STEAP2

Chr 7

STEAP2 metalloreductase

Also known as: IPCA1, PCANAP1, PUMPCn, STAMP1, STMP

NCBI Gene: 261729ENSG00000157214UniProt: Q8NFT2

This gene is a member of the STEAP family and encodes a multi-pass membrane protein that localizes to the Golgi complex, the plasma membrane, and the vesicular tubular structures in the cytosol. A highly similar protein in mouse has both ferrireductase and cupric reductase activity, and stimulates the cellular uptake of both iron and copper in vitro. Increased transcriptional expression of the human gene is associated with prostate cancer progression. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

101
ClinVar variants
12
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— STEAP2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
12 Pathogenic / Likely Pathogenic· 76 VUS of 101 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.
0.97LOEUF
pLI 0.000
Z-score 1.68
OE 0.62 (0.41–0.97)
Tolerant

Typical tolerance to LoF variation

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.
0.75Z-score
OE missense 0.87 (0.78–0.97)
223 obs / 257.0 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.0.62 (0.41–0.97)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.87 (0.78–0.97)
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.0.70
0≤1.21.6
LoF obs/exp: 14 / 22.6Missense obs/exp: 223 / 257.0Syn Z: 2.22

ClinVar Variant Classifications

101 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11
Likely Pathogenic1
VUS76
Likely Benign10
Benign1
Conflicting2
11
Pathogenic
1
Likely Pathogenic
76
VUS
10
Likely Benign
1
Benign
2
Conflicting

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
57
19
0
76
Likely Benign
0
3
6
1
10
Benign
0
1
0
0
1
Conflicting
—2
Total061371101

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

View in ClinVar →

Protein Context — Lollipop Plot

STEAP2 · 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
Single-cell analysis of treatment-resistant prostate cancer: Implications of cell state changes for cell surface antigen-targeted therapies.
Zaidi S et al.·Proc Natl Acad Sci U S A
2024
Expression and prognostic analyses of the significance of STEAP1 and STEAP2 in lung cancer.
Liu T et al.·World J Surg Oncol
2022
STEAP2 promotes osteosarcoma progression by inducing epithelial-mesenchymal transition via the PI3K/AKT/mTOR signaling pathway and is regulated by EFEMP2.
Zhang D et al.·Cancer Biol Ther
2022
STEAP2 is down-regulated in breast cancer tissue and suppresses PI3K/AKT signaling and breast cancer cell invasion in vitro and in vivo.
Yang Q et al.·Cancer Biol Ther
2020
Unveiling the role of copper metabolism and STEAP2 in idiopathic pulmonary fibrosis molecular landscape.
Wang Y et al.·J Cell Mol Med
2024
METTL3-mediated m6A modification of STEAP2 mRNA inhibits papillary thyroid cancer progress by blocking the Hedgehog signaling pathway and epithelial-to-mesenchymal transition.
Zhu Y et al.·Cell Death Dis
2022
STEAP proteins: from structure to applications in cancer therapy.
Gomes IM et al.·Mol Cancer Res
2012Review
A role for STEAP2 in prostate cancer progression.
Whiteland H et al.·Clin Exp Metastasis
2014
Exploring STEAP1 Expression in Prostate Cancer Cells in Response to Androgen Deprivation and in Small Extracellular Vesicles.
Bizzaro CL et al.·Mol Cancer Res
2025
STEAP1 protein overexpression is an independent marker for biochemical recurrence in prostate carcinoma.
Ihlaseh-Catalano SM et al.·Histopathology
2013
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