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

GZMM Gene

protein-coding   GIFtS: 53
GCID: GC19P000544

granzyme M (lymphocyte met-ase 1)

 Explore 1 disease affiliated with
GZMM via our new
 Human Malady Compendium 
Biological research products
for GZMM
    

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

Aliases
Granzyme M (Lymphocyte Met-Ase 1)1 2     Lymphocyte Met-Ase 12
MET11 2 3     Met-Ase1
LMET11 2     EC 3.4.21.-3
Natural Killer Cell Granular Protease2 3     Hu-Met-13
Met-1 Serine Protease2 3     Met-Ase1
HU-Met-12     EC 3.4.218
Granzyme M2     

External Ids:    HGNC: 47121   Entrez Gene: 30042   Ensembl: ENSG000001975407   OMIM: 6003115   UniProtKB: P511243   

Export aliases for GZMM gene to outside databases

Previous GC identifers: GC19P000554 GC19P000579 GC19P000484 GC19P000495 GC19P000314


(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 GZMM:
Human natural killer (NK) cells and activated lymphocytes express and store a distinct subset of neutral serine
proteases together with proteoglycans and other immune effector molecules in large cytoplasmic granules. These serine
proteases are collectively termed granzymes and include 4 distinct gene products: granzyme A, granzyme B, granzyme H,
and the protein encoded by this gene, granzyme M. Two transcript variants encoding different isoforms have been found
for this gene. (provided by RefSeq, Apr 2012)

UniProtKB/Swiss-Prot: GRAM_HUMAN, P51124
Function: Cleaves peptide substrates after methionine, leucine, and norleucine. Physiological substrates include EZR,
alpha-tubulins and the apoptosis inhibitor BIRC5/Survivin. Promotes caspase activation and subsequent apoptosis of
target cells

Gene Wiki entry for GZMM


(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_000019.9  NC_018930.1  NT_011255.14  
Regulatory elements:
   SABiosciences Regulatory transcription factor binding sites in the GZMM gene promoter:
         ATF-2   MyoD   c-Jun   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidGZMM promoter sequence
   Search SABiosciences Chromatin IP Primers for GZMM

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


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

Entrez Gene cytogenetic band: 19p13.3   Ensembl cytogenetic band:  19p13.3   HGNC cytogenetic band: 19p13.3

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

GeneLoc information about chromosome 19         GeneLoc Exon Structure

GeneLoc location for GC19P000544:  view genomic region     (about GC identifiers)

Start:
544,027 bp from pter      End:
549,919 bp from pter
Size:
5,893 bases      Orientation:
plus strand

(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: GRAM_HUMAN, P51124 (See protein sequence)
Recommended Name: Granzyme M precursor  
Size: 257 amino acids; 27545 Da
Subcellular location: Secreted. Cytoplasmic granule. Note=Granules of large granular lymphocytes
5 PDB 3D structures from and Proteopedia for GZMM:
1LZP (3D)        2ZGC (3D)        2ZGH (3D)        2ZGJ (3D)        2ZKS (3D)    

Explore the universe of human proteins at neXtProt for GZMM: NX_P51124

Post-translational modifications:

  • View modification sites using PhosphoSitePlus2
  • View neXtProt modification sites for NX_P51124

  • 4/8 DME Specific Peptides for GZMM (P51124) (see all 8)
     DLALLQL  CGGVLVH  SGGPLVC  GDSGGPL 

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

    REFSEQ proteins (2 alternative transcripts): 
    NP_001245280.1  NP_005308.1  

    ENSEMBL proteins: 
     ENSP00000264553  
    Reactome Protein details: P51124
    Human Recombinant Protein Products: 
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    Novus Biologicals GZMM Proteins
    Novus Biologicals GZMM Lysate
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    Browse ProSpec Recombinant Proteins
    Uscn Proteins for GZMM

    Gene Ontology (GO): 1 cellular component term (GO ID links to tree view):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005576extracellular region IEA--


    GZMM for ontologies           About GeneDecksing



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    Uscn ELISAs and CLIAs for GZMM


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

    GZMM for domains           About GeneDecksing

    4 InterPro domains/families:
     IPR001314 Peptidase_S1A
     IPR001254 Peptidase_S1
     IPR018114 Peptidase_S1_AS
     IPR009003 Trypsin-like_Pept_dom

    Graphical View of Domain Structure for InterPro Entry P51124

    ProtoNet protein and cluster: P51124

    2 Blocks protein families:
    IPB001254 Serine protease
    IPB001314 Chymotrypsin serine protease family (S1) signature


    UniProtKB/Swiss-Prot: GRAM_HUMAN, P51124
    Similarity: Belongs to the peptidase S1 family. Granzyme subfamily
    Similarity: Contains 1 peptidase S1 domain


    (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: GRAM_HUMAN, P51124
    Function: Cleaves peptide substrates after methionine, leucine, and norleucine. Physiological substrates include EZR,
    alpha-tubulins and the apoptosis inhibitor BIRC5/Survivin. Promotes caspase activation and subsequent apoptosis of
    target cells

         Genatlas biochemistry entry for GZMM:
    natural killer cells granule serine protease,cleaving after methionine (Met-ase)

    Enzyme Numbers (IUBMB): EC 3.4.212 EC 3.4.21.-1

    miRNA
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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:0004175endopeptidase activity ----
    GO:0004252serine-type endopeptidase activity IEA--
    GO:0005515protein binding ----
    GO:0008236serine-type peptidase activity TAS7713495


    GZMM for ontologies           About GeneDecksing


    4 GenomeRNAi human phenotypes for GZMM:
     Decreased BPV1 E2 protein expr  Decreased cell number and incr  Increased G1 DNA content  Increased HPV18 LCR reporter a 

    Animal Models:
         1 MGI mutant phenotype (inferred from 1 allele(MGI details for Gzmm):
     immune system 

    GZMM 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

    Unified GeneCards pathways  About this table 
    See pathways by source

    Super-pathwaycontained gene-specific pathways
    1Immune System
    Immune System1.00
    Innate Immune System0.46
    2Cleavage of Alpha-1-Microglobulin
    Initial triggering of complement0.60
    Complement cascade0.47
    3Granzyme Pathway
    Granzyme Pathway1.00
    4Activation of C3 and C5
    Alternative complement activation0.33

    Pathway sources
    See GeneCards unified pathways
    Show all pathways

    1 Downloadable PowerPoint Slide of QIAGEN Pathway Central Maps for GZMM
        Granzyme Pathway

    5        Reactome Pathways for GZMM
        Alternative complement activation
    Complement cascade
    Immune System
    Initial triggering of complement
    Innate Immune System



    GZMM for pathways           About GeneDecksing

    Interactions:

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

    5/12 Interacting proteins for GZMM (P511243) via UniProtKB, MINT, STRING, and/or I2D (see all 12)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    CASP3P425743I2D: score=1 
    DFFAO002733I2D: score=1 
    EZRP153113I2D: score=1 
    NPM1P067483I2D: score=1 
    PAK2Q131773I2D: score=1 
    About this table

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

    GO IDQualified GO termEvidencePubMed IDs
    GO:0006508proteolysis IEA--
    GO:0006915apoptotic process IEA--
    GO:0019835cytolysis IEA--
    GO:0045087innate immune response IEA--


    GZMM 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

    GZMM for compounds           About GeneDecksing

    EMD Millipore small molecules for GZMM:
    Small Molecule - inhibitor
    Browse drugs & compounds from Enzo Life Sciences

    Browse Tocris compounds for GZMM
    1 Novoseek chemical compound relationship for GZMM gene    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    serine 61.8 14 14725853 (2), 7713495 (2), 8245461 (1), 12506019 (1) (see all 8)

    Search CenterWatch for drugs/clinical trials and news about GZMM / GRAM 

    (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 GZMM gene (2 alternative transcripts): 
    NM_001258351.1  NM_005317.3  

    Unigene Cluster for GZMM:

    Granzyme M (lymphocyte met-ase 1)
    Hs.465511  [show with all ESTs]
    Unigene Representative Sequence: NM_005317
    2 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000592501 ENST00000264553(uc002low.1)

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      QIAGEN QuantiTect SYBR Green Assays in human, mouse, rat GZMM
      QIAGEN QuantiFast Probe-based Assays in human, mouse, rat GZMM

    Additional cDNA sequence: 

    BC025701.1 L23134.1 

    1 DOTS entry:

    DT.400411 

    12 AceView cDNA sequences:

    L23134 NM_005317 BM987422 BC025701 BI835971 CD366947 BI823094 BI838272 
    AI910778 AW044312 AI124941 T91241 

    GeneLoc Exon Structure

    2 Alternative Splicing Database (ASD) splice patterns (SP) for GZMM    About this scheme

    ExUns: 1a · 1b ^ 2 ^ 3 ^ 4 ^ 5a · 5b
    SP1:                                          
    SP2:                                          


    ECgene alternative splicing isoforms for GZMM

    (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

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

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

    About this image
    See GZMM Protein Expression from SPIRE MOPED and PaxDB
    Genevestigator expression for GZMM

    SOURCE GeneReport for Unigene cluster: Hs.465511

    UniProtKB/Swiss-Prot: GRAM_HUMAN, P51124
    Tissue specificity: Highly and constitutively expressed in activated natural killer (NK) cells

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    In Situ
    Assay Products:
     

     
    Search Advanced Cell Diagnostics for RNAscope RNA in situ hybridization assays for GZMM

    (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 GZMM gene from 3/13 species (see all 13)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    chicken
    (Gallus gallus)
    Aves LOC1008591241 granzyme M-like 62.95(n)
    52.07(a)
      100859124  XM_003642876.1  XP_003642924.1 
    zebrafish
    (Danio rerio)
    Actinopterygii CR558302.26
    AL954146.16
    --
    31(a)
    28(a)
    possible ortholog
    possible ortholog
    11(3640652-3646662)
    23(37542555-37552094)
    fruit fly
    (Drosophila melanogaster)
    Insecta CG169986
    CG328086
    (see all 49)
    --
    29(a)
    29(a)
    (see all 49)
    possible ortholog
    possible ortholog
    (see all 49)
    3L(7532160-7532936)
    X(1362763-1363679)


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

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
    About This Section
    Paralogs for GZMM gene
    PRTN32  GZMH2  GZMK2  PRSS572  CTSG2  CFD2  ELANE2  CMA12  
    AZU12  GZMA2  GZMB2  
    18/70 SIMAP similar genes for GZMM using alignment to 1 protein entry:     GRAM_HUMAN(see all similar genes):
    KLK4    PRSS57    DF    KLK8    PRSSL1    CFD
    PRSS1    CELA3A    F12    GZMK    KLK5    CTRB1
    CTRB2    CTRL    CTSG    KLK9    CELA1    CORIN

    GZMM for paralogs           About GeneDecksing



    (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

    10/31 NCBI SNPs in GZMM are shown (see all 31    About this table
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 19 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs2001560471,2
    --544728(+) CCCTC-/ACCTCC 2 -- int10--------
    rs1487751721,2
    --544729(+) CCTCC-/TCTCCC 1 -- int10--------
    rs2011376321,2
    --544733(+) CCTCC-/TCTCAT 1 -- int10--------
    rs2006907481,2
    C--544734(+) GATGAA/GGGAGG 1 -- int10--------
    rs1851623121,2
    --546371(+) CTGTCA/GCTACT 1 -- int10--------
    rs1477539071,2
    --546398(+) TAGCCA/GGACGT 1 -- int10--------
    rs1426162621,2
    --546402(+) CGGACA/GTGGTG 1 -- int10--------
    rs1464607281,2
    --546456(+) GAATCA/GCTTGA 1 -- int10--------
    rs1895781751,2
    --546513(+) TCCAGA/GCTGGG 1 -- int10--------
    rs1386815591,2
    --546577(+) GCTCAC/TACCTG 1 -- int10--------

    HapMap Linkage Disequilibrium report for GZMM (544027 - 549919 bp)
    Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
    Database of Genomic Variants (DGV): 1 variation for GZMM
         1 CNV: 30050

    SABiosciences Cancer Mutation PCR Assays
    QIAGEN SeqTarget long-range PCR primers in human, mouse, rat for resequencing GZMM
    DNA2.0 Custom Variant and Variant Library Synthesis for GZMM

    (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.)
    About This Section

    GZMM for disorders           About GeneDecksing

    OMIM gene information: 600311    OMIM disorders: --

    1 disease for GZMM:    About MalaCards
    arrhythmogenic right ventricular dysplasia

    2 Novoseek disease relationships for GZMM gene    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    tumors 19.9 8 20406824 (2), 19673685 (1), 16219538 (1), 19542453 (1) (see all 5)
    leukemia 6.57 1 8245461 (1)


    Export disorders for GZMM 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 GZMM gene, integrated from 9 sources (see all 32):
    (articles sorted by number of sources associating them with GZMM)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Cleavage of survivin by Granzyme M triggers degradati on of the survivin-X-linked inhibitor of apoptosis protein (XIAP) complex to fr ee caspase activity leading to cytolysis of target tumor cells. (PubMed id 20406824)1, 2, 9 Hu D....Fan Z. (2010)
    2. Structural basis for proteolytic specificity of the h uman apoptosis-inducing granzyme M. (PubMed id 19542453)1, 2, 9 Wu L....Fan Z. (2009)
    3. Met-ase: cloning and distinct chromosomal location of a serine protease preferentially expressed in human natural killer cells. (PubMed id 8245461)1, 2, 9 Smyth M.J.... Trapani J.A. (1993)
    4. The human Met-ase gene (GZMM): structure, sequence, and close physical linkage to the serine protease gene cluster on 19p13.3. (PubMed id 7713495)1, 2, 9 Pilat D.... Jenne D.E. (1994)
    5. NK cell protease granzyme M targets alpha-tubulin and disorganizes the microtubule network. (PubMed id 18523284)1, 2 Bovenschen N....Kummer J.A. (2008)
    6. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PubMed id 15489334)1, 2 Gerhard D.S....Malek J. (2004)
    7. The gene encoding a human natural killer cell granule serine protease, Met-ase 1, maps to chromosome 19p13.3. (PubMed id 8119738)1, 3 Baker E....Smyth M.J. (1994)
    8. Granzyme M is a regulatory protease that inactivates proteinase inhibitor 9, an endogenous inhibitor of granzyme B. (PubMed id 15494398)1, 9 Mahrus S....Craik C.S. (2004)
    9. Granzyme M mediates a novel form of perforin-dependent cell death. (PubMed id 15028722)1, 9 Kelly J.M....Smyth M.J. (2004)
    10. Nucleophosmin is cleaved and inactivated by the cytotoxic granule protease granzyme M during natural killer cell-mediated killing. (PubMed id 19103589)1, 9 Cullen S.P....Martin S.J. (2009)

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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: 3004 HGNC: 4712 AceView: GZMM Ensembl:ENSG00000197540 euGenes: HUgn3004
    ECgene: GZMM H-InvDB: GZMM

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

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