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Aliases for GREM1 Gene

Aliases for GREM1 Gene

  • Gremlin 1, DAN Family BMP Antagonist 2 3 5
  • Cysteine Knot Superfamily 1, BMP Antagonist 1 2 3 4
  • 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
  • CKTSF1B1 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
  • GREMLIN 3
  • DUP15q 3
  • CRCS4 3
  • HMPS1 3
  • CRAC1 3
  • PIG2 3
  • HMPS 3
  • MPSH 3

External Ids for GREM1 Gene

Previous HGNC Symbols for GREM1 Gene

  • CKTSF1B1
  • CRAC1

Previous GeneCards Identifiers for GREM1 Gene

  • GC15P030728
  • GC15P030797
  • GC15P033010
  • GC15P009872

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 Hereditary Mixed Polyposis Syndrome and Hereditary Mixed Polyposis Syndrome 1. Among its related pathways are Angiogenesis (CST) and Wnt / Hedgehog / Notch. GO annotations related to this gene include cytokine activity and BMP binding. 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 CIViC summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for GREM1 Gene

Genomics for GREM1 Gene

Regulatory Elements for GREM1 Gene

Enhancers for GREM1 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH15G032860 1.5 FANTOM5 Ensembl ENCODE dbSUPER 12.8 +144.0 143963 2.4 L3MBTL2 GFI1B SIN3A MAX CEBPG EBF1 ZIC2 OSR2 JUND SMARCA4 GREM1 ENSG00000212415 SCG5 LOC105370757 ENSG00000254912 PIR38190 PIR33047
GH15G032681 1.6 FANTOM5 Ensembl ENCODE dbSUPER 11.6 -32.7 -32706 6.8 FOXA2 SAP130 MAX RAD21 ZNF644 YY1 PRDM10 FOS MAFK NFE2L2 GREM1 SCG5 ENSG00000212415 GC15P032691 LOC105370757
GH15G032854 1.5 FANTOM5 Ensembl ENCODE dbSUPER 11.9 +138.4 138375 3.0 CTCF JUN TEAD4 SIN3A ZNF644 TEAD3 ZSCAN5C SCRT2 FOS NFE2L2 GREM1 ENSG00000212415 PIR38190 PIR33047
GH15G032818 1.7 FANTOM5 Ensembl ENCODE dbSUPER 10.5 +101.4 101424 1.8 PKNOX1 ZNF133 FEZF1 GLIS2 FOS TSHZ1 ZNF518A ZNF610 ZNF585B PBX2 ENSG00000212415 GREM1 PIR43820 PIR40350
GH15G032827 1.3 FANTOM5 ENCODE dbSUPER 13 +112.0 111971 4.3 PKNOX1 INSM2 FEZF1 ZEB2 EP300 OSR2 ZNF121 JUND BCL6B SCRT2 GREM1 LOC105370757 SCG5 ENSG00000212415 ARHGAP11A PIR43820 ENSG00000259392
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around GREM1 on UCSC Golden Path with GeneCards custom track

Promoters for GREM1 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000074619 -74 201 MXI1 SUZ12 POLR2A TEAD4 SIN3A EZH2

Genomic Location for GREM1 Gene

Chromosome:
15
Start:
32,717,974 bp from pter
End:
32,745,107 bp from pter
Size:
27,134 bases
Orientation:
Plus strand

Genomic View for GREM1 Gene

Genes around GREM1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
GREM1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
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:
    O60565-GREM1_HUMAN
    Recommended name:
    Gremlin-1
    Protein Accession:
    O60565
    Secondary Accessions:
    • Q52LV3
    • Q8N914
    • Q8N936

    Protein attributes for GREM1 Gene

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

    Three dimensional structures from OCA and Proteopedia for GREM1 Gene

    Alternative splice isoforms for GREM1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for GREM1 Gene

Post-translational modifications for GREM1 Gene

  • Glycosylation at posLast=4242
  • Modification sites at PhosphoSitePlus

Other Protein References for GREM1 Gene

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for GREM1 (GREM1)

Protein Products

No data available for DME Specific Peptides for GREM1 Gene

Domains & Families for GREM1 Gene

Gene Families for GREM1 Gene

Protein Domains for GREM1 Gene

Graphical View of Domain Structure for InterPro Entry

O60565

UniProtKB/Swiss-Prot:

GREM1_HUMAN :
  • Belongs to the DAN family.
Family:
  • Belongs to the DAN family.
genes like me logo Genes that share domains with GREM1: view

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

Animal Models for GREM1 Gene

MGI Knock Outs for GREM1:

Animal Model Products

Inhibitory RNA Products

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for GREM1 Gene

Localization for GREM1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for GREM1 Gene

Secreted.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for GREM1 gene
Compartment Confidence
extracellular 5
nucleus 2
plasma membrane 1
cytoskeleton 1
cytosol 1

Gene Ontology (GO) - Cellular Components for GREM1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IEA --
GO:0005615 extracellular space NAS 9660951
GO:0009986 cell surface IEA --
genes like me logo Genes that share ontologies with GREM1: view

Pathways & Interactions 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

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 IEA --
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

No data available for SIGNOR curated interactions for GREM1 Gene

Drugs & Compounds for GREM1 Gene

(4) Drugs for GREM1 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(1) Additional Compounds for GREM1 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
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:

Inhibitory RNA Products

Clone Products

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

ExUns: 1a · 1b ^ 2a · 2b ^ 3a · 3b · 3c · 3d
SP1: -
SP2: -
SP3:

Relevant External Links for GREM1 Gene

GeneLoc Exon Structure for
GREM1
ECgene alternative splicing isoforms for
GREM1

Expression for GREM1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE 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 (x6.7).

Protein differential expression in normal tissues from HIPED for GREM1 Gene

This gene is overexpressed in Amniocyte (27.2), Gallbladder (23.9), and Bone marrow mesenchymal stem cell (8.9).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for GREM1 Gene



NURSA nuclear receptor signaling pathways regulating expression of GREM1 Gene:

GREM1

SOURCE GeneReport for Unigene cluster for GREM1 Gene:

Hs.40098

mRNA Expression by UniProt/SwissProt for GREM1 Gene:

O60565-GREM1_HUMAN
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.

Evidence on tissue expression from TISSUES for GREM1 Gene

  • Intestine(4.6)
  • Skin(4.4)
  • Liver(4.2)
  • Nervous system(3.4)
  • Lung(2.8)
  • Stomach(2.8)
  • Gall bladder(2.3)
  • Blood(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for GREM1 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • digestive
Organs:
Abdomen:
  • intestine
  • large intestine
  • small intestine
  • stomach
Pelvis:
  • rectum
genes like me logo Genes that share expression patterns with GREM1: view

Primer Products

No data available for Protein tissue co-expression partners for GREM1 Gene

Orthologs for GREM1 Gene

This gene was present in the common ancestor of animals.

Orthologs for GREM1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia GREM1 34 35
  • 99.46 (n)
oppossum
(Monodelphis domestica)
Mammalia GREM1 35
  • 97 (a)
OneToOne
cow
(Bos Taurus)
Mammalia GREM1 34 35
  • 93.66 (n)
dog
(Canis familiaris)
Mammalia GREM1 34 35
  • 93.3 (n)
rat
(Rattus norvegicus)
Mammalia Grem1 34
  • 90.22 (n)
mouse
(Mus musculus)
Mammalia Grem1 34 16 35
  • 89.31 (n)
chicken
(Gallus gallus)
Aves GREM1 34 35
  • 77.11 (n)
lizard
(Anolis carolinensis)
Reptilia -- 35
  • 77 (a)
OneToMany
-- 35
  • 46 (a)
OneToMany
-- 35
  • 32 (a)
OneToMany
tropical clawed frog
(Silurana tropicalis)
Amphibia grem1 34
  • 72.41 (n)
African clawed frog
(Xenopus laevis)
Amphibia Cktsf1b1 34
zebrafish
(Danio rerio)
Actinopterygii LOC100005728 34
  • 73.68 (n)
grem1a 35 35
  • 62 (a)
OneToMany
GREM1 (2 of 3) 35
  • 60 (a)
OneToMany
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP007994 34
  • 65.75 (n)
worm
(Caenorhabditis elegans)
Secernentea F35B12.10 35
  • 13 (a)
OneToMany
Species where no ortholog for GREM1 was found in the sources mined by GeneCards:
  • 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

ENSEMBL:
Gene Tree for GREM1 (if available)
TreeFam:
Gene Tree for GREM1 (if available)

Paralogs for GREM1 Gene

Paralogs for GREM1 Gene

(2) 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
rs111262341 Likely benign 32,730,793(+) TCCCC(C/G)CGCCA intron-variant, reference, missense
rs146429140 Likely benign 32,720,217(+) ACCCA(C/T)GCTCT intron-variant, upstream-variant-2KB
rs183257520 Likely benign 32,729,893(+) TGAGA(A/G)TAAGT intron-variant
rs768670395 Likely benign 32,719,675(+) ACTGA(G/T)TAAAA intron-variant, upstream-variant-2KB
rs78005246 Uncertain significance 32,730,999(+) ACCAT(C/T)CACGA reference, synonymous-codon

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

Variant ID Type Subtype PubMed ID
dgv4456n54 CNV gain 21841781
esv2422296 CNV duplication 17116639
esv33337 CNV gain+loss 17666407
esv3892661 CNV gain 25118596
nsv1052620 CNV gain 25217958
nsv456785 CNV gain 19166990
nsv483039 CNV gain 15286789
nsv568913 CNV gain 21841781
nsv568916 CNV loss 21841781
nsv832961 CNV gain 17160897

Variation tolerance for GREM1 Gene

Residual Variation Intolerance Score: 36.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.51; 11.16% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for GREM1 Gene

Human Gene Mutation Database (HGMD)
GREM1
SNPedia medical, phenotypic, and genealogical associations of SNPs for
GREM1

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

Disorders for GREM1 Gene

MalaCards: The human disease database

(16) MalaCards diseases for GREM1 Gene - From: GeneTests, Orphanet, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
hereditary mixed polyposis syndrome
  • hmps
hereditary mixed polyposis syndrome 1
  • colorectal adenoma and carcinoma 1
anisometropia
pauci-immune glomerulonephritis
sclerosteosis
  • cortical hyperostosis with syndactyly
- elite association - COSMIC cancer census association via MalaCards
Search GREM1 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

GREM1_HUMAN
  • 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}.

Relevant External Links for GREM1

Genetic Association Database (GAD)
GREM1
Human Genome Epidemiology (HuGE) Navigator
GREM1
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
GREM1
genes like me logo Genes that share disorders with GREM1: view

No data available for Genatlas for GREM1 Gene

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 22 64
  2. Hereditary mixed polyposis syndrome is caused by a 40-kb upstream duplication that leads to increased and ectopic expression of the BMP antagonist GREM1. (PMID: 22561515) Jaeger E. … Tomlinson I. (Nat. Genet. 2012) 2 3 4 64
  3. A GREM1 gene variant associates with diabetic nephropathy. (PMID: 20150533) McKnight A.J. … Maxwell A.P. (J. Am. Soc. Nephrol. 2010) 3 22 46 64
  4. 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 22 46 64
  5. 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 22 64

Products for GREM1 Gene

Sources for GREM1 Gene

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