STEAP1

Summary

STEAP1 (STEAP family member 1, HGNC:11378) is a protein-coding gene on chromosome 7q21.13, encoding STEAP1 protein (Q9UHE8). Does not function as a metalloreductase due to the absence of binding sites for the electron-donating substrate NADPH.

This gene is predominantly expressed in prostate tissue, and is found to be upregulated in multiple cancer cell lines. The gene product is predicted to be a six-transmembrane protein, and was shown to be a cell surface antigen significantly expressed at cell-cell junctions.

Source: NCBI Gene 26872 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 62 total
• Druggable target: yes
• MANE Select transcript: NM_012449

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11378
Approved symbol	STEAP1
Name	STEAP family member 1
Location	7q21.13
Locus type	gene with protein product
Status	Approved
Aliases	PRSS24
Ensembl gene	ENSG00000164647
Ensembl biotype	protein_coding
OMIM	604415
Entrez	26872

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000297205, ENST00000412573, ENST00000475789, ENST00000892309, ENST00000927745, ENST00000927746, ENST00000955229, ENST00000955230, ENST00000955231

RefSeq mRNA: 1 — MANE Select: NM_012449 NM_012449

CCDS: CCDS5614

Canonical transcript exons

ENST00000297205 — 5 exons

Exon	Start	End
ENSE00001275931	90154469	90154543
ENSE00001775636	90161914	90162078
ENSE00001886334	90164477	90164827
ENSE00003600148	90159758	90159872
ENSE00003667293	90160805	90161317

Expression profiles

Bgee: expression breadth ubiquitous, 233 present calls, max score 97.30.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.7507 / max 314.2367, expressed in 1180 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
79434	10.6145	1054
79432	1.1563	570
79431	0.5399	319
79433	0.3985	238
204513	0.0415	13

Top tissues by expression

290 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
pericardium	UBERON:0002407	97.30	gold quality
cartilage tissue	UBERON:0002418	94.93	gold quality
prostate gland	UBERON:0002367	94.76	gold quality
tendon of biceps brachii	UBERON:0008188	93.99	gold quality
calcaneal tendon	UBERON:0003701	92.50	gold quality
parietal pleura	UBERON:0002400	92.49	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.83	gold quality
mucosa of transverse colon	UBERON:0004991	91.55	gold quality
adipose tissue of abdominal region	UBERON:0007808	91.35	gold quality
adipose tissue	UBERON:0001013	91.20	gold quality
peritoneum	UBERON:0002358	91.07	gold quality
omental fat pad	UBERON:0010414	91.07	gold quality
connective tissue	UBERON:0002384	90.68	gold quality
tendon	UBERON:0000043	90.67	gold quality
gall bladder	UBERON:0002110	89.52	gold quality
vermiform appendix	UBERON:0001154	89.36	gold quality
pleura	UBERON:0000977	89.35	gold quality
right lobe of liver	UBERON:0001114	88.93	gold quality
mucosa of sigmoid colon	UBERON:0004993	88.86	gold quality
colonic mucosa	UBERON:0000317	88.57	gold quality
subcutaneous adipose tissue	UBERON:0002190	88.53	gold quality
lower esophagus mucosa	UBERON:0035834	88.53	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.45	gold quality
transverse colon	UBERON:0001157	87.68	gold quality
nasal cavity epithelium	UBERON:0005384	87.54	gold quality
tibia	UBERON:0000979	87.52	gold quality
mucosa of urinary bladder	UBERON:0001259	87.47	gold quality
rectum	UBERON:0001052	87.44	gold quality
nasal cavity mucosa	UBERON:0001826	86.75	gold quality
caecum	UBERON:0001153	86.73	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-1	yes	75.20
E-CURD-46	yes	12.68
E-ANND-3	yes	9.34
E-MTAB-8530	no	400.09

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 31)

• Peptide STEAP-292.2L (MLAVFLPIV) may have potential as an antitumor peptide vaccine. (PMID:15958640)
• STEAP mRNA is used here as a marker to evaluate biological samples from individuals suspected of having cancers, and may provide prognostic information useful in defining appropriate therapeutic options. (PMID:18793824)
• STEAP1 is over-expressed in breast cancer and down-regulated by 17beta-estradiol. (PMID:18958632)
• STEAPs may represent novel markers of mesenchymal stem cells in man as well as mice. (PMID:19196137)
• Data suggest that zoledronic acid may affect cancer cells also by targeting the gene expression of STEAP. (PMID:19915386)
• Studies suggest that activated human gammadelta T cells can efficiently present PRAME and STEAP1-derived epitopes and allow breaking tolerance against these tumor-associated self-antigens. (PMID:21928126)
• EWS-FLI1 mediated overexpression of STEAP1 increases the invasiveness and oxidative stress levels of Ewing tumor cells. (PMID:22080479)
• STEAP1 is associated with the invasive behavior and oxidative stress phenotype of Ewing tumors, an unanticipated oncogenic function of STEAP1. (PMID:22080479)
• A total of 62.3% of the Ewing’s Sarcoma samples displayed detectable STEAP1 expression with predominant localization of the protein at the plasma membrane. (PMID:22317770)
• STEAP1 overexpression predicts improved outcome of Ewing’s sarcoma patients, possibly due to enhanced sensitivity towards ROS-generating chemotherapeutics. (PMID:22317770)
• STEAP1 is down-regulated by dihydrotestosterone and estradiols in LNCaP cells and in rat prostate. (PMID:23060075)
• The findings provide evidence that STEAP1 is a biomarker of worse prognosis in prostate carcinomas patients. (PMID:24025158)
• Data indicate that six transmembrane epithelial antigen of the prostate 1 (STEAP1) is consistently overexpressed in malignant prostate tissue, namely adenocarcinoma and prostatic intraepithelial neoplasia (PIN) lesions. (PMID:24239460)
• These findings highlight the ability of immuno-PET with (89)Zr-2109A to detect acute changes in STEAP1 expression (PMID:25453051)
• Data suggest a solid basis for further research into understanding how six-transmembrane epithelial antigen of prostate member 1 (STEAP1) activities may affect cancer progression. (PMID:27792302)
• High STEAP1 expression is associated with prostate cancer. (PMID:29464393)
• The expression of STEAP-1 is significantly associated with high-grade Gleason scores and seminal vesicle invasion of PCa. (PMID:30027616)
• Low STEAP1 expression was associated with Breast Cancer Metastasis. (PMID:30253922)
• we identified high STEAP1 transcript levels leading to reduced ROS production that prevented apoptosis via the NRF2 pathway in CRC cells as a pathological mechanism in CRC. (PMID:30401882)
• Six-transmembrane epithelial antigen of the prostate 1 expression promotes ovarian cancer metastasis by aiding progression of epithelial-to-mesenchymal transition. (PMID:32382787)
• Cryo-electron microscopy structure and potential enzymatic function of human six-transmembrane epithelial antigen of the prostate 1 (STEAP1). (PMID:32409586)
• The Tumor Suppressive Roles and Prognostic Values of STEAP Family Members in Breast Cancer. (PMID:32802887)
• A research of STEAP1 regulated gastric cancer cell proliferation, migration and invasion in vitro and in vivos. (PMID:33128353)
• Clinical significance of STEAP1 extracellular vesicles in prostate cancer. (PMID:33589770)
• Identification of a New Transcriptional Co-Regulator of STEAP1 in Ewing’s Sarcoma. (PMID:34073779)
• Predictive potential of STEAP family for survival, immune microenvironment and therapy response in glioma. (PMID:34649092)
• The Prognostic Value and Immunological Role of STEAP1 in Pan-Cancer: A Result of Data-Based Analysis. (PMID:35313641)
• STEAP1 regulation and its influence modulating the response of LNCaP prostate cancer cells to bicalutamide, enzalutamide and apalutamide. (PMID:36660947)
• Inhibition of STEAP1 ameliorates inflammation and ferroptosis of acute lung injury caused by sepsis in LPS-induced human pulmonary microvascular endothelial cells. (PMID:37209327)
• Proteomic analysis of STEAP1 knockdown in human LNCaP prostate cancer cells. (PMID:37315586)
• Six Transmembrane Epithelial Antigen 1 as a Prognostic Biomarker in Carcinomas: A Meta-Analysis. (PMID:38062846)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Steap1	ENSMUSG00000015652
rattus_norvegicus	Steap1	ENSRNOG00000000017

Paralogs (4): STEAP1B (ENSG00000105889), STEAP3 (ENSG00000115107), STEAP4 (ENSG00000127954), STEAP2 (ENSG00000157214)

Protein

Protein identifiers

STEAP1 protein — Q9UHE8 (reviewed: Q9UHE8)

Alternative names: Six-transmembrane epithelial antigen of prostate 1

All UniProt accessions (2): Q9UHE8, H7C0D8

UniProt curated annotations — full annotation on UniProt →

Function. Does not function as a metalloreductase due to the absence of binding sites for the electron-donating substrate NADPH. Promotes Fe(3+) reduction when fused to the NADPH-binding domain of STEAP4.

Subunit / interactions. Homotrimer.

Subcellular location. Endosome membrane. Cell membrane.

Tissue specificity. Ubiquitously expressed. Highly expressed in prostate tumors.

Similarity. Belongs to the STEAP family.

RefSeq proteins (1): NP_036581* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013130	Fe3_Rdtase_TM_dom	Domain
IPR051267	STEAP_metalloreductase	Family

Pfam: PF01794

UniProt features (34 total): helix 14, transmembrane region 6, binding site 6, sequence variant 2, turn 2, strand 2, chain 1, domain 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6Y9B	ELECTRON MICROSCOPY	2.97
8UCD	ELECTRON MICROSCOPY	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UHE8-F1	84.46	0.76

Antibody-complex structures (SAbDab): 2 — 6Y9B, 8UCD

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (6): 175 (axial binding residue); 237; 254; 268 (axial binding residue); 140; 161

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 152 (showing top): MODULE_52, STAEGE_EWING_FAMILY_TUMOR, XU_GH1_AUTOCRINE_TARGETS_UP, WEI_MYCN_TARGETS_WITH_E_BOX, TCF4_Q5, CATTTCA_MIR203, KOYAMA_SEMA3B_TARGETS_UP, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, AFP1_Q6, AFFAR_YY1_TARGETS_DN, LEF1_Q6, GOCC_CELL_CELL_JUNCTION, RIGGI_EWING_SARCOMA_PROGENITOR_UP, KOBAYASHI_EGFR_SIGNALING_24HR_DN, PODAR_RESPONSE_TO_ADAPHOSTIN_UP

GO Biological Process (0):

GO Molecular Function (3): heme binding (GO:0020037), metal ion binding (GO:0046872), protein binding (GO:0005515)

GO Cellular Component (5): endosome (GO:0005768), plasma membrane (GO:0005886), cell-cell junction (GO:0005911), endosome membrane (GO:0010008), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
tetrapyrrole binding	1
cation binding	1
binding	1
endomembrane system	1
cytoplasmic vesicle	1
membrane	1
cell periphery	1
anchoring junction	1
endosome	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

658 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
STEAP1	PSCA	O43653	751
STEAP1	SLC11A2	P49281	717
STEAP1	FOLH1	Q04609	698
STEAP1	CYBRD1	Q53TN4	667
STEAP1	TFRC	P02786	583
STEAP1	KLK3	P07288	568
STEAP1	SLC39A14	Q15043	519
STEAP1	SLC40A1	Q9NP59	507
STEAP1	HAMP	P81172	506
STEAP1	COL5A2	P05997	499
STEAP1	EGFR	P00533	490
STEAP1	CALD1	Q05682	481
STEAP1	TFR2	Q9UP52	479
STEAP1	IREB2	P48200	477
STEAP1	SLC31A1	O15431	463

IntAct

9 interactions, top by confidence:

A	B	Type	Score
STEAP1B	STEAP1	psi-mi:“MI:0915”(physical association)	0.590
STEAP1	PSMD2	psi-mi:“MI:0915”(physical association)	0.490
CD81	STX3	psi-mi:“MI:0914”(association)	0.350
CD81	PVR	psi-mi:“MI:0914”(association)	0.350
CD81	CD276	psi-mi:“MI:0914”(association)	0.350
STEAP1	GOLPH3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (12): STEAP1 (Affinity Capture-MS), GOLPH3 (Affinity Capture-MS), STEAP1 (Affinity Capture-RNA), PSMD2 (Two-hybrid), STEAP1 (Proximity Label-MS), STEAP1 (Proximity Label-MS), STEAP1 (Proximity Label-MS), STEAP1 (Proximity Label-MS), STEAP1 (Proximity Label-MS), STEAP1 (Affinity Capture-MS), STEAP1 (Positive Genetic), STEAP1 (Proximity Label-MS)

ESM2 similar proteins: A2AWR3, A2BFP5, F1QF89, O70536, P0C1Q3, P18537, Q1LWG4, Q4V8A1, Q4V8K1, Q502J0, Q53P98, Q5NVQ2, Q5R5C5, Q5RKL5, Q60457, Q61263, Q658P3, Q672J9, Q672K1, Q687X5, Q6AXF6, Q6INU7, Q6NZ63, Q6Q3F5, Q6T3U4, Q6ZNA5, Q71B07, Q7L5N7, Q7SXZ1, Q7Z3F1, Q810K3, Q8BYI6, Q8CI59, Q8CIR4, Q8IWX5, Q8K2C9, Q8K385, Q8R2R1, Q923B6, Q924V1

Diamond homologs: Q4V8K1, Q5RKL5, Q658P3, Q687X5, Q6NZ63, Q8BWB6, Q8CI59, Q8NFT2, Q923B6, Q9CWR7, Q9GL50, Q9UHE8, O29370

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

62 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	53
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

835 predictions. Top by Δscore:

Variant	Effect	Δscore
7:90154528:C:G	donor_gain	1.0000
7:90154540:GTGG:G	donor_gain	1.0000
7:90159752:TTACA:T	acceptor_loss	1.0000
7:90159755:CA:C	acceptor_loss	1.0000
7:90159756:A:AC	acceptor_loss	1.0000
7:90159756:AGGT:A	acceptor_gain	1.0000
7:90159757:GGTG:G	acceptor_gain	1.0000
7:90159858:G:GT	donor_gain	1.0000
7:90159868:ATTTG:A	donor_loss	1.0000
7:90159869:TTTG:T	donor_loss	1.0000
7:90159870:TTGGT:T	donor_loss	1.0000
7:90159871:TG:T	donor_loss	1.0000
7:90159872:GGTA:G	donor_loss	1.0000
7:90159873:GT:G	donor_loss	1.0000
7:90159874:T:A	donor_loss	1.0000
7:90160916:G:GT	donor_gain	1.0000
7:90160917:A:T	donor_gain	1.0000
7:90161899:T:G	acceptor_gain	1.0000
7:90161902:A:AG	acceptor_gain	1.0000
7:90161903:C:G	acceptor_gain	1.0000
7:90161909:G:A	acceptor_gain	1.0000
7:90161912:A:AG	acceptor_gain	1.0000
7:90161913:G:GG	acceptor_gain	1.0000
7:90161913:GGTCC:G	acceptor_gain	1.0000
7:90154523:TC:T	donor_gain	0.9900
7:90154538:GA:G	donor_gain	0.9900
7:90154539:AGTGG:A	donor_loss	0.9900
7:90154541:TGGG:T	donor_loss	0.9900
7:90154542:GG:G	donor_gain	0.9900
7:90154543:GG:G	donor_gain	0.9900

AlphaMissense

2242 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:90161255:A:C	S179R	0.996
7:90161257:T:A	S179R	0.996
7:90161257:T:G	S179R	0.996
7:90161966:A:T	E217V	0.993
7:90161189:T:A	W157R	0.992
7:90161189:T:C	W157R	0.992
7:90161222:A:C	S168R	0.991
7:90161224:T:A	S168R	0.991
7:90161224:T:G	S168R	0.991
7:90161243:C:G	H175D	0.990
7:90161203:A:C	R161S	0.989
7:90161203:A:T	R161S	0.989
7:90162064:T:C	F250L	0.988
7:90162066:T:A	F250L	0.988
7:90162066:T:G	F250L	0.988
7:90164528:T:C	F272L	0.988
7:90164530:T:A	F272L	0.988
7:90164530:T:G	F272L	0.988
7:90161275:G:C	R185S	0.987
7:90161275:G:T	R185S	0.987
7:90161076:C:A	P119Q	0.986
7:90161245:T:A	H175Q	0.986
7:90161245:T:G	H175Q	0.986
7:90161966:A:C	E217A	0.986
7:90161983:G:A	G223R	0.986
7:90161983:G:C	G223R	0.986
7:90164516:C:G	H268D	0.985
7:90161956:T:A	W214R	0.984
7:90161956:T:C	W214R	0.984
7:90164585:T:C	F291L	0.984

dbSNP variants (sampled 300 via entrez): RS1000363727 (7:90157348 A>T), RS1001449463 (7:90157876 G>A), RS1002591534 (7:90159941 G>C), RS1002795990 (7:90152608 G>T), RS1003361596 (7:90165115 G>A), RS1003433663 (7:90164680 T>C), RS1003647331 (7:90161617 T>C), RS1003805381 (7:90154405 G>A), RS1003916381 (7:90161289 A>G), RS1004295817 (7:90157773 C>A,T), RS1004314915 (7:90156380 G>A), RS1004348490 (7:90163790 C>G), RS1004485700 (7:90164030 T>C), RS1004839468 (7:90158563 G>A,C), RS1004870529 (7:90158222 C>T)

Disease associations

OMIM: gene MIM:604415 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002097_41	Coronary artery calcification	6.000000e-06
GCST010118_151	Type 2 diabetes	2.000000e-15

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004723	coronary artery calcification

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3712956 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other protein — Tumour-associated antigens

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
xaluritamig	Binding	10.5	pKd

CTD chemical–gene interactions

65 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	9
sodium arsenite	decreases expression, increases abundance, increases expression	4
trichostatin A	affects cotreatment, increases expression	3
Air Pollutants	increases abundance, increases expression, decreases expression	3
mercuric bromide	increases expression, affects cotreatment	2
entinostat	increases expression, affects cotreatment	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	increases expression, affects cotreatment, affects expression	2
Cisplatin	affects response to substance, affects cotreatment, affects expression	2
Estradiol	affects cotreatment, increases expression, decreases expression	2
Nickel	increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
Tretinoin	decreases expression	2
Cyclosporine	increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
Particulate Matter	increases abundance, increases expression, decreases expression	2
dicrotophos	decreases expression	1
bisphenol A	decreases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
beta-lapachone	increases expression	1
sulforaphane	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	decreases expression	1
cupric chloride	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
monomethylarsonous acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D5ZS	PC3-STEAP-1	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.