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GDF15 growth differentiation factor 15 [ Homo sapiens (human) ]

Gene ID: 9518, updated on 13-Apr-2024

Summary

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Official Symbol
GDF15provided by HGNC
Official Full Name
growth differentiation factor 15provided by HGNC
Primary source
HGNC:HGNC:30142
See related
Ensembl:ENSG00000130513 MIM:605312; AllianceGenome:HGNC:30142
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
HG; PDF; MIC1; PLAB; MIC-1; NAG-1; PTGFB; GDF-15
Summary
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]
Expression
Biased expression in placenta (RPKM 62.0), prostate (RPKM 53.1) and 11 other tissues See more
Orthologs
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Genomic context

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Location:
19p13.11
Exon count:
2
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (18386158..18389176)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (18515920..18523324)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (18496968..18499986)

Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124904654 Neighboring gene RNA, 7SL, cytoplasmic 513, pseudogene Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:18451278-18451965 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr19:18454745-18455584 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr19:18455585-18456422 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr19:18456925-18457507 Neighboring gene pyroglutamyl-peptidase I Neighboring gene ReSE screen-validated silencer GRCh37_chr19:18460464-18460672 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:18472794-18473579 Neighboring gene Sharpr-MPRA regulatory region 798 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr19:18484262-18485461 Neighboring gene ReSE screen-validated silencer GRCh37_chr19:18486310-18486537 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:18491252-18491819 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:18496512-18497334 Neighboring gene microRNA 3189 Neighboring gene leucine rich repeat containing 25 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:18518971-18519471 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10391 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10392 Neighboring gene single stranded DNA binding protein 4 Neighboring gene CRISPRi-validated cis-regulatory element chr19.2899 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:18526865-18527500 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10393 Neighboring gene ReSE screen-validated silencer GRCh37_chr19:18528379-18528618 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10395 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:18534153-18534654 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:18534655-18535154 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10396 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10397 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14318 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:18541209-18541757 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:18541758-18542305 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10398 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10399 Neighboring gene inositol-3-phosphate synthase 1

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: 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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Related articles in PubMed

  1. GDF15 Promotes the Osteogenic Cell Fate of Periodontal Ligament Fibroblasts, thus Affecting Their Mechanobiological Response. Lösch L, et al. Int J Mol Sci, 2023 Jun 11. PMID 37373159, Free PMC Article
  2. Growth differentiation factor 15 (GDF-15) in kidney diseases. Delrue C, et al. Adv Clin Chem, 2023. PMID 37268330
  3. GDF-15 Is Associated with Poor Physical Function in Prefrail Older Adults with Diabetes. Merchant RA, et al. J Diabetes Res, 2023. PMID 37152099, Free PMC Article
  4. The association of growth differentiation factor-15 levels and osteoporosis in patients with thalassemia. Teawtrakul N, et al. Am J Med Sci, 2023 Aug. PMID 37146903
  5. Significance of localized expression of full-length growth differentiation factor-15 in cachexia of advanced non-small cell lung cancer. Morita-Tanaka S, et al. Support Care Cancer, 2023 Apr 28. PMID 37115357

See all (594) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. GDF15 as a key disease target and biomarker: linking chronic lung diseases and ageing.
    Title: GDF15 as a key disease target and biomarker: linking chronic lung diseases and ageing.
  2. Evaluation of the relationship between atherosclerosis and Helicobacter pylori infection with measurement of growth differentiation factor 15 and atherosclerosis indicators in adults with no comorbidity.
    Title: Evaluation of the relationship between atherosclerosis and Helicobacter pylori infection with measurement of growth differentiation factor 15 and atherosclerosis indicators in adults with no comorbidity.
  3. TGF-beta Isoforms and GDF-15 in the Development and Progression of Atherosclerosis.
    Title: TGF-β Isoforms and GDF-15 in the Development and Progression of Atherosclerosis.
  4. Incremental values of AOPP, IL-6, and GDF15 for identifying arteriosclerosis in patients with obstructive sleep apnea.
    Title: Incremental values of AOPP, IL-6, and GDF15 for identifying arteriosclerosis in patients with obstructive sleep apnea.
  5. GDF15 is a dynamic biomarker of the integrated stress response in the central nervous system.
    Title: GDF15 is a dynamic biomarker of the integrated stress response in the central nervous system.
  6. GDF-15 Inhibits ADP-Induced Human Platelet Aggregation through the GFRAL/RET Signaling Complex.
    Title: GDF-15 Inhibits ADP-Induced Human Platelet Aggregation through the GFRAL/RET Signaling Complex.
  7. GDF15 Modulates the Zoledronic-Acid-Induced Hyperinflammatory Mechanoresponse of Periodontal Ligament Fibroblasts.
    Title: GDF15 Modulates the Zoledronic-Acid-Induced Hyperinflammatory Mechanoresponse of Periodontal Ligament Fibroblasts.
  8. Associations of circulating GDF15 with combined cognitive frailty and depression in older adults of the MARK-AGE study.
    Title: Associations of circulating GDF15 with combined cognitive frailty and depression in older adults of the MARK-AGE study.
  9. GDF15 linked to maternal risk of nausea and vomiting during pregnancy.
    Title: GDF15 linked to maternal risk of nausea and vomiting during pregnancy.
  10. Protein biomarkers GDF15 and FGF21 to differentiate mitochondrial hepatopathies from other pediatric liver diseases.
    Title: Protein biomarkers GDF15 and FGF21 to differentiate mitochondrial hepatopathies from other pediatric liver diseases.
Submit: New GeneRIF Correction See all GeneRIFs (582)

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

Associated conditions

Description Tests
Hyperemesis gravidarum, susceptibility to
MedGen: CN376898 OMIM: 620730 GeneReviews: Not available
not available

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables cytokine activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables cytokine activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables growth factor activity IEA
Inferred from Electronic Annotation
more info
  
enables hormone activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein homodimerization activity IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in GDF15-GFRAL signaling pathway IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in SMAD protein signal transduction IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in cell-cell signaling TAS
Traceable Author Statement
more info
 PubMed 
involved_in cellular response to chemical stress IEA
Inferred from Electronic Annotation
more info
  
involved_in negative regulation of appetite IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in negative regulation of growth hormone receptor signaling pathway ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in negative regulation of leukocyte migration IEA
Inferred from Electronic Annotation
more info
  
involved_in negative regulation of multicellular organism growth ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in positive regulation of MAPK cascade IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of MAPK cascade IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of fatty acid oxidation IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of myoblast fusion IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in reduction of food intake in response to dietary excess IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in response to metformin IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in signal transduction TAS
Traceable Author Statement
more info
 PubMed 
involved_in transforming growth factor beta receptor signaling pathway TAS
Traceable Author Statement
more info
 PubMed 
Component Evidence Code Pubs
located_in Golgi apparatus IDA
Inferred from Direct Assay
more info
  
colocalizes_with collagen-containing extracellular matrix HDA PubMed 
located_in cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
located_in extracellular exosome HDA PubMed 
located_in extracellular region IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in extracellular space IBA
Inferred from Biological aspect of Ancestor
more info
  
is_active_in extracellular space IDA
Inferred from Direct Assay
more info
 PubMed 
located_in extracellular space IDA
Inferred from Direct Assay
more info
 PubMed 
located_in nucleus IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
growth/differentiation factor 15
Names
NRG-1
NSAID (nonsteroidal anti-inflammatory drug)-activated protein 1
NSAID-activated gene 1 protein
NSAID-regulated gene 1 protein
PTGF-beta
macrophage inhibitory cytokine 1
non-steroidal anti-inflammatory drug-activated gene-1
placental TGF-beta
placental bone morphogenetic protein
prostate differentiation factor

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.

mRNA and Protein(s)

  1. NM_004864.4 → NP_004855.2  growth/differentiation factor 15 preproprotein

    See identical proteins and their annotated locations for NP_004855.2

    Status: REVIEWED

    Source sequence(s)
    BC008962, BQ901034
    Consensus CDS
    CCDS12376.1
    UniProtKB/Swiss-Prot
    O14629, P78360, Q99988, Q9BWA0, Q9NRT0
    Related
    ENSP00000252809.3, ENST00000252809.3
    Conserved Domains (2) summary
    smart00204
    Location:211 → 308
    TGFB; Transforming growth factor-beta (TGF-beta) family
    cl26309
    Location:23 → 147
    MscS_TM; Mechanosensitive ion channel inner membrane domain 1

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000019.10 Reference GRCh38.p14 Primary Assembly

    Range
    18386158..18389176
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060943.1 Alternate T2T-CHM13v2.0

    Range
    18515920..18523324
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054322715.1 → XP_054178690.1  growth/differentiation factor 15 isoform X1

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q99988.3 GenPept UniProtKB/Swiss-Prot:Q99988

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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