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MT-ND4L Gene

protein-coding   GIFtS: 42
GCID: GCMTP010472

Mitochondrially Encoded NADH Dehydrogenase 4L

(Previous name: NADH dehydrogenase 4L)
(Previous symbol: MTND4L)
  See MT-ND4L-related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Mitochondrially Encoded NADH Dehydrogenase 4L1     Complex I ND4L Subunit1
MTND4L1 2 3     NADH Dehydrogenase 4L1
ND4L2 3     NADH-Ubiquinone Oxidoreductase Chain 4L1
NADH Dehydrogenase Subunit 4L2 3     NADH Dehydrogenase, Subunit 4L (Complex I)2
EC 1.6.5.33 8     NADH4L3

External Ids:    HGNC: 74601   Entrez Gene: 45392   Ensembl: ENSG000002129077   OMIM: 5160045   UniProtKB: P039013   

Export aliases for MT-ND4L gene to outside databases

Previous GC identifer: GC00U921591


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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GeneCards Summary for MT-ND4L Gene:
MT-ND4L (mitochondrially encoded NADH dehydrogenase 4L) is a protein-coding gene. Diseases associated with MT-ND4L include leber hereditary optic neuropathy, and mitochondrial disorders.

UniProtKB/Swiss-Prot: NU4LM_HUMAN, P03901
Function: Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) that is
believed to belong to the minimal assembly required for catalysis. Complex I functions in the transfer of
electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be
ubiquinone (By similarity)

Gene Wiki entry for MT-ND4L Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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Regulatory elements:
   Search for regulatory transcription factor binding sites for MT-ND4L
         Other transcription factors

Browse SwitchGear Promoter luciferase reporter plasmids
   Search Chromatin IP Primers for MT-ND4L

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat MT-ND4L


Genomic Location:
Chromosome:MT   

Ensembl cytogenetic band:  MT   HGNC chromosome: mitochondria

GeneLoc information about chromosome MT         GeneLoc Exon Structure

GeneLoc location for GCMTP010472:       (about GC identifiers)

Start:
10,470 bp from pter      End:
10,766 bp from pter
Size:
297 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., and/or eBioscience,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., and/or eBioscience, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: NU4LM_HUMAN, P03901 (See protein sequence)
Recommended Name: NADH-ubiquinone oxidoreductase chain 4L  
Size: 98 amino acids; 10741 Da

Explore the universe of human proteins at neXtProt for MT-ND4L: NX_P03901

Selected DME Specific Peptides for MT-ND4L (P03901) (see all 11)
 VGLALLV  LLCLEGM  ISLLGML  LANIVPI 


ENSEMBL proteins: 
 ENSP00000354728  
Reactome Protein details: P03901

MT-ND4L Human Recombinant Protein Products:

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(According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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HGNC Gene Families:
comI: Mitochondrial respiratory chain complex / Complex I

1 InterPro protein domain:
 IPR001133 NADH_UbQ_OxRdtase_chain4L/K

Graphical View of Domain Structure for InterPro Entry P03901

ProtoNet protein and cluster: P03901

1 Blocks protein domain: IPB003214 Mitochodrial NADH-ubiquinone oxidoreductase

UniProtKB/Swiss-Prot: NU4LM_HUMAN, P03901
Similarity: Belongs to the complex I subunit 4L family


Find genes that share domains with MT-ND4L           About GenesLikeMe


(According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Molecular Function:

     UniProtKB/Swiss-Prot Summary: NU4LM_HUMAN, P03901
Function: Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) that is
believed to belong to the minimal assembly required for catalysis. Complex I functions in the transfer of
electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be
ubiquinone (By similarity)
Catalytic activity: NADH + ubiquinone + 5 H(+)(In) = NAD(+) + ubiquinol + 4 H(+)(Out)

     Enzyme Number (IUBMB): EC 1.6.5.31 2

     Gene Ontology (GO): 2 molecular function terms:    About this table

GO IDQualified GO termEvidencePubMed IDs
GO:0008137NADH dehydrogenase (ubiquinone) activity ----
GO:0016651oxidoreductase activity, acting on NAD(P)H ----
     
Find genes that share ontologies with MT-ND4L           About GenesLikeMe


Phenotypes:
     1 GenomeRNAi human phenotype for MT-ND4L:
 Increased viability after born 

Animal Models:
   inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for MT-ND4L
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miRNA
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miRTarBase miRNAs that target MT-ND4L:
hsa-mir-196a-5p (MIRT048170), hsa-let-7c-5p (MIRT051743), hsa-mir-15a-3p (MIRT038985), hsa-let-7b-5p (MIRT052064)

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Inhib. RNA
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(According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Subcellular locations from UniProtKB/Swiss-Prot
NU4LM_HUMAN, P03901: Mitochondrion membrane; Multi-pass membrane protein (By similarity)
Subcellular locations from COMPARTMENTS: 

CompartmentConfidence
mitochondrion5
plasma membrane3
extracellular1

Gene Ontology (GO): 3 cellular component terms:    About this table

GO IDQualified GO termEvidencePubMed IDs
GO:0005743mitochondrial inner membrane ----
GO:0005747mitochondrial respiratory chain complex I ----
GO:0016021integral component of membrane ----

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(SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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SuperPaths for MT-ND4L About    
See pathways by source

SuperPathContained pathways About
1Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins.
Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins.0.81
Oxidative phosphorylation0.64
Respiratory electron transport0.81
Parkinson's disease0.57
Electron Transport Chain0.75
Oxidative phosphorylation0.51
The citric acid (TCA) cycle and respiratory electron transport0.71
2Metabolism
Metabolism0.38
Metabolic pathways0.38


Find genes that share SuperPaths with MT-ND4L           About GenesLikeMe

Pathways by source                                                                                                                                                                 See SuperPaths
Show all pathways


2 BioSystems Pathways for MT-ND4L
    Oxidative phosphorylation
Electron Transport Chain

1 Reactome Pathway for MT-ND4L
    Respiratory electron transport


3 Kegg Pathways  (Kegg details for MT-ND4L):
    Oxidative phosphorylation
Metabolic pathways
Parkinson's disease

    Custom Pathway & Disease-focused RT2 Profiler PCR Arrays for MT-ND4L
Interactions:

    Search GeneGlobe Interaction Network for MT-ND4L

STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

Selected Interacting proteins for MT-ND4L (P039013 ENSP000003547284) via UniProtKB, MINT, STRING, and/or I2D (see all 63)
InteractantInteraction Details
GeneCardExternal ID(s)
ENSG00000236063O958703, ENSP000004069654I2D: score=1 STRING: ENSP00000406965
ABHD16AO958703I2D: score=1 
ENSG00000206403O958703I2D: score=1 
ENSG00000224552O958703I2D: score=1 
ENSG00000230475O958703I2D: score=1 
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Gene Ontology (GO): Selected biological process terms (see all 6):    About this table

GO IDQualified GO termEvidencePubMed IDs
GO:0006120mitochondrial electron transport, NADH to ubiquinone ----
GO:0022904respiratory electron transport chain ----
GO:0042773ATP synthesis coupled electron transport ----
GO:0044237cellular metabolic process ----
GO:0044281small molecule metabolic process ----

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(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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Browse Small Molecules at EMD Millipore
   Browse drugs & compounds from Enzo Life Sciences
  Browse compounds at ApexBio 

Browse Tocris compounds for MT-ND4L (NU4LM)

9 HMDB Compounds for MT-ND4L    About this table
CompoundSynonyms CAS #PubMed Ids
FAD1H-Purin-6-amine flavin dinucleotide (see all 21)146-14-5--
IronArmco iron (see all 19)7439-89-6--
NAD3-Carbamoyl-1-D-ribofuranosylpyridinium hydroxide 5'-ester with adenosine 5'-pyrophosphate (see all 28)53-84-9--
NADH1,4-Dihydronicotinamide adenine dinucleotide (see all 17)58-68-4--
QH2CoQH2 (see all 5)56275-39-9--
SulfideSulfide (see all 4)18496-25-8--
Ubiquinol 8ubiquinol-8 (see all 2)56275-39-9--
Ubiquinone Q1Coenzyme Q (see all 9)727-81-1--
Ubiquinone Q22-(3,7-dimethyl-2,6-octadienyl)-5,6-dimethoxy-3-methyl-2,5-Cyclohexadiene-1,4-dione (see all 7)606-06-4--

1 DrugBank Compound for MT-ND4L    About this table
CompoundSynonyms CAS #TypeActionsPubMed Ids
NADHbeta-DPNH (see all 18)606-68-8target--17139284 17016423

1 Novoseek inferred chemical compound relationship for MT-ND4L gene    About this table
Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
nadh 61.4 1 7628554 (1)



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(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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1 Ensembl transcript including schematic representation, and UCSC links where relevant:
ENST00000361335
miRNA
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Primer
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GeneLoc Exon Structure


(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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MT-ND4L expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS <intensity>2/3
CGAP TAG: --
MT-ND4L Expression
About this image

MT-ND4L Protein expression data from MOPED1, PaxDb2 and MaxQB3 --
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In Situ
Assay Products:
 

 
Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for MT-ND4L

(Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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This gene was present in the common ancestor of chordates.

Orthologs for MT-ND4L gene from Selected species (see all 10)    About this table
Organism Taxonomic
classification
Gene Description Human
Similarity
Orthology
Type
Details
mouse
(Mus musculus)
Mammalia mt-Nd4l5
ND4L1
mitochondrially encoded NADH dehydrogenase 4L5
ND4L1
69.05(n)1
67.35(a)1
  MT5
177201  ND4L_345386061  NP_904336.11 
 98775 
chicken
(Gallus gallus)
Aves MT-ND4L6
NADH-ubiquinone oxidoreductase chain 4L
49(a)
1 ↔ 1
MT(11196-11492) ENSGALG00000021719
lizard
(Anolis carolinensis)
Reptilia ND4L6
--
Uncharacterized protein
46(a)
45(a)
many → 1
many → 1
MT(9800-10096)
GL343313.1(1189119-1189415)
zebrafish
(Danio rerio)
Actinopterygii mt-nd4l6
NADH dehydrogenase 4L, mitochondrial
51(a)
1 ↔ 1
MT(11009-11305) ENSDARG00000063916


ENSEMBL Gene Tree for MT-ND4L (if available)
TreeFam Gene Tree for MT-ND4L (if available)

(Paralogs according to 1HomoloGene,
2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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Paralogs for MT-ND4L gene
2 SIMAP similar genes for MT-ND4L using alignment to 1 protein entry:     NU4LM_HUMAN:
NADH4L    ND4L

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Selected Pseudogenes.org Pseudogenes for MT-ND4L (see all 31)
PGOHUM00000238399 PGOHUM00000242817 PGOHUM00000247126 PGOHUM00000248718 PGOHUM00000248889


(SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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5 SNPs for MT-ND4L    About this table                                 

Genomic DataTranscription Related DataAllele Frequencies
SNP IDValidClinical
significance
Chr MT posSequence#AA
Chg
TypeMore#Allele
freq
PopTotal
sample
More
----------
VAR_0083974
Leber hereditary optic neuropathy (LHON)4--see VAR_0083972 V A mis40--------
VAR_0084964
Colorectal cancer4--see VAR_0084962 C R mis40--------
VAR_0086054
----see VAR_0086052 M I mis40--------
VAR_0086074
----see VAR_0086072 I T mis40--------
VAR_0086064
----see VAR_0086062 N S mis40--------

HapMap Linkage Disequilibrium report for MT-ND4L (10470 - 10766 bp)

Structural Variations
      Database of Genomic Variants (DGV) variations for MT-ND4L: --
Human Gene Mutation Database (HGMD): MT-ND4L
Site Specific Mutation Identification with PCR Assays
Search QIAGEN SeqTarget long-range PCR primers for resequencing MT-ND4L
DNA2.0 Custom Variant and Variant Library Synthesis for MT-ND4L

(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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OMIM gene information: 516004    OMIM disorders: --

UniProtKB/Swiss-Prot: NU4LM_HUMAN, P03901
  • Leber hereditary optic neuropathy (LHON) [MIM:535000]: A maternally inherited disease resulting in acute
    or subacute loss of central vision, due to optic nerve dysfunction. Cardiac conduction defects and neurological
    defects have also been described in some patients. LHON results from primary mitochondrial DNA mutations
    affecting the respiratory chain complexes. Note=The disease is caused by mutations affecting the gene represented
    in this entry

  • 2 diseases for MT-ND4L:    
    About MalaCards
    leber hereditary optic neuropathy    mitochondrial disorders

    2 diseases from the University of Copenhagen DISEASES database for MT-ND4L:
    Leber hereditary optic neuropathy     Mitochondrial myopathy

    Find genes that share disorders with MT-ND4L           About GenesLikeMe

    GeneTests: MT-ND4L
    GeneReviews: MT-ND4L

    Export disorders for MT-ND4L gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for MT-ND4L gene, integrated from 10 sources (see all 24):
    (articles sorted by number of sources associating them with MT-ND4L)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Sequence and organization of the human mitochondrial genome. (PubMed id 7219534)1, 2 Anderson S.... Young I.G. (Nature 1981)
    2. Phylogenetic analysis of Leber's hereditary optic neuropathy mitochondrial DNA's indicates multiple independent occurrences of the common mutations. (PubMed id 8680405)2, 9 Brown M.D.... Wallace D.C. (Hum. Mutat. 1995)
    3. Toward an understanding of the protein interaction network of the human liver. (PubMed id 21988832)1 Wang J....Yang X. (Mol. Syst. Biol. 2011)
    4. MtSNPscore: a combined evidence approach for assessing cumulative impact of mitochondrial variations in disease. (PubMed id 19758471)1 Bhardwaj A....Tiwari S. (BMC Bioinformatics 2009)
    5. Comprehensive analysis of common mitochondrial DNA variants and colorectal cancer risk. (PubMed id 19050702)1 Webb E....Houlston R.S. (Br. J. Cancer 2008)
    6. A novel PCLN-1 gene mutation in familial hypomagnesemia with hypercalciuria and atypical phenotype. (PubMed id 17123117)1 Sanjad S.A....Lifton R.P. (Pediatr. Nephrol. 2007)
    7. Drugs, their targets and the nature and number of drug targets. (PubMed id 17016423)7 Imming P....Meyer A. (Nat Rev Drug Discov 2006)
    8. How many drug targets are there? (PubMed id 17139284)7 Overington J.P....Hopkins A.L. (Nat Rev Drug Discov 2006)
    9. Single nucleotide polymorphisms over the entire mtDNA genome that increase the power of forensic testing in Caucasians. (PubMed id 14760490)2 Coble M.D.... Parsons T.J. (Int. J. Legal Med. 2004)
    10. Lineage-specific selection in human mtDNA: lack of polymorphisms in a segment of MTND5 gene in haplogroup J. (PubMed id 12949126)2 Moilanen J.S.... Majamaa K. (Mol. Biol. Evol. 2003)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 4539 HGNC: 7460 Ensembl:ENSG00000212907 euGenes: HUgn4539 ECgene: MT-ND4L Kegg: 4539
    H-InvDB: MT-ND4L

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for MT-ND4L Pharmacogenomics, SNPs, Pathways
    GeneReviewshttp://www.ncbi.nlm.nih.gov/books/NBK1116/?term=MT-ND4L[genesymbol]

    (Patent information from GeneIP,
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    IP news from LifeMap Sciences, Inc.)
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