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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 61
  • 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 and Familial Glucocorticoid Deficiency. Among its related pathways are Pyruvate metabolism and Citric Acid (TCA) cycle and NAD metabolism. 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

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

Genomics for NNT Gene

Regulatory Elements for NNT Gene

Enhancers for NNT Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH05G043554 1.1 ENCODE 24.6 -46.3 -46315 3.2 ARNT CREB3L1 ARID4B SIN3A DMAP1 ZNF2 ZNF207 ZNF143 KLF13 ZNF263 ENSG00000248240 NNT ZNF131 RPL29P12 C5orf34 EEF1A1P19 NNT-AS1 ENSG00000249492 LOC153684 FGF10-AS1
GH05G043631 1.3 Ensembl ENCODE dbSUPER 20.3 +28.7 28696 0.4 HDGF CTCF PKNOX1 MAX RAD21 RFX5 YY1 ZNF664 POLR2A ZNF143 NNT NNT-AS1 GC05M043668
GH05G043768 1.2 Ensembl ENCODE dbSUPER 14.7 +167.3 167349 2.3 BRD4 ATF1 ZNF175 CEBPG PYGO2 ZNF644 ZNF584 ZNF197 L3MBTL2 ZNF740 NNT NNT-AS1 RPL29P12 ENSG00000249276
GH05G043482 1.2 ENCODE 13.2 -117.7 -117682 5.6 CREB3L1 AGO1 FEZF1 DMAP1 YY1 ZNF143 SP3 ZNF610 GLIS1 NBN EEF1A1P19 ZNF131 RPL29P12 ENSG00000248240 NNT CCL28 ENSG00000249492 PAIP1 LOC153684 FGF10-AS1
GH05G043601 1.1 ENCODE 14.3 +0.3 340 3.6 HDGF PKNOX1 ARNT ARID4B SIN3A ZNF2 YY1 ZNF766 FOS SP3 NNT-AS1 NNT ZNF131 C5orf34 CCL28
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around NNT on UCSC Golden Path with GeneCards custom track

Promoters for NNT Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000180214 511 2401 HDGF PKNOX1 ARNT ARID4B SIN3A FEZF1 ZNF2 YY1 ZNF766 FOS

Genomic Location for NNT Gene

Chromosome:
5
Start:
43,602,689 bp from pter
End:
43,707,405 bp from pter
Size:
104,717 bases
Orientation:
Plus strand

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 Lys55
  • Modification sites at PhosphoSitePlus

Domains & Families for NNT Gene

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

No data available for Gene Families for NNT Gene

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

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

CRISPR Products

miRNA for NNT Gene

miRTarBase miRNAs that target NNT

Inhibitory RNA Products

Clone Products

Flow Cytometry 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

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,IDA 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
2'-Monophosphoadenosine 5'-Diphosphoribose Experimental Pharma Target 0
7-thionicotinamide-adenine-dinucleotide phosphate Experimental Pharma Target 0
NADH Nutra Target 0
NAD Pharma Full agonist, Agonist 0

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

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:

CRISPR Products

Inhibitory RNA Products

Clone Products

Flow Cytometry 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(4.5)
  • Muscle(4.5)
  • Nervous system(3.6)
  • Adrenal gland(3.3)
  • Pancreas(2.7)
  • Blood(2.6)
  • 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
Organs:
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

Primer Products

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 34 35
  • 99.6 (n)
mouse
(Mus musculus)
Mammalia Nnt 35
  • 94 (a)
OneToOne
dog
(Canis familiaris)
Mammalia NNT 34 35
  • 92.33 (n)
oppossum
(Monodelphis domestica)
Mammalia NNT 35
  • 92 (a)
OneToOne
cow
(Bos Taurus)
Mammalia NNT 34 35
  • 91.71 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia NNT 35
  • 90 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Nnt 34
  • 86.49 (n)
chicken
(Gallus gallus)
Aves NNT 34 35
  • 78.53 (n)
lizard
(Anolis carolinensis)
Reptilia NNT 35
  • 90 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia nnt 34
  • 76.92 (n)
zebrafish
(Danio rerio)
Actinopterygii nnt 34 35
  • 72.29 (n)
-- 34
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.10162 34
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP003167 34
  • 61.92 (n)
worm
(Caenorhabditis elegans)
Secernentea nnt-1 36 34 35
  • 59.75 (n)
sea squirt
(Ciona savignyi)
Ascidiacea CSA.6124 35
  • 67 (a)
OneToOne
bread mold
(Neurospora crassa)
Ascomycetes NCU01140 34
  • 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 Sequence Context AA Info Type
rs370273690 Pathogenic, Glucocorticoid deficiency 4 with or without mineralocorticoid deficiency (GCCD4) [MIM:614736] 43,702,652(+) GCTAA(C/G/T)GACAC reference, synonymous-codon, missense
rs371979800 Glucocorticoid deficiency 4 with or without mineralocorticoid deficiency (GCCD4) [MIM:614736] 43,653,144(+) CCCTC(A/G)GAGTC reference, missense
rs387907232 Pathogenic, Glucocorticoid deficiency 4 with or without mineralocorticoid deficiency (GCCD4) [MIM:614736] 43,649,300(+) AAATG(C/T)AATCT reference, missense
rs387907233 Pathogenic, Glucocorticoid deficiency 4 with or without mineralocorticoid deficiency (GCCD4) [MIM:614736] 43,700,172(+) GCTGC(C/T)GGCTG reference, missense
rs387907234 Pathogenic, Glucocorticoid deficiency 4 with or without mineralocorticoid deficiency (GCCD4) [MIM:614736] 43,702,647(+) TTGGA(C/G)CTAAT reference, missense

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)

Relevant External Links for NNT Gene

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

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

Disorders for NNT Gene

MalaCards: The human disease database

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

Disorder Aliases PubMed IDs
glucocorticoid deficiency 4
  • glucocorticoid deficiency 4 with or without mineralocorticoid deficiency
familial glucocorticoid deficiency
  • acth resistance
achalasia-addisonianism-alacrimia syndrome
  • triple-a syndrome
adrenal rest tumor
  • adrenal rest neoplasm
image syndrome
  • intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies
- elite association - COSMIC cancer census association via MalaCards
Search NNT in MalaCards View complete list of genes associated with diseases

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.

Relevant External Links for NNT

Genetic Association Database (GAD)
NNT
Human Genome Epidemiology (HuGE) Navigator
NNT
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
NNT
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) Ware J. … Zieger B. (DNA Seq. 1997) 2 3 4 22 64
  2. The cDNA sequence of proton-pumping nicotinamide nucleotide transhydrogenase from man and mouse. (PMID: 8616157) Lagberg E.M. … Rydstrom J. (Biochim. Biophys. Acta 1996) 3 4 22 64
  3. Mutations in NNT encoding nicotinamide nucleotide transhydrogenase cause familial glucocorticoid deficiency. (PMID: 22634753) Meimaridou E. … Metherell L.A. (Nat. Genet. 2012) 3 4 64
  4. Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression. (PMID: 20877624) Hendrickson S.L. … O'Brien S.J. (PLoS ONE 2010) 3 46 64
  5. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PMID: 15489334) Gerhard D.S. … Malek J. (Genome Res. 2004) 3 4 64

Products for NNT Gene

Sources for NNT Gene

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