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 glyc... See more...

Aliases for GREM2 Gene

Aliases for GREM2 Gene

  • Gremlin 2, DAN Family BMP Antagonist 2 3 5
  • Protein Related To DAN And Cerberus 2 3 4
  • Cysteine Knot Superfamily 1, BMP Antagonist 2 3 4
  • DAN Domain Family Member 3 3 4
  • Gremlin-2 3 4
  • CKTSF1B2 3 4
  • DAND3 3 4
  • PRDC 3 4
  • Gremlin 2, Cysteine Knot Superfamily, Homolog (Xenopus Laevis) 2
  • Gremlin 2, Cysteine Knot Superfamily, Homolog 3
  • Gremlin 2 2
  • STHAG9 3

External Ids for GREM2 Gene

Previous GeneCards Identifiers for GREM2 Gene

  • GC01M236979
  • GC01M238719
  • GC01M240652
  • GC01M211110

Summaries for GREM2 Gene

Entrez Gene Summary for GREM2 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. [provided by RefSeq, Jul 2008]

GeneCards Summary for GREM2 Gene

GREM2 (Gremlin 2, DAN Family BMP Antagonist) is a Protein Coding gene. Diseases associated with GREM2 include Tooth Agenesis, Selective, 9 and Tooth Agenesis. Among its related pathways are Signaling by BMP and Signaling by GPCR. Gene Ontology (GO) annotations related to this gene include protein homodimerization activity and heparin binding. An important paralog of this gene is GREM1.

UniProtKB/Swiss-Prot Summary for GREM2 Gene

  • Cytokine that inhibits the activity of BMP2 and BMP4 in a dose-dependent manner, and thereby modulates signaling by BMP family members. Contributes to the regulation of embryonic morphogenesis via BMP family members. Antagonizes BMP4-induced suppression of progesterone production in granulosa cells.

Additional gene information for GREM2 Gene

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for GREM2 Gene

Genomics for GREM2 Gene

GeneHancer (GH) Regulatory Elements for GREM2 Gene

Promoters and enhancers for GREM2 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH01J240611 Promoter/Enhancer 1.8 EPDnew Ensembl ENCODE CraniofacialAtlas 500.7 +1.2 1171 3.4 ZNF10 ZBTB26 ZEB1 ATF2 MXI1 ZBTB17 YY1 POLR2A ZBTB11 REPIN1 GREM2 HSALNG0011916
GH01J240575 Enhancer 0.8 ENCODE CraniofacialAtlas 12.2 +35.8 35808 1.3 EP300 GABPA POLR2H GATA3 IKZF1 NFATC3 BHLHE40 TBX21 MTA2 IKZF2 GREM2 ENSG00000231440 ENSG00000226014 lnc-RGS7-3
GH01J240399 Enhancer 1.1 FANTOM5 Ensembl ENCODE 8 +212.7 212671 2 ZSCAN5C JUND FOS ZIC2 REST ZNF510 OSR2 FOSL2 CEBPB FOSL1 ENSG00000233519 GREM2 RF00994-108 FMN2
GH01J240306 Enhancer 1.1 FANTOM5 Ensembl ENCODE 6.8 +302.4 302401 7.2 ZSCAN5C TCF12 FOS ZNF10 EP300 WT1 BRCA1 FOSL2 CEBPB RCOR1 FMN2 GREM2 ENSG00000252317 piR-50852-015
GH01J240233 Enhancer 1.1 FANTOM5 Ensembl ENCODE dbSUPER 4.2 +376.2 376243 4.6 FOS ATF2 GATA3 USF1 EZH2 JUND RCOR1 GATA2 YY1 POLR2A GREM2 piR-50852-015 lnc-GREM2-12 FMN2
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around GREM2 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for GREM2

Top Transcription factor binding sites by QIAGEN in the GREM2 gene promoter:
  • CUTL1
  • FOXO1
  • FOXO1a
  • GATA-6
  • HOXA3
  • IRF-2
  • RORalpha1
  • S8
  • SEF-1 (1)
  • USF1

Genomic Locations for GREM2 Gene

Genomic Locations for GREM2 Gene
chr1:240,489,573-240,612,272
(GRCh38/hg38)
Size:
122,700 bases
Orientation:
Minus strand
chr1:240,652,873-240,775,462
(GRCh37/hg19)
Size:
122,590 bases
Orientation:
Minus strand

Genomic View for GREM2 Gene

Genes around GREM2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
GREM2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for GREM2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for GREM2 Gene

Proteins for GREM2 Gene

  • Protein details for GREM2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9H772-GREM2_HUMAN
    Recommended name:
    Gremlin-2
    Protein Accession:
    Q9H772
    Secondary Accessions:
    • Q86UD9

    Protein attributes for GREM2 Gene

    Size:
    168 amino acids
    Molecular mass:
    19320 Da
    Quaternary structure:
    • Homodimer. Interacts with BMP2, BMP4 and BMP7, but has lower affinity for BMP7 than for BMP2 and BMP4. Binds heparin; this impairs the interaction with BMP2.

neXtProt entry for GREM2 Gene

Post-translational modifications for GREM2 Gene

Other Protein References for GREM2 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for GREM2 Gene

Domains & Families for GREM2 Gene

Gene Families for GREM2 Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Predicted secreted proteins

Protein Domains for GREM2 Gene

Suggested Antigen Peptide Sequences for GREM2 Gene

GenScript: Design optimal peptide antigens:
  • Protein related to DAN and cerberus (GREM2_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9H772

UniProtKB/Swiss-Prot:

GREM2_HUMAN :
  • Belongs to the DAN family.
Family:
  • Belongs to the DAN family.
genes like me logo Genes that share domains with GREM2: view

Function for GREM2 Gene

Molecular function for GREM2 Gene

UniProtKB/Swiss-Prot Function:
Cytokine that inhibits the activity of BMP2 and BMP4 in a dose-dependent manner, and thereby modulates signaling by BMP family members. Contributes to the regulation of embryonic morphogenesis via BMP family members. Antagonizes BMP4-induced suppression of progesterone production in granulosa cells.

Phenotypes From GWAS Catalog for GREM2 Gene

Gene Ontology (GO) - Molecular Function for GREM2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005125 cytokine activity IEA --
GO:0008201 heparin binding ISS --
GO:0036122 BMP binding IEA --
GO:0042802 identical protein binding IEA --
GO:0042803 protein homodimerization activity IEA --
genes like me logo Genes that share ontologies with GREM2: view
genes like me logo Genes that share phenotypes with GREM2: view

Human Phenotype Ontology for GREM2 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for GREM2 Gene

MGI Knock Outs for GREM2:

Animal Model Products

  • Taconic Biosciences Mouse Models for GREM2

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for GREM2

Clone Products

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for GREM2 Gene

Localization for GREM2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for GREM2 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 GREM2 gene
Compartment Confidence
extracellular 5
plasma membrane 2
cytoskeleton 2
nucleus 2
cytosol 2
mitochondrion 1
endoplasmic reticulum 1
endosome 1
lysosome 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for GREM2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS --
GO:0005615 extracellular space IEA --
genes like me logo Genes that share ontologies with GREM2: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for GREM2 Gene

Pathways & Interactions for GREM2 Gene

genes like me logo Genes that share pathways with GREM2: view

Pathways by source for GREM2 Gene

2 Reactome pathways for GREM2 Gene
1 KEGG pathway for GREM2 Gene

Interacting Proteins for GREM2 Gene

;

Gene Ontology (GO) - Biological Process for GREM2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007275 multicellular organism development IEA --
GO:0010172 embryonic body morphogenesis ISS --
GO:0019221 cytokine-mediated signaling pathway ISS --
GO:0030509 BMP signaling pathway TAS --
GO:0030514 negative regulation of BMP signaling pathway IEA --
genes like me logo Genes that share ontologies with GREM2: view

No data available for SIGNOR curated interactions for GREM2 Gene

Drugs & Compounds for GREM2 Gene

(3) Drugs for GREM2 Gene - From: PharmGKB and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Allopurinol Approved Pharma 198
genes like me logo Genes that share compounds with GREM2: view

Transcripts for GREM2 Gene

mRNA/cDNA for GREM2 Gene

1 REFSEQ mRNAs :
3 NCBI additional mRNA sequence :
1 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for GREM2

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for GREM2 Gene

No ASD Table

Relevant External Links for GREM2 Gene

GeneLoc Exon Structure for
GREM2

Expression for GREM2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for GREM2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for GREM2 Gene

This gene is overexpressed in Liver (x7.5) and Small Intestine - Terminal Ileum (x4.5).

Protein differential expression in normal tissues from HIPED for GREM2 Gene

This gene is overexpressed in Milk (31.0), Gallbladder (23.9), and Bone marrow mesenchymal stem cell (14.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for GREM2 Gene



Protein tissue co-expression partners for GREM2 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for GREM2

SOURCE GeneReport for Unigene cluster for GREM2 Gene:

Hs.98206

Evidence on tissue expression from TISSUES for GREM2 Gene

  • Intestine(4.4)
  • Nervous system(4.4)
  • Liver(2.1)
genes like me logo Genes that share expression patterns with GREM2: view

No data available for mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for GREM2 Gene

Orthologs for GREM2 Gene

This gene was present in the common ancestor of animals.

Orthologs for GREM2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia GREM2 31 30
  • 99.8 (n)
OneToOne
dog
(Canis familiaris)
Mammalia GREM2 31 30
  • 95.63 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Grem2 17 31 30
  • 92.26 (n)
oppossum
(Monodelphis domestica)
Mammalia GREM2 31
  • 92 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Grem2 30
  • 91.07 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia GREM2 31
  • 83 (a)
OneToOne
chicken
(Gallus gallus)
Aves GREM2 31 30
  • 83.63 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia GREM2 31
  • 81 (a)
OneToOne
zebrafish
(Danio rerio)
Actinopterygii grem2 31 30
  • 73.09 (n)
OneToMany
GREM2 (2 of 2) 31
  • 52 (a)
OneToMany
prdc 30
worm
(Caenorhabditis elegans)
Secernentea F35B12.10 31
  • 13 (a)
OneToMany
Species where no ortholog for GREM2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • 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)
  • cow (Bos Taurus)
  • 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)
  • 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)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)

Evolution for GREM2 Gene

ENSEMBL:
Gene Tree for GREM2 (if available)
TreeFam:
Gene Tree for GREM2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for GREM2: view image

Paralogs for GREM2 Gene

Paralogs for GREM2 Gene

(2) SIMAP similar genes for GREM2 Gene using alignment to 1 proteins:

  • GREM2_HUMAN
genes like me logo Genes that share paralogs with GREM2: view

Variants for GREM2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for GREM2 Gene

SNP ID Clinical significance and condition Chr 01 pos Variation AA Info Type
rs1057519288 Pathogenic: Tooth agenesis, selective, 9. Tooth agenesis, selective, 9 (STHAG9) [MIM:617275] 240,493,068(-) C/Ap.Glu136Asp MISSENSE_VARIANT
rs142343894 Tooth agenesis, selective, 9 (STHAG9) [MIM:617275] p.Gln76Glu
rs373941682 Pathogenic: Tooth agenesis, selective, 9. Tooth agenesis, selective, 9 (STHAG9) [MIM:617275] 240,493,438(-) G/Ap.Ala13Val MISSENSE_VARIANT
rs34188522 - p.Val131Ile

Additional dbSNP identifiers (rs#s) for GREM2 Gene

Structural Variations from Database of Genomic Variants (DGV) for GREM2 Gene

Variant ID Type Subtype PubMed ID
esv1001491 CNV insertion 20482838
esv1005597 CNV deletion 20482838
esv2178515 CNV deletion 18987734
esv2304550 CNV deletion 18987734
esv2657340 CNV deletion 23128226
esv2675840 CNV deletion 23128226
esv2726029 CNV deletion 23290073
esv2726040 CNV deletion 23290073
esv2741207 CNV deletion 23290073
esv3447917 CNV insertion 20981092
esv3589316 CNV loss 21293372
nsv523917 CNV loss 19592680
nsv956712 CNV deletion 24416366

Variation tolerance for GREM2 Gene

Residual Variation Intolerance Score: 52.4% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.43; 9.34% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for GREM2 Gene

Human Gene Mutation Database (HGMD)
GREM2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
GREM2

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for GREM2 Gene

Disorders for GREM2 Gene

MalaCards: The human disease database

(10) MalaCards diseases for GREM2 Gene - From: UniProtKB/Swiss-Prot, OMIM, ClinVar, GTR, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
tooth agenesis, selective, 9
  • sthag9
tooth agenesis
  • familial tooth agenesis
sclerosteosis
  • sost
norrie disease
  • nd
visual agnosia
  • primary visual agnosia
- elite association - COSMIC cancer census association via MalaCards
Search GREM2 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

GREM2_HUMAN
  • Tooth agenesis, selective, 9 (STHAG9) [MIM:617275]: A form of selective tooth agenesis, a common anomaly characterized by the congenital absence of one or more teeth. Selective tooth agenesis without associated systemic disorders has sometimes been divided into 2 types: oligodontia, defined as agenesis of 6 or more permanent teeth, and hypodontia, defined as agenesis of less than 6 teeth. The number in both cases does not include absence of third molars (wisdom teeth). STHAG9 inheritance is autosomal dominant. {ECO:0000269 PubMed:26416033}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for GREM2

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with GREM2: view

No data available for Genatlas for GREM2 Gene

Publications for GREM2 Gene

  1. Identification and characterization of human CKTSF1B2 and CKTSF1B3 genes in silico. (PMID: 15254711) Katoh M … Katoh M (Oncology reports 2004) 3 4 23 54
  2. GREMLIN 2 Mutations and Dental Anomalies. (PMID: 26416033) Kantaputra PN … Ketudat Cairns JR (Journal of dental research 2015) 3 4 54
  3. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PMID: 20379614) Rose JE … Uhl GR (Molecular medicine (Cambridge, Mass.) 2010) 3 41 54
  4. Follow-up examination of linkage and association to chromosome 1q43 in multiple sclerosis. (PMID: 19626040) McCauley JL … Haines JL (Genes and immunity 2009) 3 41 54
  5. The DNA sequence and biological annotation of human chromosome 1. (PMID: 16710414) Gregory SG … Prigmore E (Nature 2006) 3 4 54

Products for GREM2 Gene

Sources for GREM2 Gene