TXNRD2 (thioredoxin reductase 2)

Gene

• Entrez ID: 10587
• Gene name: Thioredoxin reductase 2
• Gene symbol: TXNRD2
• Synonyms (NCBI Gene): GCCD5, SELZ, TR, TR-BETA, TR3, TRXR2, TXNR2
• Chromosome: 22
• Chromosome location: 22q11.21
• 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 fla

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs200606822	T>A	Conflicting-interpretations-of-pathogenicity, likely-benign	Coding sequence variant, genic downstream transcript variant, non coding transcript variant, missense variant
rs202059967	A>C,G	Uncertain-significance, likely-benign, likely-pathogenic	Stop gained, synonymous variant, non coding transcript variant, genic downstream transcript variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT005748	hsa-miR-17-3p	Luciferase reporter assay, Quantitative proteomic approach, Western blot	21203553
MIRT044324	hsa-miR-106b-5p	CLASH	23622248
MIRT039271	hsa-miR-671-5p	CLASH	23622248
MIRT495538	hsa-miR-7851-3p	PAR-CLIP	22291592
MIRT495537	hsa-miR-3929	PAR-CLIP	22291592
MIRT495536	hsa-miR-4419b	PAR-CLIP	22291592
MIRT495535	hsa-miR-4478	PAR-CLIP	22291592
MIRT495534	hsa-miR-6765-3p	PAR-CLIP	22291592
MIRT495533	hsa-miR-619-5p	PAR-CLIP	22291592
MIRT495532	hsa-miR-6506-5p	PAR-CLIP	22291592
MIRT495531	hsa-miR-5191	PAR-CLIP	22291592
MIRT495530	hsa-miR-6762-3p	PAR-CLIP	22291592
MIRT005748	hsa-miR-17-3p	qRT-PCR, Western blot	27505139
MIRT495538	hsa-miR-7851-3p	PAR-CLIP	22291592
MIRT495537	hsa-miR-3929	PAR-CLIP	22291592
MIRT495536	hsa-miR-4419b	PAR-CLIP	22291592
MIRT495535	hsa-miR-4478	PAR-CLIP	22291592
MIRT495534	hsa-miR-6765-3p	PAR-CLIP	22291592
MIRT495533	hsa-miR-619-5p	PAR-CLIP	22291592
MIRT495532	hsa-miR-6506-5p	PAR-CLIP	22291592
MIRT495531	hsa-miR-5191	PAR-CLIP	22291592
MIRT495530	hsa-miR-6762-3p	PAR-CLIP	22291592
MIRT1465591	hsa-miR-1343	CLIP-seq
MIRT1465592	hsa-miR-151-5p	CLIP-seq
MIRT1465593	hsa-miR-151b	CLIP-seq
MIRT1465594	hsa-miR-193a-5p	CLIP-seq
MIRT1465595	hsa-miR-3176	CLIP-seq
MIRT1465596	hsa-miR-3922-3p	CLIP-seq
MIRT1465597	hsa-miR-4757-5p	CLIP-seq
MIRT1465598	hsa-miR-4793-5p	CLIP-seq
MIRT2139950	hsa-miR-1909	CLIP-seq
MIRT2139951	hsa-miR-3692	CLIP-seq
MIRT2139952	hsa-miR-4464	CLIP-seq
MIRT2139953	hsa-miR-4748	CLIP-seq
MIRT2396550	hsa-miR-146b-3p	CLIP-seq
MIRT2396551	hsa-miR-3173-5p	CLIP-seq
MIRT2396552	hsa-miR-874	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000305	Process	Response to oxygen radical	TAS	10455115
GO:0004791	Function	Thioredoxin-disulfide reductase (NADPH) activity	IBA
GO:0004791	Function	Thioredoxin-disulfide reductase (NADPH) activity	IEA
GO:0004791	Function	Thioredoxin-disulfide reductase (NADPH) activity	ISS
GO:0004791	Function	Thioredoxin-disulfide reductase (NADPH) activity	TAS	9923614
GO:0005515	Function	Protein binding	IPI	20413580
GO:0005737	Component	Cytoplasm	IBA
GO:0005739	Component	Mitochondrion	HTP	34800366
GO:0005739	Component	Mitochondrion	IBA
GO:0005739	Component	Mitochondrion	IDA	10215850
GO:0005739	Component	Mitochondrion	IEA
GO:0005759	Component	Mitochondrial matrix	TAS
GO:0005829	Component	Cytosol	IBA
GO:0005829	Component	Cytosol	IDA
GO:0006979	Process	Response to oxidative stress	IEA
GO:0010269	Process	Response to selenium ion	IEA
GO:0016491	Function	Oxidoreductase activity	IEA
GO:0016668	Function	Oxidoreductase activity, acting on a sulfur group of donors, NAD(P) as acceptor	IEA
GO:0030424	Component	Axon	IEA
GO:0030425	Component	Dendrite	IEA
GO:0042803	Function	Protein homodimerization activity	IEA
GO:0042803	Function	Protein homodimerization activity	ISS
GO:0043025	Component	Neuronal cell body	IEA
GO:0044877	Function	Protein-containing complex binding	IEA
GO:0045454	Process	Cell redox homeostasis	IBA
GO:0045454	Process	Cell redox homeostasis	IEA
GO:0045454	Process	Cell redox homeostasis	IMP	24601690
GO:0050660	Function	Flavin adenine dinucleotide binding	IEA
GO:0055093	Process	Response to hyperoxia	IEA
GO:0098869	Process	Cellular oxidant detoxification	IEA

Other IDs

• MIM: 606448
• HGNC: 18155
• e!Ensembl: ENSG00000184470

Protein

• UniProt ID: Q9NNW7
• Protein name: Thioredoxin reductase 2, mitochondrial (EC 1.8.1.9) (Selenoprotein Z) (SelZ) (TR-beta) (Thioredoxin reductase TR3)
• Protein function: Involved in the control of reactive oxygen species levels and the regulation of mitochondrial redox homeostasis (PubMed:24601690). Maintains thioredoxin in a reduced state. May play a role in redox-regulated cell signaling. {ECO:0000250|UniProtK
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF07992	Pyr_redox_2	40 → 375	Pyridine nucleotide-disulphide oxidoreductase	Domain
  PF02852	Pyr_redox_dim	395 → 508	Pyridine nucleotide-disulphide oxidoreductase, dimerisation domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Highly expressed in the prostate, ovary, liver, testis, uterus, colon and small intestine. Intermediate levels in brain, skeletal muscle, heart and spleen. Low levels in placenta, pancreas, thymus and peripheral blood leukocytes. Accor
• Sequence:

  MAAMAVALRGLGGRFRWRTQAVAGGVRGAARGAAAGQRDYDLLVVGGGSGGLACAKEAAQ
  LGRKVAVVDYVEPSPQGTRWGLGGTCVNVGCIPKKLMHQAALLGGLIQDAPNYGWEVAQP
  VPHDWRKMAEAVQNHVKSLNWGHRVQLQDRKVKYFNIKASFVDEHTVCGVAKGGKEILLS
  ADHIIIATGGRPRYPTHIEGALEYGITSDDIFWLKESPGKTLVVGASYVALECAGFLTGI
  GLDTTIMMRSIPLRGFDQQMSSMVIEHMASHGTRFLRGCAPSRVRRLPDGQLQVTWEDST
  TGKEDTGTFDTVLWAIGRVPDTRSLNLEKAGVDTSPDTQKILVDSREATSVPHIYAIGDV
  VEGRPELTPIAIMAGRLLVQRLFGGSSDLMDYDNVPTTVFTPLEYGCVGLSEEEAVARHG
  QEHVEVYHAHYKPLEFTVAGRDASQCYVKMVCLREPPQLVLGLHFLGPNAGEVTQGFALG
  IKCGASYAQVMRTVGIHPTCSEEVVKLRISKRSGLDPTVTGCUG

• Sequence length: 524

Pathways

KEGG:

Selenocompound metabolism
Pathways in cancer
Hepatocellular carcinoma

Reactome:

Detoxification of Reactive Oxygen Species

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Benign; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTISM SPECTRUM DISORDER	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTISM SPECTRUM DISORDERS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CARDIOMYOPATHIES	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cardiomyopathy	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CARDIOMYOPATHY, DILATED	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CARDIOMYOPATHY, HYPERTROPHIC, FAMILIAL	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cardiovascular phenotype	Conflicting classifications of pathogenicity; Uncertain significance; Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cholangiocarcinoma	Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colon adenocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COLOR VISION DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DILATED CARDIOMYOPATHY	—	GenCC	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ependymoma	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
FAMILIAL GLUCOCORTICOID DEFICIENCY	—	Disgenet, GWAS catalog, Orphanet Disgenet, GWAS catalog, Orphanet Disgenet, GWAS catalog, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
FAMILIAL ISOLATED DILATED CARDIOMYOPATHY	—	GWAS catalog, Orphanet GWAS catalog, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
FAMILIAL OR IDIOPATHIC DILATED CARDIOMYOPATHY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GLAUCOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GLAUCOMA, OPEN-ANGLE	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Glucocorticoid deficiency 5	Uncertain significance; Conflicting classifications of pathogenicity; Benign; Likely benign	ClinVar ClinVar, Disgenet, GWAS catalog, HPO ClinVar, Disgenet, GWAS catalog, HPO ClinVar, Disgenet, GWAS catalog, HPO	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Lung cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OPEN-ANGLE GLAUCOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Benign; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PRIMARY ANGLE CLOSURE GLAUCOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Primary dilated cardiomyopathy	Conflicting classifications of pathogenicity; Uncertain significance; Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Primary familial hypertrophic cardiomyopathy	Uncertain significance; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PROSTATIC NEOPLASMS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SYMPTOMS OF DEPRESSION	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thymoma	Benign; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyroid cancer, nonmedullary, 1	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TXNRD2-associated Cardiomyopathy	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TXNRD2-related disorder	Likely benign; Conflicting classifications of pathogenicity; Benign; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine carcinosarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Relationship Type	References	Evidence Score
22q11 Deletion Syndrome	Associate	31220439	★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Associate	16868544, 20003265, 33885357	★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Associate	22615972	★☆☆☆☆ Found in Text Mining only
Cryptorchidism	Associate	38011841	★☆☆☆☆ Found in Text Mining only
Diabetes Gestational	Associate	38093364	★☆☆☆☆ Found in Text Mining only
Diabetic Nephropathies	Associate	34545296	★☆☆☆☆ Found in Text Mining only
DiGeorge Syndrome	Associate	26221035	★☆☆☆☆ Found in Text Mining only
Familial Glucocorticoid Deficiency 1	Associate	38011841	★☆☆☆☆ Found in Text Mining only
Fibrosis	Associate	23597419	★☆☆☆☆ Found in Text Mining only
Glaucoma Open Angle	Associate	30317457, 32476818, 33726755	★☆☆☆☆ Found in Text Mining only
Hyperoxia	Stimulate	28045936	★☆☆☆☆ Found in Text Mining only
Kashin Beck Disease	Associate	24058403	★☆☆☆☆ Found in Text Mining only
Lung Neoplasms	Associate	33332541	★☆☆☆☆ Found in Text Mining only
Lymphoma	Associate	18422776	★☆☆☆☆ Found in Text Mining only
Penis agenesis	Associate	38011841	★☆☆☆☆ Found in Text Mining only
Personality Disorders	Associate	26847995	★☆☆☆☆ Found in Text Mining only
Prostatic Neoplasms	Associate	21716162, 23133653, 25284284, 26847995, 27197287	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Rectal Neoplasms	Associate	22615972	★☆☆☆☆ Found in Text Mining only