STEAP4: A Key Metalloreductase in Metabolic and Inflammatory Pathways
Explore the STEAP4 gene, its protein function, associated diseases, expression patterns, and clinical significance.
Gene Information Card
| Symbol | STEAP4 |
|---|---|
| Full Name | STEAP family member 4 |
| Gene Type | protein coding |
| Chromosomal Location | 7q21.3 |
| NCBI Gene ID | 79689 ncbi.nlm.nih.gov/gene/79689 |
| Ensembl ID | ENSG00000106554 |
| UniProt ID | Q687X5 |
| OMIM ID | 611098 |
| HGNC ID | 21923 |
| Aliases | STAMP2, TNFAIP9, TIARP |
Description
STEAP4 (STEAP family member 4) encodes a six-transmembrane protein that functions as a metalloreductase, reducing Fe3+ to Fe2+ and Cu2+ to Cu1+, thereby facilitating metal ion uptake. It is induced by inflammatory cytokines such as TNF-alpha and is involved in cellular redox balance, adipocyte differentiation, and glucose metabolism. STEAP4 is expressed in various tissues, including adipose tissue, liver, and placenta, and has been implicated in metabolic disorders, inflammatory diseases, and cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Type 2 Diabetes | Reduced STEAP4 expression in adipose tissue leads to impaired insulin signaling and increased inflammation, contributing to insulin resistance. | Multiple studies show decreased STEAP4 mRNA in adipose tissue of diabetic patients; overexpression improves insulin sensitivity in vitro. |
| Obesity | STEAP4 is downregulated in adipose tissue of obese individuals, correlating with increased inflammation and metabolic dysfunction. | Clinical cohorts and animal models demonstrate reduced STEAP4 in obesity; knockout mice exhibit worsened metabolic profile. |
| Rheumatoid Arthritis | STEAP4 is upregulated in synovial tissue and may modulate inflammatory responses and joint damage. | Expression detected in synovial fibroblasts; TNF-alpha induces STEAP4, suggesting a protective role. |
| Inflammatory Bowel Disease | Altered STEAP4 expression in intestinal epithelium may affect metal homeostasis and inflammation. | Limited studies show differential expression in IBD tissues; functional studies ongoing. |
| Prostate Cancer | STEAP4 expression is altered in prostate cancer, potentially affecting metal-dependent processes and tumor progression. | Expression data from cancer databases; functional role under investigation. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adipose tissue | High | High expression in subcutaneous and visceral fat. |
| Liver | Moderate | Expressed in hepatocytes; involved in metabolic regulation. |
| Placenta | High | Strong expression in syncytiotrophoblasts. |
| Heart | Low | Low expression in cardiac tissue. |
| Lung | Low | Minimal expression in lung tissue. |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Adipocytes | High | Differentiated adipocytes show high STEAP4 expression. |
| Macrophages | Moderate | Induced by inflammatory stimuli. |
| Hepatocytes | Moderate | Expression in liver cell lines. |
| Synovial fibroblasts | Moderate | Upregulated in inflammatory conditions. |
| Endothelial cells | Low | Low basal expression. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs10489202 | SNP (intronic) | Minor allele frequency ~0.2 | Associated with metabolic traits in some studies; functional impact unclear. |
| rs8120 | SNP (3' UTR) | Minor allele frequency ~0.3 | Potential effect on mRNA stability; linked to obesity in certain populations. |
| c.101C>T (p.Ala34Val) | Missense | Rare | Reported in a patient with insulin resistance; functional studies show reduced metalloreductase activity. |
| c.457G>A (p.Gly153Ser) | Missense | Rare | Found in cancer samples; effect on protein function not fully characterized. |
Mutation functional classification
Loss of Function (LOF)
Mutations that reduce STEAP4 metalloreductase activity or protein stability may impair iron/copper homeostasis, leading to metabolic dysfunction and increased inflammation.
Gain of Function (GOF)
No clear gain-of-function mutations have been reported; overexpression studies suggest beneficial metabolic effects, but pathological gain-of-function is not established.
Dominant Negative (DN)
No evidence for dominant-negative effects; STEAP4 likely functions as a homodimer, but mutations with dominant-negative properties have not been described.
View complete mutation data：
Gene Ontology (GO)
| • oxidoreductase activity | • ferric-chelate reductase activity |
| • cupric reductase activity | • metal ion binding |
| • plasma membrane | • integral component of membrane |
| • response to tumor necrosis factor | • cellular iron ion homeostasis |
| • cellular copper ion homeostasis | • adipocyte differentiation |
| • glucose homeostasis |
Pathways
• Metal ion transport and homeostasis
• TNF-alpha signaling pathway
• Insulin signaling pathway
• Adipogenesis
• Inflammatory response
Protein Summary
STEAP4 is a 6-transmembrane protein localized to the plasma membrane and endosomes. It functions as a metalloreductase, reducing Fe3+ to Fe2+ and Cu2+ to Cu1+, which is essential for metal ion uptake. The protein is induced by TNF-alpha and other inflammatory cytokines, linking inflammation to metal metabolism. STEAP4 plays a role in adipocyte differentiation, insulin sensitivity, and glucose homeostasis. Its expression is regulated by nutritional and hormonal signals, and dysregulation is associated with metabolic and inflammatory diseases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| STEAP4 Knockout HEK293 Cell Line | EDJ-KQ2601 | Human | 79689 | Details Get a Quote |
| STEAP4 Knockout HeLa Cell Line | EDJ-KQ21941 | Human | 79689 | Details Get a Quote |
| STEAP4 Knockout A-549 Cell Line | EDJ-KQ65721 | Human | 79689 | Details Get a Quote |
| STEAP4 Knockout HCT 116 Cell Line | EDJ-KQ74138 | Human | 79689 | Details Get a Quote |
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