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TXNRD2 thioredoxin reductase 2 [ Homo sapiens (human) ]

Gene ID: 10587, updated on 2-Nov-2024

Summary

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Official Symbol
TXNRD2provided by HGNC
Official Full Name
thioredoxin reductase 2provided by HGNC
Primary source
HGNC:HGNC:18155
See related
Ensembl:ENSG00000184470 MIM:606448; AllianceGenome:HGNC:18155
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
TR; TR3; SELZ; GCCD5; TRXR2; TXNR2; TR-BETA
Summary
The protein encoded by this gene belongs to the pyridine nucleotide-disulfide oxidoreductase family, and is a member of the thioredoxin (Trx) system. Three thioredoxin reductase (TrxR) isozymes are found in mammals. TrxRs are selenocysteine-containing flavoenzymes, which reduce thioredoxins, as well as other substrates, and play a key role in redox homoeostasis. This gene encodes a mitochondrial form important for scavenging reactive oxygen species in mitochondria. It functions as a homodimer containing FAD, and selenocysteine (Sec) at the active site. Sec is encoded by 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, which is necessary for the recognition of UGA as a Sec codon rather than as a stop signal. Alternatively spliced transcript variants encoding different isoforms, including a few localized in the cytosol and some lacking the C-terminal Sec residue, have been found for this gene. [provided by RefSeq, Jun 2017]
Expression
Ubiquitous expression in adrenal (RPKM 8.7), prostate (RPKM 8.7) and 25 other tissues See more
Orthologs
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Genomic context

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See TXNRD2 in Genome Data Viewer
Location:
22q11.21
Exon count:
22
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 22 NC_000022.11 (19875522..19941818, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 22 NC_060946.1 (20252392..20319509, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 22 NC_000022.10 (19863045..19929341, complement)

Chromosome 22 - NC_000022.11Genomic Context describing neighboring genes Neighboring gene G protein subunit beta 1 like Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:19840887-19841505 Neighboring gene uncharacterized LOC124905080 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18663 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:19856194-19857136 Neighboring gene retrotransposon Gag like 10 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:19864911-19865712 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:19866515-19867316 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:19867317-19868118 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:19868119-19868920 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:19868921-19869722 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:19878079-19878587 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:19878588-19879096 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:19879097-19879604 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:19879605-19880113 Neighboring gene ReSE screen-validated silencer GRCh37_chr22:19880414-19880618 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:19883730-19884368 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:19889902-19890838 Neighboring gene ribosomal protein L8 pseudogene 5 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr22:19894389-19895588 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:19904338-19904948 Neighboring gene endogenous retrovirus group K member 24 Gag polyprotein-like Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:19928490-19929059 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:19927919-19928489 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13467 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13468 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13469 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18664 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18665 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:19931341-19931910 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:19931911-19932479 Neighboring gene Sharpr-MPRA regulatory region 10527 Neighboring gene Sharpr-MPRA regulatory region 2516 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:19940787-19941410 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:19941411-19942032 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:19942297-19942948 Neighboring gene ReSE screen-validated silencer GRCh37_chr22:19943251-19943418 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:19949617-19950332 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:19950333-19951048 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:19951049-19951764 Neighboring gene catechol-O-methyltransferase Neighboring gene microRNA 4761 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:19970318-19971255 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:19971256-19972192 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:19973130-19974065 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13470 Neighboring gene ARVCF delta catenin family member Neighboring gene uncharacterized LOC124905082

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Mutations in the mitochondrial thioredoxin reductase gene TXNRD2 cause dilated cardiomyopathy. Sibbing D, et al. Eur Heart J, 2011 May. PMID 21247928
  2. Insight into the role of TXNRD2 in steroidogenesis through a novel homozygous TXNRD2 splice variant. Brachet C, et al. Eur J Endocrinol, 2024 Aug 5. PMID 39097530
  3. Inhibition of TrxR2 suppressed NSCLC cell proliferation, metabolism and induced cell apoptosis through decreasing antioxidant activity. Bu L, et al. Life Sci, 2017 Jun 1. PMID 28414076
  4. [TrxR2 gene polymorphisms may not be associated with the susceptibility to Kashin-Beck disease]. Lu W, et al. Nan Fang Yi Ke Da Xue Xue Bao, 2010 Oct. PMID 20965815
  5. TrxR2 deficiencies promote chondrogenic differentiation and induce apoptosis of chondrocytes through mitochondrial reactive oxygen species. Yan J, et al. Exp Cell Res, 2016 May 15. PMID 27107686

See all (87) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Insight into the role of TXNRD2 in steroidogenesis through a novel homozygous TXNRD2 splice variant.
    Title: Insight into the role of TXNRD2 in steroidogenesis through a novel homozygous TXNRD2 splice variant.
  2. Association analysis of variants rs35934224 in TXNRD2 and rs6478746 in LMX1B in primary angle-closure and pseudoexfoliation glaucoma.
    Title: Association analysis of variants rs35934224 in TXNRD2 and rs6478746 in LMX1B in primary angle-closure and pseudoexfoliation glaucoma.
  3. TXNRD2 (rs35934224) CT genotype and primary open-angle glaucoma: correspondenceReply to ""TXNRD2 (rs35934224) CT genotype and primary open-angle glaucoma: correspondence""Primary open-angle glaucomaGenome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open-angle glaucomaGenome-wide association study of primary open-angle glaucoma in continental and admixed African popula...
    Title: TXNRD2 (rs35934224) CT genotype and primary open-angle glaucoma: correspondenceReply to "TXNRD2 (rs35934224) CT genotype and primary open-angle glaucoma: correspondence"Primary open-angle glaucomaGenome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open-angle glaucomaGenome-wide association study of primary open-angle glaucoma in continental and admixed African populations.
  4. TXNRD2 (rs35934224) CT genotype as possible protective marker for primary open-angle glaucoma in a Brazilian population.
    Title: TXNRD2 (rs35934224) CT genotype as possible protective marker for primary open-angle glaucoma in a Brazilian population.
  5. miR-195-5p exerts tumor-suppressive functions in human lung cancer cells through targeting TrxR2.
    Title: miR-195-5p exerts tumor-suppressive functions in human lung cancer cells through targeting TrxR2.
  6. The aim of the study was to investigate the association between rs5859 in Sep15, rs1139793 in TrxR2 polymorphisms with the risks of KBD and to detect the expression of AP-1 pathway.
    Title: The study on polymorphisms of Sep15 and TrxR2 and the expression of AP-1 signaling pathway in Kashin-Beck disease.
  7. Based on recent research, it has been reported that the modulation of the Trx/TrxR system may be considered as a new target in the management of the metabolic syndrome, insulin resistance, and type 2 diabetes, as well as in the treatment of hypertension and atherosclerosis. In this review evidence about a possible role of this system as a marker of the metabolic syndrome is reported. [review]
    Title: The role of the thioredoxin/thioredoxin reductase system in the metabolic syndrome: towards a possible prognostic marker?
  8. TrxR2 was overexpressed in non-small-cell lung cancer cells; our results suggest that TrxR2 acts as an oncogenic gene in the context of lung cancer progression
    Title: Inhibition of TrxR2 suppressed NSCLC cell proliferation, metabolism and induced cell apoptosis through decreasing antioxidant activity.
  9. p53R2 acts as a positive regulator of TrxR2 activity in mitochondria both under normal physiological conditions and during the cellular response to DNA damage
    Title: p53R2 regulates thioredoxin reductase activity through interaction with TrxR2.
  10. TrxR2 deficiency-induced impaired proliferation and death of chondrocytes may be the pathological mechanism of the osteoarthropathy due to Selenium deficiency.
    Title: TrxR2 deficiencies promote chondrogenic differentiation and induce apoptosis of chondrocytes through mitochondrial reactive oxygen species.
Submit: New GeneRIF Correction See all GeneRIFs (34)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Glucocorticoid deficiency 5
MedGen: C4540522 OMIM: 617825 GeneReviews: Not available
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EBI GWAS Catalog

Description
Genome wide association study of SNP-, gene-, and pathway-based approaches to identify genes influencing susceptibility to Staphylococcus aureus infections.
EBI GWAS Catalog
Genome-wide association analyses identify three new susceptibility loci for primary angle closure glaucoma.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
matrix gag HIV-1 MA upregulates TXNRD2 (TR3) gene expression in HepG2 cells PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables flavin adenine dinucleotide binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein homodimerization activity ISS
Inferred from Sequence or Structural Similarity
more info
  
enables protein-containing complex binding IEA
Inferred from Electronic Annotation
more info
  
enables thioredoxin-disulfide reductase (NADPH) activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables thioredoxin-disulfide reductase (NADPH) activity ISS
Inferred from Sequence or Structural Similarity
more info
  
Process Evidence Code Pubs
involved_in cell redox homeostasis IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in cell redox homeostasis IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in cellular oxidant detoxification IEA
Inferred from Electronic Annotation
more info
  
involved_in response to hyperoxia IEA
Inferred from Electronic Annotation
more info
  
involved_in response to oxygen radical TAS
Traceable Author Statement
more info
 PubMed 
involved_in response to selenium ion IEA
Inferred from Electronic Annotation
more info
  
involved_in response to xenobiotic stimulus IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in axon IEA
Inferred from Electronic Annotation
more info
  
is_active_in cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
  
is_active_in cytosol IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytosol IDA
Inferred from Direct Assay
more info
  
located_in dendrite IEA
Inferred from Electronic Annotation
more info
  
located_in mitochondrial matrix TAS
Traceable Author Statement
more info
  
located_in mitochondrion HTP PubMed 
is_active_in mitochondrion IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in mitochondrion IDA
Inferred from Direct Assay
more info
 PubMed 
located_in neuronal cell body IEA
Inferred from Electronic Annotation
more info
  

General protein information

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Preferred Names
thioredoxin reductase 2, mitochondrial
Names
selenoprotein Z
thioredoxin reductase 3
thioredoxin reductase TR3
thioredoxin reductase beta
NP_001269441.1
NP_001339229.1
NP_001339230.1
NP_001339231.1
NP_001339232.1
NP_006431.2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_011835.1 RefSeqGene

    Range
    4845..71320
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_417

mRNA and Protein(s)

  1. NM_001282512.3 → NP_001269441.1  thioredoxin reductase 2, mitochondrial isoform 5 precursor

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) lacks several exons in the 3' coding region, and contains an alternate 3' terminal exon compared to variant 1. The resulting isoform (5) is shorter, with a distinct C-terminus (lacking selenocysteine) compared to isoform 1.
    Source sequence(s)
    AC000078, AF044212, AF106697, BM678200, BX109590, CD742908
    Consensus CDS
    CCDS63402.1
    UniProtKB/TrEMBL
    E7EWK1, Q6M1B7
    Related
    ENSP00000334451.9, ENST00000334363.14
    Conserved Domains (2) summary
    pfam00070
    Location:220 → 295
    Pyr_redox; Pyridine nucleotide-disulphide oxidoreductase
    cl14785
    Location:124 → 190
    FMT_C_like; Carboxy-terminal domain of Formyltransferase and similar domains

  2. NM_001352300.2 → NP_001339229.1  thioredoxin reductase 2, mitochondrial isoform 2 precursor

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2, also known as TrxR2A) uses an alternate in-frame acceptor splice site at an internal coding exon, and contains an unspliced 3' UTR compared to variant 1. The resulting isoform (2) is 1 aa shorter than isoform 1. It is localized to the mitochondria, and its overexpression results in increased apoptosis (PMID:16298692).
    Source sequence(s)
    AF044212, AF106697, AF166126, AF201385
    Consensus CDS
    CCDS87001.1
    UniProtKB/TrEMBL
    A0A182DWF3
    Related
    ENSP00000383363.1, ENST00000400519.6
    Conserved Domains (1) summary
    cl27343
    Location:38 → 523
    Pyr_redox_dim; Pyridine nucleotide-disulphide oxidoreductase, dimerisation domain

  3. NM_001352301.2 → NP_001339230.1  thioredoxin reductase 2, mitochondrial isoform 3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) contains an alternate 5' terminal exon, and uses an alternate in-frame translation initiation codon compared to variant 1. The resulting isoform (3) has a distinct and shorter N-terminus lacking the N-terminal mitochondrial targeting signal, compared to isoform 1, so it is likely localized in the cytosol.
    Source sequence(s)
    AB019695, AF044212, AF166126
    Consensus CDS
    CCDS86999.1
    UniProtKB/TrEMBL
    A0A182DWF2
    Related
    ENSP00000383362.1, ENST00000400518.5
    Conserved Domains (1) summary
    cl27343
    Location:9 → 494
    Pyr_redox_dim; Pyridine nucleotide-disulphide oxidoreductase, dimerisation domain

  4. NM_001352302.2 → NP_001339231.1  thioredoxin reductase 2, mitochondrial isoform 4

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) contains an alternate 5' terminal exon, which results in translation initiation from an in-frame downstream start codon compared to variant 1. The encoded isoform (4, also known as hTR3c) has a shorter N-terminus compared to isoform 1. It is localized in the cytosol (PMID:16774913).
    Source sequence(s)
    AF044212, AF166126, AF166127
    Consensus CDS
    CCDS86998.1
    UniProtKB/TrEMBL
    A0A182DWF2
    Related
    ENSP00000485128.2, ENST00000542719.6
    Conserved Domains (1) summary
    cl27343
    Location:1 → 428
    Pyr_redox_dim; Pyridine nucleotide-disulphide oxidoreductase, dimerisation domain

  5. NM_001352303.2 → NP_001339232.1  thioredoxin reductase 2, mitochondrial isoform 6

    Status: REVIEWED

    Description
    Transcript Variant: This variant (6) contains alternate 5' and 3' terminal exons compared to variant 1. The resulting shorter isoform (6, also known as hTR3b) has distinct N- and C- termini compared to isoform 1, and lacks selenocysteine. It is localized in the cytosol (PMID:16774913).
    Source sequence(s)
    AC000078, AC000090, AF044212, BM678200, BX109590, BX957216, CD742908
    Consensus CDS
    CCDS87000.1
    UniProtKB/TrEMBL
    A0A096LPD9, Q6M1B7
    Related
    ENSP00000485543.1, ENST00000491939.6
    Conserved Domains (1) summary
    cl27343
    Location:7 → 288
    Pyr_redox_dim; Pyridine nucleotide-disulphide oxidoreductase, dimerisation domain

  6. NM_006440.5 → NP_006431.2  thioredoxin reductase 2, mitochondrial isoform 1 precursor

    See identical proteins and their annotated locations for NP_006431.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the predominant transcript and encodes the longest isoform (1, also known as hTR3a). This isoform is localized to the mitochondria (PMID:16774913).
    Source sequence(s)
    AF044212, AF106697, R46611
    Consensus CDS
    CCDS42981.1
    UniProtKB/Swiss-Prot
    O95840, Q96IJ2, Q9H2Z5, Q9NNW7, Q9NZV3, Q9NZV4, Q9P2Y0, Q9P2Y1, Q9UQU8
    UniProtKB/TrEMBL
    A0A182DWF3
    Related
    ENSP00000383365.1, ENST00000400521.7
    Conserved Domains (4) summary
    TIGR01438
    Location:39 → 524
    TGR; thioredoxin and glutathione reductase selenoprotein
    pfam00070
    Location:220 → 295
    Pyr_redox; Pyridine nucleotide-disulphide oxidoreductase
    pfam02852
    Location:396 → 505
    Pyr_redox_dim; Pyridine nucleotide-disulphide oxidoreductase, dimerization domain
    cl14785
    Location:124 → 190
    FMT_C_like; Carboxy-terminal domain of Formyltransferase and similar domains

RNA

  1. NR_147957.2 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (7) uses an alternate acceptor splice site at the penultimate exon compared to variant 1. It is represented as non-coding because the use of the 5'-most translation start codon, as used in variant 1, renders this transcript a candidate for nonsense-mediated mRNA decay (NMD).
    Source sequence(s)
    AF044212, AF106697, AF166126, AK097708
    Related
    ENST00000474308.5

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000022.11 Reference GRCh38.p14 Primary Assembly

    Range
    19875522..19941818 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060946.1 Alternate T2T-CHM13v2.0

    Range
    20252392..20319509 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_145747.1: Suppressed sequence

    Description
    NM_145747.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.

  2. NM_145748.1: Suppressed sequence

    Description
    NM_145748.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9NNW7.3 GenPept UniProtKB/Swiss-Prot:Q9NNW7

Gene LinkOut

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