STEAP4

Chr 7

STEAP4 metalloreductase

Also known as: STAMP2, SchLAH, TIARP, TNFAIP9

NCBI Gene: 79689ENSG00000127954UniProt: Q687X5

The protein encoded by this gene belongs to the STEAP (six transmembrane epithelial antigen of prostate) family, and resides in the golgi apparatus. It functions as a metalloreductase that has the ability to reduce both Fe(3+) to Fe(2+) and Cu(2+) to Cu(1+), using NAD(+) as acceptor. Studies in mice and human suggest that this gene maybe involved in adipocyte development and metabolism, and may contribute to the normal biology of the prostate cell, as well as prostate cancer progression. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2011]

57
ClinVar variants
12
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— STEAP4
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
12 Pathogenic / Likely Pathogenic· 40 VUS of 57 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.03LOEUF
pLI 0.000
Z-score 1.45
OE 0.66 (0.43–1.03)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.84Z-score
OE missense 0.85 (0.76–0.95)
208 obs / 245.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.66 (0.43–1.03)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.85 (0.76–0.95)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.96
0≤1.21.6
LoF obs/exp: 14 / 21.2Missense obs/exp: 208 / 245.2Syn Z: 0.27

ClinVar Variant Classifications

57 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11
Likely Pathogenic1
VUS40
Likely Benign3
Benign2
11
Pathogenic
1
Likely Pathogenic
40
VUS
3
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
11
0
11
Likely Pathogenic
0
0
1
0
1
VUS
0
33
7
0
40
Likely Benign
0
2
0
1
3
Benign
0
2
0
0
2
Total03719157

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

STEAP4 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Copper metabolism in cell death and autophagy.
Xue Q et al.·Autophagy
2023Review
Enzalutamide-Resistant STEAP4(+) MyoCAF Secrete Phosphatidylcholine to Foster Progression by Activating Stemness in Hormone-Sensitive Prostate Cancer.
Wang W et al.·Adv Sci (Weinh)
2025
STEAP4 facilitates growth, migration, and invasion of prostate carcinoma through upregulation of NOTCH4.
Fan S et al.·FASEB J
2025
Clinical and functional significance of STEAP4-splice variant in CD14(+) monocytes in patients with rheumatoid arthritis.
Ebe H et al.·Clin Exp Immunol
2018Cohort
Lithium Exposure Causes Trophoblast Cuproptosis by Upregulating FOXO1/STEAP4 Axis in Unexplained Miscarriage.
Xing S et al.·Adv Sci (Weinh)
2025
Single-cell transcriptomic analysis reveals differential cell subpopulations and distinct phenotype transition in normal and dissected ascending aorta.
He YB et al.·Mol Med
2022
Expression and clinical significance of obesity-associated gene STEAP4 in obese children.
Xu HM et al.·Genet Mol Res
2016
Biological characteristics of molecular subtypes of ulcerative colitis characterized by ferroptosis and neutrophil infiltration.
Sun S et al.·Sci Rep
2024
STEAP4 and HIF-1α gene expressions in visceral and subcutaneous adipose tissue of the morbidly obese patients.
Ozmen F et al.·Mol Immunol
2016Cohort
Functional analysis and transcriptional regulation of porcine six transmembrane epithelial antigen of prostate 4 (STEAP4) gene and its novel variant in hepatocytes.
Wang SB et al.·Int J Biochem Cell Biol
2013Functional
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools