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NKX6-2 Gene

protein-coding   GIFtS: 47
GCID: GC10M134598

NK6 Homeobox 2

(Previous names: NK6 transcription factor related, locus 2 (Drosophila))
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(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
NK6 Homeobox 21 2     Glial And Testis-Specific Homeobox Protein2
NKX6B2 3 5     Homeobox 6B2
Homeobox Protein NK-6 Homolog B2 3     Homeobox Protein Nkx-6.22
GTX2 3     NK Homeobox Family 6, B2
NKX6.22 5     NK6 Transcription Factor Related, Locus 22
NK6 Transcription Factor Related, Locus 2 (Drosophila)1     

External Ids:    HGNC: 193211   Entrez Gene: 845042   Ensembl: ENSG000001488267   OMIM: 6059555   UniProtKB: Q9C0563   

Export aliases for NKX6-2 gene to outside databases

Previous GC identifers: GC10U990123 GC10M134475 GC10M134032 GC10M134448 GC10M128149


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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GeneCards Summary for NKX6-2 Gene:
NKX6-2 (NK6 homeobox 2) is a protein-coding gene. GO annotations related to this gene include transcription regulatory region sequence-specific DNA binding and sequence-specific DNA binding transcription factor activity. An important paralog of this gene is NKX2-1.

Gene Wiki entry for NKX6-2 Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:
NC_000010.10  NC_018921.2  NT_030059.14  
Regulatory elements:
   Regulatory transcription factor binding sites in the NKX6-2 gene promoter:
         STAT1   Pax-6   STAT1beta   STAT1alpha   MEF-2A   POU2F1   POU2F1a   Sox9   SEF-1 (1)   aMEF-2   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidNKX6-2 promoter sequence
   Search Chromatin IP Primers for NKX6-2

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat NKX6-2


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

Entrez Gene cytogenetic band: 10q26   Ensembl cytogenetic band:  10q26.3   HGNC cytogenetic band: 10q26.3

NKX6-2 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
NKX6-2 gene location

GeneLoc information about chromosome 10         GeneLoc Exon Structure

GeneLoc location for GC10M134598:  view genomic region     (about GC identifiers)

Start:
134,598,297 bp from pter      End:
134,599,556 bp from pter
Size:
1,260 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., and/or eBioscience,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., and/or eBioscience, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: NKX62_HUMAN, Q9C056 (See protein sequence)
Recommended Name: Homeobox protein Nkx-6.2  
Size: 277 amino acids; 29263 Da
Secondary accessions: Q5JSF3

Explore the universe of human proteins at neXtProt for NKX6-2: NX_Q9C056

Explore proteomics data for NKX6-2 at MOPED

Post-translational modifications: 

  • Modification sites at neXtProt
  • Modification sites at PhosphoSitePlus

  • See NKX6-2 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins: NP_796374.1  
    ENSEMBL proteins: 
     ENSP00000357581  

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    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    HGNC Gene Families:
    NKL: Homeoboxes / ANTP class : NKL subclass

    5 InterPro protein domains:
     IPR020479 Homeobox_metazoa
     IPR000047 HTH_motif
     IPR017970 Homeobox_CS
     IPR001356 Homeobox_dom
     IPR009057 Homeodomain-like

    Graphical View of Domain Structure for InterPro Entry Q9C056

    ProtoNet protein and cluster: Q9C056

    1 Blocks protein domain: IPB000047 Lambda and other repressor helix-turn-helix signature

    UniProtKB/Swiss-Prot: NKX62_HUMAN, Q9C056
    Similarity: Contains 1 homeobox DNA-binding domain


    Find genes that share domains with NKX6-2           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, 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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         Gene Ontology (GO): 4 molecular function terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000976transcription regulatory region sequence-specific DNA binding IEA--
    GO:0003677DNA binding ----
    GO:0003700sequence-specific DNA binding transcription factor activity NAS11210186
    GO:0043565sequence-specific DNA binding ----
         
    Find genes that share ontologies with NKX6-2           About GenesLikeMe


    Phenotypes:
         7 MGI mutant phenotypes (inferred from 5 alleles(MGI details for Nkx6-2):
     behavior/neurological  cellular  mortality/aging  nervous system  normal 
     renal/urinary system  vision/eye 

    Find genes that share phenotypes with NKX6-2           About GenesLikeMe

    Animal Models:
         MGI mouse knock-out Nkx6-2Nkx6-tm1Qiu for NKX6-2

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for NKX6-2
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    3 qRT-PCR Assays for microRNAs that regulate NKX6-2:
    hsa-miR-520d-5p hsa-miR-524-5p hsa-miR-32*
    SwitchGear 3'UTR luciferase reporter plasmidNKX6-2 3' UTR sequence
    Inhib. RNA
    Products:
        
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    Predesigned siRNA for gene silencing in human, mouse, rat NKX6-2

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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for NKX6-2


    (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
    NKX62_HUMAN, Q9C056: Nucleus (Probable)
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    nucleus5
    cytosol2

    Gene Ontology (GO): 1 cellular component term:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005634nucleus NAS11210186

    Find genes that share ontologies with NKX6-2           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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        Custom Pathway & Disease-focused RT2 Profiler PCR Arrays for NKX6-2
    Interactions:

        Search GeneGlobe Interaction Network for NKX6-2

    STRING Interaction Network Preview (showing 4 interactants - click image to see more details)

    4 Interacting proteins for NKX6-2 (ENSP000003575814) via UniProtKB, MINT, STRING, and/or I2D
    InteractantInteraction Details
    GeneCardExternal ID(s)
    NACAENSP000004038174STRING: ENSP00000403817
    HNF1BENSP000002258934STRING: ENSP00000225893
    --ENSP000003971004STRING: ENSP00000397100
    --ENSP000002403494STRING: ENSP00000240349
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 13):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000122negative regulation of transcription from RNA polymerase II promoter IEA--
    GO:0006355regulation of transcription, DNA-templated NAS11210186
    GO:0010454negative regulation of cell fate commitment IEA--
    GO:0010455positive regulation of cell fate commitment IEA--
    GO:0021912regulation of transcription from RNA polymerase II promoter involved in spinal cord motor neuron fate specification IEA--

    Find genes that share ontologies with NKX6-2           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 NKX6-2 (NKX62)



    (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 NKX6-2 gene: 
    NM_177400.2  

    Unigene Cluster for NKX6-2:

    NK6 homeobox 2
    Hs.134013  [show with all ESTs]
    Unigene Representative Sequence: NM_177400
    1 Ensembl transcript including schematic representation, and UCSC links where relevant:
    ENST00000368592(uc001llr.2)
    miRNA
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    3 qRT-PCR Assays for microRNAs that regulate NKX6-2:
    hsa-miR-520d-5p hsa-miR-524-5p hsa-miR-32*
    SwitchGear 3'UTR luciferase reporter plasmidNKX6-2 3' UTR sequence
    Inhib. RNA
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      QuantiTect SYBR Green Assays in human, mouse, rat NKX6-2
      QuantiFast Probe-based Assays in human, mouse, rat NKX6-2

    Additional mRNA sequence: 

    BC101635.1 BC104823.1 

    1 DOTS entry:

    DT.75147528 

    2 AceView cDNA sequences:

    AI870533 NM_177400 

    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™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    NKX6-2 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: ACCGAGAGCC
    NKX6-2 Expression
    About this image


    NKX6-2 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 10) fully expand
     
     Pancreas (Endocrine System)    fully expand to see all 4 entries
             Acinar Cells Pancreatic Acini
     
     Brain (Nervous System)    fully expand to see all 10 entries
             Caudal Ganglionic Eminence Progenitor Cells Caudal Ganglionic Eminence
             Oligodendrocyte-like cells
     
     Neural Tube (Nervous System)    fully expand to see all 6 entries
             Caudal Ganglionic Eminence Progenitor Cells Caudal Ganglionic Eminence
             Mesencephalic Basal Plate
     
     Spinal Cord (Nervous System)    fully expand to see all 4 entries
             Myelinating Oligodendrocyte Cells Spinal Cord White Matter
             Oligodendrocyte-like cells
     
     Epithelial Cells
             Acinar Cells Pancreatic Acini
    NKX6-2 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    NKX6-2 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.134013

    UniProtKB/Swiss-Prot: NKX62_HUMAN, Q9C056
    Tissue specificity: Highest expression in brain

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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)
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    This gene was present in the common ancestor of animals.

    Orthologs for NKX6-2 gene from Selected species (see all 13)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Nkx6-21 , 5 NK6 homeobox 21, 5 88.57(n)1
    97.11(a)1
      7 (84.57 cM)5
    149121  NM_183248.31  NP_899071.21 
     1395793775 
    chicken
    (Gallus gallus)
    Aves NKX6-21 NK6 homeobox 2 80.63(n)
    85.66(a)
      395591  NM_001199548.1  NP_001186477.1 
    lizard
    (Anolis carolinensis)
    Reptilia NKX6-26
    NK6 homeobox 2
    76(a)
    1 ↔ 1
    3(59167657-59167960)
    tropical clawed frog
    (Xenopus tropicalis)
    Amphibia nkx6-21 NK6 homeobox 2 72.99(n)
    79.18(a)
      100038084  XM_002937790.2  XP_002937836.1 
    zebrafish
    (Danio rerio)
    Actinopterygii nkx6.21 NK6 homeobox 2 72.99(n)
    77.7(a)
      565782  NM_001135784.2  NP_001129256.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta HGTX6
    HGTX
    24(a)
    1 → many
    3L(14576322-14592640)


    ENSEMBL Gene Tree for NKX6-2 (if available)
    TreeFam Gene Tree for NKX6-2 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for NKX6-2 gene
    NKX2-12  NKX6-12  HMX32  TLX22  NKX3-12  TLX12  NKX2-32  HMX22  
    NKX6-32  NKX3-22  NKX2-62  NKX2-82  NKX2-52  NKX2-22  NKX2-42  HMX12  
    TLX32  
    2 SIMAP similar genes for NKX6-2 using alignment to 1 protein entry:     NKX62_HUMAN:
    NKX6-1    NKX6-3

    Find genes that share paralogs with NKX6-2           About GenesLikeMe



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for NKX6-2 (see all 73)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 10 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs28040041,2
    C,F,A,H--134597898(-) CCGCTC/TGGCCG 1 -- ds500116Minor allele frequency- T:0.25NS NA WA EA 1830
    rs1437232891,2
    --134598046(+) CGAGGC/TGAGGC 1 -- ds50010--------
    rs2019234711,2
    --134598443(+) GCCGCC/GGCCGC 2 R G mis10--------
    rs2015440411,2
    --134598645(+) TTGCGA/CCACTT 2 W C mis10--------
    rs1481019981,2
    C--134598709(+) GCGGGA/GCCCGG 1 -- int10--------
    rs2008791591,2
    C--134598997(+) GGCGGA/GGTCCC 1 -- int10--------
    rs1995133961,2
    C--134599339(+) AAGCCC/GGCCGG 2 A syn10--------
    rs2014258671,2
    C,F--134599389(+) GGCCAT/GGTTGT 2 /M /L mis11Minor allele frequency- G:0.01EU 541
    rs1851953391,2
    --134599855(+) TCCCCA/GGGGAC 1 -- us2k10--------
    rs27373981,2
    C,F,H--134599872(-) CAAGCG/TGGATT 1 -- us2k115Minor allele frequency- T:0.12NS NA CSA WA 1715

    HapMap Linkage Disequilibrium report for NKX6-2 (134598297 - 134599556 bp)

    Structural Variations
         Database of Genomic Variants (DGV) Selected variations for NKX6-2 (see all 29):    About this table    
    Variant IDTypeSubtypePubMed ID
    nsv509378CNV Insertion20534489
    nsv470977CNV Loss18288195
    dgv853n71CNV Loss21882294
    dgv858n71CNV Loss21882294
    dgv859n71CNV Loss21882294
    nsv896149CNV Loss21882294
    nsv832032CNV Loss17160897
    nsv832034CNV Loss17160897
    nsv896182CNV Loss21882294
    dgv857n71CNV Loss21882294

    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing NKX6-2
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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.)
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    OMIM gene information: 605955    OMIM disorders: --

    1 disease from the University of Copenhagen DISEASES database for NKX6-2:
    Neutropenia

    Find genes that share disorders with NKX6-2           About GenesLikeMe


    Export disorders for NKX6-2 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 NKX6-2 gene, integrated from 10 sources (see all 14):
    (articles sorted by number of sources associating them with NKX6-2)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Cloning, expression and chromosomal location of NKX6B to 10q26, a region frequently deleted in brain tumors. (PubMed id 11210186)1, 2, 3, 9 Lee S.-H.... Belouchi A. (Mamm. Genome 2001)
    2. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PubMed id 15489334)2 Gerhard D.S.... Malek J. (Genome Res. 2004)
    3. The DNA sequence and comparative analysis of human chromosome 10. (PubMed id 15164054)2 Deloukas P.... Rogers J. (Nature 2004)
    4. 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. (Proc. Natl. Acad. Sci. U.S.A. 2002)
    5. Gtx, an oligodendrocyte-specific homeodomain protein, has repressor activity. (PubMed id 10931524)9 Awatramani R....Kamholz J. (J. Neurosci. Res. 2000)
    6. Antisense masking reveals contributions of mRNA-rRNA base pairing to translation of Gtx and FGF2 mRNAs. (PubMed id 18832380)9 Panopoulos P. and Mauro V.P. (J. Biol. Chem. 2008)
    7. Co-localization of Nkx6.2 and Nkx2.2 homeodomain proteins in differentiated myelinating oligodendrocytes. (PubMed id 19780200)9 Cai J....Qiu M. (Glia 2010)
    8. Regulation of myelin development. (PubMed id 9050362)9 Kamholz J.A. (Mult. Scler. 1996)
    9. The Gtx homeodomain transcription factor exerts neuroprotection using its homeodomain. (PubMed id 14754886)9 Hashimoto Y....Nishimoto I. (J. Biol. Chem. 2004)
    10. Development of a gene-trap vector with a highly sensitive fluorescent protein reporter system for expression profiling. (PubMed id 18615730)9 Tanaka T.S....Stanford W.L. (Genesis 2008)

    (in PubMed, OMIM, and NCBI Bookshelf)
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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: 84504 HGNC: 19321 AceView: NKX6-2 Ensembl:ENSG00000148826 euGenes: HUgn84504
    ECgene: NKX6-2 H-InvDB: NKX6-2

    (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 NKX6-2 Pharmacogenomics, SNPs, Pathways

    (Patent information from GeneIP,
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    Patent Information for NKX6-2 gene:
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