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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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STEAP4
STEAP4 metalloreductase
Chromosome 7 · 7q21.12
NCBI Gene: 79689Ensembl: ENSG00000127954.14HGNC: HGNC:21923UniProt: Q687X5
54PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
ferric-chelate reductase (NADPH) activityplasma membraneextracellular exosomemembranealcohol drinkingacute tonsillitisadolescent idiopathic scoliosisIntrahepatic cholestasis of pregnancy
✦AI Summary

STEAP4 is an integral membrane metalloreductase that functions as a key regulator of cellular iron and copper homeostasis and metabolic function 1. The protein mediates NADPH-dependent reduction of Fe(3+) chelates and Cu(2+) ions through sequential transmembrane electron transfer involving FAD and heme cofactors 2. STEAP4 plays a crucial role in systemic metabolic homeostasis by integrating inflammatory and metabolic responses 3. Expression is significantly downregulated in adipose tissue of obese children and adults, correlating negatively with blood pressure, lipid levels, glucose, and inflammatory markers like IL-6 and TNF-α 45. The protein demonstrates tissue-specific expression patterns, with higher levels in visceral versus subcutaneous adipose tissue that decrease with increasing BMI 5. STEAP4 promotes cell survival and proliferation through AKT/mTOR signaling while regulating oxidative stress responses 6. Recent studies indicate STEAP4 can contribute to cuproptosis, a copper-dependent cell death mechanism, when upregulated by transcription factors like FOXO1 7. Genome-wide association studies have linked STEAP4 mutations to metabolic disorders including obesity, metabolic syndrome, and type 2 diabetes 1.

Sources cited
1
STEAP4 functions as a metalloreductase in iron and copper homeostasis and is linked to metabolic disorders
PMID: 28576871
2
STEAP4 mentioned in context of copper metabolism and cellular processes
PMID: 37055935
3
STEAP4 is downregulated in obese patients and improves glucose uptake and insulin sensitivity
PMID: 24627165
4
STEAP4 expression is significantly lower in adipose tissue of obese children and correlates with metabolic parameters
PMID: 27808366
5
STEAP4 shows tissue-specific expression patterns in visceral vs subcutaneous adipose tissue
PMID: 27058639
6
STEAP4 regulates cell proliferation and apoptosis through AKT/mTOR signaling
PMID: 37866665
7
STEAP4 upregulation by FOXO1 increases intracellular copper levels and causes cuproptosis
PMID: 40855689
Disease Associationsⓘ20
alcohol drinkingOpen Targets
0.19Weak
acute tonsillitisOpen Targets
0.19Weak
adolescent idiopathic scoliosisOpen Targets
0.18Weak
Intrahepatic cholestasis of pregnancyOpen Targets
0.13Weak
hepatocellular carcinomaOpen Targets
0.12Weak
posterior cortical atrophyOpen Targets
0.10Suggestive
neoplasmOpen Targets
0.09Suggestive
colorectal carcinomaOpen Targets
0.08Suggestive
arthritisOpen Targets
0.08Suggestive
breast cancerOpen Targets
0.08Suggestive
experimental autoimmune encephalomyelitisOpen Targets
0.08Suggestive
chronic kidney diseaseOpen Targets
0.08Suggestive
rheumatoid arthritisOpen Targets
0.08Suggestive
gastric cancerOpen Targets
0.07Suggestive
oral squamous cell carcinomaOpen Targets
0.07Suggestive
allergic rhinitisOpen Targets
0.07Suggestive
head and neck squamous cell carcinomaOpen Targets
0.07Suggestive
pulmonary arterial hypertensionOpen Targets
0.07Suggestive
SepsisOpen Targets
0.07Suggestive
lung carcinomaOpen Targets
0.06Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
EEA1Protein interaction74%TMEM120BShared pathway25%CLYBLShared pathway25%FAM120BShared pathway25%CDADC1Shared pathway25%STEAP3Shared pathway25%
Tissue Expression6 tissues
Lung
100%
Liver
68%
Heart
68%
Brain
11%
Bone Marrow
9%
Ovary
8%
Gene Interaction Network
Click a node to explore
STEAP4EEA1TMEM120BCLYBLFAM120BCDADC1STEAP3
PROTEIN STRUCTURE
Preparing viewer…
PDB6HCY · 3.10 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.11LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.83 [0.64–1.11]
RankingsWhere STEAP4 stands among ~20K protein-coding genes
  • #8,377of 20,598
    Most Researched54
  • #11,329of 17,882
    Most Constrained (LOEUF)1.11
Genes detectedSTEAP4
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Copper metabolism in cell death and autophagy.
PMID: 37055935
Autophagy · 2023
1.00
2
STEAP4 and insulin resistance.
PMID: 24627165
Endocrine · 2014
0.90
3
Lithium Exposure Causes Trophoblast Cuproptosis by Upregulating FOXO1/STEAP4 Axis in Unexplained Miscarriage.
PMID: 40855689
Adv Sci (Weinh) · 2025
0.80
4
STEAP4: its emerging role in metabolism and homeostasis of cellular iron and copper.
PMID: 28576871
J Endocrinol · 2017
0.70
5
STEAP4 modulates cell proliferation and oxidative stress in benign prostatic hyperplasia.
PMID: 37866665
Cell Signal · 2024
0.60