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POLG Gene

protein-coding   GIFtS: 63
GCID: GC15M089859

Polymerase (DNA Directed), Gamma

  See POLG-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
Polymerase (DNA Directed), Gamma1 2     MIRAS2 5
POLG12 3 5     MTDPS4A2 5
POLGA2 3 5     MTDPS4B2 5
Mitochondrial DNA Polymerase Catalytic Subunit2 3     PEO2 5
MDP12 3     SANDO2 5
PolG-alpha2 3     SCAE2 5
EC 2.7.7.73 8     DNA Polymerase Subunit Gamma-12

External Ids:    HGNC: 91791   Entrez Gene: 54282   Ensembl: ENSG000001405217   OMIM: 1747635   UniProtKB: P540983   

Export aliases for POLG gene to outside databases

Previous GC identifers: GC15M086198 GC15M083225 GC15M087446 GC15M087589 GC15M087559 GC15M087660 GC15M065971


(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 POLG Gene:
Mitochondrial DNA polymerase is heterotrimeric, consisting of a homodimer of accessory subunits plus a catalytic
subunit. The protein encoded by this gene is the catalytic subunit of mitochondrial DNA polymerase. The encoded
protein contains a polyglutamine tract near its N-terminus that may be polymorphic. Defects in this gene are a
cause of progressive external ophthalmoplegia with mitochondrial DNA deletions 1 (PEOA1), sensory ataxic
neuropathy dysarthria and ophthalmoparesis (SANDO), Alpers-Huttenlocher syndrome (AHS), and mitochondrial
neurogastrointestinal encephalopathy syndrome (MNGIE). Two transcript variants encoding the same protein have
been found for this gene. (provided by RefSeq, Jul 2008)

GeneCards Summary for POLG Gene:
POLG (polymerase (DNA directed), gamma) is a protein-coding gene. Diseases associated with POLG include autosomal recessive progressive external ophthalmoplegia, and ataxia neuropathy spectrum. GO annotations related to this gene include chromatin binding and DNA-directed DNA polymerase activity.

UniProtKB/Swiss-Prot: DPOG1_HUMAN, P54098
Function: Involved in the replication of mitochondrial DNA. Associates with mitochondrial DNA

Gene Wiki entry for POLG 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:
   Regulatory transcription factor binding sites in the POLG gene promoter:
         STAT5B   STAT1   STAT4   HTF   STAT6   STAT1beta   STAT5A   STAT1alpha   STAT2   STAT3   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidPOLG promoter sequence
   Search Chromatin IP Primers for POLG

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


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

Entrez Gene cytogenetic band: 15q25   Ensembl cytogenetic band:  15q26.1   HGNC cytogenetic band: 15q24

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

GeneLoc information about chromosome 15         GeneLoc Exon Structure

GeneLoc location for GC15M089859:  view genomic region     (about GC identifiers)

Start:
89,859,534 bp from pter      End:
89,878,092 bp from pter
Size:
18,559 bases      Orientation:
minus 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., eBioscience, and/or antibodies-online,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., eBioscience, and/or antibodies-online, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, Cloud-Clone Corp, antibodies-online, and/or others.)
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UniProtKB/Swiss-Prot: DPOG1_HUMAN, P54098 (See protein sequence)
Recommended Name: DNA polymerase subunit gamma-1  
Size: 1239 amino acids; 139562 Da
Cofactor: Magnesium
Subunit: Heterotrimer composed of a catalytic subunit and a homodimer of accessory subunits
1 PDB 3D structure from and Proteopedia for POLG:
3IKM (3D)    
Secondary accessions: Q8NFM2 Q92515

Explore the universe of human proteins at neXtProt for POLG: NX_P54098

Explore proteomics data for POLG at MOPED

Post-translational modifications: 

  • Ubiquitination2 at Lys371, Lys379, Lys601, Lys633, Lys755, Lys768, Lys796, Lys934, Lys947, Lys981,
                                 Lys1040, Lys1060, Lys1198, Lys1228
  • Modification sites at PhosphoSitePlus
  • Selected DME Specific Peptides for POLG (P54098) (see all 25)
     CISIHDE  AFFSAVD  GHNVSFD  GSELKAM 


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

    REFSEQ proteins (2 alternative transcripts): 
    NP_001119603.1  NP_002684.1  

    ENSEMBL proteins: 
     ENSP00000268124   ENSP00000399851   ENSP00000432885   ENSP00000431395   ENSP00000433502  
     ENSP00000432389   ENSP00000434937  

    POLG Human Recombinant Protein Products:

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    Novus Biologicals POLG Protein
    Browse Sino Biological Recombinant Proteins
    Browse Sino Biological Cell Lysates
    Browse ProSpec Recombinant Proteins
    Browse Proteins at Cloud-Clone Corp.

     
    Search eBioscience for Proteins for POLG 

     
    antibodies-online proteins for POLG (2 products) 

     
    antibodies-online peptides for POLG

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    antibodies-online antibodies for POLG (35 products) 

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    Browse CLIAs at Cloud-Clone Corp.
    Search eBioscience for ELISAs for POLG 
    antibodies-online kits for POLG (6 products) 


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    HGNC Gene Families:
    POL: DNA polymerases

    5 InterPro protein domains:
     IPR016265 DNA-dir_DNA_pol_A_mt_sub
     IPR019760 DNA-dir_DNA_pol_A_CS
     IPR001098 DNA-dir_DNA_pol_A_palm_dom
     IPR012337 RNaseH-like_dom
     IPR002297 DNA-dir_DNA_pol_A_mt

    Graphical View of Domain Structure for InterPro Entry P54098

    ProtoNet protein and cluster: P54098

    2 Blocks protein domains:
    IPB001098 DNA-directed DNA polymerase
    IPB002297 DNA-polymerase gamma (family A) signature


    UniProtKB/Swiss-Prot: DPOG1_HUMAN, P54098
    Similarity: Belongs to the DNA polymerase type-A family


    Find genes that share domains with POLG           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, 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: DPOG1_HUMAN, P54098
    Function: Involved in the replication of mitochondrial DNA. Associates with mitochondrial DNA
    Catalytic activity: Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1)

         Genatlas biochemistry entry for POLG:
    polymerase,(DNA directed) gamma,139.5kDa mitochondrial,with a (CAG)n repeat in the first exon,not altered in
    disorders with mitochondrial genome instability

         Enzyme Number (IUBMB): EC 2.7.7.71 2

         Gene Ontology (GO): Selected molecular function terms (see all 7):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0002020protease binding IPI14739292
    GO:0003676nucleic acid binding ----
    GO:0003677DNA binding IEA--
    GO:0003682chromatin binding IDA18063578
    GO:0003887DNA-directed DNA polymerase activity IDA15164064
         
    Find genes that share ontologies with POLG           About GenesLikeMe


    Phenotypes:
         1 GenomeRNAi human phenotype for POLG:
     Synthetic lethal with Ras 

         Selected MGI mutant phenotypes (inferred from 5 alleles(MGI details for Polg) (see all 20):
     adipose tissue  cardiovascular system  cellular  digestive/alimentary  embryogenesis 
     endocrine/exocrine gland  growth/size/body  hearing/vestibular/ear  hematopoietic system  homeostasis/metabolism 
     immune system  integument  mortality/aging  muscle  nervous system 

    Find genes that share phenotypes with POLG           About GenesLikeMe

    Animal Models:
         MGI mouse knock-out Polgtm1.2Lrsn for POLG

       genOway: Develop your customized and physiologically relevant rodent model for POLG

    miRNA
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    miRTarBase miRNAs that target POLG:
    hsa-mir-221-3p (MIRT046950), hsa-mir-484 (MIRT041750), hsa-mir-615-3p (MIRT039938), hsa-mir-296-3p (MIRT038412), hsa-mir-26b-5p (MIRT028963)

    Block miRNA regulation of human, mouse, rat POLG using miScript Target Protectors
    2 qRT-PCR Assays for microRNAs that regulate POLG:
    hsa-miR-4293 hsa-miR-450b-5p
    SwitchGear 3'UTR luciferase reporter plasmidPOLG 3' UTR sequence
    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
    DPOG1_HUMAN, P54098: Mitochondrion. Mitochondrion matrix, mitochondrion nucleoid
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    mitochondrion5
    nucleus2
    cytosol1

    Gene Ontology (GO): 4 cellular component terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005739mitochondrion TAS8884268
    GO:0005743mitochondrial inner membrane IEA--
    GO:0005760gamma DNA polymerase complex IEA--
    GO:0042645mitochondrial nucleoid IDA18063578

    Find genes that share ontologies with POLG           About GenesLikeMe


    (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 POLG About    
    See pathways by source

    SuperPathContained pathways About
    1Metabolism
    Metabolic pathways0.38
    2Chks in Checkpoint Regulation
    DNA Repair Mechanisms0.32
    3Nucleotide Metabolism
    Nucleotide Metabolism
    4Cell Cycle Control of Chromosomal Replication
    Cell Cycle Control of Chromosomal Replication


    Find genes that share SuperPaths with POLG           About GenesLikeMe

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    2 Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for POLG
        DNA Repair Mechanisms
    Cell Cycle Control of Chromosomal Replication

    1 BioSystems Pathway for POLG
        Nucleotide Metabolism


    1 Kegg Pathway  (Kegg details for POLG):
        Metabolic pathways

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

        GeneGlobe Interaction Network for POLG

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

    Selected Interacting proteins for POLG (P540981, 2, 3 ENSP000002681244) via UniProtKB, MINT, STRING, and/or I2D (see all 106)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    POLG2Q9UHN11, 2, 3EBI-852624,EBI-852642 MINT-6167836 I2D: score=4 
    AGPAT1Q999433I2D: score=1 
    ENSG00000206324Q999433I2D: score=1 
    ENSG00000226467Q999433I2D: score=1 
    ENSG00000227642Q999433I2D: score=1 
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 7):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0006259DNA metabolic process TAS8884268
    GO:0006260DNA replication ----
    GO:0006261DNA-dependent DNA replication TAS3619920
    GO:0006264mitochondrial DNA replication IEA--
    GO:0006287base-excision repair, gap-filling IDA15177179

    Find genes that share ontologies with POLG           About GenesLikeMe



    (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 POLG (DPOG1)

    7 HMDB Compounds for POLG    About this table
    CompoundSynonyms CAS #PubMed Ids
    MagnesiumMagnesium (see all 2)7439-95-4--
    Phosphoric acidacide phosphorique (FRENCH) (see all 20)7664-38-2--
    Pyrophosphate(4-)Diphosphoric acid ion (see all 10)14000-31-8--
    Thymidine 5'-triphosphate2'-Deoxythymidine 5'-triphosphate (see all 13)365-08-2--
    dATP2'-Deoxy-5'-ATP (see all 8)1927-31-7--
    dCTP2'-deoxycytidine-5'-triphosphate (see all 4)2056-98-6--
    dGTP2'-Deoxyguanosine 5'-triphosphate (see all 4)2564-35-4--

    Selected Novoseek inferred chemical compound relationships for POLG gene (see all 32)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    nucleoside 79.6 40 19287302 (3), 10949849 (1), 19364868 (1), 15319672 (1) (see all 34)
    stavudine 72.7 4 19364868 (2), 15373054 (1), 14767983 (1)
    dgtp 68.2 2 17354649 (1), 1921985 (1)
    diethyl dithiocarbamate 67 7 15373054 (1), 14767983 (1), 17452351 (1), 18375634 (1) (see all 5)
    zidovudine 66.5 6 18504416 (1), 1671889 (1), 1748434 (1), 8156147 (1) (see all 6)
    dttp 64.9 4 2164928 (3)
    fiau 64.7 2 8622980 (2)
    didanosine 62.3 2 15373054 (1), 14767983 (1)
    ddttp 60.2 3 1691020 (1), 11077262 (1)
    triphosphate 54.1 4 8293572 (3), 11376566 (1)

    1 PharmGKB related drug/compound annotation for POLG gene    About this table
    Drug/compound PharmGKB Annotation
    valproic acid



    Find genes that share compounds with POLG           About GenesLikeMe



    (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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    REFSEQ mRNAs for POLG gene (2 alternative transcripts): 
    NM_001126131.1  NM_002693.2  

    13 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000268124(uc002bns.4 uc002bnr.4) ENST00000442287 ENST00000530292
    ENST00000526671 ENST00000530715 ENST00000528881 ENST00000532584 ENST00000526314
    ENST00000526398 ENST00000526573 ENST00000533857 ENST00000532363 ENST00000525806

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    hsa-miR-4293 hsa-miR-450b-5p
    SwitchGear 3'UTR luciferase reporter plasmidPOLG 3' UTR sequence
    Inhib. RNA
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      QuantiTect SYBR Green Assays in human, mouse, rat POLG
      QuantiFast Probe-based Assays in human, mouse, rat POLG

    Selected AceView cDNA sequences (see all 196):

    NM_002693 BE384049 BG259445 BM914584 CA437790 BX101895 AI436164 BM915136 
    BC050559 BQ010981 U60325 BU508425 BM699635 CD108663 AA934352 BM468562 
    BE903223 BM562117 AW192997 AI865047 BM557159 BE255263 BQ688760 CD615430 

    GeneLoc Exon Structure

    Selected Alternative Splicing Database (ASD) splice patterns (SP) for POLG (see all 22)    About this scheme

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

    ExUns: 12d ^ 13a · 13b ^ 14 ^ 15a · 15b ^ 16a · 16b ^ 17a · 17b · 17c ^ 18 ^ 19 ^ 20a · 20b ^ 21a · 21b · 21c ^ 22 ^ 23 ^ 24 ^ 25 ^ 26a · 26b · 26c ^ 27
    SP1:              -                                                                                                                                             
    SP2:              -                                                                                                                                             
    SP3:              -                                                                                                                                             
    SP4:                                                                                                                                                            
    SP5:                                                                                                                                                            


    ECgene alternative splicing isoforms for POLG

    (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)
    About This Section

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


    POLG expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     
     Heart (Cardiovascular System)
             Cardiac Crescent Cells Cardiac Crescent
    POLG Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    POLG Protein Expression
        Custom PCR Arrays for POLG
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    In Situ
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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for POLG

    (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)
    About This Section

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

    Orthologs for POLG gene from Selected species (see all 21)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Polg1 , 5 polymerase (DNA directed), gamma1, 5 87.21(n)1
    88(a)1
      7 (45.04 cM)5
    189751  NM_017462.21  NP_059490.21 
     794487915 
    chicken
    (Gallus gallus)
    Aves POLG1 polymerase (DNA directed), gamma 74.39(n)
    74.89(a)
      404292  XM_425079.4  XP_425079.4 
    lizard
    (Anolis carolinensis)
    Reptilia POLG6
    polymerase (DNA directed), gamma
    71(a)
    1 ↔ 1
    GL343444.1(273262-327180)
    African clawed frog
    (Xenopus laevis)
    Amphibia LOC3978512 DNA polymerase gamma 75.04(n)    U49509.1 
    zebrafish
    (Danio rerio)
    Actinopterygii Dr.197902 Transcribed sequence with weak similarity to protein more 77.37(n)    BM775631.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta tam1 , 3 DNA dependent DNA replication 3'-5'
    exodeoxyribonuclease3
    tamas1
    44(a)3
    54.73(n)1
    50.48(a)1
      2 34D63
    347921  NM_057473.41  NP_476821.11 
    worm
    (Caenorhabditis elegans)
    Secernentea Y57A10A.153   -- 37(a)   II(12189777-12199859)   --
    baker's yeast
    (Saccharomyces cerevisiae)
    Saccharomycetes MIP1(YOR330C)4
    MIP11
    Catalytic subunit of the mitochondrial DNA polymerase; more4
    MIP11
    49.25(n)1
    44.62(a)1
      15(943385-939621)4
    8545081, 4  NP_014975.21, 4 


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

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    (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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    Polymorphic Variants from UniProtKB/Swiss-Prot
    DPOG1_HUMAN, P54098: The poly-Gln region seems to be polymorphic


    Selected SNPs for POLG (see all 848)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 15 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs23074401,2,,4
    C,F,HProgressive external ophthalmoplegia with mitochondrial DNA deletions autosomal recessive (PEOB)4 non-pathogenic169586814(-) AGGACC/TGCTAC 4 R C mis1 ese313Minor allele frequency- T:0.00NA NS EA EU 7223
    rs1219180541,2,,4
    C,FProgressive external ophthalmoplegia with mitochondrial DNA deletions autosomal recessive (PEOB)4 pathogenic169591687(-) GCAATG/CGACCT 4 /R /G mis12Minor allele frequency- C:0.00NA EU 5869
    rs1139940961,2,,4
    C,FProgressive external ophthalmoplegia with mitochondrial DNA deletions autosomal recessive (PEOB)4 pathogenic169593866(-) GACCCC/TGGGCC 4 P L mis12Minor allele frequency- T:0.00NA EU 5849
    rs617527831,2,,4
    C,FSensory ataxic neuropathy dysarthria and ophthalmoparesis (SANDO)4 untested169595174(+) CAGCCC/ACCTCG 4 /G /V mis12Minor allele frequency- A:0.01NA EU 5851
    rs1458430731,2,,4
    C,FProgressive external ophthalmoplegia with mitochondrial DNA deletions autosomal recessive (PEOB)4 --69595425(+) ATCATT/CGGCCA 4 /N /D mis12Minor allele frequency- C:0.00NA EU 5835
    rs1139940951,2,,4
    C,FSensory ataxic neuropathy dysarthria and ophthalmoparesis (SANDO)4 pathogenic169595428(-) ATCTGG/ACCAAT 4 /T /A mis12Minor allele frequency- A:0.00NA EU 5821
    rs617527841,2,,4
    C,FProgressive external ophthalmoplegia with mitochondrial DNA deletions autosomal recessive (PEOB)4 --69598360(+) TGTGCC/GCCACC 4 A G mis12Minor allele frequency- G:0.00NA EU 5875
    rs1139940941,2,,4
    C,FProgressive external ophthalmoplegia with mitochondrial DNA deletions autosomal recessive (PEOB)4 pathogenic169598411(-) CCCTAC/TTGGTG 4 T I mis12Minor allele frequency- T:0.00NA EU 5871
    VAR_0588914
    Mitochondrial DNA depletion syndrome 4A (MTDPS4A)4--see VAR_0588912 T S mis40--------
    VAR_0588764
    Progressive external ophthalmoplegia with mitochondrial DNA deletions autosomal recessive (PEOB)4--see VAR_0588762 G D mis40--------

    HapMap Linkage Disequilibrium report for POLG (89859534 - 89878092 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 10 variations for POLG:    About this table    
    Variant IDTypeSubtypePubMed ID
    esv2676746CNV Deletion23128226
    esv2749999CNV Deletion23290073
    esv2750001CNV Deletion23290073
    esv2678873CNV Deletion23128226
    esv1642918CNV Deletion17803354
    esv2672032CNV Deletion23128226
    esv2750000CNV Deletion23290073
    esv270532CNV Insertion20981092
    esv23656CNV Loss19812545
    nsv833086CNV Loss17160897

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

    (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: 174763   
    OMIM disorders: 258450  157640  613662  203700  607459  
    UniProtKB/Swiss-Prot: DPOG1_HUMAN, P54098
  • Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, 1 (PEOA1)
    [MIM:157640]: A disorder is characterized by progressive weakness of ocular muscles and levator muscle of the
    upper eyelid. In a minority of cases, it is associated with skeletal myopathy, which predominantly involves axial
    or proximal muscles and which causes abnormal fatigability and even permanent muscle weakness. Ragged-red fibers
    and atrophy are found on muscle biopsy. A large proportion of chronic ophthalmoplegias are associated with other
    symptoms, leading to a multisystemic pattern of this disease. Additional symptoms are variable, and may include
    cataracts, hearing loss, sensory axonal neuropathy, ataxia, depression, hypogonadism, and parkinsonism. Note=The
    disease is caused by mutations affecting the gene represented in this entry
  • Progressive external ophthalmoplegia with mitochondrial DNA deletions autosomal recessive (PEOB)
    [MIM:258450]: A severe form of progressive external ophthalmoplegia. It is clinically more heterogeneous than the
    autosomal dominant forms. Note=The disease is caused by mutations affecting the gene represented in this entry
  • Sensory ataxic neuropathy dysarthria and ophthalmoparesis (SANDO) [MIM:607459]: A systemic disorder
    resulting from mitochondrial dysfunction associated with mitochondrial depletion in skeletal muscle and
    peripheral nerve tissue. The clinical triad of symptoms consists of sensory ataxic neuropathy, dysarthria, and
    ophthalmoparesis. However, the phenotype varies widely, even within the same family, and can also include
    myopathy, seizures, and hearing loss. An atypical form of the disease is characterized by headaches and/or
    seizures manifesting in childhood or adolescence, followed by development of cerebellar and sensory ataxia,
    dysarthria, progressive external ophthalmoplegia, and myoclonus in early adulthood. Note=The disease is caused by
    mutations affecting the gene represented in this entry
  • Mitochondrial DNA depletion syndrome 4A (MTDPS4A) [MIM:203700]: An autosomal recessive hepatocerebral
    syndrome due to mitochondrial dysfunction. The typical course of the disease includes severe developmental delay,
    intractable seizures, liver failure, and death in childhood. Refractory seizures, cortical blindness, progressive
    liver dysfunction, and acute liver failure after exposure to valproic acid are considered diagnostic features.
    The neuropathological hallmarks are neuronal loss, spongiform degeneration, and astrocytosis of the visual
    cortex. Liver biopsy results show steatosis, often progressing to cirrhosis. Note=The disease is caused by
    mutations affecting the gene represented in this entry
  • Mitochondrial DNA depletion syndrome 4B (MTDPS4B) [MIM:613662]: An autosomal recessive progressive
    multisystem disorder due to mitochondrial dysfunction. It is clinically characterized by chronic gastrointestinal
    dysmotility and pseudo-obstruction, cachexia, progressive external ophthalmoplegia, axonal sensory ataxic
    neuropathy, and muscle weakness. Note=The disease is caused by mutations affecting the gene represented in this
    entry
  • Leigh syndrome (LS) [MIM:256000]: An early-onset progressive neurodegenerative disorder characterized by
    the presence of focal, bilateral lesions in one or more areas of the central nervous system including the
    brainstem, thalamus, basal ganglia, cerebellum and spinal cord. Clinical features depend on which areas of the
    central nervous system are involved and include subacute onset of psychomotor retardation, hypotonia, ataxia,
    weakness, vision loss, eye movement abnormalities, seizures, and dysphagia. Note=The disease is caused by
    mutations affecting the gene represented in this entry

  • Selected diseases for POLG (see all 32):    
    About MalaCards
    autosomal recessive progressive external ophthalmoplegia    ataxia neuropathy spectrum    polg-related ataxia neuropathy spectrum disorders    myoclonic epilepsy myopathy sensory ataxia
    polg-related disorders    polg-related mitochondrial dna depletion syndrome, mngie form    premature menopause    autosomal dominant progressive external ophthalmoplegia
    status epilepticus    sensory ataxic neuropathy, dysarthria, and ophthalmoparesis    childhood myocerebrohepatopathy spectrum disorders    mitochondrial dna depletion syndrome, mngie form
    mitochondrial dna depletion syndrome 4b    alpers syndrome    nephronophthisis 15    ophthalmoplegia
    mitochondrial neurogastrointestinal encephalopathy disease    febrile infection-related epilepsy syndrome    mitochondrial dna depletion syndrome 1    cerebral folate deficiency

    8 diseases from the University of Copenhagen DISEASES database for POLG:
    Chronic progressive external ophthalmoplegia     Neuropathy     Brain disease     Myopathy
    Leigh disease     Mitochondrial encephalomyopathy     Spinocerebellar ataxia     Lactic acidosis

    Find genes that share disorders with POLG           About GenesLikeMe

    Selected Novoseek inferred disease relationships for POLG gene (see all 38)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    alpers syndrome 96.8 44 16545482 (4), 15929042 (2), 16177225 (2), 18294203 (2) (see all 24)
    progressive external ophthalmoplegia 94.8 43 12210792 (2), 12707443 (2), 12825077 (2), 12565911 (2) (see all 32)
    mitochondrial diseases 89.3 29 16401742 (3), 20083238 (2), 15913923 (2), 19251978 (1) (see all 21)
    mngie 83.8 7 12825077 (2), 19942242 (1), 19252805 (1)
    acidosis lactic 75 9 12859329 (1), 15373054 (1), 18680693 (1), 11508132 (1) (see all 6)
    mitochondrial myopathies 74.2 5 16155436 (1), 1324428 (1), 20399836 (1), 8156147 (1) (see all 5)
    lipodystrophy 68.6 19 19275594 (6), 15905734 (1)
    myopathy 65.2 3 15477547 (1), 15917273 (1), 8293572 (1)
    coenzyme q10 deficiency 63.4 2 16155436 (1), 17053512 (1)
    infertility male 62.1 13 15650046 (2), 11687794 (2), 18798765 (1), 14688158 (1) (see all 8)

    Genetic Association Database (GAD): POLG
    Human Genome Epidemiology (HuGE) Navigator: POLG (37 documents)

    Export disorders for POLG 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 POLG gene, integrated from 10 sources (see all 364):
    (articles sorted by number of sources associating them with POLG)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Clinical and genetic heterogeneity in progressive external ophthalmoplegia due to mutations in polymerase gamma. (PubMed id 12975295)1, 2, 4, 9 Filosto M....DiMauro S. (Arch. Neurol. 2003)
    2. Novel Twinkle (PEO1) gene mutations in Mendelian progressive external ophthalmoplegia. (PubMed id 18575922)1, 2, 4, 9 Virgilio R.... Comi G.P. (J. Neurol. 2008)
    3. Mutation of the linker region of the polymerase gamma-1 (POLG1) gene associated with progressive external ophthalmoplegia and Parkinsonism. (PubMed id 17420318)1, 2, 4, 9 Hudson G.... Chinnery P.F. (Arch. Neurol. 2007)
    4. Frequent polymorphism of the mitochondrial DNA polymerase gamma gene (POLG) in patients with normal spermiograms and unexplained subfertility. (PubMed id 14688158)1, 4, 9 Jensen M....Rajpert-De Meyts E. (Hum. Reprod. 2004)
    5. Relationship between polymerase gamma (POLG) polymorphisms and antiretroviral therapy-induced lipodystrophy in HIV-1 infected patients: a case-control study. (PubMed id 19275594)1, 4, 9 Chiappini F....Lemoine A. (Curr. HIV Res. 2009)
    6. Parkinsonism, premature menopause, and mitochondrial DNA polymerase gamma mutations: clinical and molecular genetic study. (PubMed id 15351195)1, 2, 9 Luoma P.... Suomalainen A. (Lancet 2004)
    7. Association of novel POLG mutations and multiple mitochondrial DNA deletions with variable clinical phenotypes in a Spanish population. (PubMed id 16401742)1, 2, 9 Gonzalez-Vioque E.... Martin M.A. (Arch. Neurol. 2006)
    8. The unfolding clinical spectrum of POLG mutations. (PubMed id 19578034)1, 4, 9 Blok M.J....Smeets H.J. (J. Med. Genet. 2009)
    9. Molecular analysis of ANT1, TWINKLE and POLG in patients with multiple deletions or depletion of mitochondrial DNA by a dHPLC-based assay. (PubMed id 16639411)1, 2, 9 Naiemi M....Paquis-Flucklinger V. (Eur. J. Hum. Genet. 2006)
    10. Analysis of mutant DNA polymerase gamma in patients with mitochondrial DNA depletion. (PubMed id 18828154)1, 2, 9 Taanman J.-W....Schapira A.H.V. (Hum. Mutat. 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: 5428 HGNC: 9179 AceView: POLG Ensembl:ENSG00000140521 euGenes: HUgn5428
    ECgene: POLG Kegg: 5428 H-InvDB: POLG

    (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 POLG Pharmacogenomics, SNPs, Pathways
    GeneReviewshttp://www.ncbi.nlm.nih.gov/books/NBK1116/?term=POLG[genesymbol]
    NIEHS-SNPshttp://egp.gs.washington.edu/data/polg/

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    Patent Information for POLG gene:
    Search GeneIP for patents involving POLG

    GeneCards and IP:
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