STEAP4

Summary

STEAP4 (STEAP4 metalloreductase, HGNC:21923) is a protein-coding gene on chromosome 7q21.12, encoding Metalloreductase STEAP4 (Q687X5). Integral membrane protein that functions as a NADPH-dependent ferric-chelate reductase, using NADPH from one side of the membrane to reduce a Fe(3+) chelate that is bound on the other side of the membrane.

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.

Source: NCBI Gene 79689 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 43 total
• MANE Select transcript: NM_024636

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21923
Approved symbol	STEAP4
Name	STEAP4 metalloreductase
Location	7q21.12
Locus type	gene with protein product
Status	Approved
Aliases	FLJ23153, TIARP, STAMP2, SchLAH
Ensembl gene	ENSG00000127954
Ensembl biotype	protein_coding
OMIM	611098
Entrez	79689

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000301959, ENST00000380079, ENST00000414498, ENST00000879105, ENST00000969824, ENST00000969825

RefSeq mRNA: 3 — MANE Select: NM_024636 NM_001205315, NM_001205316, NM_024636

CCDS: CCDS43611, CCDS56494

Canonical transcript exons

ENST00000380079 — 5 exons

Exon	Start	End
ENSE00001120706	88283814	88284271
ENSE00001163797	88280915	88281079
ENSE00001483677	88282641	88283168
ENSE00001871078	88306792	88306894
ENSE00001917465	88270892	88279628

Expression profiles

Bgee: expression breadth ubiquitous, 239 present calls, max score 99.71.

FANTOM5 (CAGE): breadth broad, TPM avg 11.5550 / max 1115.3984, expressed in 499 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
84748	11.2290	488
84749	0.1486	90
84751	0.1152	63
84750	0.0623	41

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pericardium	UBERON:0002407	99.71	gold quality
palpebral conjunctiva	UBERON:0001812	98.46	gold quality
synovial joint	UBERON:0002217	98.46	gold quality
vena cava	UBERON:0004087	97.92	gold quality
skin of hip	UBERON:0001554	97.09	gold quality
subcutaneous adipose tissue	UBERON:0002190	96.65	gold quality
cauda epididymis	UBERON:0004360	96.41	gold quality
heart right ventricle	UBERON:0002080	96.38	gold quality
parietal pleura	UBERON:0002400	96.38	gold quality
bronchial epithelial cell	CL:0002328	96.33	gold quality
peritoneum	UBERON:0002358	96.22	gold quality
omental fat pad	UBERON:0010414	96.22	gold quality
adipose tissue of abdominal region	UBERON:0007808	96.19	gold quality
adipose tissue	UBERON:0001013	96.12	gold quality
mucosa of paranasal sinus	UBERON:0005030	95.90	gold quality
connective tissue	UBERON:0002384	95.62	gold quality
lower lobe of lung	UBERON:0008949	95.12	gold quality
right lobe of thyroid gland	UBERON:0001119	95.07	gold quality
penis	UBERON:0000989	93.91	gold quality
left uterine tube	UBERON:0001303	93.60	gold quality
left adrenal gland	UBERON:0001234	93.52	gold quality
superficial temporal artery	UBERON:0001614	93.46	gold quality
saphenous vein	UBERON:0007318	93.35	gold quality
urethra	UBERON:0000057	93.28	gold quality
calcaneal tendon	UBERON:0003701	93.20	gold quality
left lobe of thyroid gland	UBERON:0001120	93.11	gold quality
caput epididymis	UBERON:0004358	93.09	gold quality
right adrenal gland	UBERON:0001233	93.06	gold quality
layer of synovial tissue	UBERON:0007616	93.02	gold quality
adrenal cortex	UBERON:0001235	93.01	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-HCAD-36	yes	2016.62
E-GEOD-130148	yes	1927.60
E-MTAB-9841	yes	1358.61
E-GEOD-135922	yes	27.78
E-MTAB-9801	yes	6.08
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, CEBPA, CEBPB, GLI1, STAT3

miRNA regulators (miRDB)

158 targeting STEAP4, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-559	99.95	72.28	3609

Literature-anchored findings (GeneRIF, showing 39)

• Human WAT STAMP2 associates with obesity and insulin resistance independently of adiponectin. (PMID:18381574)
• Down-regulation of STEAP4 is associated with obesity in humans. (PMID:18430367)
• TIARP/STAMP2 is highly upregulated in 3T3-L1 cells and hMSC-Ad by IL-1beta and might, therefore, modulate proinflammatory and insulin resistance-inducing effects of IL-1beta. (PMID:19289123)
• STEAP4 associates with focal adhesion kinase (FAK) and regulate the activity of FAK through Y397 phosphorylation. (PMID:19787193)
• Results demonstrate that STEAP4 does not influence human adipocyte differentiation, but it participates in regulating the insulin sensitivity of human adipocytes. (PMID:20127040)
• common polymorphisms of STAMP2 are unlikely to significantly contribute to the risk of the metabolic syndrome in the general population (PMID:20382686)
• Fourteen novel and six known single nucleotide polymorphisms (SNPs) including 2 nonsynonymous SNPs in the STEAP4 gene were identified. SNPs rs8122 and rs1981529 were significantly associated with the metabolic syndrome phenotype in females. (PMID:21044749)
• There was no association of the three polymorphisms (rs8122, rs1981529 and rs34741656) in the STAMP2 gene with essential hypertension in Xinjiang Uygur population. (PMID:21287513)
• STEAP 4 genetic polymorphisms may be associated with metabolic syndrome risk in Chinese Uygur population. (PMID:21287516)
• The knockdown of STEAP4 inhibits insulin-stimulated glucose transport and GLUT4 translocation via the attenuated phosphorylation of Akt, independent of the effects of EEA1. (PMID:21468601)
• STEAP4 might potentially suppress the pathogenesis of TNFalpha-induced arthritis such as rheumatoid arthritis. (PMID:21633911)
• STEAP4 genetic variations are likely to be associated with obesity-related insulin resistance in Uygur Chinese general population. (PMID:21718614)
• Decreased STAMP2 expression (mRNA and protein) might reflect visceral adipose dysfunction in subjects with obesity and type 2 diabetes. (PMID:21849520)
• an association of the common variation rs1981529 (Gly75Asp, 224A/G) in the STEAP4 gene with obesity in Uygur general population (PMID:21933608)
• STEAP4 is expressed on monocytes and neutrophils in peripheral blood of patients with rheumatoid arthritis. (PMID:22244520)
• STAMP2 antagonizes HBx-mediated hepatocyte dysfunction, thereby protecting hepatocytes from hepatitis B virus gene expression. (PMID:23095254)
• three polymorphisms (rs8122, rs1981529 and rs34741656) of STAMP2 gene may be not related with type 2 diabetes mellitus in Xinjiang Uygur population (PMID:23134829)
• Our results show increased mRNA expression of STEAP4 and NGAL in human visceral adipose tissue in obese patients. (PMID:23179203)
• STEAP4 was highly induced in human adipose cells differentiated in the presence of 1,25D. (PMID:23553608)
• Our findings revealed that STAMP2 gene polymorphisms are likely to significantly contribute to the risk of MetS in male Han Chinese population. (PMID:23953178)
• may interact with mitochondria [review] (PMID:24643198)
• These data suggest that STAMP2 is required for prostate cancer progression and thus may serve as a novel therapeutic target. (PMID:25680860)
• Some SNPs of the STEAP4 gene altered the risk of developing a metabolic syndrome in the Han Chinese population. (PMID:26510124)
• a down regulation of STEAP4 and up-regulation of HIF-1alpha are observed in morbidly obese patients (PMID:27058639)
• The expression of TNFAIP9 significantly decreased in the adipose tissue of obese children, and its levels are closely related to blood lipid level, insulin resistance, and obesity. (PMID:27706555)
• the expression of STEAP4 was significantly downregulated in the adipose tissue of obese children. (PMID:27808366)
• These findings suggest that increased STEAP4 mRNA expression is associated with inflammatory stimuli, whereas lower STEAP4 expression is associated with obesity in human islets. (PMID:28405880)
• STEAP4 plays role in metal homeostasis is critical to the maintenance of cellular homeostasis , and in preventing the onset of metabolic disease. [review] (PMID:28576871)
• this study identified specific up-regulation of spliced variant STEAP4 in rheumatoid arthritis monocytes. This variant of STEAP4 might play a crucial role in the production of TNF-alpha and IL-6 through NF-kappaB and STAT-3 pathways, resulting in the generation of rheumatoid arthritis (PMID:29080328)
• cryo-electron microscopy structures of human STEAP4 in absence and presence of Fe(3+)-NTA, are reported. (PMID:30337524)
• Enhancing STAMP2 expression with cilostazol represents a potential therapeutic avenue for treatment of NAFLD. (PMID:30366981)
• Hepatic STAMP2 mediates recombinant FGF21-induced improvement of hepatic iron overload in nonalcoholic fatty liver disease. (PMID:32721044)
• The Tumor Suppressive Roles and Prognostic Values of STEAP Family Members in Breast Cancer. (PMID:32802887)
• The six-transmembrane protein Stamp2 ameliorates pulmonary vascular remodeling and pulmonary hypertension in mice. (PMID:33188479)
• Predictive potential of STEAP family for survival, immune microenvironment and therapy response in glioma. (PMID:34649092)
• Stamp2 Protects From Maladaptive Structural Remodeling and Systolic Dysfunction in Post-Ischemic Hearts by Attenuating Neutrophil Activation. (PMID:34691017)
• sSTEAP4 regulates cellular homeostasis and improves high-fat-diet-caused oxidative stress in hepatocytes. (PMID:35227772)
• STEAP4 promoter methylation correlates with tumorigenesis of hepatocellular carcinoma. (PMID:35390632)
• STEAP4 modulates cell proliferation and oxidative stress in benign prostatic hyperplasia. (PMID:37866665)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	steap4	ENSDARG00000055901
mus_musculus	Steap4	ENSMUSG00000012428
rattus_norvegicus	Steap4	ENSRNOG00000008602

Paralogs (4): STEAP1B (ENSG00000105889), STEAP3 (ENSG00000115107), STEAP2 (ENSG00000157214), STEAP1 (ENSG00000164647)

Protein

Protein identifiers

Metalloreductase STEAP4 — Q687X5 (reviewed: Q687X5)

Alternative names: Six-transmembrane epithelial antigen of prostate 4, SixTransMembrane protein of prostate 2, Tumor necrosis factor, alpha-induced protein 9

All UniProt accessions (2): Q687X5, C9JS50

UniProt curated annotations — full annotation on UniProt →

Function. Integral membrane protein that functions as a NADPH-dependent ferric-chelate reductase, using NADPH from one side of the membrane to reduce a Fe(3+) chelate that is bound on the other side of the membrane. Mediates sequential transmembrane electron transfer from NADPH to FAD and onto heme, and finally to the Fe(3+) chelate. Can also reduce Cu(2+) to Cu(1+). Plays a role in systemic metabolic homeostasis, integrating inflammatory and metabolic responses. Associated with obesity and insulin-resistance. Involved in inflammatory arthritis, through the regulation of inflammatory cytokines. Inhibits anchorage-independent cell proliferation.

Subunit / interactions. Homotrimer. Interacts with PTK2/FAK1; the interaction may regulate PTK2 phosphorylation.

Subcellular location. Cell membrane. Golgi apparatus membrane. Early endosome membrane.

Tissue specificity. Ubiquitous. Highly expressed in adipose tissue. Expressed in placenta, lung, heart and prostate. Detected at lower levels in liver, skeletal muscle, pancreas, testis and small intestine. Highly expressed in joints of patients with rheumatoid arthritis and localized with CD68 cells, a marker for macrophages.

Cofactor. Can also utilize FMN. Can also utilize riboflavin.

Induction. By TNF and IL1B/interleukin-1 beta in adipose tissue. Up-regulated by androgens, including testosterone and dihydrotestosterone (DHT).

Similarity. Belongs to the STEAP family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q687X5-1	1	yes
Q687X5-2	2

RefSeq proteins (3): NP_001192244, NP_001192245, NP_078912* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013130	Fe3_Rdtase_TM_dom	Domain
IPR028939	P5C_Rdtase_cat_N	Domain
IPR036291	NAD(P)-bd_dom_sf	Homologous_superfamily
IPR051267	STEAP_metalloreductase	Family

Pfam: PF01794, PF03807

Catalyzed reactions (Rhea), 2 shown:

• 2 Fe(2+) + NADP(+) + H(+) = 2 Fe(3+) + NADPH (RHEA:71767)
• 2 Cu(+) + NADP(+) + H(+) = 2 Cu(2+) + NADPH (RHEA:71771)

UniProt features (74 total): helix 23, binding site 17, strand 15, transmembrane region 6, turn 6, sequence variant 2, chain 1, glycosylation site 1, splice variant 1, mutagenesis site 1, domain 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6HCY	ELECTRON MICROSCOPY	3.1
6HD1	ELECTRON MICROSCOPY	3.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q687X5-F1	91.03	0.79

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 (17): 67; 81–85; 106; 139; 140; 148; 171; 217; 269; 290; 304 (axial binding residue); 307 …

Glycosylation sites (1): 323

Mutagenesis-validated functional residues (1):

Position	Phenotype
138	strongly reduced enzyme activity. no effect on trimerization and on heme binding.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-917977	Transferrin endocytosis and recycling
R-HSA-382551	Transport of small molecules
R-HSA-917937	Iron uptake and transport

MSigDB gene sets: 185 (showing top): GOBP_TRANSITION_METAL_ION_TRANSPORT, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_INTRACELLULAR_IRON_ION_HOMEOSTASIS, GOBP_IRON_ION_TRANSPORT, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, GOBP_COPPER_ION_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_PROTEIN_TRIMERIZATION, CHARAFE_BREAST_CANCER_BASAL_VS_MESENCHYMAL_UP, SHEDDEN_LUNG_CANCER_GOOD_SURVIVAL_A4, MARTIN_NFKB_TARGETS_UP, MARTIN_VIRAL_GPCR_SIGNALING_UP

GO Biological Process (6): copper ion import (GO:0015677), iron import into cell (GO:0033212), fat cell differentiation (GO:0045444), protein homotrimerization (GO:0070207), monoatomic ion transport (GO:0006811), iron ion transport (GO:0006826)

GO Molecular Function (7): cupric reductase (NADH) activity (GO:0008823), electron transfer activity (GO:0009055), heme binding (GO:0020037), metal ion binding (GO:0046872), ferric-chelate reductase (NADPH) activity (GO:0052851), FAD binding (GO:0071949), oxidoreductase activity (GO:0016491)

GO Cellular Component (9): Golgi membrane (GO:0000139), nucleoplasm (GO:0005654), endosome (GO:0005768), plasma membrane (GO:0005886), endosome membrane (GO:0010008), membrane (GO:0016020), early endosome membrane (GO:0031901), extracellular exosome (GO:0070062), Golgi apparatus (GO:0005794)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Iron uptake and transport	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
bounding membrane of organelle	2
cellular anatomical structure	2
endomembrane system	2
copper ion transport	1
iron ion transport	1
intracellular iron ion homeostasis	1
establishment of localization in cell	1
cell differentiation	1
protein homooligomerization	1
protein trimerization	1
transport	1
transition metal ion transport	1
oxidoreductase activity, acting on metal ions, NAD or NADP as acceptor	1
molecular_function	1
tetrapyrrole binding	1
cation binding	1
ferric-chelate reductase activity	1
flavin adenine dinucleotide binding	1
catalytic activity	1
Golgi apparatus	1
nuclear lumen	1
cytoplasmic vesicle	1
membrane	1
cell periphery	1
endosome	1
cytoplasmic vesicle membrane	1
early endosome	1
endosome membrane	1
extracellular vesicle	1
cytoplasm	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

833 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
STEAP4	EEA1	Q15075	738
STEAP4	TGM4	P49221	649
STEAP4	PYCR1	P32322	648
STEAP4	KLKB1	P03952	642
STEAP4	ACP3	P15309	638
STEAP4	KLK2	P20151	611
STEAP4	FUS	P35637	596
STEAP4	ZNF154	Q13106	575
STEAP4	KLK3	P07288	552
STEAP4	SLC25A37	Q9NYZ2	514
STEAP4	TEX47	Q8TBZ9	513
STEAP4	MSMB	P08118	497
STEAP4	GBA1	P04062	493
STEAP4	AR	P10275	482
STEAP4	PTK2	Q05397	480

IntAct

6 interactions, top by confidence:

A	B	Type	Score
STEAP4	AKT2	psi-mi:“MI:0915”(physical association)	0.370
Npc1	ESYT2	psi-mi:“MI:0914”(association)	0.350
GOT1	A2ML1	psi-mi:“MI:0914”(association)	0.350
SSUH2	IGLC7	psi-mi:“MI:0914”(association)	0.350
AGPAT1	A2ML1	psi-mi:“MI:0914”(association)	0.350

BioGRID (9): STEAP4 (Proximity Label-MS), STEAP4 (Affinity Capture-MS), STEAP4 (Affinity Capture-MS), STEAP4 (Affinity Capture-MS), STEAP4 (Affinity Capture-MS), STEAP4 (Affinity Capture-MS), STEAP4 (Synthetic Lethality), STEAP4 (Two-hybrid), STEAP4 (Two-hybrid)

ESM2 similar proteins: A3A9H6, A3KPR5, A5D9A7, C4IYS8, P0AEL1, P10897, P34465, P49447, Q04453, Q0WRW8, Q2Y9R4, Q3T130, Q497B2, Q4V8K1, Q503V1, Q53TN4, Q5CZL8, Q5RAJ4, Q5RCZ2, Q5RKJ2, Q5U2W7, Q5XGD7, Q60720, Q67ZF6, Q687X5, Q6DDR3, Q6I681, Q6INU7, Q6NS09, Q6P1H1, Q7XMK3, Q8L856, Q8NBI2, Q8VCZ2, Q8VYH6, Q91577, Q923B6, Q925G2, Q93ZH9, Q95204

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	35
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

845 predictions. Top by Δscore:

Variant	Effect	Δscore
7:88282841:C:CT	acceptor_gain	1.0000
7:88282842:A:T	acceptor_gain	1.0000
7:88284272:C:CC	acceptor_gain	1.0000
7:88279478:TGATC:T	donor_gain	0.9900
7:88282841:C:T	acceptor_gain	0.9900
7:88283024:T:TA	donor_gain	0.9900
7:88283024:TCC:T	donor_gain	0.9900
7:88283039:G:C	donor_gain	0.9900
7:88283051:A:AC	donor_gain	0.9900
7:88283052:C:CC	donor_gain	0.9900
7:88284267:CATAA:C	acceptor_gain	0.9900
7:88284269:TAA:T	acceptor_gain	0.9900
7:88306787:CCCA:C	donor_loss	0.9900
7:88306789:CAC:C	donor_loss	0.9900
7:88306790:A:C	donor_loss	0.9900
7:88306791:C:A	donor_loss	0.9900
7:88279245:C:G	acceptor_gain	0.9800
7:88279536:CCAT:C	donor_gain	0.9800
7:88279629:C:CC	acceptor_gain	0.9800
7:88282838:C:CT	acceptor_gain	0.9800
7:88282854:C:CT	acceptor_gain	0.9800
7:88279480:A:AC	donor_gain	0.9700
7:88282636:TTTA:T	donor_loss	0.9700
7:88282637:TTA:T	donor_loss	0.9700
7:88282638:TACC:T	donor_loss	0.9700
7:88282639:ACCTG:A	donor_loss	0.9700
7:88282640:C:T	donor_loss	0.9700
7:88282848:G:C	acceptor_gain	0.9700
7:88282855:A:T	acceptor_gain	0.9700
7:88283025:C:A	donor_gain	0.9700

AlphaMissense

2965 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:88280927:G:C	F379L	0.995
7:88280927:G:T	F379L	0.995
7:88280929:A:G	F379L	0.995
7:88280936:C:A	W376C	0.993
7:88280936:C:G	W376C	0.993
7:88283027:A:G	W200R	0.991
7:88283027:A:T	W200R	0.991
7:88280955:A:T	V370D	0.990
7:88280977:C:G	G363R	0.990
7:88280977:C:T	G363R	0.990
7:88282769:A:G	W286R	0.990
7:88282769:A:T	W286R	0.990
7:88279598:A:G	C394R	0.989
7:88281001:C:A	G355W	0.989
7:88281001:C:G	G355R	0.989
7:88281001:C:T	G355R	0.989
7:88281010:C:G	G352R	0.989
7:88281010:C:T	G352R	0.989
7:88282756:C:G	R290P	0.989
7:88279606:A:G	L391P	0.988
7:88282752:C:A	K291N	0.988
7:88282752:C:G	K291N	0.988
7:88282765:A:G	M287T	0.988
7:88283955:G:C	S105R	0.988
7:88283955:G:T	S105R	0.988
7:88283957:T:G	S105R	0.988
7:88279429:C:G	R450P	0.987
7:88280919:A:T	V382D	0.987
7:88280976:C:T	G363E	0.987
7:88279618:C:T	G387D	0.986

dbSNP variants (sampled 300 via entrez): RS1000017750 (7:88295654 G>A,C), RS1000023687 (7:88290658 T>C), RS1000093600 (7:88286560 C>G), RS1000216726 (7:88283437 G>T), RS1000291580 (7:88276705 G>A), RS1000297175 (7:88279651 T>A,C,G), RS1000380963 (7:88297381 A>T), RS1000516990 (7:88305002 G>T), RS1000630965 (7:88278209 T>C), RS1000670094 (7:88298215 A>G), RS1000783895 (7:88270905 A>G), RS1000815302 (7:88270710 T>C), RS1001093208 (7:88304062 A>C,G), RS1001104168 (7:88284833 A>G), RS1001115699 (7:88277927 A>G)

Disease associations

OMIM: gene MIM:611098 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST005042_10	Restless legs syndrome	2.000000e-34

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	increases expression, decreases expression, affects cotreatment	4
Nickel	decreases expression, increases expression	3
Benzo(a)pyrene	affects methylation, increases expression	2
Progesterone	affects cotreatment, increases expression	2
Smoke	decreases expression	2
Tobacco Smoke Pollution	affects expression	2
Particulate Matter	affects expression, increases abundance, decreases expression	2
triphenyl phosphate	affects expression	1
glycidyl methacrylate	decreases expression	1
sodium arsenate	decreases expression, increases abundance	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
sulforaphane	decreases expression	1
tobacco tar	decreases expression, decreases reaction	1
diallyl disulfide	decreases expression, decreases reaction	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
2,2’,4,4’,5-brominated diphenyl ether	increases expression	1
licochalcone B	decreases expression	1
incobotulinumtoxinA	increases expression	1
Troglitazone	decreases expression	1
Air Pollutants	affects expression, increases abundance, decreases expression	1
Air Pollutants, Occupational	decreases expression	1
Arsenic	decreases expression, increases abundance	1
Calcitriol	increases expression, affects cotreatment	1
Lipopolysaccharides	increases expression, affects response to substance, affects cotreatment	1
Naled	affects expression	1
Silicon Dioxide	increases expression	1

Clinical trials (associated diseases)

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