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Aliases for NNT Gene

Aliases for NNT Gene

  • Nicotinamide Nucleotide Transhydrogenase 2 3 4 5
  • Pyridine Nucleotide Transhydrogenase 3 4
  • EC 1.6.1.2 4 56
  • NAD(P) Transhydrogenase, Mitochondrial 3
  • GCCD4 3

External Ids for NNT Gene

Previous GeneCards Identifiers for NNT Gene

  • GC05P043918
  • GC05P044779
  • GC05P043602
  • GC05P043648

Summaries for NNT Gene

Entrez Gene Summary for NNT Gene

  • 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]

GeneCards Summary for NNT Gene

NNT (Nicotinamide Nucleotide Transhydrogenase) is a Protein Coding gene. Diseases associated with NNT include Glucocorticoid Deficiency 4 With Or Without Mineralocorticoid Deficiency and Familial Glucocorticoid Deficiency. Among its related pathways are Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins. and Pyruvate metabolism and Citric Acid (TCA) cycle. Gene Ontology (GO) annotations related to this gene include oxidoreductase activity and NADP binding.

UniProtKB/Swiss-Prot for NNT Gene

  • The transhydrogenation between NADH and NADP is coupled to respiration and ATP hydrolysis and functions as a proton pump across the membrane. May play a role in reactive oxygen species (ROS) detoxification in the adrenal gland.

Gene Wiki entry for NNT Gene

Additional gene information for NNT Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for NNT Gene

Genomics for NNT Gene

GeneHancer (GH) Regulatory Elements for NNT Gene

Promoters and enhancers for NNT Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH05I043601 Promoter/Enhancer 2 EPDnew Ensembl ENCODE 564.3 +0.3 339 3.6 HDGF PKNOX1 CLOCK SMAD1 ARNT ARID4B SIN3A ZNF2 YY1 ZNF766 NNT-AS1 NNT RPL29P12 TMEM267 ZNF131 EEF1A1P19 ANXA2R ENSG00000272382 CCL28
GH05I043554 Promoter/Enhancer 2 EPDnew Ensembl ENCODE 24.6 -46.3 -46315 3.2 SMAD1 ARNT ARID4B SIN3A DMAP1 ZNF2 ZNF143 SP3 REST SMARCB1 PAIP1 NNT C5orf34 ENSG00000249492 ENSG00000248240 EEF1A1P19 NNT-AS1 RPL29P12 FGF10-AS1 LOC153684
GH05I043513 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE 13.5 -88.0 -87963 3.1 HDGF PKNOX1 SMAD1 ARID4B SIN3A DMAP1 ZNF2 YY1 SLC30A9 POLR2B ENSG00000248240 C5orf34 ZNF131 EEF1A1P19 RPL29P12 ENSG00000249492 NNT LOC648987 ANXA2R ENSG00000272382
GH05I043482 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE 13.2 -117.7 -117682 5.6 HDGF PKNOX1 SMAD1 ARNT ARID4B SIN3A FEZF1 DMAP1 ZNF2 YY1 TMEM267 ENSG00000249492 ZNF131 EEF1A1P19 RPL29P12 C5orf34 NNT CCL28 HMGCS1 ENSG00000248240
GH05I043631 Enhancer 1.1 Ensembl ENCODE dbSUPER 20.3 +28.7 28696 0.4 HDGF CTCF PKNOX1 MAX SIN3A RAD21 RFX5 YY1 POLR2A ZNF143 NNT NNT-AS1 GC05M043668
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around NNT on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the NNT gene promoter:

Genomic Locations for NNT Gene

Genomic Locations for NNT Gene
chr5:43,602,689-43,707,405
(GRCh38/hg38)
Size:
104,717 bases
Orientation:
Plus strand
chr5:43,602,791-43,707,507
(GRCh37/hg19)

Genomic View for NNT Gene

Genes around NNT on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
NNT Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for NNT Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for NNT Gene

Proteins for NNT Gene

  • Protein details for NNT Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q13423-NNTM_HUMAN
    Recommended name:
    NAD(P) transhydrogenase, mitochondrial
    Protein Accession:
    Q13423
    Secondary Accessions:
    • Q16796
    • Q2TB60
    • Q8N3V4

    Protein attributes for NNT Gene

    Size:
    1086 amino acids
    Molecular mass:
    113896 Da
    Quaternary structure:
    • Homodimer.

    Three dimensional structures from OCA and Proteopedia for NNT Gene

neXtProt entry for NNT Gene

Selected DME Specific Peptides for NNT Gene

Q13423:
  • VTPALHSPLM
  • VPYDIVLEMDEIN
  • PLMSVTNAISG
  • IAGMPVLEVWK
  • LPQLVAAFHSLVG
  • FFTGQITAAGKVPPAK
  • GSSGAILSYIMC
  • DALSSMANI
  • IHPVAGR
  • VLVIGANDTVN
  • IGGADMPVV

Post-translational modifications for NNT Gene

  • Ubiquitination at isoforms=55
  • Modification sites at PhosphoSitePlus

Domains & Families for NNT Gene

Gene Families for NNT Gene

Human Protein Atlas (HPA):
  • Disease related genes
  • Enzymes
  • Plasma proteins
  • Potential drug targets
  • Predicted intracellular proteins
  • Predicted membrane proteins

Graphical View of Domain Structure for InterPro Entry

Q13423

UniProtKB/Swiss-Prot:

NNTM_HUMAN :
  • In the N-terminal section; belongs to the AlaDH/PNT family.
Family:
  • In the N-terminal section; belongs to the AlaDH/PNT family.
  • In the C-terminal section; belongs to the PNT beta subunit family.
genes like me logo Genes that share domains with NNT: view

Function for NNT Gene

Molecular function for NNT Gene

GENATLAS Biochemistry:
nicotinamide nucleotide transhydrogenase,integral protein of the inner mitochondrial membrane,proton-pumping,ortholog to bovin and mouse enzymes
UniProtKB/Swiss-Prot CatalyticActivity:
NADPH + NAD(+) = NADP(+) + NADH.
UniProtKB/Swiss-Prot Function:
The transhydrogenation between NADH and NADP is coupled to respiration and ATP hydrolysis and functions as a proton pump across the membrane. May play a role in reactive oxygen species (ROS) detoxification in the adrenal gland.

Enzyme Numbers (IUBMB) for NNT Gene

Phenotypes From GWAS Catalog for NNT Gene

Gene Ontology (GO) - Molecular Function for NNT Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003957 NAD(P)+ transhydrogenase (B-specific) activity TAS 9524818
GO:0008746 NAD(P)+ transhydrogenase activity IEA,EXP 10673423
GO:0008750 NAD(P)+ transhydrogenase (AB-specific) activity IBA --
GO:0016491 oxidoreductase activity IEA --
GO:0050661 NADP binding IDA 10673423
genes like me logo Genes that share ontologies with NNT: view
genes like me logo Genes that share phenotypes with NNT: view

Human Phenotype Ontology for NNT Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Model Products

  • Taconic Biosciences Mouse Models for NNT

miRNA for NNT Gene

miRTarBase miRNAs that target NNT

Clone Products

No data available for Animal Models , Transcription Factor Targets and HOMER Transcription for NNT Gene

Localization for NNT Gene

Subcellular locations from UniProtKB/Swiss-Prot for NNT Gene

Mitochondrion inner membrane; Multi-pass membrane protein; Matrix side.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for NNT gene
Compartment Confidence
mitochondrion 5
plasma membrane 3
peroxisome 1
endoplasmic reticulum 1
cytosol 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for NNT Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005739 mitochondrion IDA --
GO:0005743 mitochondrial inner membrane TAS 10673423
GO:0005746 mitochondrial respiratory chain TAS 10673423
GO:0016020 membrane IEA,HDA 19946888
GO:0016021 integral component of membrane IEA --
genes like me logo Genes that share ontologies with NNT: view

Pathways & Interactions for NNT Gene

genes like me logo Genes that share pathways with NNT: view

Pathways by source for NNT Gene

Gene Ontology (GO) - Biological Process for NNT Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006099 tricarboxylic acid cycle TAS 10673423
GO:0006740 NADPH regeneration IBA --
GO:0015992 proton transport IEA,TAS 10673423
GO:0055114 oxidation-reduction process IEA,TAS 10673423
GO:0072593 reactive oxygen species metabolic process IMP 22634753
genes like me logo Genes that share ontologies with NNT: view

No data available for SIGNOR curated interactions for NNT Gene

Drugs & Compounds for NNT Gene

(9) Drugs for NNT Gene - From: DrugBank, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
NADH Approved Nutra Target 0
2'-Monophosphoadenosine 5'-Diphosphoribose Experimental Pharma Target 0
7-thionicotinamide-adenine-dinucleotide phosphate Experimental Pharma Target 0
NAD Pharma Full agonist, Agonist 0

(3) Additional Compounds for NNT Gene - From: Novoseek and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
NADP
  • Adenine-nicotinamide dinucleotide phosphate
  • b-NADP
  • b-Nicotinamide adenine dinucleotide phosphate
  • b-TPN
  • beta-NADP
53-59-8
nadph
  • 2'-(Dihydrogen phosphate) 5'-(trihydrogen pyrophosphate) Adenosine 5'-ester with 1,4-dihydro-1-b-D-ribofuranosylnicotinamide
  • 2'-(Dihydrogen phosphate) 5'-(trihydrogen pyrophosphate) Adenosine 5'-ester with 1,4-dihydro-1-beta-delta-ribofuranosylnicotinamide
  • Adenosine 5'-(trihydrogen diphosphate) 2'-(dihydrogen phosphate) P'-5'-ester with 1,4-dihydro-1-beta-D-ribofuranosyl-3-pyridinecarboxamide
  • Adenosine 5'-(trihydrogen diphosphate) 2'-(dihydrogen phosphate) P'-5'-ester with 1,4-dihydro-1-beta-delta-ribofuranosyl-3-pyridinecarboxamide
  • b-NADPH
53-57-6
genes like me logo Genes that share compounds with NNT: view

Transcripts for NNT Gene

Unigene Clusters for NNT Gene

Nicotinamide nucleotide transhydrogenase:
Representative Sequences:

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for NNT Gene

No ASD Table

Relevant External Links for NNT Gene

GeneLoc Exon Structure for
NNT
ECgene alternative splicing isoforms for
NNT

Expression for NNT Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for NNT Gene

mRNA differential expression in normal tissues according to GTEx for NNT Gene

This gene is overexpressed in Heart - Left Ventricle (x6.9), Muscle - Skeletal (x6.1), and Heart - Atrial Appendage (x4.0).

Protein differential expression in normal tissues from HIPED for NNT Gene

This gene is overexpressed in Heart (23.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for NNT Gene



Protein tissue co-expression partners for NNT Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of NNT Gene:

NNT

SOURCE GeneReport for Unigene cluster for NNT Gene:

Hs.482043

mRNA Expression by UniProt/SwissProt for NNT Gene:

Q13423-NNTM_HUMAN
Tissue specificity: Widely expressed with expression most readily detectable in adrenal, heart, kidney, thyroid and adipose tissues.

Evidence on tissue expression from TISSUES for NNT Gene

  • Heart(4.7)
  • Liver(4.6)
  • Muscle(4.5)
  • Nervous system(3.6)
  • Adrenal gland(3.3)
  • Pancreas(2.7)
  • Blood(2.5)
  • Kidney(2.5)
  • Lung(2.1)

Phenotype-based relationships between genes and organs from Gene ORGANizer for NNT Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • endocrine
  • immune
  • integumentary
  • nervous
  • skeleton
Regions:
Head and neck:
  • brain
  • ear
  • head
  • jaw
  • mandible
  • maxilla
  • mouth
  • neck
  • pituitary gland
  • skull
Thorax:
  • chest wall
  • clavicle
  • heart
  • rib
  • rib cage
  • scapula
  • sternum
Abdomen:
  • adrenal gland
Pelvis:
  • pelvis
Limb:
  • ankle
  • arm
  • digit
  • elbow
  • femur
  • fibula
  • finger
  • foot
  • forearm
  • hand
  • hip
  • humerus
  • knee
  • lower limb
  • radius
  • shin
  • shoulder
  • thigh
  • tibia
  • toe
  • ulna
  • upper limb
  • wrist
General:
  • blood
  • peripheral nerve
  • peripheral nervous system
  • skin
  • spinal column
  • sweat gland
  • vertebrae
  • white blood cell
genes like me logo Genes that share expression patterns with NNT: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery for NNT Gene

Orthologs for NNT Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for NNT Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia NNT 33 34
  • 99.6 (n)
mouse
(Mus musculus)
Mammalia Nnt 34
  • 94 (a)
OneToOne
dog
(Canis familiaris)
Mammalia NNT 33 34
  • 92.33 (n)
oppossum
(Monodelphis domestica)
Mammalia NNT 34
  • 92 (a)
OneToOne
cow
(Bos Taurus)
Mammalia NNT 33 34
  • 91.71 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia NNT 34
  • 90 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Nnt 33
  • 86.49 (n)
chicken
(Gallus gallus)
Aves NNT 33 34
  • 78.53 (n)
lizard
(Anolis carolinensis)
Reptilia NNT 34
  • 90 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia nnt 33
  • 76.92 (n)
zebrafish
(Danio rerio)
Actinopterygii nnt 33 34
  • 72.29 (n)
-- 33
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.10162 33
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP003167 33
  • 61.92 (n)
worm
(Caenorhabditis elegans)
Secernentea nnt-1 35 33 34
  • 59.75 (n)
sea squirt
(Ciona savignyi)
Ascidiacea CSA.6124 34
  • 67 (a)
OneToOne
bread mold
(Neurospora crassa)
Ascomycetes NCU01140 33
  • 56.96 (n)
Species where no ortholog for NNT was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for NNT Gene

ENSEMBL:
Gene Tree for NNT (if available)
TreeFam:
Gene Tree for NNT (if available)

Paralogs for NNT Gene

No data available for Paralogs for NNT Gene

Variants for NNT Gene

Sequence variations from dbSNP and Humsavar for NNT Gene

SNP ID Clin Chr 05 pos Variation AA Info Type
rs370273690 pathogenic, Glucocorticoid deficiency 4 with or without mineralocorticoid deficiency, Glucocorticoid deficiency 4 with or without mineralocorticoid deficiency (GCCD4) [MIM:614736] 43,702,652(+) T/C/G coding_sequence_variant, missense_variant, synonymous_variant
rs371979800 Glucocorticoid deficiency 4 with or without mineralocorticoid deficiency (GCCD4) [MIM:614736] 43,653,144(+) G/A coding_sequence_variant, missense_variant
rs387907232 pathogenic, Glucocorticoid deficiency 4 with or without mineralocorticoid deficiency, Glucocorticoid deficiency 4 with or without mineralocorticoid deficiency (GCCD4) [MIM:614736] 43,649,300(+) C/T coding_sequence_variant, missense_variant
rs387907233 pathogenic, Glucocorticoid deficiency 4 with or without mineralocorticoid deficiency, Glucocorticoid deficiency 4 with or without mineralocorticoid deficiency (GCCD4) [MIM:614736] 43,700,172(+) T/C coding_sequence_variant, missense_variant
rs387907234 pathogenic, Glucocorticoid deficiency 4 with or without mineralocorticoid deficiency, Glucocorticoid deficiency 4 with or without mineralocorticoid deficiency (GCCD4) [MIM:614736] 43,702,647(+) G/C coding_sequence_variant, missense_variant

Structural Variations from Database of Genomic Variants (DGV) for NNT Gene

Variant ID Type Subtype PubMed ID
esv3565873 CNV deletion 23714750
esv3575840 CNV gain 25503493
esv3604904 CNV gain 21293372
esv3604910 CNV gain 21293372
nsv830275 CNV gain 17160897
nsv950677 CNV deletion 24416366
nsv968171 CNV duplication 23825009

Variation tolerance for NNT Gene

Residual Variation Intolerance Score: 6.75% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 5.64; 72.74% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for NNT Gene

Human Gene Mutation Database (HGMD)
NNT
SNPedia medical, phenotypic, and genealogical associations of SNPs for
NNT

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for NNT Gene

Disorders for NNT Gene

MalaCards: The human disease database

(8) MalaCards diseases for NNT Gene - From: HGMD, OMIM, ClinVar, GTR, Orphanet, Swiss-Prot, DISEASES, and GeneCards

UniProtKB/Swiss-Prot

NNTM_HUMAN
  • Glucocorticoid deficiency 4 with or without mineralocorticoid deficiency (GCCD4) [MIM:614736]: A rare, potentially lethal, autosomal recessive disorder characterized by resistance to ACTH action on the adrenal cortex, adrenal insufficiency and an inability of the adrenal cortex to produce cortisol. It usually presents in the neonatal period or in early childhood with episodes of hypoglycemia and other symptoms related to cortisol deficiency, including failure to thrive, recurrent illnesses or infections, convulsions, and shock. In a small number of patients hypoglycemia can be sufficiently severe and persistent that it leads to serious long-term neurological damage or death. The diagnosis is readily confirmed with a low plasma cortisol measurement in the presence of an elevated ACTH level, and normal aldosterone and plasma renin measurements. {ECO:0000269 PubMed:22634753}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for NNT

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with NNT: view

No data available for Genatlas for NNT Gene

Publications for NNT Gene

  1. Cloning and deduced amino acid sequence of human nicotinamide nucleotide transhydrogenase. (PMID: 9524818) Zieger B … Ware J (DNA sequence : the journal of DNA sequencing and mapping 1997) 2 3 4 22 58
  2. The cDNA sequence of proton-pumping nicotinamide nucleotide transhydrogenase from man and mouse. (PMID: 8616157) Arkblad EL … Rydström J (Biochimica et biophysica acta 1996) 3 4 22 58
  3. Mutations in NNT encoding nicotinamide nucleotide transhydrogenase cause familial glucocorticoid deficiency. (PMID: 22634753) Meimaridou E … Metherell LA (Nature genetics 2012) 3 4 58
  4. Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression. (PMID: 20877624) Hendrickson SL … O'Brien SJ (PloS one 2010) 3 44 58
  5. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PMID: 15489334) Gerhard DS … MGC Project Team (Genome research 2004) 3 4 58

Products for NNT Gene

Sources for NNT Gene

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