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

ATG4D Gene

protein-coding   GIFtS: 52
GCID: GC19P010654

autophagy related 4D, cysteine peptidase

(Previous names: AUT-like 4, cysteine endopeptidase (S. cerevisiae), APG4...)
(Previous symbols: AUTL4, APG4D)
  Search for ATG4D
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(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, and/or 10fRNAdb)
About This Section

Aliases
Autophagy Related 4D, Cysteine Peptidase1 2     APG4 Autophagy 4 Homolog D2
APG4D1 2 3     ATG4 Autophagy Related 4 Homolog D2
AUTL41 2 3     AUT-Like 4, Cysteine Endopeptidase2
APG4-D1 2     Autophagin-43
Autophagy-Related Cysteine Endopeptidase 42 3     Cysteine Protease ATG4D2
Autophagy-Related Protein 4 Homolog D2 3     Cysteine Protease Involved In Autophagy2
AUT-Like 4 Cysteine Endopeptidase2 3     Autophagin-43
APG4 Autophagy 4 Homolog D (S. Cerevisiae)1     EC 3.4.22.-3
ATG4 Autophagy Related 4 Homolog D (S. Cerevisiae)1     EC 3.4.228
AUT-Like 4, Cysteine Endopeptidase (S. Cerevisiae)1     

External Ids:    HGNC: 207891   Entrez Gene: 849712   Ensembl: ENSG000001307347   OMIM: 6113405   UniProtKB: Q86TL03   

Export aliases for ATG4D gene to outside databases

Previous GC identifers: GC19P010518 GC19P010232


(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 ATG4D:
Autophagy is the process by which endogenous proteins and damaged organelles are destroyed intracellularly. Autophagy
is postulated to be essential for cell homeostasis and cell remodeling during differentiation, metamorphosis,
non-apoptotic cell death, and aging. Reduced levels of autophagy have been described in some malignant tumors, and a
role for autophagy in controlling the unregulated cell growth linked to cancer has been proposed. This gene encodes a
member of the autophagin protein family. The encoded protein is also designated as a member of the C-54 family of
cysteine proteases. (provided by RefSeq, Jul 2008)

UniProtKB/Swiss-Prot: ATG4D_HUMAN, Q86TL0
Function: Cysteine protease required for autophagy, which cleaves the C-terminal part of either MAP1LC3, GABARAPL2 or
GABARAP, allowing the liberation of form I. A subpopulation of form I is subsequently converted to a smaller form
(form II). Form II, with a revealed C-terminal glycine, is considered to be the phosphatidylethanolamine
(PE)-conjugated form, and has the capacity for the binding to autophagosomes




(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_011295.11  
Regulatory elements:
   SABiosciences Regulatory transcription factor binding sites in the ATG4D gene promoter:
         HOXA5   YY1   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidATG4D promoter sequence
   Search SABiosciences Chromatin IP Primers for ATG4D

Epigenetics:
QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat ATG4D


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

Entrez Gene cytogenetic band: 19p13.2   Ensembl cytogenetic band:  19p13.2   HGNC cytogenetic band: 19p13.2

ATG4D Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
ATG4D gene location

GeneLoc information about chromosome 19         GeneLoc Exon Structure

GeneLoc location for GC19P010654:  view genomic region     (about GC identifiers)

Start:
10,654,571 bp from pter      End:
10,664,094 bp from pter
Size:
9,524 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: ATG4D_HUMAN, Q86TL0 (See protein sequence)
Recommended Name: Cysteine protease ATG4D  
Size: 474 amino acids; 52922 Da
Subcellular location: Cytoplasm (Probable)

Explore the universe of human proteins at neXtProt for ATG4D: NX_Q86TL0

Post-translational modifications:

  • View modification sites using PhosphoSitePlus2
  • View neXtProt modification sites for NX_Q86TL0

  • 4/9 DME Specific Peptides for ATG4D (Q86TL0) (see all 9)
     KMDPSCT  AGDWYGP  FPLESFHC  WLTYRRDFP 

    ATG4D Protein expression data from MOPED and PaxDb:    About this image 
    Estimated protein expression log10 (pmol).

    REFSEQ proteins: NP_116274.3  
    ENSEMBL proteins: 
     ENSP00000467906   ENSP00000468290   ENSP00000465716   ENSP00000311318   ENSP00000467407  
     ENSP00000467223   ENSP00000465089   ENSP00000466439   ENSP00000468780   ENSP00000466759  
     ENSP00000467694   ENSP00000441375  

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    Uscn Proteins for ATG4D

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

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005737cytoplasm ISS12446702


    ATG4D 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

    ATG4D for domains           About GeneDecksing

    1 InterPro domain/family:
     IPR005078 Peptidase_C54

    Graphical View of Domain Structure for InterPro Entry Q86TL0

    ProtoNet protein and cluster: Q86TL0

    UniProtKB/Swiss-Prot: ATG4D_HUMAN, Q86TL0
    Similarity: Belongs to the peptidase C54 family


    (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: ATG4D_HUMAN, Q86TL0
    Function: Cysteine protease required for autophagy, which cleaves the C-terminal part of either MAP1LC3, GABARAPL2 or
    GABARAP, allowing the liberation of form I. A subpopulation of form I is subsequently converted to a smaller form
    (form II). Form II, with a revealed C-terminal glycine, is considered to be the phosphatidylethanolamine
    (PE)-conjugated form, and has the capacity for the binding to autophagosomes
    Enzyme regulation: Inhibited by N-ethylmaleimide

    Enzyme Numbers (IUBMB): EC 3.4.222 EC 3.4.22.-1

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    Gene Ontology (GO): 2 molecular function terms (GO ID links to tree view):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004197cysteine-type endopeptidase activity ISS12446702
    GO:0008234cysteine-type peptidase activity ----


    ATG4D for ontologies           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
    1Regulation of IFNA signaling
    Regulation of autophagy0.26

    Pathway sources
    See GeneCards unified pathways
    Show all pathways



    1         Kegg Pathway  (Kegg details for ATG4D):
        Regulation of autophagy


    ATG4D for pathways           About GeneDecksing

    Interactions:

        Search SABiosciences Gene Network CentralTM Interacting Genes and Proteins Networks for ATG4D

    STRING Interaction Network Preview (showing 1 interactants - click image to see more details)

    5 Interacting proteins for ATG4D (Q86TL03 ENSP000003113184) via UniProtKB, MINT, STRING, and/or I2D
    InteractantInteraction Details
    GeneCardExternal ID(s)
    TAF12Q165143I2D: score=5 
    CASP3P425743I2D: score=1 
    CASP8Q147903I2D: score=1 
    GABARAPO951663I2D: score=1 
    UBCENSP000003448184STRING: ENSP00000344818
    About this table

    Gene Ontology (GO): 3 biological process terms (GO ID links to tree view):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0006508proteolysis IEA--
    GO:0006914autophagy IEA--
    GO:0015031protein transport IEA--


    ATG4D 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
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    Browse Tocris compounds for ATG4D
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    (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,
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    About This Section

    REFSEQ mRNAs for ATG4D gene: 
    NM_032885.4  

    Unigene Cluster for ATG4D:

    Autophagy related 4D, cysteine peptidase
    Hs.512799  [show with all ESTs]
    Unigene Representative Sequence: BC068992
    13 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000586417 ENST00000590096 ENST00000588857 ENST00000585752 ENST00000309469(uc010xlg.2 uc002mov.3 uc010xlh.2 uc010dxh.3 uc010dxi.3 uc010dxj.3)
    ENST00000588667 ENST00000586477 ENST00000586863 ENST00000589753 ENST00000587256
    ENST00000588972 ENST00000585437 ENST00000540862

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    8/21 QIAGEN miScript miRNA Assays for microRNAs that regulate ATG4D (see all 21):
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    Additional cDNA sequence: 

    AJ312332.1 AK056210.1 AK223383.1 AK294676.1 AK314712.1 AK316454.1 BC007639.1 BC016845.1 
    BC068992.1 

    10 DOTS entries:

    DT.445212  DT.121643657  DT.121504211  DT.91700205  DT.100775345  DT.95167995  DT.121504204  DT.97858898 
    DT.100038930  DT.91700605 

    24/127 AceView cDNA sequences (see all 127):

    BC007639 CB851811 BQ897613 BU728461 BQ687308 AW246095 BM710114 BQ685882 
    AW024282 BU157350 AI971639 F30370 BQ879986 BQ685568 BQ880521 BU553580 
    AW024569 NM_032885 AJ312332 CB161138 CF140182 BC068992 AW170307 BF475364 

    GeneLoc Exon Structure

    5/9 Alternative Splicing Database (ASD) splice patterns (SP) for ATG4D (see all 9)    About this scheme

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


    ECgene alternative splicing isoforms for ATG4D

    (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

    ATG4D expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS
    CGAP TAG: TCGGGTGTGG

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

    About this image
    See ATG4D Protein Expression from SPIRE MOPED and PaxDB
    Genevestigator expression for ATG4D

    SOURCE GeneReport for Unigene cluster: Hs.512799

    UniProtKB/Swiss-Prot: ATG4D_HUMAN, Q86TL0
    Tissue specificity: Mainly expressed in skeletal muscle and, to a lower extent, in testis

        SABiosciences Expression via Pathway-Focused PCR Array including ATG4D: 
              Autophagy in human mouse rat

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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 ATG4D gene from 5/20 species (see all 20)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Atg4d1 , 5 autophagy-related 4D (yeast)5
    autophagy related 4D, cysteine peptidase1
    84(n)1
    86.47(a)1
      9 (7.75 cM)5
    2350401  NM_153583.91  NP_705811.81 
     212652995 
    lizard
    (Anolis carolinensis)
    Reptilia ATG4D6
    --
    59(a)
    1 ↔ 1
    2(80349575-80358232)
    zebrafish
    (Danio rerio)
    Actinopterygii LOC7959331 cysteine protease ATG4D-like 58.5(n)
    54.7(a)
      795933  XM_001333057.2  XP_001333093.2 
    fruit fly
    (Drosophila melanogaster)
    Insecta CG61941 CG6194 54.65(n)
    50.16(a)
      41868  NM_142195.1  NP_650452.1 
    worm
    (Caenorhabditis elegans)
    Secernentea atg-4.21 Protein ATG-4.2 46.5(n)
    38.64(a)
      3565022  NM_069807.2  NP_502208.1 


    ENSEMBL Gene Tree for ATG4D (if available)
    TreeFam Gene Tree for ATG4D (if available) 

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
    About This Section
    Paralogs for ATG4D gene
    ATG4C2  ATG4A2  ATG4B2  
    4 SIMAP similar genes for ATG4D using alignment to 12 protein entries:     ATG4D_HUMAN (see all proteins):
    ATG4C    DKFZp686G0859    ATG4A    ATG4B

    ATG4D 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

    10/201 NCBI SNPs in ATG4D are shown (see all 201    About this table
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 19 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs1490560091,2
    --10652718(+) AAGAGC/TGAAAC 1 -- us2k10--------
    rs1831318251,2
    --10652925(+) CCAGGA/GGTGGC 1 -- us2k10--------
    rs1431025541,2
    --10652934(+) GCCAGA/GCACGG 1 -- us2k10--------
    rs1881048691,2
    --10652947(+) GCCCAA/CGCCTG 1 -- us2k10--------
    rs124595441,2
    C,F,H,--10653018(+) TCCTGG/ACTAAC 1 -- us2k15Minor allele frequency- A:0.42NA CSA 12
    rs124595471,2
    C,F,H,--10653070(+) CAGGCG/CTGGTG 1 -- us2k14Minor allele frequency- C:0.50NA 8
    rs1462648291,2
    --10653123(+) AGAATA/GGTGTG 1 -- us2k10--------
    rs1381327351,2
    --10653180(+) CTCCAA/GCCTGG 1 -- us2k10--------
    rs1114282491,2
    C,--10653204(+) ACTCCG/ATCTCA 1 -- us2k11Minor allele frequency- A:0.50WA 2
    rs340755361,2
    C--10653209(+) GTCTC-/AAAAAA 1 -- us2k11Minor allele frequency- A:0.50NA 2

    HapMap Linkage Disequilibrium report for ATG4D (10654571 - 10664094 bp)
    Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
          Database of Genomic Variants (DGV) variations for ATG4D: --

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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

    ATG4D for disorders           About MalaCards

    ATG4D for disorders           About GeneDecksing

    OMIM gene information: 611340    OMIM disorders: --


    Export disorders for ATG4D 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 ATG4D gene integrated from 9 sources:
    (articles sorted by number of sources associating them with ATG4D)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Human autophagins, a family of cysteine proteinases potentially implicated in cell degradation by autophagy. (PubMed id 12446702)1, 2, 3 Marino G....Lopez-Otin C. (2003)
    2. 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)
    3. Caspase cleavage of Atg4D stimulates GABARAP-L1 proce ssing and triggers mitochondrial targeting and apoptosis. (PubMed id 19549685)1, 9 Betin V.M. and Lane J.D. (2009)
    4. A cryptic mitochondrial targeting motif in Atg4D links caspase cleavage with mitochondrial import and oxidative stress. (PubMed id 22441018)1 Betin V.M....Lane J.D. (2012)
    5. Systematic and quantitative assessment of the ubiquiti n-modified proteome. (PubMed id 21906983)1 Kim W....Gygi S.P. (2011)
    6. hORFeome v3.1: a resource of human open reading frames representing over 10,000 human genes. (PubMed id 17207965)1 Lamesch P.... Vidal M. (2007)
    7. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PubMed id 14702039)1 Ota T.... Sugano S. (2004)
    8. Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. (PubMed id 12477932)1 Strausberg R.L....Marra M.A. (2002)
    9. Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. (PubMed id 8125298)1 Maruyama K. and Sugano S. (1994)

    (in PubMed, OMIM, and NCBI Bookshelf)
    About This Section
     ANDOR
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    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)
    About This Section
    Entrez Gene: 84971 HGNC: 20789 AceView: APG4D Ensembl:ENSG00000130734 euGenes: HUgn84971
    ECgene: ATG4D Kegg: 84971 H-InvDB: ATG4D

    (According to HUGE)
    About This Section
      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
    Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
    About This Section
    NameDescription
    PharmGKB entry for ATG4D Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for ATG4D Genetics and Cytogenetics in Oncology and Haematology

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
    About This Section
    Patent Information for ATG4D gene:
    Search GeneIP for patents involving ATG4D

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



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    GeneCards Homepage - Last full update: 18 Mar 2013 - Incrementals: 21 Mar 2013 , 15 Apr 2013 , 26 Apr 2013

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