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Aliases for GREM1 Gene

Aliases for GREM1 Gene

  • Gremlin 1, DAN Family BMP Antagonist 2 3
  • Cysteine Knot Superfamily 1, BMP Antagonist 1 2 3 4
  • CKTSF1B1 3 4 6
  • Down-Regulated In Mos-Transformed Cells Protein 3 4
  • Cell Proliferation-Inducing Gene 2 Protein 3 4
  • Colorectal Adenoma And Carcinoma 1 2 3
  • DAN Domain Family Member 2 3 4
  • DAND2 3 4
  • IHG-2 3 4
  • DRM 3 4
  • Gremlin 1, Cysteine Knot Superfamily, Homolog (Xenopus Laevis) 2
  • Gremlin 1, Cysteine Knot Superfamily, Homolog 3
  • Increased In High Glucose Protein 2 4
  • Increased In High Glucose-2 3
  • Gremlin 1-Like Protein 3
  • Gremlin 1 2
  • Gremlin-1 3
  • C15DUPq 3
  • DUP15q 3
  • CRCS4 3
  • HMPS1 3
  • CRAC1 3
  • PIG2 3
  • HMPS 3
  • MPSH 3

External Ids for GREM1 Gene

Previous Symbols for GREM1 Gene

  • CKTSF1B1
  • CRAC1

Summaries for GREM1 Gene

Entrez Gene Summary for GREM1 Gene

  • 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]

GeneCards Summary for GREM1 Gene

GREM1 (Gremlin 1, DAN Family BMP Antagonist) is a Protein Coding gene. Diseases associated with GREM1 include colorectal adenoma and pauci-immune glomerulonephritis. Among its related pathways are Angiogenesis (CST) and TGF-beta/Smad Signaling. GO annotations related to this gene include cytokine activity and protein tyrosine kinase activator activity. An important paralog of this gene is GREM2.

UniProtKB/Swiss-Prot for GREM1 Gene

  • 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).

No data available for Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for GREM1 Gene

Genomics for GREM1 Gene

Genomic Location for GREM1 Gene

32,717,974 bp from pter
32,745,107 bp from pter
27,134 bases
Plus strand

Genomic View for GREM1 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for GREM1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for GREM1 Gene

Proteins for GREM1 Gene

  • Protein details for GREM1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Protein Accession:
    Secondary Accessions:
    • Q52LV3
    • Q8N914
    • Q8N936

    Protein attributes for GREM1 Gene

    184 amino acids
    Molecular mass:
    20697 Da
    Quaternary structure:
    • Interacts with SLIT1 and SLIT2 in a glycosylation-dependent manner.

    Alternative splice isoforms for GREM1 Gene


neXtProt entry for GREM1 Gene

Proteomics data for GREM1 Gene at MOPED

Post-translational modifications for GREM1 Gene

  • Modification sites at PhosphoSitePlus
  • Glycosylation at Asn42

Other Protein References for GREM1 Gene

No data available for DME Specific Peptides for GREM1 Gene

Domains for GREM1 Gene

Protein Domains for GREM1 Gene

Graphical View of Domain Structure for InterPro Entry



  • Contains 1 CTCK (C-terminal cystine knot-like) domain.:
    • O60565
  • Belongs to the DAN family.:
    • O60565
genes like me logo Genes that share domains with GREM1: view

No data available for Gene Families for GREM1 Gene

Function for GREM1 Gene

Molecular function for GREM1 Gene

UniProtKB/Swiss-Prot 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).
UniProtKB/Swiss-Prot Induction: By high glucose through TGFB1-mediated pathways in mesangial cell. Down-regulated in tumor cell lines.

LifeMap Function Summary for GREM1 Gene

During embryonic development, GREM1 as signaling molecule is secreted from the following cells
It affects the following cells:

Gene Ontology (GO) - Molecular Function for GREM1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005125 cytokine activity IEA --
GO:0005515 protein binding IPI 16545136
GO:0016015 morphogen activity ISS 9660951
GO:0030297 transmembrane receptor protein tyrosine kinase activator activity ISS --
GO:0036122 BMP binding ISS 9660951
genes like me logo Genes that share ontologies with GREM1: view
genes like me logo Genes that share phenotypes with GREM1: view

miRNA for GREM1 Gene

miRTarBase miRNAs that target GREM1

No data available for Enzyme Numbers (IUBMB) , Animal Models , Transcription Factor Targeting and HOMER Transcription for GREM1 Gene

Localization for GREM1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for GREM1 Gene


Subcellular locations from

Jensen Localization Image for GREM1 Gene COMPARTMENTS Subcellular localization image for GREM1 gene
Compartment Confidence
extracellular 4

Gene Ontology (GO) - Cellular Components for GREM1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005615 extracellular space NAS 9660951
GO:0009986 cell surface IEA --
genes like me logo Genes that share ontologies with GREM1: view

Pathways for GREM1 Gene

genes like me logo Genes that share pathways with GREM1: view

Pathways by source for GREM1 Gene

2 Cell Signaling Technology pathways for GREM1 Gene
1 BioSystems pathway for GREM1 Gene

Interacting Proteins for GREM1 Gene

Gene Ontology (GO) - Biological Process for GREM1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000902 cell morphogenesis IDA 16545136
GO:0001525 angiogenesis --
GO:0001658 branching involved in ureteric bud morphogenesis IEA --
GO:0002042 cell migration involved in sprouting angiogenesis ISS 9660951
GO:0002092 positive regulation of receptor internalization ISS 9660951
genes like me logo Genes that share ontologies with GREM1: view

Compounds for GREM1 Gene

(5) Novoseek inferred chemical compound relationships for GREM1 Gene

Compound -log(P) Hits PubMed IDs
cystine 52.9 2
cysteine 27.5 6
dexamethasone 4.49 1
glucose 0 5
tyrosine 0 2
genes like me logo Genes that share compounds with GREM1: view

Transcripts for GREM1 Gene

Unigene Clusters for GREM1 Gene

Gremlin 1, DAN family BMP antagonist:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for GREM1 Gene

ExUns: 1a · 1b ^ 2a · 2b ^ 3a · 3b · 3c · 3d
SP1: -
SP2: -

Relevant External Links for GREM1 Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for GREM1 Gene

mRNA expression in normal human tissues for GREM1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for GREM1 Gene

This gene is overexpressed in Esophagus - Gastroesophageal Junction (6.7).

Integrated Proteomics: protein expression from ProteomicsDB and MOPED for GREM1 Gene

SOURCE GeneReport for Unigene cluster for GREM1 Gene Hs.40098

mRNA Expression by UniProt/SwissProt for GREM1 Gene

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.
genes like me logo Genes that share expressions with GREM1: view

Orthologs for GREM1 Gene

This gene was present in the common ancestor of animals.

Orthologs for GREM1 Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia GREM1 35
  • 99.46 (n)
  • 100 (a)
GREM1 36
  • 100 (a)
(Bos Taurus)
Mammalia GREM1 35
  • 93.66 (n)
  • 100 (a)
GREM1 36
  • 100 (a)
(Canis familiaris)
Mammalia GREM1 35
  • 93.3 (n)
  • 99.46 (a)
GREM1 36
  • 99 (a)
(Mus musculus)
Mammalia Grem1 35
  • 89.31 (n)
  • 97.83 (a)
Grem1 16
Grem1 36
  • 98 (a)
(Monodelphis domestica)
Mammalia GREM1 36
  • 97 (a)
(Rattus norvegicus)
Mammalia Grem1 35
  • 90.22 (n)
  • 98.37 (a)
(Gallus gallus)
Aves GREM1 35
  • 77.11 (n)
  • 83.52 (a)
GREM1 36
  • 83 (a)
(Anolis carolinensis)
Reptilia -- 36
  • 77 (a)
-- 36
  • 32 (a)
-- 36
  • 46 (a)
African clawed frog
(Xenopus laevis)
Amphibia Cktsf1b1 35
tropical clawed frog
(Silurana tropicalis)
Amphibia grem1 35
  • 72.41 (n)
  • 83.33 (a)
(Danio rerio)
Actinopterygii GREM1 (2 of 3) 36
  • 60 (a)
grem1a 36
  • 62 (a)
grem1a 36
  • 62 (a)
LOC100005728 35
  • 73.68 (n)
  • 75.66 (a)
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP007994 35
  • 65.75 (n)
  • 63.3 (a)
(Caenorhabditis elegans)
Secernentea F35B12.10 36
  • 13 (a)
Species with no ortholog for GREM1:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • platypus (Ornithorhynchus anatinus)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for GREM1 Gene

Gene Tree for GREM1 (if available)
Gene Tree for GREM1 (if available)

Paralogs for GREM1 Gene

Paralogs for GREM1 Gene

Selected SIMAP similar genes for GREM1 Gene using alignment to 4 proteins:

genes like me logo Genes that share paralogs with GREM1: view

Variants for GREM1 Gene

Sequence variations from dbSNP and Humsavar for GREM1 Gene

SNP ID Clin Chr 15 pos Sequence Context AA Info Type MAF
rs10318 -- 32,733,778(+) CATAC(C/T)TATTA utr-variant-3-prime
rs1129456 -- 32,734,466(+) TGCTT(A/T)AATCA utr-variant-3-prime
rs1129488 -- 32,733,238(+) CAACA(A/T)TAAAG utr-variant-3-prime
rs1406389 -- 32,717,277(-) CTAAA(A/T)GACCG upstream-variant-2KB
rs1528734 -- 32,723,005(+) ATTTA(A/G)TGATA intron-variant

Structural Variations from Database of Genomic Variants (DGV) for GREM1 Gene

Variant ID Type Subtype PubMed ID
esv33337 CNV Gain+Loss 17666407
esv2422296 CNV Duplication 17116639
nsv483039 CNV Gain 15286789
nsv456785 CNV Gain 19166990
nsv832961 CNV Gain 17160897

Relevant External Links for GREM1 Gene

HapMap Linkage Disequilibrium report
Human Gene Mutation Database (HGMD)

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for GREM1 Gene

Disorders for GREM1 Gene


  • Polyposis syndrome, mixed hereditary 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. {ECO:0000269 PubMed:22561515}. Note=The disease is caused by mutations 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). {ECO:0000269 PubMed:22561515}.

(6) Novoseek inferred disease relationships for GREM1 Gene

Disease -log(P) Hits PubMed IDs
diabetic nephropathies 61.5 23
renal disease 28.6 5
gastric cancer 17 1
tumors 0 6
carcinoma 0 3

Relevant External Links for GREM1

Genetic Association Database (GAD)
Human Genome Epidemiology (HuGE) Navigator
genes like me logo Genes that share disorders with GREM1: view

Publications for GREM1 Gene

  1. The Xenopus dorsalizing factor Gremlin identifies a novel family of secreted proteins that antagonize BMP activities. (PMID: 9660951) Hsu D.R. … Harland R.M. (Mol. Cell 1998) 2 3 4 23
  2. IHG-2, a mesangial cell gene induced by high glucose, is human gremlin. Regulation by extracellular glucose concentration, cyclic mechanical strain, and transforming growth factor-beta1. (PMID: 10744662) McMahon R. … Brady H.R. (J. Biol. Chem. 2000) 3 4 23
  3. DRM/GREMLIN (CKTSF1B1) maps to human chromosome 15 and is highly expressed in adult and fetal brain. (PMID: 10894942) Topol L.Z. … Blair D.G. (Cytogenet. Cell Genet. 2000) 3 4 23
  4. A GREM1 gene variant associates with diabetic nephropathy. (PMID: 20150533) McKnight A.J. … Maxwell A.P. (J. Am. Soc. Nephrol. 2010) 3 23 48
  5. Evaluation of gremlin 1 (GREM1) as a candidate susceptibility gene for albuminuria-related traits in Mexican Americans with type 2 diabetes mellitus. (PMID: 19577778) Thameem F. … Abboud H.E. (Metab. Clin. Exp. 2009) 3 23 48

Products for GREM1 Gene

Sources for GREM1 Gene

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