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DLD Gene

protein-coding   GIFtS: 71
GCID: GC07P107531

Dihydrolipoamide Dehydrogenase

(Previous names: dihydrolipoamide dehydrogenase (E3 component of pyruvate...)
(Previous symbols: LAD, GCSL)
  See 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
Dihydrolipoamide Dehydrogenase1 2 3     DLDH2
LAD1 2 3 5     E32
GCSL1 2 3     diaphorase2
PHE32 3 5     Dihydrolipoyl Dehydrogenase, Mitochondrial2
Glycine Cleavage System L Protein2 3     E3 Component Of Pyruvate Dehydrogenase Complex, 2-Oxo-Glutarate Complex,
Branched Chain Keto Acid Dehydrogenase Complex2
EC 1.8.1.43 8     Glycine Cleavage System Protein L2
DLDD2 5     Lipoamide Dehydrogenase2
2-Oxo-Glutarate Complex1     Lipoamide Reductase2
Branched Chain Keto Acid Dehydrogenase Complex1     Lipoyl Dehydrogenase2
Dihydrolipoamide Dehydrogenase (E3 Component Of Pyruvate Dehydrogenase
Complex, 2-Oxo-Glutarate Complex, Branched Chain Keto Acid Dehydrogenase
Complex)1
     EC 1.8.18
E3 Component Of Pyruvate Dehydrogenase Complex1     

External Ids:    HGNC: 28981   Entrez Gene: 17382   Ensembl: ENSG000000911407   OMIM: 2383315   UniProtKB: P096223   

Export aliases for DLD gene to outside databases

Previous GC identifers: GC07P106015 GC07P107078 GC07P107092 GC07P107125 GC07P107318 GC07P101894


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for DLD Gene:
This gene encodes a member of the class-I pyridine nucleotide-disulfide oxidoreductase family. The encoded protein
has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions.
In homodimeric form, the encoded protein functions as a dehydrogenase and is found in several multi-enzyme
complexes that regulate energy metabolism. However, as a monomer, this protein can function as a protease.
Mutations in this gene have been identified in patients with E3-deficient maple syrup urine disease and lipoamide
dehydrogenase deficiency. Alternative splicing results in multiple transcript variants. (provided by RefSeq, Jan
2014)

GeneCards Summary for DLD Gene:
DLD (dihydrolipoamide dehydrogenase) is a protein-coding gene. Diseases associated with DLD include dihydrolipoamide dehydrogenase e3 deficiency, and cutaneous anthrax. GO annotations related to this gene include dihydrolipoyl dehydrogenase activity and flavin adenine dinucleotide binding.

UniProtKB/Swiss-Prot: DLDH_HUMAN, P09622
Function: Lipoamide dehydrogenase is a component of the glycine cleavage system as well as of the alpha-ketoacid
dehydrogenase complexes. Involved in the hyperactivation of spermatazoa during capacitation and in the
spermatazoal acrosome reaction

Gene Wiki entry for DLD (Dihydrolipoamide dehydrogenase) 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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RefSeq DNA sequence:
NC_000007.14  NC_018918.2  NT_007933.16  
Regulatory elements:
   Regulatory transcription factor binding sites in the DLD gene promoter:
         AP-1   ATF-2   NF-AT   E47   CP2   Hand1   c-Jun   TGIF   NF-AT1   Hlf   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 4): DLD promoter sequence
   Search Chromatin IP Primers for DLD

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat DLD


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 7q31-q32   Ensembl cytogenetic band:  7q31.1   HGNC cytogenetic band: 7q31-q32

DLD Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
DLD gene location

GeneLoc information about chromosome 7         GeneLoc Exon Structure

GeneLoc location for GC07P107531:  view genomic region     (about GC identifiers)

Start:
107,531,415 bp from pter      End:
107,572,175 bp from pter
Size:
40,761 bases      Orientation:
plus strand

1 alternative location:
Chr7+,CRA_TCAG 106,892,712-106,922,768     

(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, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., 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: DLDH_HUMAN, P09622 (See protein sequence)
Recommended Name: Dihydrolipoyl dehydrogenase, mitochondrial precursor  
Size: 509 amino acids; 54177 Da
Cofactor: Binds 1 FAD per subunit (By similarity)
Subunit: Homodimer. Eukaryotic pyruvate dehydrogenase complexes are organized about a core consisting of the
oligomeric dihydrolipoamide acetyl-transferase, around which are arranged multiple copies of pyruvate
dehydrogenase, dihydrolipoamide dehydrogenase and protein X bound by non-covalent bonds
Miscellaneous: The active site is a redox-active disulfide bond
Sequence caution: Sequence=BAD92940.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
5 PDB 3D structures from and Proteopedia for DLD:
1ZMC (3D)        1ZMD (3D)        1ZY8 (3D)        2F5Z (3D)        3RNM (3D)    
Secondary accessions: B2R5X0 Q14131 Q14167 Q59EV8 Q8WTS4

Explore the universe of human proteins at neXtProt for DLD: NX_P09622

Explore proteomics data for DLD at MOPED

Post-translational modifications: 

  • Tyrosine phosphorylated (By similarity)1
  • Ubiquitination2 at Lys104, Lys132, Lys143, Lys320, Lys346, Lys440
  • Modification sites at PhosphoSitePlus
  • Selected DME Specific Peptides for DLD (P09622) (see all 22)
     HPTLSEA  PGITIDE  GPGGYVA  GGYVAAI 


    See DLD Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (4 alternative transcripts): 
    NP_000099.2  NP_001276679.1  NP_001276680.1  NP_001276681.1  

    ENSEMBL proteins: 
     ENSP00000205402   ENSP00000402593   ENSP00000390667   ENSP00000417016   ENSP00000387542  
     ENSP00000409590   ENSP00000388077   ENSP00000442399  
    Reactome Protein details: P09622

    DLD Human Recombinant Protein Products:

    Browse Purified and Recombinant Proteins at EMD Millipore
    Browse R&D Systems for human recombinant proteins
    Browse recombinant and purified proteins available from Enzo Life Sciences
    OriGene Purified Protein for DLD
    OriGene Protein Over-expression Lysate for DLD
    OriGene MassSpec for DLD
    OriGene Custom Protein Services for DLD
    GenScript Custom Purified and Recombinant Proteins Services for DLD
    Novus Biologicals DLD Proteins
    Novus Biologicals DLD Lysate
    Browse Sino Biological Recombinant Proteins
    Browse Sino Biological Cell Lysates
    ProSpec Recombinant Protein for DLD
    Cloud-Clone Corp. Proteins for DLD

    DLD Antibody Products:

    Browse EMD Millipore's Extensive Line of Mono- and Polyclonal Antibodies
    Browse R&D Systems for Antibodies
    OriGene Antibodies for DLD
    OriGene Custom Antibody Services for DLD
    Novus Biologicals DLD Antibodies
    Abcam antibodies for DLD
    Cloud-Clone Corp. Antibodies for DLD
    ThermoFisher Antibody for DLD
    LSBio Antibodies in human, mouse, rat for DLD

    DLD Assay Products:

    Browse Kits and Assays available from EMD Millipore
    OriGene Custom Assay Services for DLD
    Browse R&D Systems for biochemical assays
    GenScript Custom Assay Services for DLD
    Browse Enzo Life Sciences for kits & assays
    Cloud-Clone Corp. ELISAs for DLD
    Cloud-Clone Corp. CLIAs for DLD


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    Selected InterPro protein domains (see all 7):
     IPR013027 FAD_pyr_nucl-diS_OxRdtase
     IPR006258 Lipoamide_DH
     IPR012999 Pyr_OxRdtase_I_AS
     IPR004099 Pyr_nucl-diS_OxRdtase_dimer
     IPR016156 FAD/NAD-linked_Rdtase_dimer

    Graphical View of Domain Structure for InterPro Entry P09622

    ProtoNet protein and cluster: P09622

    3 Blocks protein domains:
    IPB001100 Pyridine nucleotide-disulphide oxidoreductase
    IPB001327 Pyridine nucleotide-disulphide oxidoreductase
    IPB013027 FAD-dependent pyridine nucleotide reductase signature


    UniProtKB/Swiss-Prot: DLDH_HUMAN, P09622
    Similarity: Belongs to the class-I pyridine nucleotide-disulfide oxidoreductase family


    DLD for domains           About GeneDecksing


    (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, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: DLDH_HUMAN, P09622
    Function: Lipoamide dehydrogenase is a component of the glycine cleavage system as well as of the alpha-ketoacid
    dehydrogenase complexes. Involved in the hyperactivation of spermatazoa during capacitation and in the
    spermatazoal acrosome reaction
    Catalytic activity: Protein N(6)-(dihydrolipoyl)lysine + NAD(+) = protein N(6)-(lipoyl)lysine + NADH

         Genatlas biochemistry entry for DLD:
    dihydrolipoyl dehydrogenase (E3 component of pyruvate,2-oxo-ketoglutarate and branched chain keto acid
    dehydrogenase complexes),inner mitochondrial membrane

         Enzyme Numbers (IUBMB): EC 1.8.1.41 2 EC 1.8.12

         Gene Ontology (GO): 4 molecular function terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004148dihydrolipoyl dehydrogenase activity IEA--
    GO:0016491oxidoreductase activity ----
    GO:0016668oxidoreductase activity, acting on a sulfur group of donors, NAD(P) as acceptor ----
    GO:0050660flavin adenine dinucleotide binding IEA--
         
    DLD for ontologies           About GeneDecksing


    Phenotypes:
         3 MGI mutant phenotypes (inferred from 1 allele(MGI details for Dld):
     embryogenesis  growth/size/body  mortality/aging 

    DLD for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-out Dldtm1Ptl for DLD

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for DLD
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for DLD

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for DLD
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for DLD

    miRNA
    Products:
        
    miRTarBase miRNAs that target DLD:
    hsa-mir-16-5p (MIRT031565), hsa-mir-99a-5p (MIRT048620)

    Block miRNA regulation of human, mouse, rat DLD using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate DLD (see all 29):
    hsa-miR-4286 hsa-miR-4272 hsa-miR-488 hsa-miR-570 hsa-miR-515-5p hsa-miR-374c hsa-miR-499-5p hsa-miR-3658
    SwitchGear 3'UTR luciferase reporter plasmidDLD 3' UTR sequence
    Inhib. RNA
    Products:
        
    OriGene RNAi products in human, mouse, rat for DLD
    Predesigned siRNA for gene silencing in human, mouse, rat DLD

    Gene Editing
    Products:
    DNA2.0 Custom Protein Engineering Service for DLD

    Clone
    Products:
         
    OriGene clones in human, mouse for DLD (see all 7)
    OriGene ORF clones in mouse, rat for DLD
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector: DLD (NM_000108)
    Sino Biological Human cDNA Clone for DLD
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for DLD
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat DLD

    Cell Line
    Products:
         
    GenScript Custom overexpressing Cell Line Services for DLD
    Browse ESI BIO Cell Lines and PureStem Progenitors for DLD 
    In Situ Assay
    Products:
       

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for DLD


    (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
    DLDH_HUMAN, P09622: Mitochondrion matrix
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    mitochondrion5
    nucleus4
    cytosol2
    vacuole2

    Gene Ontology (GO): Selected cellular component terms (see all 6):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005634nucleus IDA--
    GO:0005730NOT nucleolus IDA--
    GO:0005739mitochondrion IDA--
    GO:0005759mitochondrial matrix TAS--
    GO:0005929cilium IEA--

    DLD for ontologies           About GeneDecksing


    (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 DLD About   (see all 12)  
    See pathways by source

    SuperPathSelected contained pathways About (see all per SuperPath)
    1Citric acid cycle (TCA cycle)
    Citric acid cycle (TCA cycle)0.55
    pyruvate decarboxylation to acetyl CoA0.00
    Citrate cycle (TCA cycle)0.55
    Regulation of pyruvate dehydrogenase (PDH) complex0.00
    Pyruvate metabolism and Citric Acid (TCA) cycle0.49
    Pyruvate metabolism0.00
    conversion of glucose to acetyl CoA and entry into the TCA cycle0.43
    TCA cycle0.00
    2Metabolism of amino acids and derivatives
    Lysine catabolism0.00
    Branched-chain amino acid catabolism0.00
    Metabolism of amino acids and derivatives
    2-oxoglutarate decarboxylation to succinyl-CoA0.00
    3Valine, leucine and isoleucine degradation
    Valine, leucine and isoleucine degradation0.31
    valine degradation I0.00
    isoleucine degradation I0.00
    4Glycolysis and gluconeogenesis short map
    Glycolysis and Gluconeogenesis0.60
    Glycolysis / Gluconeogenesis0.46
    5Metabolism
    Metabolism0.38
    Metabolic pathways0.38

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways


    Selected BioSystems Pathways for DLD (see all 14)
        TCA Cycle
    2-oxoisovalerate decarboxylation to isobutanoyl-CoA
    isoleucine degradation I
    pyruvate decarboxylation to acetyl CoA
    Glycolysis and Gluconeogenesis


    5 Reactome Pathways for DLD
        Pyruvate metabolism
    Lysine catabolism
    Citric acid cycle (TCA cycle)
    Regulation of pyruvate dehydrogenase (PDH) complex
    Branched-chain amino acid catabolism


    Selected Kegg Pathways  (Kegg details for DLD) (see all 7):
        Glycolysis / Gluconeogenesis
    Citrate cycle (TCA cycle)
    Glycine, serine and threonine metabolism
    Valine, leucine and isoleucine degradation
    Pyruvate metabolism


    DLD for pathways           About GeneDecksing

        Pathway & Disease-focused RT2 Profiler PCR Arrays including DLD: 
              Amino Acid Metabolism II in human mouse rat
              Amino Acid Metabolism I in human mouse rat
              Molecular Toxicology PathwayFinder 384HT in human mouse rat
              Glucose Metabolism in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for DLD

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

    Selected Interacting proteins for DLD (P096222, 3 ENSP000002054024) via UniProtKB, MINT, STRING, and/or I2D (see all 431)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    GLDCP233782, 3, ENSP000003707374MINT-8079030 I2D: score=1 STRING: ENSP00000370737
    SUCLA2Q9P2R72, 3, ENSP000003679234MINT-8079030 I2D: score=1 STRING: ENSP00000367923
    HSPD1P108092, 3MINT-8079030 I2D: score=1 
    KARSQ150462, 3MINT-8079030 I2D: score=1 
    ENSG00000096150P622693I2D: score=1 
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 16):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0006090pyruvate metabolic process TAS--
    GO:0006099tricarboxylic acid cycle TAS--
    GO:0006120mitochondrial electron transport, NADH to ubiquinone IEA--
    GO:0006508proteolysis IEA--
    GO:0006554lysine catabolic process TAS--

    DLD for ontologies           About GeneDecksing



    (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 DLD (DLDH)

    Selected HMDB Compounds for DLD (see all 16)    About this table
    CompoundSynonyms CAS #PubMed Ids
    2-Hydroxybutyric acid(RS)-2-Hydroxybutyrate (see all 29)600-15-76688766
    3-Deoxy-D-glycero-D-galacto-2-nonulosonic acid2-KDN (see all 18)22594-61-2--
    Acetyl-CoAS-Acetyl coenzyme A (see all 13)72-89-9--
    Carbon dioxideCarbon oxide (see all 5)124-38-9--
    Coenzyme AAcetoacetyl coenzyme A sodium salt (see all 21)85-61-0--
    Dihydrolipoamidedihydrolipoamide (see all 6)3884-47-7--
    FAD1H-Purin-6-amine flavin dinucleotide (see all 21)146-14-5--
    Glutaryl-CoAglutaryl-CoA (see all 2)103192-48-9--
    HypothiocyaniteCyanosulfoxylate;Hypothiocyanite;OSCN-Hypothiocyanite ion;N,6-didehydro-3,6-dihydro-3-methyl-Adenosine 63296-34-4--
    LipoamideLipozyme (see all 25)940-69-2--

    3 DrugBank Compounds for DLD    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    NADHbeta-DPNH (see all 18)606-68-8target--17314104 17017892 17315258
    Flavin-Adenine Dinucleotide-- 146-14-5target--10592235
    Nicotinamide-Adenine-Dinucleotide-- 53-84-9target--10592235

    Selected Novoseek inferred chemical compound relationships for DLD gene (see all 20)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    dihydrolipoamide 98.6 193 14645106 (6), 8894701 (6), 1541297 (5), 15888450 (5) (see all 80)
    lipoamide 90.4 12 9934985 (1), 10806385 (1), 11368334 (1), 18362926 (1) (see all 11)
    pyruvate 82.1 63 18362926 (2), 15712224 (2), 16442803 (2), 20385101 (2) (see all 27)
    alpha-ketoglutarate 78 24 8619544 (2), 8731379 (2), 12464489 (1), 16045627 (1) (see all 10)
    2-oxo acid 76 6 10806385 (1), 1959888 (1), 9278141 (1), 7674838 (1)
    alpha lipoic acid 71.1 10 7669066 (2), 11368334 (1), 19393031 (1), 10218658 (1)
    nad+ 61.3 6 8289259 (1), 2033038 (1), 10336857 (1), 15946682 (1) (see all 5)
    nadh 53.2 3 11316579 (1), 10193578 (1), 15946682 (1)
    lactate 26.6 9 17160884 (2), 8289259 (1), 8968745 (1), 16233312 (1) (see all 5)
    peroxynitrite 15.4 1 16045627 (1)



    DLD for compounds           About GeneDecksing



    (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, Primers from OriGene, and/or QIAGEN )
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    REFSEQ mRNAs for DLD gene (4 alternative transcripts): 
    NM_000108.4  NM_001289750.1  NM_001289751.1  NM_001289752.1  

    Unigene Cluster for DLD:

    Dihydrolipoamide dehydrogenase
    Hs.131711  [show with all ESTs]
    Unigene Representative Sequence: NM_000108
    14 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000205402(uc010ljm.1 uc003vet.3 uc011kmg.2 uc011kmh.2 uc011kmi.2)
    ENST00000485066 ENST00000415325 ENST00000417551 ENST00000440410 ENST00000437604
    ENST00000453354 ENST00000450038 ENST00000451081 ENST00000460577 ENST00000494441
    ENST00000478414 ENST00000489184 ENST00000537148
    miRNA
    Products:
         
    Block miRNA regulation of human, mouse, rat DLD using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate DLD (see all 29):
    hsa-miR-4286 hsa-miR-4272 hsa-miR-488 hsa-miR-570 hsa-miR-515-5p hsa-miR-374c hsa-miR-499-5p hsa-miR-3658
    SwitchGear 3'UTR luciferase reporter plasmidDLD 3' UTR sequence
    Inhib. RNA
    Products:
         
    OriGene RNAi products in human, mouse, rat for DLD
    Predesigned siRNA for gene silencing in human, mouse, rat DLD
    Clone
    Products:
         
    OriGene clones in human, mouse for DLD (see all 7)
    OriGene ORF clones in mouse, rat for DLD
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector: DLD (NM_000108)
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for DLD
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat DLD
    Primer
    Products:
        
    OriGene qPCR primer pairs and template standards for DLD
    OriGene qSTAR qPCR primer pairs in human, mouse for DLD
    Pre-validated RT2 qPCR Primer Assay in human, mouse, rat DLD
      QuantiTect SYBR Green Assays in human, mouse, rat DLD
      QuantiFast Probe-based Assays in human, mouse, rat DLD

    Additional mRNA sequence: 

    AB209703.1 AK225289.1 AK225301.1 AK294146.1 AK295080.1 AK297508.1 AK300077.1 AK310220.1 
    AK312346.1 BC018648.2 BC018696.2 J03490.1 J03620.1 

    18 DOTS entries:

    DT.218690  DT.97797315  DT.100845548  DT.75170598  DT.100845544  DT.100845543  DT.210154  DT.121075590 
    DT.121075600  DT.206518  DT.121075585  DT.95305202  DT.100758912  DT.121075584  DT.121075588  DT.121075591 
    DT.121075616  DT.95305240 

    Selected AceView cDNA sequences (see all 409):

    BM749634 BG675041 AW029390 CA390332 AW237581 BU508139 CA393802 CB124554 
    AA939188 BM828625 BM464989 AI143302 BU507830 BM966773 CB160838 AU120894 
    BM874612 BP341041 AV707522 CB158218 AU130545 CR625204 AA232891 AI129544 

    GeneLoc Exon Structure

    Selected Alternative Splicing Database (ASD) splice patterns (SP) for DLD (see all 8)    About this scheme

    ExUns: 1a · 1b · 1c · 1d ^ 2 ^ 3 ^ 4 ^ 5 ^ 6a · 6b · 6c ^ 7 ^ 8a · 8b · 8c ^ 9a · 9b ^ 10 ^ 11 ^ 12 ^ 13a · 13b ^ 14 ^ 15 ^ 16a · 16b
    SP1:                          -                                   -     -     -                       -                                                         
    SP2:                          -                                   -                                                                                             
    SP3:                          -                 -                 -     -     -                       -                                                         
    SP4:                          -                                   -     -                                                                                       
    SP5:                                                              -     -                                                                                       


    ECgene alternative splicing isoforms for DLD

    (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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    DLD expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: GCTGGAGCTA
    DLD Expression
    About this image


    DLD expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 16) fully expand
     
     Brain (Nervous System)    fully expand to see all 8 entries
             Cerebral Cortex
     
     Kidney (Urinary System)
             Metanephros
     
     Thymus (Hematopoietic System)
             Thymus
     
     Eye (Sensory Organs)
             Lens
     
     Neural Tube (Nervous System)
             Telencephalon
    DLD Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    DLD Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.131711
        Pathway & Disease-focused RT2 Profiler PCR Arrays including DLD: 
              Amino Acid Metabolism II in human mouse rat
              Amino Acid Metabolism I in human mouse rat
              Molecular Toxicology PathwayFinder 384HT in human mouse rat
              Glucose Metabolism in human mouse rat

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    (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 eukaryotes.

    Orthologs for DLD gene from Selected species (see all 30)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Dld1 , 5 dihydrolipoamide dehydrogenase1, 5 90.57(n)1
    94.89(a)1
      12 (13.43 cM)5
    133821  NM_007861.41  NP_031887.21 
     313315645 
    chicken
    (Gallus gallus)
    Aves DLD1 dihydrolipoamide dehydrogenase 80.31(n)
    89.57(a)
      417699  NM_001030727.1  NP_001025898.1 
    lizard
    (Anolis carolinensis)
    Reptilia DLD6
    dihydrolipoamide dehydrogenase
    85(a)
    1 ↔ 1
    5(97771705-97793169)
    African clawed frog
    (Xenopus laevis)
    Amphibia dld-prov2 dihydrolipoamide dehydrogenase (E3 component of pyruvate dehydrogenase complex, 2-oxo-glutarate complex, branched chain keto acid dehydrogenase complex) less 78.55(n)    BC056016.1 
    zebrafish
    (Danio rerio)
    Actinopterygii Dr.10512 Danio rerio mRNA similar to dihydrolipoamide dehydrogenase (E3 component of pyruvate dehydrogenase complex, 2-oxo-glutarate complex, branched chain keto acid dehydrogenase complex) (cDNA clone MGC55583 IMAGE2643379), complete cds less 77.32(n)    BC044432.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta CG74301 , 3 dihydrolipoamide dehydrogenase3
    CG74301
    67(a)3
    60.05(n)1
    68.92(a)1
      75A63
    399881  NM_140760.31  NP_649017.11 
    worm
    (Caenorhabditis elegans)
    Secernentea LLC1.33
    dld-11
    dihydrolipoamide dehydrogenase3
    dld-11
    66(a)3
    64.41(n)1
    72.67(a)1
      IV(14464583-14465767)3
    1783871  NM_001268881.11  NP_001255810.11 
    baker's yeast
    (Saccharomyces cerevisiae)
    Saccharomycetes LPD1(YFL018C)4
    LPD11
    Dihydrolipoamide dehydrogenase, the lipoamide dehydrogenase component (E3) of the pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase multi-enzyme complexes less4
    LPD11
    60.55(n)1
    58.75(a)1
      6(103127-101628)4
    8505271, 4  NP_116635.11, 4 
    thale cress
    (Arabidopsis thaliana)
    eudicotyledons mtLPD21 mtLPD2 59.78(n)
    58.28(a)
      820984  NM_112601.3  NP_566570.3 
    rice
    (Oryza sativa)
    Liliopsida Os.15062 Oryza sativa (japonica cultivar-group) cDNA cloneJ013072D16, full insert sequence less 73.83(n)    NM_183836.1 


    ENSEMBL Gene Tree for DLD (if available)
    TreeFam Gene Tree for DLD (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for DLD gene
    3 SIMAP similar genes for DLD using alignment to 7 protein entries:     DLDH_HUMAN (see all proteins):
    GSR    TXNRD2    TXNRD1

    DLD for paralogs           About GeneDecksing



    (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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    Selected SNPs for DLD (see all 773)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 7 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    VAR_0158204
    Dihydrolipoamide dehydrogenase deficiency (DLDD)4--see VAR_0158202 G C mis40--------
    VAR_0069074
    Dihydrolipoamide dehydrogenase deficiency (DLDD)4--see VAR_0069072 K E mis40--------
    VAR_0158214
    Dihydrolipoamide dehydrogenase deficiency (DLDD)4--see VAR_0158212 R G mis40--------
    VAR_0069084
    Dihydrolipoamide dehydrogenase deficiency (DLDD)4--see VAR_0069082 P L mis40--------
    rs1219649901,2
    Cpathogenic1110914844(+) TGCAGG/TGTTCA 2 G C mis11Minor allele frequency- T:0.00NA 4546
    rs1219649921,2
    Cpathogenic1110916687(+) GTGTTG/AAAGGA 2 /K /E mis11Minor allele frequency- A:0.00EU 1323
    rs1137740701,2
    C--106894103(+) AGAGC-/TTTA/ 
    TTTATTTA
    TTTAT
    1 -- int11CSA 2
    rs344681751,2
    C--106910236(+) GTCTC-/AAAAAA 1 -- int10--------
    rs113732141,2
    C--107531832(+) GGAGGC/-CGGGC 1 -- int13Minor allele frequency- -:0.00NA CSA 6
    rs719505411,2
    C--107532977(+) TTTAT-/TTTA  
            
    TTATT
    1 -- int10--------

    HapMap Linkage Disequilibrium report for DLD (107531415 - 107572175 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 3 variations for DLD:    About this table    
    Variant IDTypeSubtypePubMed ID
    esv34192CNV Loss18971310
    nsv831088CNV Loss17160897
    esv259654OTHER Complex20981092

    Human Gene Mutation Database (HGMD): DLD
    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing DLD
    DNA2.0 Custom Variant and Variant Library Synthesis for DLD

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 238331   
    OMIM disorders: 246900  
    UniProtKB/Swiss-Prot: DLDH_HUMAN, P09622
  • Dihydrolipoamide dehydrogenase deficiency (DLDD) [MIM:246900]: An autosomal recessive metabolic disorder
    characterized biochemically by a combined deficiency of the branched-chain alpha-keto acid dehydrogenase complex
    (BCKDC), pyruvate dehydrogenase complex (PDC), and alpha-ketoglutarate dehydrogenase complex (KGDC). Clinically,
    affected individuals have lactic acidosis and neurologic deterioration due to sensitivity of the central nervous
    system to defects in oxidative metabolism. Note=The disease is caused by mutations affecting the gene represented
    in this entry

  • Selected diseases for DLD (see all 45):    
    About MalaCards
    dihydrolipoamide dehydrogenase e3 deficiency    cutaneous anthrax    lipoamide dehydrogenase deficiency    dihydrolipoamide dehydrogenase deficiency
    maple syrup urine disease type 3    coenzyme q10 deficiency, primary, 1    alpha-ketoglutarate dehydrogenase deficiency    pyruvate dehydrogenase e3-binding protein deficiency
    maple syrup urine disease    pyruvate decarboxylase deficiency    maple syrup urine disease type 2    pearson syndrome
    lactic acidosis    mitochondrial dna deletion syndromes    metabolic acidosis    mitochondrial dna-associated leigh syndrome and narp
    protein s deficiency    friedreich ataxia    primary biliary cirrhosis    microcephaly

    3 diseases from the University of Copenhagen DISEASES database for DLD:
    Maple syrup urine disease     Lactic acidosis     Cutaneous anthrax

    DLD for disorders           About GeneDecksing

    8 Novoseek inferred disease relationships for DLD gene    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    primary lactic acidosis 89.5 2 11687750 (1)
    acidosis lactic 61.9 2 11687750 (1), 8652022 (1)
    biliary cirrhosis primary 40 5 7674838 (2), 1959888 (1)
    metabolic acidosis 29.1 2 9540846 (1)
    microcephaly 27.2 2 12925875 (1)
    shock 0 1 18281682 (1)
    hypoglycemia 0 2 12925875 (1)
    alzheimers disease 0 4 17342416 (2), 8619544 (1)

    Genatlas disease: DLD
    lactate acidosis,congenital,with elevated branched chain aminoacids presenting as Leigh syndrome characterized by
    lactate acidosis bilaterally symmetrical necrotic lesions in the brainstem,basal ganglia,thalamus and spinal
    cord,occuring predominantly in infants

    Genetic Association Database (GAD): DLD
    Human Genome Epidemiology (HuGE) Navigator: DLD (4 documents)

    Export disorders for DLD 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 DLD gene, integrated from 10 sources (see all 157):
    (articles sorted by number of sources associating them with DLD)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Structural insight into interactions between dihydrolipoamide dehydrogenase (E3) and E3 binding protein of human pyruvate dehydrogenase complex. (PubMed id 16442803)1, 2, 9 Brautigam C.A....Chuang D.T. (Structure 2006)
    2. How dihydrolipoamide dehydrogenase-binding protein binds dihydrolipoamide dehydrogenase in the human pyruvate dehydrogenase complex. (PubMed id 16263718)1, 2, 9 Ciszak E.M.... Patel M.S. (J. Biol. Chem. 2006)
    3. Identification of two missense mutations in a dihydrolipoamide dehydrogenase-deficient patient. (PubMed id 8506365)1, 2, 9 Liu T.-C.... Patel M.S. (Proc. Natl. Acad. Sci. U.S.A. 1993)
    4. Characterization of the transcriptional regulatory region of the human dihydrolipoamide dehydrogenase gene. (PubMed id 1332063)1, 2, 9 Johanning G.L.... Patel M.S. (Proc. Natl. Acad. Sci. U.S.A. 1992)
    5. Molecular basis of lipoamide dehydrogenase deficiency in Ashkenazi Jews. (PubMed id 9934985)1, 2, 9 Shaag A....Elpeleg O.N. (Am. J. Med. Genet. 1999)
    6. The structure of the human dihydrolipoamide dehydrogenase gene (DLD) and its upstream elements. (PubMed id 8406489)1, 2, 9 Feigenbaum A.S. and Robinson B.H. (Genomics 1993)
    7. Crystal structure of human dihydrolipoamide dehydrogenase: NAD+/NADH binding and the structural basis of disease-causing mutations. (PubMed id 15946682)1, 2, 9 Brautigam C.A.... Chuang D.T. (J. Mol. Biol. 2005)
    8. Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression. (PubMed id 20877624)1, 4 Hendrickson S.L....O'Brien S.J. (PLoS ONE 2010)
    9. Genome-wide association identifies multiple ulcerative colitis susceptibility loci. (PubMed id 20228799)1, 4 McGovern D.P....Seielstad M. (Nat. Genet. 2010)
    10. Ulcerative colitis-risk loci on chromosomes 1p36 and 12q15 found by genome-wide association study. (PubMed id 19122664)1, 4 Silverberg M.S....Duerr R.H. (Nat. Genet. 2009)

    (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: 1738 HGNC: 2898 AceView: DLD Ensembl:ENSG00000091140 euGenes: HUgn1738
    ECgene: DLD Kegg: 1738 H-InvDB: DLD

    (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 DLD Pharmacogenomics, SNPs, Pathways
    GeneReviewshttp://www.ncbi.nlm.nih.gov/books/NBK1116/?term=DLD[genesymbol]

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for DLD gene:
    Search GeneIP for patents involving DLD

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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