GDF15 (Growth Differentiation Factor 15): A Stress-Responsive Cytokine with Diagnostic and Therapeutic Relevance
Explore the gene, protein, expression, mutations, and clinical significance of GDF15, a key biomarker in inflammation, cancer, and metabolic disorders.
Gene Information Card
| Symbol | GDF15 |
|---|---|
| Full Name | Growth Differentiation Factor 15 |
| Gene Type | Protein coding |
| Chromosomal Location | 19p13.11 |
| NCBI Gene ID | 9518 ncbi.nlm.nih.gov/gene/9518 |
| Ensembl ID | ENSG00000130513 |
| UniProt ID | Q99988 |
| OMIM ID | 605312 |
| HGNC ID | 4385 |
| Aliases | MIC-1, NAG-1, PLAB, PDF, PTGFB, GDF-15 |
Description
GDF15 (Growth Differentiation Factor 15) is a divergent member of the transforming growth factor-beta (TGF-beta) superfamily. It is synthesized as a precursor protein that is cleaved to produce a mature, secreted cytokine. GDF15 expression is low in most normal tissues but is markedly induced under stress conditions, including inflammation, tissue injury, and cancer. It plays a role in regulating appetite, energy metabolism, and inflammatory responses, and is a well-established biomarker for various diseases, including cancer, cardiovascular disease, and preeclampsia.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | GDF15 is overexpressed in many tumors; it promotes tumor progression via immune evasion and angiogenesis, and is associated with cachexia. | High expression in tumor tissues and serum; prognostic marker in multiple cancers (COSMIC, literature). |
| Cardiovascular disease | Elevated GDF15 levels are associated with adverse outcomes in heart failure and atherosclerosis; it may reflect inflammatory stress. | Clinical studies show correlation with disease severity (ClinVar, literature). |
| Preeclampsia | Increased GDF15 in maternal serum is linked to placental stress and inflammation. | Clinical biomarker studies (OMIM, literature). |
| Metabolic disorders | GDF15 regulates appetite and energy balance; elevated levels are seen in obesity and type 2 diabetes, possibly as a compensatory response. | Genetic and clinical studies (UniProt, literature). |
| Inflammatory diseases | GDF15 is induced by inflammatory cytokines and may modulate immune responses. | Experimental models and clinical observations (NCBI Gene, literature). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 0.8 | Low |
| Placenta | 10.2 | High |
| Kidney | 1.5 | Low |
| Prostate | 2.3 | Low |
| Adipose tissue | 0.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver cancer) | 1.2 | Low baseline; inducible by stress |
| MCF7 (breast cancer) | 3.5 | Moderate; associated with tumor progression |
| A549 (lung cancer) | 2.8 | Moderate; induced by inflammatory stimuli |
| PC3 (prostate cancer) | 4.1 | High; linked to aggressive phenotype |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs1058587 (H6D) | Missense | ~30% (global) | May affect protein stability and function; associated with altered cancer risk in some studies. |
| rs4808793 | Intronic | ~20% | Potential regulatory variant; linked to GDF15 expression levels. |
| rs1227731 | Missense | ~5% | Rare; functional impact unclear. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in GDF15 are rare and may lead to reduced appetite regulation and metabolic dysregulation, but no clear disease phenotype has been established.
Gain of Function (GOF)
Gain-of-function mutations are not well characterized; overexpression of wild-type GDF15 is common in cancer and is associated with poor prognosis.
Dominant Negative (DN)
No dominant-negative mutations have been reported for GDF15.
View complete mutation data：
Gene Ontology (GO)
Pathways
• TGF-beta signaling pathway (KEGG hsa04350)
• Cytokine-cytokine receptor interaction (KEGG hsa04060)
• Regulation of appetite and energy metabolism (via GFRAL receptor)
Protein Summary
The GDF15 protein is synthesized as a 308-amino acid precursor with a signal peptide and a prodomain. After cleavage, the mature protein (112 amino acids) forms a disulfide-linked dimer. It signals through the GDNF family receptor alpha-like (GFRAL) and co-receptor RET, primarily in the brainstem, to regulate appetite and energy balance. GDF15 is also involved in inflammatory responses and tissue repair. Its expression is induced by cellular stress, and it is often overexpressed in tumors, contributing to cancer-associated cachexia and immune evasion.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GDF15 Knockout HEK293 Cell Line | EDJ-KQ1131 | Human | 9518 | Details Get a Quote |
| GDF15 Knockout A-549 Cell Line | EDJ-KQ20336 | Human | 9518 | Details Get a Quote |
| GDF15 Knockout HCT 116 Cell Line | EDJ-KQ20337 | Human | 9518 | Details Get a Quote |
| GDF15 Knockout HeLa Cell Line | EDJ-KQ20338 | Human | 9518 | Details Get a Quote |
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