 2018138019-A/156104: Polycomb-Associated Non-Coding RNAs.MA447414 - JP 2018138019-A/19340: Polycomb-Associated Non-Coding RNAs.MA441406 - JP 2018138019-A/13332: Polycomb-Associated Non-Coding RNAs.JD199431 - Sequence 180455 from Patent EP1572962.JD558648 - Sequence 539672 from Patent EP1572962.JD452162 - Sequence 433186 from Patent EP1572962.JD452163 - Sequence 433187 from Patent EP1572962.AK057064 - Homo sapiens cDNA FLJ32502 fis, clone SKNSH2000550.JD542594 - Sequence 523618 from Patent EP1572962.JD440885 - Sequence 421909 from Patent EP1572962.JD205216 - Sequence 186240 from Patent EP1572962.JD175647 - Sequence 156671 from Patent EP1572962.JD331868 - Sequence 312892 from Patent EP1572962.JD182657 - Sequence 163681 from Patent EP1572962.JD084194 - Sequence 65218 from Patent EP1572962.JD561444 - Sequence 542468 from Patent EP1572962.JD282011 - Sequence 263035 from Patent EP1572962.JD230123 - Sequence 211147 from Patent EP1572962.JD269715 - Sequence 250739 from Patent EP1572962.
Other Names for This Gene
Alternate Gene Symbols: CKTSF1B1, DAND2, DRM, GREM1_HUMAN, NM_013372, O60565, PIG2, Q52LV3, Q8N914, Q8N936, uc328sod.1, uc328sod.2UCSC ID: ENST00000651154.1_4RefSeq Accession: NM_013372.7 Protein: O60565
(aka GREM1_HUMAN)
Gene Model Information
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for a detailed description of the fields of the table above.
Methods, Credits, and Use Restrictions
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for details on how this gene model was made and data restrictions if any.
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
