This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homo... See more...

Aliases for GDF15 Gene

Aliases for GDF15 Gene

  • Growth Differentiation Factor 15 2 3 5
  • Prostate Differentiation Factor 2 3 4
  • Non-Steroidal Anti-Inflammatory Drug-Activated Gene-1 2 3
  • Placental Bone Morphogenetic Protein 3 4
  • Growth/Differentiation Factor 15 3 4
  • Macrophage Inhibitory Cytokine 1 3 4
  • NSAID-Activated Gene 1 Protein 3 4
  • NSAID-Regulated Gene 1 Protein 3 4
  • Placental TGF-Beta 3 4
  • GDF-15 3 4
  • MIC-1 3 4
  • NAG-1 3 4
  • NRG-1 3 4
  • PTGFB 3 4
  • MIC1 3 4
  • PLAB 3 4
  • PDF 3 4
  • NSAID (Nonsteroidal Anti-Inflammatory Drug)-Activated Protein 1 3
  • Macrophage Inhibitory Cytokine-1 2
  • PTGF-Beta 3

External Ids for GDF15 Gene

Previous GeneCards Identifiers for GDF15 Gene

  • GC00U914343
  • GC19P018318
  • GC19P018358
  • GC19P018496
  • GC19P018613
  • GC19P020499
  • GC19P020641
  • GC19P018542
  • GC19P018556
  • GC19P018720
  • GC19P019032
  • GC19P019349
  • GC19P019680
  • GC19P020047
  • GC19P020359

Summaries for GDF15 Gene

Entrez Gene Summary for GDF15 Gene

  • This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer. The protein is expressed in a broad range of cell types, acts as a pleiotropic cytokine and is involved in the stress response program of cells after cellular injury. Increased protein levels are associated with disease states such as tissue hypoxia, inflammation, acute injury and oxidative stress. [provided by RefSeq, Aug 2016]

GeneCards Summary for GDF15 Gene

GDF15 (Growth Differentiation Factor 15) is a Protein Coding gene. Diseases associated with GDF15 include Pulmonary Systemic Sclerosis and Oral Cavity Cancer. Among its related pathways are p70S6K Signaling and Activation of cAMP-Dependent PKA. Gene Ontology (GO) annotations related to this gene include cytokine activity and transforming growth factor beta receptor binding. An important paralog of this gene is BMP6.

UniProtKB/Swiss-Prot Summary for GDF15 Gene

  • Regulates food intake, energy expenditure and body weight in response to metabolic and toxin-induced stresses (PubMed:28953886, PubMed:28846097, PubMed:28846098, PubMed:28846099, PubMed:23468844, PubMed:29046435). Binds to its receptor, GFRAL, and activates GFRAL-expressing neurons localized in the area postrema and nucleus tractus solitarius of the brainstem (PubMed:28953886, PubMed:28846097, PubMed:28846098, PubMed:28846099). It then triggers the activation of neurons localized within the parabrachial nucleus and central amygdala, which contitutes part of the 'emergency circuit' that shapes feeding responses to stressful conditions (PubMed:28953886). On hepatocytes, inhibits growth hormone signaling (By similarity).

Gene Wiki entry for GDF15 Gene

Additional gene information for GDF15 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for GDF15 Gene

Genomics for GDF15 Gene

GeneHancer (GH) Regulatory Elements for GDF15 Gene

Promoters and enhancers for GDF15 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
GH19J018372 Promoter/Enhancer 2.8 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 762.4 +6.5 6531 18.3 SIN3A ZNF24 ZBTB40 SP1 CTCF SREBF1 ZBTB6 LCORL MLX FOXA1 GDF15 ENSG00000268030 NR2C2AP UPF1 IQCN MAU2 COLGALT1 ENSG00000268938 MEF2B MVB12A
GH19J018392 Promoter/Enhancer 1.3 FANTOM5 Ensembl ENCODE 7 +18.9 18915 3.1 SMARCE1 SMARCA4 MTA1 IKZF1 DPF2 PRDM10 HDAC1 SOX6 RUNX3 HDAC2 IFI30 LRRC25 IQCN LSM4 PGPEP1 GDF15 ELL SSBP4 KCNN1 ARRDC2
GH19J018368 Enhancer 1 ENCODE CraniofacialAtlas dbSUPER 8.8 -5.6 -5592 2.2 NR2F6 L3MBTL2 ZNF121 CBFA2T2 NR2C1 POLR2A NCOR1 BCOR ZNF592 NFIL3 GDF15 KCNN1 piR-57133-311 RF00017-2898 PGPEP1
GH19J018734 Promoter/Enhancer 2 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 1.2 +364.7 364676 9.6 MLX RBPJ SMARCE1 NR2F1 NR2F6 L3MBTL2 ZNF652 ELF3 ZFX SP1 CRTC1 COMP CRLF1 KXD1 GDF1 GDF15 piR-38242 lnc-COMP-1
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around GDF15 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the GDF15 gene promoter:
  • AP-1
  • ATF-2
  • c-Jun
  • C/EBPbeta
  • PPAR-gamma1
  • PPAR-gamma2
  • STAT3

Genomic Locations for GDF15 Gene

Genomic Locations for GDF15 Gene
chr19:18,374,731-18,389,176
(GRCh38/hg38)
Size:
14,446 bases
Orientation:
Plus strand
chr19:18,485,541-18,499,986
(GRCh37/hg19)
Size:
14,446 bases
Orientation:
Plus strand

Genomic View for GDF15 Gene

Genes around GDF15 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
GDF15 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for GDF15 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for GDF15 Gene

Proteins for GDF15 Gene

  • Protein details for GDF15 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q99988-GDF15_HUMAN
    Recommended name:
    Growth/differentiation factor 15
    Protein Accession:
    Q99988
    Secondary Accessions:
    • O14629
    • P78360
    • Q9BWA0
    • Q9NRT0

    Protein attributes for GDF15 Gene

    Size:
    308 amino acids
    Molecular mass:
    34140 Da
    Quaternary structure:
    • Homodimer; disulfide-linked (PubMed:29046435). Interacts with GFRAL; ligand of GFRAL which mediates GDF15 internalization and cellular signaling through interaction with RET (PubMed:28953886, PubMed:28846097, PubMed:28846098, PubMed:28846099).

    Three dimensional structures from OCA and Proteopedia for GDF15 Gene

neXtProt entry for GDF15 Gene

Post-translational modifications for GDF15 Gene

  • Glycosylation at Ser44 and Asn70
  • Modification sites at PhosphoSitePlus

Other Protein References for GDF15 Gene

Antibody Products

  • Abcam antibodies for GDF15

No data available for DME Specific Peptides for GDF15 Gene

Domains & Families for GDF15 Gene

Gene Families for GDF15 Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Plasma proteins
  • Predicted intracellular proteins
  • Predicted secreted proteins

Suggested Antigen Peptide Sequences for GDF15 Gene

GenScript: Design optimal peptide antigens:
  • Prostate differentiation factor (GDF15_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q99988

UniProtKB/Swiss-Prot:

GDF15_HUMAN :
  • Belongs to the TGF-beta family.
Family:
  • Belongs to the TGF-beta family.
genes like me logo Genes that share domains with GDF15: view

Function for GDF15 Gene

Molecular function for GDF15 Gene

UniProtKB/Swiss-Prot Function:
Regulates food intake, energy expenditure and body weight in response to metabolic and toxin-induced stresses (PubMed:28953886, PubMed:28846097, PubMed:28846098, PubMed:28846099, PubMed:23468844, PubMed:29046435). Binds to its receptor, GFRAL, and activates GFRAL-expressing neurons localized in the area postrema and nucleus tractus solitarius of the brainstem (PubMed:28953886, PubMed:28846097, PubMed:28846098, PubMed:28846099). It then triggers the activation of neurons localized within the parabrachial nucleus and central amygdala, which contitutes part of the 'emergency circuit' that shapes feeding responses to stressful conditions (PubMed:28953886). On hepatocytes, inhibits growth hormone signaling (By similarity).
UniProtKB/Swiss-Prot Induction:
Expression is up-regulated by obesity.

Phenotypes From GWAS Catalog for GDF15 Gene

Gene Ontology (GO) - Molecular Function for GDF15 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005125 cytokine activity IBA,TAS 21873635
GO:0005160 transforming growth factor beta receptor binding IBA 21873635
GO:0005515 protein binding IPI 19060904
GO:0008083 growth factor activity IEA --
GO:0042803 protein homodimerization activity IDA,IEA 29046435
genes like me logo Genes that share ontologies with GDF15: view
genes like me logo Genes that share phenotypes with GDF15: view

Animal Models for GDF15 Gene

MGI Knock Outs for GDF15:

Animal Model Products

  • Taconic Biosciences Mouse Models for GDF15

CRISPR Products

Clone Products

Cell Line Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for GDF15 Gene

Localization for GDF15 Gene

Subcellular locations from UniProtKB/Swiss-Prot for GDF15 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 GDF15 gene
Compartment Confidence
extracellular 5
nucleus 5
golgi apparatus 4
cytoskeleton 2
cytosol 2
plasma membrane 1
mitochondrion 1
endoplasmic reticulum 1
peroxisome 0

Subcellular locations from the

Human Protein Atlas (HPA)
  • Golgi apparatus (4)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for GDF15 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS,IDA 28572090
GO:0005615 extracellular space IBA,IDA 25893289
GO:0005634 nucleus IDA 25893289
GO:0005737 cytoplasm IDA 25893289
GO:0005794 Golgi apparatus IDA --
genes like me logo Genes that share ontologies with GDF15: view

Pathways & Interactions for GDF15 Gene

PathCards logo

SuperPathways for GDF15 Gene

SuperPathway Contained pathways
1 Apoptotic Pathways in Synovial Fibroblasts
.85
.85
.84
.84
.74
.72
.66
.65
.64
.62
.61
.60
.57
.57
2 GPCR Pathway
.73
.73
.62
.59
.58
.58
.55
3 ERK Signaling
.61
.61
.58
.51
.49
4 Nanog in Mammalian ESC Pluripotency
.61
.61
.59
.48
5 CREB Pathway
.68
.68
.63
.50
genes like me logo Genes that share pathways with GDF15: view

Pathways by source for GDF15 Gene

1 BioSystems pathway for GDF15 Gene
1 KEGG pathway for GDF15 Gene
54 Qiagen pathways for GDF15 Gene
  • 14-3-3 Induced Intracellular Signaling
  • Actin-Based Motility by Rho Family GTPases
  • Activation of cAMP-Dependent PKA
  • Activation of PKA through GPCR
  • Activation of PKC through GPCR
3 Cell Signaling Technology pathways for GDF15 Gene

SIGNOR curated interactions for GDF15 Gene

Is activated by:

Gene Ontology (GO) - Biological Process for GDF15 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000187 activation of MAPK activity IDA 28953886
GO:0002023 reduction of food intake in response to dietary excess IEA,IDA 28846097
GO:0007165 signal transduction TAS 9326641
GO:0007179 transforming growth factor beta receptor signaling pathway TAS 9348093
GO:0007267 cell-cell signaling TAS 9326641
genes like me logo Genes that share ontologies with GDF15: view

Drugs & Compounds for GDF15 Gene

(9) Drugs for GDF15 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(9) Additional Compounds for GDF15 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with GDF15: view

Transcripts for GDF15 Gene

mRNA/cDNA for GDF15 Gene

CRISPR Products

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for GDF15 Gene

No ASD Table

Relevant External Links for GDF15 Gene

GeneLoc Exon Structure for
GDF15
ECgene alternative splicing isoforms for
GDF15

Expression for GDF15 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for GDF15 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for GDF15 Gene

This gene is overexpressed in Bladder (x7.8), Kidney - Cortex (x6.3), Prostate (x5.0), and Pancreas (x4.1).

Protein differential expression in normal tissues from HIPED for GDF15 Gene

This gene is overexpressed in Amniocyte (24.2), Placenta (15.9), Lung (13.7), and Bone marrow mesenchymal stem cell (6.3).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for GDF15 Gene



NURSA nuclear receptor signaling pathways regulating expression of GDF15 Gene:

GDF15

SOURCE GeneReport for Unigene cluster for GDF15 Gene:

Hs.616962

mRNA Expression by UniProt/SwissProt for GDF15 Gene:

Q99988-GDF15_HUMAN
Tissue specificity: Highly expressed in placenta, with lower levels in prostate and colon and some expression in kidney (PubMed:9348093). Detected in plasma (at protein level) (PubMed:28572090, PubMed:29046435).

Evidence on tissue expression from TISSUES for GDF15 Gene

  • Muscle(4.6)
  • Skin(4.6)
  • Lung(4.3)
  • Intestine(4.1)
  • Kidney(3.9)
  • Liver(3.8)
  • Pancreas(2.9)
  • Blood(2.4)
  • Heart(2.4)
  • Nervous system(2.2)
genes like me logo Genes that share expression patterns with GDF15: view

No data available for Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for GDF15 Gene

Orthologs for GDF15 Gene

This gene was present in the common ancestor of animals.

Orthologs for GDF15 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia GDF15 33 32
  • 98.05 (n)
OneToOne
cow
(Bos Taurus)
Mammalia GDF15 33 32
  • 74.54 (n)
OneToOne
dog
(Canis familiaris)
Mammalia GDF15 33 32
  • 74.34 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia Gdf15 32
  • 68.86 (n)
mouse
(Mus musculus)
Mammalia Gdf15 17 33 32
  • 68.62 (n)
oppossum
(Monodelphis domestica)
Mammalia GDF15 33
  • 34 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia GDF15 33
  • 34 (a)
OneToOne
zebrafish
(Danio rerio)
Actinopterygii ndr1 33
  • 13 (a)
ManyToMany
worm
(Caenorhabditis elegans)
Secernentea daf-7 33
  • 14 (a)
OneToOne
Species where no ortholog for GDF15 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)
  • chicken (Gallus gallus)
  • 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)
  • lizard (Anolis carolinensis)
  • 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 GDF15 Gene

ENSEMBL:
Gene Tree for GDF15 (if available)
TreeFam:
Gene Tree for GDF15 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for GDF15: view image

Paralogs for GDF15 Gene

genes like me logo Genes that share paralogs with GDF15: view

Variants for GDF15 Gene

Sequence variations from dbSNP and Humsavar for GDF15 Gene

SNP ID Clin Chr 19 pos Variation AA Info Type
rs1000290705 -- 18,386,761(+) C/G/T intron_variant
rs1000641221 -- 18,387,158(+) A/G intron_variant
rs1000660023 -- 18,382,196(+) A/G 5_prime_UTR_variant, genic_upstream_transcript_variant
rs1000702717 -- 18,380,679(+) G/A upstream_transcript_variant
rs1001521192 -- 18,382,496(+) T/C genic_upstream_transcript_variant, intron_variant

Structural Variations from Database of Genomic Variants (DGV) for GDF15 Gene

Variant ID Type Subtype PubMed ID
nsv2430 CNV deletion 18451855
nsv952420 CNV deletion 24416366

Variation tolerance for GDF15 Gene

Residual Variation Intolerance Score: 26.9% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 10.20; 90.45% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for GDF15 Gene

Human Gene Mutation Database (HGMD)
GDF15
SNPedia medical, phenotypic, and genealogical associations of SNPs for
GDF15

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for GDF15 Gene

Disorders for GDF15 Gene

MalaCards: The human disease database

(8) MalaCards diseases for GDF15 Gene - From: HGMD, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
pulmonary systemic sclerosis
  • lung disease with systemic sclerosis
oral cavity cancer
  • malignant neoplasm of anterior portion of floor of mouth
alpha-thalassemia
  • thalassemia, alpha-
epithelial basement membrane dystrophy
  • corneal dystrophy, epithelial basement membrane
heart disease
  • congenital heart disease
- elite association - COSMIC cancer census association via MalaCards
Search GDF15 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

GDF15_HUMAN
  • Note=Plasma levels are increased in children with concomitant heart disease and failure to thrive but not in children with heart disease and normal body weight. {ECO:0000269 PubMed:28572090}.

Additional Disease Information for GDF15

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 GDF15: view

No data available for Genatlas for GDF15 Gene

Publications for GDF15 Gene

  1. Resveratrol enhances the expression of non-steroidal anti-inflammatory drug-activated gene (NAG-1) by increasing the expression of p53. (PMID: 11895857) Baek SJ … Eling TE (Carcinogenesis 2002) 2 3 23 56
  2. Cyclooxygenase inhibitors regulate the expression of a TGF-beta superfamily member that has proapoptotic and antitumorigenic activities. (PMID: 11259636) Baek SJ … Eling TE (Molecular pharmacology 2001) 3 4 23 56
  3. Cloning and characterization of a novel member of the transforming growth factor-beta/bone morphogenetic protein family. (PMID: 9593718) Paralkar VM … Thompson DD (The Journal of biological chemistry 1998) 2 3 4 56
  4. MIC-1, a novel macrophage inhibitory cytokine, is a divergent member of the TGF-beta superfamily. (PMID: 9326641) Bootcov MR … Breit SN (Proceedings of the National Academy of Sciences of the United States of America 1997) 3 4 23 56
  5. PLAB, a novel placental bone morphogenetic protein. (PMID: 9375789) Hromas R … Lu L (Biochimica et biophysica acta 1997) 3 4 23 56

Products for GDF15 Gene

Sources for GDF15 Gene