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    NNT nicotinamide nucleotide transhydrogenase [ Homo sapiens (human) ]

    Gene ID: 23530, updated on 28-Oct-2024

    Summary

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    Official Symbol
    NNTprovided by HGNC
    Official Full Name
    nicotinamide nucleotide transhydrogenaseprovided by HGNC
    Primary source
    HGNC:HGNC:7863
    See related
    Ensembl:ENSG00000112992 MIM:607878; AllianceGenome:HGNC:7863
    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
    GCCD4
    Summary
    This gene encodes an integral protein of the inner mitochondrial membrane. The enzyme couples hydride transfer between NAD(H) and NADP(+) to proton translocation across the inner mitochondrial membrane. Under most physiological conditions, the enzyme uses energy from the mitochondrial proton gradient to produce high concentrations of NADPH. The resulting NADPH is used for biosynthesis and in free radical detoxification. [provided by RefSeq, Sep 2016]
    Expression
    Broad expression in heart (RPKM 59.4), liver (RPKM 33.2) and 24 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See NNT in Genome Data Viewer
    Location:
    5p12
    Exon count:
    25
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (43602675..43707396)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (43849920..43961029)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (43602777..43707498)

    Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15995 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr5:43580594-43581340 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_85301 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15997 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15996 Neighboring gene ReSE screen-validated silencer GRCh37_chr5:43602630-43602849 Neighboring gene poly(A) binding protein interacting protein 1 Neighboring gene Sharpr-MPRA regulatory region 11344 Neighboring gene NNT antisense RNA 1 Neighboring gene adenosylmethionine decarboxylase 1 pseudogene 3 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_85370 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_85375 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_85394 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:43708151-43708652 Neighboring gene ribosomal protein L29 pseudogene 12 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:43717701-43718325 Neighboring gene H3K27ac hESC enhancer GRCh37_chr5:43745853-43746524 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_85421 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_85427 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_85485 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_85525 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_85570 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_85621 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_85633 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_85647 Neighboring gene RNA, U6 small nuclear 381, pseudogene Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_85852 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_85853 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_85873 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr5:44236336-44236856 Neighboring gene ReSE screen-validated silencer GRCh37_chr5:44262669-44262835 Neighboring gene ReSE screen-validated silencer GRCh37_chr5:44328940-44329154 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_85945 Neighboring gene fibroblast growth factor 10 Neighboring gene VISTA enhancer hs516 Neighboring gene FGF10 intronic enhancer Neighboring gene FGF10 antisense RNA 1

    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. Three-Dimensional Model of Human Nicotinamide Nucleotide Transhydrogenase (NNT) and Sequence-Structure Analysis of its Disease-Causing Variations. Metherell LA, et al. Hum Mutat, 2016 Oct. PMID 27459240, Free PMC Article
    2. The NADP(H)-binding component (dIII) of human heart transhydrogenase: crystallization and preliminary crystallographic analysis. Peake SJ, et al. Acta Crystallogr D Biol Crystallogr, 2000 Apr. PMID 10739929
    3. Nicotinamide nucleotide transhydrogenase mutation analysis in Chinese patients with thyroid dysgenesis. Li M, et al. Am J Med Genet A, 2022 Jan. PMID 34545694
    4. Cellular Redox State Acts as Switch to Determine the Direction of NNT-Catalyzed Reaction in Cystic Fibrosis Cells. Favia M, et al. Int J Mol Sci, 2021 Jan 19. PMID 33478087, Free PMC Article
    5. Nicotinamide nucleotide transhydrogenase expression analysis in multiple sclerosis patients. Eftekharian MM, et al. Int J Neurosci, 2019 Dec. PMID 31474168

    See all (95) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Lack of NAD(P)+ transhydrogenase activity in patients with primary adrenal insufficiency due to NNT variants.
      Title: Lack of NAD(P)+ transhydrogenase activity in patients with primary adrenal insufficiency due to NNT variants.
    2. Coenzyme Q10 and nicotinamide nucleotide transhydrogenase: Sentinels for mitochondrial hydrogen peroxide signaling.
      Title: Coenzyme Q(10) and nicotinamide nucleotide transhydrogenase: Sentinels for mitochondrial hydrogen peroxide signaling.
    3. IL-1beta-associated NNT acetylation orchestrates iron-sulfur cluster maintenance and cancer immunotherapy resistance.
      Title: IL-1β-associated NNT acetylation orchestrates iron-sulfur cluster maintenance and cancer immunotherapy resistance.
    4. Nicotinamide Nucleotide Transhydrogenase Is Essential for Adrenal Steroidogenesis: Clinical and In Vitro Lessons.
      Title: Nicotinamide Nucleotide Transhydrogenase Is Essential for Adrenal Steroidogenesis: Clinical and In Vitro Lessons.
    5. Long-Term Follow-Up of Three Family Members with a Novel NNT Pathogenic Variant Causing Primary Adrenal Insufficiency.
      Title: Long-Term Follow-Up of Three Family Members with a Novel NNT Pathogenic Variant Causing Primary Adrenal Insufficiency.
    6. Nicotinamide nucleotide transhydrogenase mutation analysis in Chinese patients with thyroid dysgenesis.
      Title: Nicotinamide nucleotide transhydrogenase mutation analysis in Chinese patients with thyroid dysgenesis.
    7. NNT mediates redox-dependent pigmentation via a UVB- and MITF-independent mechanism.
      Title: NNT mediates redox-dependent pigmentation via a UVB- and MITF-independent mechanism.
    8. Cellular Redox State Acts as Switch to Determine the Direction of NNT-Catalyzed Reaction in Cystic Fibrosis Cells.
      Title: Cellular Redox State Acts as Switch to Determine the Direction of NNT-Catalyzed Reaction in Cystic Fibrosis Cells.
    9. Nicotinamide nucleotide transhydrogenase regulates mitochondrial metabolism in NSCLC through maintenance of Fe-S protein function.
      Title: Nicotinamide nucleotide transhydrogenase regulates mitochondrial metabolism in NSCLC through maintenance of Fe-S protein function.
    10. LncRNA NNT-AS1 regulates the progression of lung cancer through the NNT-AS1/miR-3666/E2F2 axis.
      Title: LncRNA NNT-AS1 regulates the progression of lung cancer through the NNT-AS1/miR-3666/E2F2 axis.
    Submit: New GeneRIF Correction See all GeneRIFs (25)

    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 4
    MedGen: C3553587 OMIM: 614736 GeneReviews: Not available
    		Compare labs

    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

    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

    Clone Names

    • MGC126502, MGC126503

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables NAD binding TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables NAD(P)+ transhydrogenase (Si-specific) activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables NADP binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables NADP binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables proton-translocating NAD(P)+ transhydrogenase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in NADPH regeneration IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in cell redox homeostasis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in cellular oxidant detoxification IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in intracellular oxygen homeostasis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of apoptotic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of hydrogen peroxide catabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of mitochondrial membrane potential IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in proton transmembrane transport TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in reactive oxygen species metabolic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in response to vitamin IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in tricarboxylic acid cycle TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in membrane HDA PubMed 
    located_in mitochondrial inner membrane TAS
    Traceable Author Statement
    more info
    		 PubMed 
    located_in mitochondrion HTP PubMed 
    located_in mitochondrion IDA
    Inferred from Direct Assay
    more info
    		  
    part_of respiratory chain complex TAS
    Traceable Author Statement
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    NAD(P) transhydrogenase, mitochondrial
    Names
    pyridine nucleotide transhydrogenase
    NP_001317955.1
    NP_036475.3
    NP_892022.2
    XP_005248331.1
    XP_005248332.1
    XP_006714524.1
    XP_011512303.1
    XP_016864782.1
    XP_054208225.1
    XP_054208226.1
    XP_054208227.1
    XP_054208228.1
    XP_054208229.1

    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_032869.1 RefSeqGene

      Range
      5492..109708
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001331026.2 → NP_001317955.1  NAD(P) transhydrogenase, mitochondrial isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR and uses a downstream in-frame start codon, compared to variant 1. The encoded isoform (2) has a shorter N-terminus, compared to isoform 1.
      Source sequence(s)
      AC010435
      Consensus CDS
      CCDS82994.1
      UniProtKB/TrEMBL
      E9PCX7, Q2TB59
      Conserved Domains (3) summary
      cd05304
      Location:2 → 301
      Rubrum_tdh; Rubrum transdehydrogenase NAD-binding and catalytic domains
      pfam02233
      Location:491 → 948
      PNTB; NAD(P) transhydrogenase beta subunit
      pfam12769
      Location:371 → 456
      PNTB_4TM; 4TM region of pyridine nucleotide transhydrogenase, mitoch

    2. NM_012343.4 → NP_036475.3  NAD(P) transhydrogenase, mitochondrial isoform 1

      See identical proteins and their annotated locations for NP_036475.3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longer isoform (1). Variants 1 and 2 encode the same isoform.
      Source sequence(s)
      AC010435, AL831822, AW771969, BC110543, DA521839
      Consensus CDS
      CCDS3949.1
      UniProtKB/Swiss-Prot
      Q13423, Q16796, Q2TB60, Q8N3V4
      UniProtKB/TrEMBL
      Q2TB59
      Related
      ENSP00000264663.5, ENST00000264663.9
      Conserved Domains (4) summary
      PRK09424
      Location:57 → 587
      pntA; NAD(P) transhydrogenase subunit alpha; Provisional
      cd05304
      Location:57 → 432
      Rubrum_tdh; Rubrum transdehydrogenase NAD-binding and catalytic domains
      pfam02233
      Location:622 → 1079
      PNTB; NAD(P) transhydrogenase beta subunit
      pfam12769
      Location:502 → 587
      PNTB_4TM; 4TM region of pyridine nucleotide transhydrogenase, mitoch

    3. NM_182977.3 → NP_892022.2  NAD(P) transhydrogenase, mitochondrial isoform 1

      See identical proteins and their annotated locations for NP_892022.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1 and 2 encode the same isoform (1).
      Source sequence(s)
      AC010435, AW771969, BC110543, BU429380
      Consensus CDS
      CCDS3949.1
      UniProtKB/Swiss-Prot
      Q13423, Q16796, Q2TB60, Q8N3V4
      UniProtKB/TrEMBL
      Q2TB59
      Related
      ENSP00000343873.4, ENST00000344920.9
      Conserved Domains (4) summary
      PRK09424
      Location:57 → 587
      pntA; NAD(P) transhydrogenase subunit alpha; Provisional
      cd05304
      Location:57 → 432
      Rubrum_tdh; Rubrum transdehydrogenase NAD-binding and catalytic domains
      pfam02233
      Location:622 → 1079
      PNTB; NAD(P) transhydrogenase beta subunit
      pfam12769
      Location:502 → 587
      PNTB_4TM; 4TM region of pyridine nucleotide transhydrogenase, mitoch

    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_000005.10 Reference GRCh38.p14 Primary Assembly

      Range
      43602675..43707396
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_005248274.6 → XP_005248331.1  NAD(P) transhydrogenase, mitochondrial isoform X1

      See identical proteins and their annotated locations for XP_005248331.1

      UniProtKB/Swiss-Prot
      Q13423, Q16796, Q2TB60, Q8N3V4
      UniProtKB/TrEMBL
      Q2TB59
      Conserved Domains (4) summary
      PRK09424
      Location:57 → 587
      pntA; NAD(P) transhydrogenase subunit alpha; Provisional
      cd05304
      Location:57 → 432
      Rubrum_tdh; Rubrum transdehydrogenase NAD-binding and catalytic domains
      pfam02233
      Location:622 → 1079
      PNTB; NAD(P) transhydrogenase beta subunit
      pfam12769
      Location:502 → 587
      PNTB_4TM; 4TM region of pyridine nucleotide transhydrogenase, mitoch

    2. XM_017009293.3 → XP_016864782.1  NAD(P) transhydrogenase, mitochondrial isoform X1

      UniProtKB/Swiss-Prot
      Q13423, Q16796, Q2TB60, Q8N3V4
      UniProtKB/TrEMBL
      Q2TB59
      Related
      ENSP00000499639.1, ENST00000662525.1
      Conserved Domains (4) summary
      PRK09424
      Location:57 → 587
      pntA; NAD(P) transhydrogenase subunit alpha; Provisional
      cd05304
      Location:57 → 432
      Rubrum_tdh; Rubrum transdehydrogenase NAD-binding and catalytic domains
      pfam02233
      Location:622 → 1079
      PNTB; NAD(P) transhydrogenase beta subunit
      pfam12769
      Location:502 → 587
      PNTB_4TM; 4TM region of pyridine nucleotide transhydrogenase, mitoch

    3. XM_011514001.4 → XP_011512303.1  NAD(P) transhydrogenase, mitochondrial isoform X1

      See identical proteins and their annotated locations for XP_011512303.1

      UniProtKB/Swiss-Prot
      Q13423, Q16796, Q2TB60, Q8N3V4
      UniProtKB/TrEMBL
      Q2TB59
      Related
      ENSP00000499249.1, ENST00000656666.1
      Conserved Domains (4) summary
      PRK09424
      Location:57 → 587
      pntA; NAD(P) transhydrogenase subunit alpha; Provisional
      cd05304
      Location:57 → 432
      Rubrum_tdh; Rubrum transdehydrogenase NAD-binding and catalytic domains
      pfam02233
      Location:622 → 1079
      PNTB; NAD(P) transhydrogenase beta subunit
      pfam12769
      Location:502 → 587
      PNTB_4TM; 4TM region of pyridine nucleotide transhydrogenase, mitoch

    4. XM_006714461.5 → XP_006714524.1  NAD(P) transhydrogenase, mitochondrial isoform X2

      See identical proteins and their annotated locations for XP_006714524.1

      UniProtKB/TrEMBL
      E9PCX7, Q2TB59
      Related
      ENSP00000426343.1, ENST00000512996.6
      Conserved Domains (3) summary
      cd05304
      Location:2 → 301
      Rubrum_tdh; Rubrum transdehydrogenase NAD-binding and catalytic domains
      pfam02233
      Location:491 → 948
      PNTB; NAD(P) transhydrogenase beta subunit
      pfam12769
      Location:371 → 456
      PNTB_4TM; 4TM region of pyridine nucleotide transhydrogenase, mitoch

    5. XM_005248275.6 → XP_005248332.1  NAD(P) transhydrogenase, mitochondrial isoform X3

      UniProtKB/TrEMBL
      B4DMN9
      Conserved Domains (2) summary
      pfam02233
      Location:122 → 579
      PNTB; NAD(P) transhydrogenase beta subunit
      pfam12769
      Location:2 → 87
      PNTB_4TM; 4TM region of pyridine nucleotide transhydrogenase, mitoch

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060929.1 Alternate T2T-CHM13v2.0

      Range
      43849920..43961029
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054352250.1 → XP_054208225.1  NAD(P) transhydrogenase, mitochondrial isoform X1

      UniProtKB/Swiss-Prot
      Q13423, Q16796, Q2TB60, Q8N3V4

    2. XM_054352252.1 → XP_054208227.1  NAD(P) transhydrogenase, mitochondrial isoform X1

      UniProtKB/Swiss-Prot
      Q13423, Q16796, Q2TB60, Q8N3V4

    3. XM_054352251.1 → XP_054208226.1  NAD(P) transhydrogenase, mitochondrial isoform X1

      UniProtKB/Swiss-Prot
      Q13423, Q16796, Q2TB60, Q8N3V4

    4. XM_054352253.1 → XP_054208228.1  NAD(P) transhydrogenase, mitochondrial isoform X2

      UniProtKB/TrEMBL
      E9PCX7

    5. XM_054352254.1 → XP_054208229.1  NAD(P) transhydrogenase, mitochondrial isoform X3

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q13423.3 GenPept UniProtKB/Swiss-Prot:Q13423

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