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Category   Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21
GIFtS

DOC2B Gene

protein-coding   GIFtS: 49
GCID: GC17M000007

double C2-like domains, beta

(Previous names: double C2-like domains, beta-like )
(Previous symbol: DOC2BL)
 Explore 6 diseases affiliated with
DOC2B via our new
 Human Malady Compendium 
Biological research products
for DOC2B
    

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, and/or 10fRNAdb)
About This Section

Aliases
Double C2-Like Domains, Beta1 2
DOC2BL1 2 3
Double C2-Like Domains, Beta-Like1
Doc2-Beta1
Double C2-Like Domain-Containing Protein Beta2
Doc2-Beta1

External Ids:    HGNC: 29861   Entrez Gene: 84472   Ensembl: ENSG000002623597   OMIM: 6045685   UniProtKB: Q141843   

Export aliases for DOC2B gene to outside databases

Previous GC identifers: GC17P000349 GC17M000091 GC17P9O0017 GC17P8G0009


(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for DOC2B:
There are at least two protein isoforms of the Double C2 protein, namely alpha (DOC2A) and beta (DOC2B), which contain
two C2-like domains. DOC2A and DOC2B are encoded by different genes; these genes are at times confused with the
unrelated DAB2 gene which was initially named DOC-2. DOC2B is expressed ubiquitously and is suggested to be involved
in Ca(2+)-dependent intracellular vesicle trafficking in various types of cells. (provided by RefSeq, Jul 2008)

UniProtKB/Swiss-Prot: DOC2B_HUMAN, Q14184
Function: Calcium sensor which positively regulates SNARE-dependent fusion of vesicles with membranes. Binds
phospholipids in a calcium-dependent manner and may act at the priming stage of fusion by modifying membrane curvature
to stimulate fusion. Involved in calcium-triggered exocytosis in chromaffin cells and calcium-dependent spontaneous
release of neurotransmitter in absence of action potentials in neuronal cells. Involved both in glucose-stimulated
insulin secretion in pancreatic cells and insulin-dependent GLUT4 transport to the plasma membrane in adipocytes (By
similarity)

Gene Wiki entry for DOC2B


(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 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section
RefSeq DNA sequence:
NC_000017.10  NC_018928.1  NT_024972.8  
Regulatory elements:
   SABiosciences Regulatory transcription factor binding sites in the DOC2B gene promoter:
         Olf-1   AP-4   Tal-1beta   E47   POU2F1   Zic1   POU2F1a   POU2F1b   Chx10   POU2F1c   
         Other transcription factors

Browse SwitchGear Promoter luciferase reporter plasmids
   Search SABiosciences Chromatin IP Primers for DOC2B

Epigenetics:
QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat DOC2B


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

Entrez Gene cytogenetic band: 17p13.3   Ensembl cytogenetic band:  17p13.3   HGNC cytogenetic band: 17p13.3

DOC2B Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
DOC2B gene location

GeneLoc information about chromosome 17         GeneLoc Exon Structure

GeneLoc location for GC17M000007:  view genomic region     (about GC identifiers)

Start:
5,810 bp from pter      End:
31,427 bp from pter
Size:
25,618 bases      Orientation:
minus strand

1 alternative location:
Chr17-,PATCHES 6,009-31,420     

(According to 1UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to 2PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, 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 Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: DOC2B_HUMAN, Q14184 (See protein sequence)
Recommended Name: Double C2-like domain-containing protein beta  
Size: 412 amino acids; 45949 Da
Subunit: Interacts with the SNARE (soluble N-ethylmaleimide-sensitive factor attached protein receptor) complex
composed of SNAP25, STX1A and VAMP2; the interaction is calcium-dependent and competitive with SYT1. Interacts with
STX4; the interaction is calcium-dependent, increased by insulin and glucose, and mediates vesicle fusion with plasma
membrane in pancreatic cells and adipocytes. Interacts with STXBP3; the interaction is direct, occurs at the cell
membrane and regulates glucose-stimulated insulin secretion. May interact with UNC13A; the interaction mediates
targeting to the plasma membrane (By similarity). Interacts with cytoplasmic dynein light chain DYNLT1
Subcellular location: Cytoplasm. Cytoplasmic granule (By similarity). Cell membrane; Peripheral membrane protein (By
similarity). Note=Translocates to the plasma membrane in a calcium-dependent manner (By similarity)

Explore the universe of human proteins at neXtProt for DOC2B: NX_Q14184

Post-translational modifications:

  • View modification sites using PhosphoSitePlus2
  • View neXtProt modification sites for NX_Q14184

  • DOC2B Protein expression data from MOPED and PaxDb:    About this image 
    Estimated protein expression log10 (pmol).

    REFSEQ proteins: NP_003576.2  
    ENSEMBL proteins: 
     ENSP00000343665  

    Human Recombinant Protein Products: 
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    OriGene Protein Over-expression Lysate: DOC2B
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    Novus Biologicals DOC2B Proteins
    Novus Biologicals DOC2B Lysates
    Browse Sino Biological Recombinant Proteins
    Browse ProSpec Recombinant Proteins
    Browse Proteins at Uscn

    Gene Ontology (GO): 5 cellular component terms (GO ID links to tree view):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005737cytoplasm ISS--
    GO:0005886plasma membrane ISS--
    GO:0008021synaptic vesicle IEA--
    GO:0015630microtubule cytoskeleton IDA--
    GO:0031201colocalizes with SNARE complex ISS--


    DOC2B for ontologies           About GeneDecksing



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    (According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
    About This Section

    DOC2B for domains           About GeneDecksing

    5/6 InterPro domains/families (see all 6):
     IPR008973 C2_Ca/lipid-bd_dom_CaLB
     IPR014638 Doc2
     IPR001565 Synaptotagmin
     IPR018029 C2_membr_targeting
     IPR020477 C2_dom

    Graphical View of Domain Structure for InterPro Entry Q14184

    ProtoNet protein and cluster: Q14184

    2 Blocks protein families:
    IPB000008 C2 domain
    IPB001565 Synaptotagmin signature


    UniProtKB/Swiss-Prot: DOC2B_HUMAN, Q14184
    Domain: C2 domain 1 is involved in binding calcium and phospholipids. C2 domain 2 may also play a role in the
    calcium-dependent targeting to membranes (By similarity)
    Similarity: Contains 2 C2 domains


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
    bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
    About This Section

    Function Summary:

         UniProtKB/Swiss-Prot: DOC2B_HUMAN, Q14184
    Function: Calcium sensor which positively regulates SNARE-dependent fusion of vesicles with membranes. Binds
    phospholipids in a calcium-dependent manner and may act at the priming stage of fusion by modifying membrane curvature
    to stimulate fusion. Involved in calcium-triggered exocytosis in chromaffin cells and calcium-dependent spontaneous
    release of neurotransmitter in absence of action potentials in neuronal cells. Involved both in glucose-stimulated
    insulin secretion in pancreatic cells and insulin-dependent GLUT4 transport to the plasma membrane in adipocytes (By
    similarity)

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    Gene Ontology (GO): 4 molecular function terms (GO ID links to tree view):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005215transporter activity IEA--
    GO:0005515protein binding ----
    GO:0005544calcium-dependent phospholipid binding ISS--
    GO:0019905syntaxin binding IEA--


    DOC2B for ontologies           About GeneDecksing


    Animal Models:
         Mouse knock-out Doc2btm1Aljg for DOC2B
         1 MGI mutant phenotype (inferred from 1 allele(MGI details for Doc2b):
     nervous system 

    DOC2B for phenotypes           About GeneDecksing


    (Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, 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 Mar 2013 via Entrez Gene).
    About This Section



    Interactions:

        Search SABiosciences Gene Network CentralTM Interacting Genes and Proteins Networks for DOC2B

    STRING Interaction Network Preview (showing 5 interactants - click image to see 23)

    5/24 Interacting proteins for DOC2B (Q141842 ENSP000003436654) via UniProtKB, MINT, STRING, and/or I2D (see all 24)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    DYNLT1ENSP000003560564STRING: ENSP00000356056
    STXBP1ENSP000003623994STRING: ENSP00000362399
    UNC13BENSP000003677564STRING: ENSP00000367756
    BET1LENSP000003722104STRING: ENSP00000372210
    BNIP1ENSP000002316684STRING: ENSP00000231668
    About this table

    Gene Ontology (GO): 5/6 biological process terms (GO ID links to tree view) (see all 6):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0006887exocytosis ----
    GO:0008104protein localization ISS--
    GO:0031340positive regulation of vesicle fusion ISS--
    GO:0032024positive regulation of insulin secretion ISS--
    GO:0045956positive regulation of calcium ion-dependent exocytosis ISS--


    DOC2B for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
    About This Section
    Browse Small Molecules at EMD Millipore
    Browse drugs & compounds from Enzo Life Sciences

    Browse Tocris compounds for DOC2B

    1 HMDB Compound for DOC2B    About this table
    CompoundSynonyms CAS #PubMed Ids
    CalciumCa (see all 2)7440-70-2--
    Search CenterWatch for drugs/clinical trials and news about DOC2B 

    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 235 Homo sapiens; Mar 10 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,
    RNAi Products from EMD Millipore,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
    Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
    About This Section

    REFSEQ mRNAs for DOC2B gene: 
    NM_003585.3  

    Unigene Cluster for DOC2B:

    Double C2-like domains, beta
    Hs.551705  [show with all ESTs]
    Unigene Representative Sequence: D70830
    2 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000343572(uc010vpx.1) ENST00000575802

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    Additional cDNA sequence: D70830.1 

    2 DOTS entries:

    DT.40113573  DT.99979978 

    6 AceView cDNA sequences:

    BM713588 BU739610 D70830 NM_003585 BF434293 BF509185 

    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™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

    DOC2B expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS
    CGAP TAG: CTTCACTCAA

    Microarray
    RNAseq (Illumina Body Map)
    (100×FPKM)½
    SAGE (Serial Analysis of Gene Expression)

    About this image

    DOC2B expression in embryonic tissues and stem cells
    Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine    About this table
    2 LifeMap In Vivo Development Anatomical Compartments/Cells 
    Tissue Anatomical Compartment CellCategory (developmental path)
    PancreasDorsal Pancreatic BudImmature Beta Progenitor CellsPancreas
    PancreasVentral Pancreatic BudImmature Beta Progenitor CellsPancreas
    Expression: Positive    Negative     Selective marker
    Experimental details: Curated     Microarrays     In-situ hybridization

    See DOC2B Protein Expression from SPIRE MOPED and PaxDB
    Genevestigator expression for DOC2B

    SOURCE GeneReport for Unigene cluster: Hs.551705

    UniProtKB/Swiss-Prot: DOC2B_HUMAN, Q14184
    Tissue specificity: Widely expressed with highest levels in brain and kidney. Expressed in pancreatic islet cells (at
    protein level)

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    In Situ
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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)
    About This Section

    This gene was present in the common ancestor of animals.

    Orthologs for DOC2B gene from 5/18 species (see all 18)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    chicken
    (Gallus gallus)
    Aves DOC2B1 double C2-like domains, beta 82.75(n)
    88.69(a)
      417624  XM_415868.2  XP_415868.2 
    lizard
    (Anolis carolinensis)
    Reptilia DOC2B6
    --

    1 ↔ 1
    AAWZ02038570(4748-9523)
    zebrafish
    (Danio rerio)
    Actinopterygii doc2b1 double C2-like domains, beta 74.03(n)
    79.95(a)
      100006713  XM_001345351.4  XP_001345387.4 
    fruit fly
    (Drosophila melanogaster)
    Insecta rabphilin-3A3 synaptic vesicle endocytosis protein
    transporter
    39(a)     --
    worm
    (Caenorhabditis elegans)
    Secernentea rbf-16
    snt-66
    SyNapTotagmin family member (snt-6)
    9(a)
    15(a)
    1 ↔ many
    possible ortholog
    III(6675748-6703943)
    II(745469-750171)


    ENSEMBL Gene Tree for DOC2B (if available)
    TreeFam Gene Tree for DOC2B (if available) 

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
    About This Section
    Paralogs for DOC2B gene
    SYTL42  SYTL52  SYTL12  DOC2A2  SYTL32  RPH3A2  SYTL22  
    9 SIMAP similar genes for DOC2B using alignment to 1 protein entry:     DOC2B_HUMAN:
    RPH3A    DOC2A    SYT1    SYT14L    SYT5    SYT2
    SYT4    SYT7    SYT11

    DOC2B for paralogs           About GeneDecksing


    2 Pseudogenes.org Pseudogenes for DOC2B
    PGOHUM00000237123 PGOHUM00000237452


    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, UniProtKB, 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) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
    About This Section

    3 NCBI SNPs in DOC2B are shown     About this table
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 17 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs1395240921,2
    --33191(+) CTTTCC/TTCCCC 1 -- ds50010--------
    rs1450519271,2
    --33276(+) GGCTTC/GTTGGA 1 -- ds50010--------
    rs1471341211,2
    --33345(+) AGGACA/GGGAGG 1 -- ds50010--------

    HapMap Linkage Disequilibrium report for DOC2B (5810 - 31427 bp)
    Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
    Database of Genomic Variants (DGV): 8 variations for DOC2B
         6 CNVs: 72723 67090 72721 102367 72722 72720
         2 Indels: 25886 25788

    SABiosciences Cancer Mutation PCR Assays
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    (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.)
    About This Section

    DOC2B for disorders           About GeneDecksing

    OMIM gene information: 604568    OMIM disorders: --

    6 diseases for DOC2B:    About MalaCards
    miller-dieker syndrome    amyotrophic lateral sclerosis    lateral sclerosis    lissencephaly
    pancreatitis    neuronitis

    Human Genome Epidemiology (HuGE) Navigator: DOC2B (1 document)

    Export disorders for DOC2B 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)
    About This Section

    PubMed articles for DOC2B gene, integrated from 9 sources (see all 15):
    (articles sorted by number of sources associating them with DOC2B)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Molecular cloning of an isoform of Doc2 having two C2-like domains. (PubMed id 8554557)1, 2, 9 Sakaguchi G.... Takai Y. (1995)
    2. Interaction of Doc2 with tctex-1, a light chain of cytoplasmic dynein. Implication in dynein-dependent vesicle transport. (PubMed id 9804756)1, 2 Nagano F.... Takai Y. (1998)
    3. Doc2, a novel synaptic vesicle protein with two repeated C2-like domains. (PubMed id 7826360)1, 3 Orita S.... Takai Y. (1995)
    4. Resequencing of 29 candidate genes in patients with familial and sporadic amyotrophic lateral sclerosis. (PubMed id 21220648)2 Daoud H....Rouleau G.A. (2011)
    5. Doc2 is a Ca2+ sensor required for asynchronous neuro transmitter release. (PubMed id 22036572)1 Yao J....Chapman E.R. (2011)
    6. Genome-wide association study implicates PARD3B-based AIDS restriction. (PubMed id 21502085)1 Troyer J.L....O'Brien S.J. (2011)
    7. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PubMed id 20379614)1 Rose J.E....Uhl G.R. (2010)
    8. Toward a confocal subcellular atlas of the human proteome. (PubMed id 18029348)1 Barbe L....Andersson-Svahn H. (2008)
    9. Doc2beta is a novel Munc18c-interacting partner and positive effector of syntaxin 4-mediated exocytosis. (PubMed id 17548353)2 Ke B....Thurmond D.C. (2007)
    10. Refinement of a 400-kb critical region allows genotypic differentiation between isolated lissencephaly, Miller-Dieker syndrome, and other phenotypes secondary to deletions of 17p13.3. (PubMed id 12621583)1 Cardoso C....Ledbetter D.H. (2003)

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    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 8447 HGNC: 2986 AceView: DOC2B Ensembl:ENSG00000262359 euGenes: HUgn8447
    ECgene: DOC2B H-InvDB: DOC2B

    (According to HUGE)
    About This Section
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    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
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    About This Section
    NameDescription
    PharmGKB entry for DOC2B Pharmacogenomics, SNPs, Pathways

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    Patent Information for DOC2B gene:
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