SELENOW

Summary

SELENOW (selenoprotein W, HGNC:10752) is a protein-coding gene on chromosome 19q13.33, encoding Selenoprotein W (P63302). Plays a role as a glutathione (GSH)-dependent antioxidant.

This gene encodes a selenoprotein containing a selenocysteine (Sec) residue, which is encoded by the UGA codon that normally signals translation termination. The 3’ UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, the Sec insertion sequence (SECIS) element that is necessary for the recognition of UGA as a Sec codon rather than as a stop signal. This protein is highly expressed in skeletal muscle, heart and brain. It belongs to the SelWTH family, which possesses a thioredoxin-like fold and a conserved CxxU (C is cysteine, U is Sec) motif, suggesting a redox function for this gene. Studies in mouse show that this selenoprotein is involved in muscle growth and differentiation, and in the protection of neurons from oxidative stress during neuronal development. A retroprocessed pseudogene of this locus has been identified on chromosome 1.

Source: NCBI Gene 6415 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 23 total
• MANE Select transcript: NM_003009

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10752
Approved symbol	SELENOW
Name	selenoprotein W
Location	19q13.33
Locus type	gene with protein product
Status	Approved
Aliases	SELW
Ensembl gene	ENSG00000178980
Ensembl biotype	protein_coding
OMIM	603235
Entrez	6415

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 6 retained_intron, 4 protein_coding_CDS_not_defined, 3 protein_coding, 1 nonsense_mediated_decay

ENST00000593892, ENST00000595509, ENST00000595615, ENST00000598083, ENST00000598273, ENST00000598956, ENST00000599302, ENST00000599590, ENST00000599627, ENST00000599874, ENST00000601048, ENST00000601419, ENST00000601937, ENST00000602163

RefSeq mRNA: 1 — MANE Select: NM_003009 NM_003009

CCDS: CCDS59402

Canonical transcript exons

ENST00000601048 — 6 exons

Exon	Start	End
ENSE00003042399	47778703	47778814
ENSE00003483396	47780725	47780749
ENSE00003544240	47781108	47781182
ENSE00003613460	47780864	47780917
ENSE00003650423	47781290	47781388
ENSE00003845747	47784290	47784682

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 99.83.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 183.8909 / max 2375.6306, expressed in 1825 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
176723	164.7023	1822
176722	12.2135	1763
176724	4.9360	1363
176719	0.8289	376
176720	0.4835	287
176726	0.2933	109
176727	0.2129	87
176725	0.0605	16
176730	0.0509	26
176728	0.0501	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	99.83	gold quality
prefrontal cortex	UBERON:0000451	99.82	gold quality
amygdala	UBERON:0001876	99.81	gold quality
right frontal lobe	UBERON:0002810	99.81	gold quality
Ammon’s horn	UBERON:0001954	99.75	gold quality
caudate nucleus	UBERON:0001873	99.74	gold quality
cingulate cortex	UBERON:0003027	99.74	gold quality
nucleus accumbens	UBERON:0001882	99.73	gold quality
inferior vagus X ganglion	UBERON:0005363	99.73	gold quality
anterior cingulate cortex	UBERON:0009835	99.73	gold quality
frontal cortex	UBERON:0001870	99.71	gold quality
parietal lobe	UBERON:0001872	99.71	gold quality
ventral tegmental area	UBERON:0002691	99.71	gold quality
Brodmann (1909) area 9	UBERON:0013540	99.71	gold quality
temporal lobe	UBERON:0001871	99.70	gold quality
postcentral gyrus	UBERON:0002581	99.70	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.70	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	99.70	gold quality
right hemisphere of cerebellum	UBERON:0014890	99.70	gold quality
pons	UBERON:0000988	99.69	gold quality
putamen	UBERON:0001874	99.67	gold quality
heart left ventricle	UBERON:0002084	99.67	gold quality
spinal cord	UBERON:0002240	99.67	gold quality
cardiac ventricle	UBERON:0002082	99.66	gold quality
cerebellar hemisphere	UBERON:0002245	99.66	gold quality
superior vestibular nucleus	UBERON:0007227	99.66	gold quality
neocortex	UBERON:0001950	99.65	gold quality
cerebellar cortex	UBERON:0002129	99.65	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.65	gold quality
right atrium auricular region	UBERON:0006631	99.64	gold quality

Single-cell (SCXA)

Detected in 22 experiment(s), a significant marker in 19.

Experiment	Marker?	Max mean expression
E-GEOD-81547	yes	877.78
E-MTAB-10287	yes	65.58
E-HCAD-10	yes	51.63
E-HCAD-1	yes	46.69
E-HCAD-11	yes	44.23
E-CURD-46	yes	38.96
E-MTAB-6701	yes	35.37
E-MTAB-8410	yes	24.38
E-MTAB-8142	yes	18.81
E-GEOD-125970	yes	16.02
E-GEOD-135922	yes	13.99
E-MTAB-6678	yes	12.89
E-GEOD-84465	yes	12.00
E-CURD-114	yes	11.67
E-MTAB-10042	yes	10.92

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MTF1, MYOD1

miRNA regulators (miRDB)

24 targeting SELENOW, 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-3064-3P	100.00	70.09	1254
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-6770-5P	98.97	66.76	1853
HSA-MIR-5001-3P	98.91	67.28	1394
HSA-MIR-4700-5P	98.63	67.43	1915
HSA-MIR-8060	98.61	66.93	1187
HSA-MIR-6754-5P	98.60	65.54	1627
HSA-MIR-6881-5P	98.16	67.38	665
HSA-MIR-211-3P	98.14	66.77	1052
HSA-MIR-8089	97.74	66.21	1698
HSA-MIR-4667-5P	97.61	66.67	1683
HSA-MIR-1910-5P	97.42	66.36	844
HSA-MIR-12128	96.67	66.98	1471
HSA-MIR-7706	95.96	63.68	172
HSA-MIR-3927-5P	94.90	68.11	399

Literature-anchored findings (GeneRIF, showing 16)

• The gene lacks canonical TATA and CAAT boxes, but has numerous Sp1 consensus binding sites upstream of multiple transcription start sites. SEPW1 is expressed in all of the 22 tissues assayed, and shows highest expression in skeletal muscle and heart. (PMID:12818432)
• SelW expression in the colon is highly sensitive to Se-depletion (PMID:15670848)
• SeW is the novel molecular target of MeHg in human neuronal cells and down-regulation of this selenoenzyme by MeHg is dependent not on generation of ROS but on depletion of GSH. (PMID:15823556)
• SEPW1 mRNA levels were maximal during G1-phase, dropped after the G1/S transition and increased again after G2/M-phase. (PMID:19387567)
• The small interfering RNA knockdown of BNIP3, IER3, and SEPW1 genes affected critical multiple myeloma endothelial cell functions correlated with the overangiogenic phenotype (PMID:19690192)
• p53 was increased in SEPW1 silenced cells and was inversely correlated with SEPW1 mRNA in cell lines with altered SEPW1 expression. (PMID:21866568)
• The present work shows that SEPW1 facilitates the G1 to S-phase transition by down-regulating expression of the cyclin-dependent kinase inhibitor p21 (PMID:21875573)
• SEPW1 silencing increases MKK4, which activates p38gamma, p38delta, and JNK2 to phosphorylate p53 on Ser-33 and cause a transient G(1) arrest. (PMID:22730327)
• In response to selenium compounds, SepW1 synthesis increased at the protein and the mRNA levels. (PMID:23830627)
• Suppression of EGFR ubiquitination by SEPW1 may be related to the putative increase in cancer risk associated with high selenium intakes. (PMID:25721765)
• SelW may have a regulatory function in redox cell signaling by interacting with 14-3-3 protein. (PMID:26474786)
• The SS concentrations that lead to a decrease in the viability of human prostate adenocarcinoma cells (line Du-145) have been selected, and the effect of sodium selenite on the expression of mRNA of the SELV, SELW, and TGR selenocysteine proteins in these cells has been analyzed. (PMID:29989584)
• Functional studies demonstrated that piRNA-36,712 interacts with RNAs produced by SEPW1P, a retroprocessed pseudogene of SEPW1, and subsequently inhibits SEPW1 expression through competition of SEPW1 mRNA with SEPW1P RNA for microRNA-7 and microRNA-324. (PMID:30636640)
• We performed a yeast two-hybrid screen on a human fetal brain cDNA library and identified FAM96B as a novel binding partner of SelW. FRET analyses confirmed the interaction between SelW’ and FAM96B. (PMID:30876693)
• Role of Selenoprotein W in participating in the progression of non-alcoholic fatty liver disease. (PMID:38460355)
• Selenoprotein W engages in overactive osteoclast differentiation in multiple myeloma. (PMID:38683225)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	selenow1	ENSDARG00000035136
mus_musculus	Selenow	ENSMUSG00000041571
rattus_norvegicus	Selenow	ENSRNOG00000051483

Paralogs (2): MIEN1 (ENSG00000141741), SELENOV (ENSG00000186838)

Protein

Protein identifiers

Selenoprotein W — P63302 (reviewed: P63302)

All UniProt accessions (2): P63302, M0QYX1

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role as a glutathione (GSH)-dependent antioxidant. May be involved in a redox-related process. May play a role in the myopathies of selenium deficiency.

Subunit / interactions. Interacts with DPYSL2, PRDX1, YWHAB, YWHAG, HSP70 and HSP90.

Subcellular location. Cytoplasm.

Tissue specificity. Ubiquitously expressed with highest levels in skeletal muscle and heart, moderate levels in brain, spinal cord, thyroid, spleen, prostate, ovary, small intestine and colon, and lowest levels in liver and lymph node.

Similarity. Belongs to the SelWTH family. Selenoprotein W subfamily.

RefSeq proteins (1): NP_003000* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011893	Selenoprotein_Rdx-typ	Family
IPR036249	Thioredoxin-like_sf	Homologous_superfamily
IPR051441	SelW_related	Family

Pfam: PF10262

UniProt features (4 total): chain 1, non-standard amino acid 1, modified residue 1, cross-link 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

No AlphaFold model available for P63302 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

Functional residue map

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

Post-translational modifications (2): 37, 10–13

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 209 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, MODULE_93, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, GOBP_MYELOID_CELL_HOMEOSTASIS, ENK_UV_RESPONSE_KERATINOCYTE_UP, GOBP_ERYTHROCYTE_HOMEOSTASIS, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, HSIAO_HOUSEKEEPING_GENES, MORI_IMMATURE_B_LYMPHOCYTE_UP, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, WATANABE_ULCERATIVE_COLITIS_WITH_CANCER_UP, FOSTER_TOLERANT_MACROPHAGE_DN, GOBP_CELLULAR_RESPONSE_TO_TOXIC_SUBSTANCE, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM4

GO Biological Process (6): response to stress (GO:0006950), response to selenium ion (GO:0010269), erythrocyte differentiation (GO:0030218), response to lipopolysaccharide (GO:0032496), selenocysteine incorporation (GO:0001514), cellular oxidant detoxification (GO:0098869)

GO Molecular Function (1): antioxidant activity (GO:0016209)

GO Cellular Component (2): cytosol (GO:0005829), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
response to stimulus	1
response to chemical	1
myeloid cell differentiation	1
erythrocyte homeostasis	1
response to molecule of bacterial origin	1
response to lipid	1
response to oxygen-containing compound	1
translational readthrough	1
cellular detoxification	1
molecular_function	1
cellular oxidant detoxification	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

342 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SELENOW	SELENOT	P62341	978
SELENOW	SELENOO	Q9BVL4	866
SELENOW	SELENOK	Q9Y6D0	858
SELENOW	MIEN1	Q9BRT3	831
SELENOW	SELENOH	Q8IZQ5	824
SELENOW	SELENOS	Q9BQE4	802
SELENOW	SELENOF	O60613	801
SELENOW	MSRB1	Q9NZV6	793
SELENOW	SECISBP2	Q96T21	787
SELENOW	SELENON	Q9NZV5	786
SELENOW	SEPHS2	Q99611	782
SELENOW	TXN	P10599	781
SELENOW	SELENOP	P49908	779
SELENOW	PRDX1	P35703	744
SELENOW	TXNRD3	Q86VQ6	741

IntAct

3 interactions, top by confidence:

A	B	Type	Score
SELENOW	E7	psi-mi:“MI:0915”(physical association)	0.370
SELENOW	TSC1	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (11): SEPW1 (Affinity Capture-RNA), SEPW1 (Affinity Capture-MS), SEPW1 (Affinity Capture-RNA), SEPW1 (Protein-RNA), SEPW1 (Affinity Capture-RNA), SEPW1 (Two-hybrid), GDPGP1 (Co-fractionation), SEPW1 (Two-hybrid), SEPW1 (Two-hybrid), SEPW1 (Two-hybrid), SEPW1 (Affinity Capture-RNA)

ESM2 similar proteins: A0K0C0, A0L3J9, A0LDN3, A3CUG3, A4X4L9, A5VTK6, A7HH87, A8JGF7, A8M723, A9GD65, A9MDK1, A9WXF1, B1ZY08, B2GKC1, B2SCQ3, B3R684, B8HFS1, B8ZU00, C0RK37, D0EYG3, L0TAD5, O19097, O83641, P0C5D0, P22989, P28624, P63300, P63301, P63302, P63303, Q02127, Q11IW3, Q1D084, Q1IW89, Q2IG40, Q2J717, Q3BUC6, Q568W0, Q579Z7, Q5E9W3

Diamond homologs: D0EYG3, O19097, P59797, P63300, P63301, P63302, P63303, Q148C8, Q568W0, Q5NVB2, Q95KL4, Q9BRT3, Q9CQ86, Q9STZ2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	14
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

964 predictions. Top by Δscore:

Variant	Effect	Δscore
19:47780862:A:AG	acceptor_gain	1.0000
19:47780863:G:GA	acceptor_gain	1.0000
19:47780863:GT:G	acceptor_gain	1.0000
19:47780863:GTA:G	acceptor_gain	1.0000
19:47780863:GTAT:G	acceptor_gain	1.0000
19:47780918:G:GG	donor_gain	1.0000
19:47781105:CAG:C	acceptor_loss	1.0000
19:47781106:A:AG	acceptor_gain	1.0000
19:47781106:A:T	acceptor_loss	1.0000
19:47781106:AGTGC:A	acceptor_gain	1.0000
19:47781107:G:GA	acceptor_gain	1.0000
19:47781107:GT:G	acceptor_gain	1.0000
19:47781107:GTGC:G	acceptor_gain	1.0000
19:47781107:GTGCG:G	acceptor_gain	1.0000
19:47781287:TA:T	acceptor_loss	1.0000
19:47781288:A:AC	acceptor_loss	1.0000
19:47781288:A:AG	acceptor_gain	1.0000
19:47781289:G:GA	acceptor_gain	1.0000
19:47781289:GA:G	acceptor_gain	1.0000
19:47781289:GAAA:G	acceptor_gain	1.0000
19:47781365:GGC:G	donor_gain	1.0000
19:47778811:ATTGG:A	donor_loss	0.9900
19:47778812:TTGG:T	donor_loss	0.9900
19:47778813:TGGTA:T	donor_loss	0.9900
19:47778814:GGT:G	donor_loss	0.9900
19:47778815:G:GG	donor_gain	0.9900
19:47778815:GTA:G	donor_loss	0.9900
19:47778816:TAAG:T	donor_loss	0.9900
19:47780616:T:A	acceptor_gain	0.9900
19:47780694:T:TA	acceptor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000140609 (19:47778744 G>A,T), RS1000162461 (19:47781861 G>A), RS1000501732 (19:47780824 C>T), RS1000959177 (19:47776941 C>A,G,T), RS1000979112 (19:47781088 C>G,T), RS1001151035 (19:47781338 G>A,T), RS1001209669 (19:47776814 C>T), RS1001579610 (19:47785063 T>G), RS1001651708 (19:47784944 C>A,G,T), RS1001952841 (19:47784147 G>A,C), RS1003012650 (19:47780581 C>A,G), RS1003439736 (19:47779362 T>G), RS1003504635 (19:47784053 C>T), RS1003516950 (19:47780404 G>A,C), RS1003528631 (19:47779506 A>C,G)

Disease associations

OMIM: gene MIM:603235 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance	5
Valproic Acid	affects cotreatment, increases expression, affects expression	5
Arsenic	affects methylation, decreases expression, increases abundance, affects cotreatment	3
Sodium Selenite	increases expression	3
methylmercuric chloride	decreases expression	2
mercuric bromide	decreases expression, affects cotreatment	2
Mercuric Chloride	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tretinoin	increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
aristolochic acid I	increases expression	1
selenomethylselenocysteine	increases expression	1
propionaldehyde	increases expression	1
sodium arsenate	decreases expression, increases abundance	1
butyraldehyde	increases expression	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
pentanal	increases expression	1
di-n-butylphosphoric acid	affects expression	1
K 7174	decreases expression	1
motexafin gadolinium	affects cotreatment, increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, increases expression, affects cotreatment	1
ICG 001	increases expression	1
dorsomorphin	affects cotreatment, decreases expression, increases expression	1
PCI 5002	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Vorinostat	increases expression	1
Aldehydes	increases expression	1
Atrazine	increases expression	1
Cadmium	increases expression	1

Clinical trials (associated diseases)

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