GREM1 gremlin 1, DAN family BMP antagonist [Homo sapiens (human)] - Gene

Summary

Official Symbol: GREM1provided by HGNC
Official Full Name: gremlin 1, DAN family BMP antagonistprovided by HGNC
Primary source: HGNC:HGNC:2001
See related: Ensembl:ENSG00000166923 MIM:603054; AllianceGenome:HGNC:2001
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: DRM; HMPS; MPSH; PIG2; CRAC1; CRCS4; DAND2; HMPS1; IHG-2; DUP15q; C15DUPq; GREMLIN; CKTSF1B1
Summary: 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]
Expression: Biased expression in gall bladder (RPKM 205.9), appendix (RPKM 84.5) and 6 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 15q13.3

Exon count:: 3

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	15	NC_000015.10 (32718004..32745106)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	15	NC_060939.1 (30514530..30541636)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	15	NC_000015.9 (33010205..33037307)

Chromosome 15 - NC_000015.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Expression of Osteopontin and Gremlin 1 Proteins in Cardiomyocytes in Ischemic Heart Failure.
Title: Expression of Osteopontin and Gremlin 1 Proteins in Cardiomyocytes in Ischemic Heart Failure.
GREM1 Negatively Regulates Osteo-/Dentinogenic Differentiation of Dental Pulp Stem Cells via Association with YWHAH.
Title: GREM1 Negatively Regulates Osteo-/Dentinogenic Differentiation of Dental Pulp Stem Cells via Association with YWHAH.
SHH regulates penile morphology and smooth muscle through a mechanism involving BMP4 and GREM1.
Title: SHH regulates penile morphology and smooth muscle through a mechanism involving BMP4 and GREM1.
BMP4 and GREM1 are targets of SHH signaling and downstream regulators of collagen in the penis.
Title: BMP4 and GREM1 are targets of SHH signaling and downstream regulators of collagen in the penis.
Unravelling the role of HAS2, GREM1, and PTGS2 gene expression in cumulus cells: implications for human oocyte development competency - a systematic review and integrated bioinformatic analysis.
Title: Unravelling the role of HAS2, GREM1, and PTGS2 gene expression in cumulus cells: implications for human oocyte development competency - a systematic review and integrated bioinformatic analysis.
Angiogenic and Fibrogenic Dual-effect of Gremlin1 on Proliferative Diabetic Retinopathy.
Title: Angiogenic and Fibrogenic Dual-effect of Gremlin1 on Proliferative Diabetic Retinopathy.
GREM1 knockdown regulates the proliferation, apoptosis and EMT of benign prostatic hyperplasia by suppressing the STAT3/c-Myc signaling.
Title: GREM1 knockdown regulates the proliferation, apoptosis and EMT of benign prostatic hyperplasia by suppressing the STAT3/c-Myc signaling.
Association between IRF6, TP63, GREM1 Gene Polymorphisms and Non-Syndromic Orofacial Cleft Phenotypes in Vietnamese Population: A Case-Control and Family-Based Study.
Title: Association between IRF6, TP63, GREM1 Gene Polymorphisms and Non-Syndromic Orofacial Cleft Phenotypes in Vietnamese Population: A Case-Control and Family-Based Study.
Regulation of Cervical Cancer Development by a Novel Circ_0000212/miR-1236-3p/GREM1 ceRNA Crosstalk.
Title: Regulation of Cervical Cancer Development by a Novel Circ_0000212/miR-1236-3p/GREM1 ceRNA Crosstalk.
Gremlin-1 in pregnancy and postpartum: relation to the fatty liver index, markers of bone health, glucose metabolism and gestational diabetes mellitus status.
Title: Gremlin-1 in pregnancy and postpartum: relation to the fatty liver index, markers of bone health, glucose metabolism and gestational diabetes mellitus status.

Submit: New GeneRIF Correction See all GeneRIFs (153)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Copy number response

Description
Copy number response Haploinsufficency No evidence available (Last evaluated 2020-08-20) ClinGen Genome Curation Page Triplosensitivity No evidence available (Last evaluated 2020-08-20) ClinGen Genome Curation Page

EBI GWAS Catalog

Description
Genome-wide association analyses identify variants in developmental genes associated with hypospadias. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies two susceptibility loci for nonsyndromic cleft lip with or without cleft palate. EBI GWAS Catalog EBI GWAS CatalogPubMed
Identification of Genetic Susceptibility Loci for Colorectal Tumors in a Genome-Wide Meta-analysis. EBI GWAS Catalog EBI GWAS CatalogPubMed
Identification of susceptibility loci for colorectal cancer in a genome-wide meta-analysis. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analysis of new genome-wide association studies of colorectal cancer risk. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH47687 (e-PCR)
- UniSTS:53301

NoName (e-PCR)
- UniSTS:483181

Grem1 (e-PCR), detects polymorphism
- UniSTS:547439

SHGC-54520 (e-PCR)
- UniSTS:2239

STS-N21113 (e-PCR)
- UniSTS:59852

NoName (e-PCR)
- UniSTS:481747

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables BMP binding	IBA Inferred from Biological aspect of Ancestor more info
enables BMP binding	IDA Inferred from Direct Assay more info	PubMed
enables BMP binding	ISS Inferred from Sequence or Structural Similarity more info	PubMed
enables cytokine activity	IEA Inferred from Electronic Annotation more info
enables morphogen activity	ISS Inferred from Sequence or Structural Similarity more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein homodimerization activity	IPI Inferred from Physical Interaction more info	PubMed
enables receptor ligand activity	IBA Inferred from Biological aspect of Ancestor more info
enables receptor ligand activity	ISS Inferred from Sequence or Structural Similarity more info	PubMed
enables transmembrane receptor protein tyrosine kinase activator activity	ISS Inferred from Sequence or Structural Similarity more info
enables vascular endothelial growth factor receptor 2 binding	ISS Inferred from Sequence or Structural Similarity more info	PubMed

Process	Evidence Code	Pubs
involved_in cardiac muscle cell differentiation	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in cardiac muscle cell myoblast differentiation	IEA Inferred from Electronic Annotation more info
involved_in cell migration involved in sprouting angiogenesis	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in cell morphogenesis	IDA Inferred from Direct Assay more info	PubMed
involved_in cell-cell signaling	IEA Inferred from Electronic Annotation more info
involved_in collagen fibril organization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in determination of dorsal identity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in embryonic limb morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in limb development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in mesenchymal to epithelial transition involved in metanephros morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of BMP signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of BMP signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of DNA-templated transcription	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of SMAD protein signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of bone mineralization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of bone mineralization involved in bone maturation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of bone remodeling	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of bone trabecula formation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of canonical Wnt signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of cell growth	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of chondrocyte differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of monocyte chemotaxis	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of osteoblast differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within negative regulation of osteoblast differentiation	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in negative regulation of osteoblast proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of osteoclast proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of angiogenesis	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of branching involved in ureteric bud morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of cell population proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of non-canonical NF-kappaB signal transduction	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of peptidyl-tyrosine autophosphorylation	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in positive regulation of protein tyrosine kinase activity	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of receptor internalization	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in positive regulation of signaling receptor activity	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of transcription by RNA polymerase II	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in proximal/distal pattern formation	IEA Inferred from Electronic Annotation more info
involved_in regulation of epithelial to mesenchymal transition	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of focal adhesion assembly	IEA Inferred from Electronic Annotation more info
NOT involved_in regulation of stress-activated MAPK cascade	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in sequestering of BMP from receptor via BMP binding	IBA Inferred from Biological aspect of Ancestor more info
involved_in signal transduction	ISS Inferred from Sequence or Structural Similarity more info
NOT involved_in signal transduction by p53 class mediator	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in ureteric bud formation	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in cell surface	IEA Inferred from Electronic Annotation more info
colocalizes_with collagen-containing extracellular matrix	HDA more info	PubMed
located_in collagen-containing extracellular matrix	HDA more info	PubMed
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info
located_in extracellular space	NAS Non-traceable Author Statement more info	PubMed

General protein information

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Preferred Names: gremlin-1

Names: 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; gremlin 1-like protein; hereditary mixed polyposis syndrome; increased in high glucose-2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_033791.2 RefSeqGene

Range

5001..32103

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_1365

mRNA and Protein(s)

NM_001191322.2 → NP_001178251.1 gremlin-1 isoform 3

See identical proteins and their annotated locations for NP_001178251.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks an in-frame segment in the CDS, as compared to variant 1. The resulting isoform (3) lacks an internal segment, as compared to isoform 1.

Source sequence(s)

AC090877, AK095972

UniProtKB/TrEMBL

B3KTR9

Conserved Domains (1) summary

pfam03045
Location:9 → 109

DAN; DAN domain
NM_001191323.2 → NP_001178252.1 gremlin-1 isoform 2 precursor

See identical proteins and their annotated locations for NP_001178252.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an in-frame segment in the CDS, as compared to variant 1. The resulting isoform (2) lacks an internal segment, as compared to isoform 1.

Source sequence(s)

AC090877, AK095890

Consensus CDS

CCDS53927.1

UniProtKB/Swiss-Prot

O60565

Related

ENSP00000453141.1, ENST00000560830.1

Conserved Domains (1) summary

pfam03045
Location:38 → 138

DAN; DAN domain
NM_001368719.1 → NP_001355648.1 gremlin-1 isoform 1 precursor

Status: REVIEWED

Source sequence(s)

AC090877

Consensus CDS

CCDS10029.1

UniProtKB/Swiss-Prot

O60565, Q52LV3, Q8N914, Q8N936

UniProtKB/TrEMBL

A6XAA7

Related

ENSP00000498763.1, ENST00000652365.1

Conserved Domains (1) summary

pfam03045
Location:72 → 179

DAN; DAN domain
NM_013372.7 → NP_037504.1 gremlin-1 isoform 1 precursor

See identical proteins and their annotated locations for NP_037504.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) is the longest transcript and encodes the longest isoform (1).

Source sequence(s)

AC090877, AK095890, W19275

Consensus CDS

CCDS10029.1

UniProtKB/Swiss-Prot

O60565, Q52LV3, Q8N914, Q8N936

UniProtKB/TrEMBL

A6XAA7

Related

ENSP00000498748.1, ENST00000651154.1

Conserved Domains (1) summary

pfam03045
Location:72 → 179

DAN; DAN domain