SELENOT

Summary

SELENOT (selenoprotein T, HGNC:18136) is a protein-coding gene on chromosome 3q25.1, encoding Thioredoxin reductase-like selenoprotein T (P62341). Selenoprotein with thioredoxin reductase-like oxidoreductase activity.

This gene encodes a selenoprotein, containing a selenocysteine (Sec) residue at the active site. Sec 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 localized in the endoplasmic reticulum. It belongs to the SelWTH family that possesses a thioredoxin-like fold and a conserved CxxU (C is cysteine, U is Sec) motif found in several redox active proteins. Studies in mice indicate a crucial role for this gene in the protection of dopaminergic neurons against oxidative stress in Parkinson’s disease, and in the control of glucose homeostasis in pancreatic beta-cells. Pseudogenes of this locus have been identified on chromosomes 9 and 5.

Source: NCBI Gene 51714 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 26 total
• MANE Select transcript: NM_016275

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18136
Approved symbol	SELENOT
Name	selenoprotein T
Location	3q25.1
Locus type	gene with protein product
Status	Approved
Aliases	SELT
Ensembl gene	ENSG00000198843
Ensembl biotype	protein_coding
OMIM	607912
Entrez	51714

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000466234, ENST00000471696, ENST00000477889, ENST00000480740, ENST00000485923, ENST00000492132

RefSeq mRNA: 1 — MANE Select: NM_016275 NM_016275

CCDS: CCDS46936

Canonical transcript exons

ENST00000471696 — 6 exons

Exon	Start	End
ENSE00001849027	150603321	150603499
ENSE00001867912	150627659	150630436
ENSE00003480999	150622385	150622495
ENSE00003488287	150627010	150627163
ENSE00003548250	150624812	150624899
ENSE00003682638	150623043	150623169

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 98.17.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 134.8780 / max 797.7769, expressed in 1824 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
39201	124.2153	1824
39202	4.9764	1382
39203	4.7259	739
39207	0.9603	497

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
islet of Langerhans	UBERON:0000006	98.17	gold quality
right adrenal gland	UBERON:0001233	97.73	gold quality
right adrenal gland cortex	UBERON:0035827	97.69	gold quality
medial globus pallidus	UBERON:0002477	97.64	gold quality
left adrenal gland	UBERON:0001234	97.55	gold quality
monocyte	CL:0000576	97.54	gold quality
leukocyte	CL:0000738	97.52	gold quality
mononuclear cell	CL:0000842	97.52	gold quality
type B pancreatic cell	CL:0000169	97.48	gold quality
stromal cell of endometrium	CL:0002255	97.46	gold quality
left adrenal gland cortex	UBERON:0035825	97.32	gold quality
prefrontal cortex	UBERON:0000451	97.21	gold quality
adrenal gland	UBERON:0002369	97.12	gold quality
adrenal cortex	UBERON:0001235	96.98	gold quality
globus pallidus	UBERON:0001875	96.97	gold quality
heart right ventricle	UBERON:0002080	96.97	gold quality
adrenal tissue	UBERON:0018303	96.92	gold quality
bone marrow cell	CL:0002092	96.85	gold quality
bone marrow	UBERON:0002371	96.77	gold quality
rectum	UBERON:0001052	96.69	gold quality
smooth muscle tissue	UBERON:0001135	96.65	gold quality
lateral nuclear group of thalamus	UBERON:0002736	96.52	gold quality
mucosa of sigmoid colon	UBERON:0004993	96.50	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.29	gold quality
corpus callosum	UBERON:0002336	96.27	gold quality
colonic mucosa	UBERON:0000317	96.19	gold quality
right coronary artery	UBERON:0001625	96.12	gold quality
descending thoracic aorta	UBERON:0002345	96.10	gold quality
substantia nigra pars reticulata	UBERON:0001966	96.09	gold quality
lymph node	UBERON:0000029	96.07	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-3929	no	981.15
E-MTAB-7303	no	259.14
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

205 targeting SELENOT, 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-8485	100.00	77.57	4731
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548AW	99.99	72.57	3559
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-4650-5P	99.98	64.69	999
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-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-4789-5P	99.98	70.76	2721

Literature-anchored findings (GeneRIF, showing 3)

• The paper reported that the full-length SELT protein contains 182 amino acids. (PMID:12775843)
• Data suggest SELT is expressed in pancreatic beta- and delta-cells; inactivation of SELT in beta-cells leads to glucose intolerance via impaired glucose homeostasis and PACAP (pituitary adenylate cyclase-activating polypeptide) insulinotropic effect. (PMID:23913443)
• The redox-active defensive Selenoprotein T as a novel stress sensor protein playing a key role in the pathophysiology of heart failure. (PMID:38643121)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	selenot1b	ENSDARG00000027595
danio_rerio	selenot1a	ENSDARG00000058354
mus_musculus	Selenot	ENSMUSG00000075700
rattus_norvegicus	Selenot	ENSRNOG00000013507
drosophila_melanogaster	SelT	FBGN0031670
caenorhabditis_elegans		WBGENE00007955
caenorhabditis_elegans		WBGENE00009238

Protein

Protein identifiers

Thioredoxin reductase-like selenoprotein T — P62341 (reviewed: P62341)

All UniProt accessions (3): P62341, F6U0C2, F8WBD0

UniProt curated annotations — full annotation on UniProt →

Function. Selenoprotein with thioredoxin reductase-like oxidoreductase activity. Protects dopaminergic neurons against oxidative stress and cell death. Involved in ADCYAP1/PACAP-induced calcium mobilization and neuroendocrine secretion. Plays a role in fibroblast anchorage and redox regulation. In gastric smooth muscle, modulates the contraction processes through the regulation of calcium release and MYLK activation. In pancreatic islets, involved in the control of glucose homeostasis, contributes to prolonged ADCYAP1/PACAP-induced insulin secretion.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Ubiquitous. Highly expressed in the endocrine pancreas.

Post-translational modifications. May contain a selenide-sulfide bond between Cys-46 and Sec-49. This bond is speculated to serve as redox-active pair.

Disease relevance. mRNA levels are increased more than 200-folds in the caudate putamen from Parkinson disease (PD) patients compared to control subjects. In conditional brain knockout mice, treatment with PD-inducing neurotoxins provoke rapid and severe parkinsonian-like motor defects.

Induction. Induced by Parkinson disease-inducing neurotoxins such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).

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

RefSeq proteins (1): NP_057359* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011893	Selenoprotein_Rdx-typ	Family
IPR019389	Selenoprotein_T	Family
IPR036249	Thioredoxin-like_sf	Homologous_superfamily

Pfam: PF10262

Catalyzed reactions (Rhea), 1 shown:

• [thioredoxin]-dithiol + NADP(+) = [thioredoxin]-disulfide + NADPH + H(+) (RHEA:20345)

UniProt features (8 total): sequence conflict 2, signal peptide 1, chain 1, transmembrane region 1, non-standard amino acid 1, cross-link 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

No AlphaFold model available for P62341 — 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 (1): 46–49

Mutagenesis-validated functional residues (1):

Position	Phenotype
49	increases ros levels induced by neurotoxins.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 230 (showing top): GOBP_INSULIN_SECRETION, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, GOBP_CELLULAR_RESPONSE_TO_CARBOHYDRATE_STIMULUS, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_HORMONE_TRANSPORT, DARWICHE_SKIN_TUMOR_PROMOTER_DN, DARWICHE_PAPILLOMA_RISK_LOW_UP, DARWICHE_PAPILLOMA_RISK_HIGH_UP, DARWICHE_SQUAMOUS_CELL_CARCINOMA_DN, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_CELL_CELL_SIGNALING, GOBP_PANCREAS_DEVELOPMENT, GOBP_TRANSLATION, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION

GO Biological Process (9): selenocysteine incorporation (GO:0001514), positive regulation of cytosolic calcium ion concentration (GO:0007204), response to glucose (GO:0009749), pancreas development (GO:0031016), insulin secretion involved in cellular response to glucose stimulus (GO:0035773), glucose homeostasis (GO:0042593), cell redox homeostasis (GO:0045454), positive regulation of growth hormone secretion (GO:0060124), cellular oxidant detoxification (GO:0098869)

GO Molecular Function (3): thioredoxin-disulfide reductase (NADPH) activity (GO:0004791), selenium binding (GO:0008430), oxidoreductase activity (GO:0016491)

GO Cellular Component (3): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
translational readthrough	1
regulation of biological quality	1
response to hexose	1
animal organ development	1
insulin secretion	1
establishment of localization in cell	1
cellular response to glucose stimulus	1
carbohydrate homeostasis	1
cellular homeostasis	1
growth hormone secretion	1
regulation of growth hormone secretion	1
positive regulation of peptide hormone secretion	1
cellular detoxification	1
antioxidant activity	1
protein-disulfide reductase [NAD(P)H] activity	1
small molecule binding	1
catalytic activity	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cellular anatomical structure	1

Protein interactions and networks

STRING

556 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SELENOT	SELENOW	P63302	978
SELENOT	SELENOK	Q9Y6D0	918
SELENOT	SELENOF	O60613	914
SELENOT	SELENOS	Q9BQE4	912
SELENOT	SELENOO	Q9BVL4	895
SELENOT	SELENON	Q9NZV5	894
SELENOT	SELENOM	Q8WWX9	893
SELENOT	SELENOH	Q8IZQ5	886
SELENOT	MIEN1	Q9BRT3	876
SELENOT	SEPHS2	Q99611	874
SELENOT	SELENOV	P59797	873
SELENOT	SECISBP2	Q96T21	869
SELENOT	MSRB1	Q9NZV6	837
SELENOT	TXN	P10599	833
SELENOT	SELENOI	Q9C0D9	823

IntAct

57 interactions, top by confidence:

A	B	Type	Score
NIPAL1	ESYT2	psi-mi:“MI:0914”(association)	0.640
EIF2B2	SLC27A2	psi-mi:“MI:0914”(association)	0.640
ALDH3B1	UBA6	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
IPPK	TMEM223	psi-mi:“MI:0914”(association)	0.530
SLC2A12	METTL15	psi-mi:“MI:0914”(association)	0.530
GDPD5	GOLIM4	psi-mi:“MI:0914”(association)	0.530
PEX19	FAM20B	psi-mi:“MI:0914”(association)	0.530
CNPY3	SELENOT	psi-mi:“MI:0914”(association)	0.530
CXCR4	TMEM120B	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM120B	psi-mi:“MI:0914”(association)	0.530
SLC22A15	ZFPL1	psi-mi:“MI:0914”(association)	0.530
TIGD3	CTPS1	psi-mi:“MI:0914”(association)	0.530
BORCS6	HSBP1	psi-mi:“MI:0914”(association)	0.530
UPK1A	TMEM223	psi-mi:“MI:0914”(association)	0.350
TEX28	NBAS	psi-mi:“MI:0914”(association)	0.350
SLC39A12	POM121C	psi-mi:“MI:0914”(association)	0.350
CNR2	ILVBL	psi-mi:“MI:0914”(association)	0.350
Npc1	ESYT2	psi-mi:“MI:0914”(association)	0.350
CCDC47	ESYT2	psi-mi:“MI:0914”(association)	0.350
NCLN	PGRMC1	psi-mi:“MI:0914”(association)	0.350
AVPR2	GXYLT2	psi-mi:“MI:0914”(association)	0.350
SV2A	ILVBL	psi-mi:“MI:0914”(association)	0.350

BioGRID (68): SELT (Affinity Capture-MS), SELT (Affinity Capture-MS), SELT (Affinity Capture-MS), SELT (Affinity Capture-MS), SELT (Affinity Capture-MS), SELT (Affinity Capture-MS), SELT (Affinity Capture-MS), SELT (Affinity Capture-MS), SELT (Affinity Capture-MS), SELT (Affinity Capture-MS), SELT (Affinity Capture-MS), SELT (Affinity Capture-MS), SELT (Affinity Capture-MS), SELT (Affinity Capture-MS), SELT (Two-hybrid)

ESM2 similar proteins: A2YMP7, A4FUZ5, A6QP01, A8WG88, F4I8Q7, O14657, P58499, P62341, P62342, Q08DK0, Q0IJ33, Q1H5H1, Q28EH9, Q502K9, Q53P98, Q5R9S8, Q5TYV0, Q5XF36, Q5XF80, Q5XIP9, Q5ZI25, Q5ZJN8, Q68G38, Q6GP98, Q6IR55, Q6PBD1, Q6PD82, Q6PHY8, Q6WRS2, Q6X4M2, Q7F613, Q7JW12, Q7ZV50, Q802F2, Q803X0, Q8K304, Q8VBZ3, Q8WQG1, Q94I55, Q9BN19

Diamond homologs: A6QP01, P62341, P62342, Q19892, Q1H5H1, Q502K9, Q5ZJN8, Q6PBD1, Q6PHY8, Q802F2, Q9BN19, Q9U3N5, Q9VMV6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	20
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

814 predictions. Top by Δscore:

Variant	Effect	Δscore
3:150603500:G:GG	donor_gain	1.0000
3:150603500:GT:G	donor_loss	1.0000
3:150603501:T:G	donor_loss	1.0000
3:150603502:G:GT	donor_loss	1.0000
3:150622380:TGCA:T	acceptor_loss	1.0000
3:150622381:GCA:G	acceptor_loss	1.0000
3:150622382:CAGT:C	acceptor_loss	1.0000
3:150622383:A:AG	acceptor_gain	1.0000
3:150622383:A:G	acceptor_loss	1.0000
3:150622383:AGT:A	acceptor_gain	1.0000
3:150622384:G:GA	acceptor_gain	1.0000
3:150622384:GT:G	acceptor_gain	1.0000
3:150622384:GTG:G	acceptor_gain	1.0000
3:150622384:GTGT:G	acceptor_gain	1.0000
3:150622384:GTGTT:G	acceptor_gain	1.0000
3:150622491:TATAG:T	donor_gain	1.0000
3:150622493:TAG:T	donor_gain	1.0000
3:150622493:TAGG:T	donor_loss	1.0000
3:150622495:GGTA:G	donor_loss	1.0000
3:150622496:G:GG	donor_gain	1.0000
3:150622496:GTA:G	donor_loss	1.0000
3:150622497:T:G	donor_loss	1.0000
3:150623038:GATA:G	acceptor_loss	1.0000
3:150623040:TA:T	acceptor_loss	1.0000
3:150623041:A:AG	acceptor_gain	1.0000
3:150623041:AGA:A	acceptor_loss	1.0000
3:150623042:G:A	acceptor_loss	1.0000
3:150623042:G:GA	acceptor_gain	1.0000
3:150623042:GAC:G	acceptor_gain	1.0000
3:150623042:GACA:G	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000002145 (3:150614875 A>G,T), RS1000030094 (3:150601650 A>C), RS1000158171 (3:150624324 C>G), RS1000266382 (3:150607741 C>T), RS1000353002 (3:150615011 C>T), RS1000540414 (3:150621467 G>A), RS1000996553 (3:150602123 A>G), RS1001112180 (3:150601850 C>A), RS1001277601 (3:150621568 G>A), RS1001439616 (3:150606758 A>C,G), RS1001488713 (3:150606242 C>G,T), RS1001518536 (3:150606569 A>G), RS1001647567 (3:150613136 A>G), RS1001666470 (3:150621274 C>A,G), RS1001794811 (3:150604896 G>A)

Disease associations

OMIM: gene MIM:607912 | 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

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression	2
Lead	affects expression, increases expression	2
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Coumestrol	increases expression	1
Estradiol	affects expression	1
Gold	decreases expression	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Smoke	increases abundance, decreases expression	1
Dronabinol	increases expression	1
Valproic Acid	increases expression	1
Antirheumatic Agents	decreases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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