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    TXNRD2 thioredoxin reductase 2 [ Homo sapiens (human) ]

    Gene ID: 10587, updated on 11-Apr-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
    mouse all
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    Genomic context

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    Location:
    22q11.21
    Exon count:
    22
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 22 NC_000022.11 (19875522..19941818, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 22 NC_060946.1 (20252392..20319509, complement)
    105.20220307 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
    • 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. 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. Sookaromdee P, et al. Arq Bras Oftalmol, 2022. PMID 35416905
    2. TXNRD2 (rs35934224) CT genotype as possible protective marker for primary open-angle glaucoma in a Brazilian population. TenĂłrio AL, et al. Arq Bras Oftalmol, 2021. PMID 34431894
    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 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
    5. Auranofin is a potent suppressor of osteosarcoma metastasis. Topkas E, et al. Oncotarget, 2016 Jan 5. PMID 26573231, Free PMC Article

    See all (81) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. 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.
    2. 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.
    3. 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.
    4. 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.
    5. 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.
    6. 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?
    7. 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.
    8. 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.
    9. 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.
    10. Evidence that the rs4485648 polymorphism of the TrxR2 gene might exert an independent effect on the development of Diabetic retinopathy.
      Title: Single nucleotide polymorphisms in the Trx2/TXNIP and TrxR2 genes of the mitochondrial thioredoxin antioxidant system and the risk of diabetic retinopathy in patients with Type 2 diabetes mellitus.
    Submit: New GeneRIF Correction See all GeneRIFs (33)

    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
    		Compare labs

    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
    		  
    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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    NEW Try the new Transcript table

    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_2023_10

    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

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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