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NNT nicotinamide nucleotide transhydrogenase [ Homo sapiens (human) ]

Gene ID: 23530, updated on 3-Apr-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
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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_2023_10 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (43602675..43707396)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (43849920..43961029)
105.20220307 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
  • 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. IL-1β-associated NNT acetylation orchestrates iron-sulfur cluster maintenance and cancer immunotherapy resistance. Han Y, et al. Mol Cell, 2023 Jun 1. PMID 37244254
  2. Nicotinamide Nucleotide Transhydrogenase Is Essential for Adrenal Steroidogenesis: Clinical and In Vitro Lessons. Bodoni AF, et al. J Clin Endocrinol Metab, 2023 May 17. PMID 36478070
  3. Long-Term Follow-Up of Three Family Members with a Novel NNT Pathogenic Variant Causing Primary Adrenal Insufficiency. Krasovec T, et al. Genes (Basel), 2022 Apr 20. PMID 35627102, Free PMC Article
  4. Nicotinamide nucleotide transhydrogenase mutation analysis in Chinese patients with thyroid dysgenesis. Li M, et al. Am J Med Genet A, 2022 Jan. PMID 34545694
  5. 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

See all (87) 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 (B-specific) activity TAS
Traceable Author Statement
more info
 PubMed 
enables NAD(P)+ transhydrogenase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables NADP binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables NADP binding IDA
Inferred from Direct Assay
more info
 PubMed 
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 negative regulation of protein phosphorylation 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 mitochondrial respirasome TAS
Traceable Author Statement
more info
 PubMed 
located_in mitochondrion IDA
Inferred from Direct Assay
more info
  

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_2023_10

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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