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Aliases for MAP3K12 Gene

Aliases for MAP3K12 Gene

  • Mitogen-Activated Protein Kinase Kinase Kinase 12 2 3 3 5
  • Dual Leucine Zipper Bearing Kinase 3 4
  • Dual Leucine Zipper Kinase DLK 2 3
  • Mixed Lineage Kinase 3 4
  • MAPK-Upstream Kinase 3 4
  • ZPK 3 4
  • DLK 3 4
  • MUK 3 4
  • Leucine Zipper Protein Kinase 3
  • Leucine-Zipper Protein Kinase 4
  • Protein Kinase MUK 3
  • EC 4
  • MEKK12 3
  • ZPKP1 3

External Ids for MAP3K12 Gene

Previous HGNC Symbols for MAP3K12 Gene

  • ZPK

Previous GeneCards Identifiers for MAP3K12 Gene

  • GC12M053870
  • GC12M053986
  • GC12M053591
  • GC12M052160
  • GC12M050914

Summaries for MAP3K12 Gene

Entrez Gene Summary for MAP3K12 Gene

  • This gene encodes a member of the serine/threonine protein kinase family. This kinase contains a leucine-zipper domain and is predominately expressed in neuronal cells. The phosphorylation state of this kinase in synaptic terminals was shown to be regulated by membrane depolarization via calcineurin. This kinase forms heterodimers with leucine zipper containing transcription factors, such as cAMP responsive element binding protein (CREB) and MYC, and thus may play a regulatory role in PKA or retinoic acid induced neuronal differentiation. Alternatively spliced transcript variants encoding different proteins have been described.[provided by RefSeq, Jul 2010]

GeneCards Summary for MAP3K12 Gene

MAP3K12 (Mitogen-Activated Protein Kinase Kinase Kinase 12) is a Protein Coding gene. Among its related pathways are Regulation of p38-alpha and p38-beta and Signal transduction_JNK pathway. Gene Ontology (GO) annotations related to this gene include protein homodimerization activity and protein kinase activity. An important paralog of this gene is MAP3K13.

UniProtKB/Swiss-Prot for MAP3K12 Gene

  • May be an activator of the JNK/SAPK pathway. Phosphorylates beta-casein, histone 1 and myelin basic protein in vitro.

Gene Wiki entry for MAP3K12 Gene

Additional gene information for MAP3K12 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for MAP3K12 Gene

Genomics for MAP3K12 Gene

GeneHancer (GH) Regulatory Elements for MAP3K12 Gene

Promoters and enhancers for MAP3K12 Gene
GeneHancer (GH) Identifier GH Type GH
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH12J053498 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE dbSUPER 672.2 -0.5 -470 5 CLOCK ZFP64 DMAP1 YY1 ZNF213 ZNF143 ZNF548 ZNF263 SP3 NFYC MAP3K12 TARBP2 ENSG00000270175 KRT1 ZNF740 HNRNPA1 ATF7 PCBP2 SP1 AAAS
GH12J053971 Promoter/Enhancer 2.8 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 42 -490.1 -490107 36.8 FEZF1 DMAP1 IRF4 YY1 ZNF213 ZNF416 ZNF143 ZNF548 SP3 NFYC HOXC8 HOXC5 HOXC11 HOXC9 HOXC6 HOXC10 GC12P054063 MIR196A2 GC12P054010 HNRNPA1
GH12J052894 Promoter/Enhancer 2.3 FANTOM5 Ensembl ENCODE dbSUPER 47.4 +597.2 597208 16.1 CLOCK MLX FEZF1 DMAP1 YY1 SLC30A9 ZNF213 E2F8 ZNF143 SP3 GC12M052900 AAAS ZNF740 PCBP2 SP1 MAP3K12 LOC100652999 ATF7 EIF4B ENSG00000257808
GH12J054277 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE dbSUPER 32.6 -780.9 -780929 7.1 CLOCK MLX DMAP1 YY1 SLC30A9 ZNF213 E2F8 ZNF143 SP3 NFYC CBX5 HNRNPA1 SP1 PCBP2 AAAS MAP3K12 ENSG00000258344 COPZ1 ATF7 TARBP2
GH12J053215 Promoter/Enhancer 2.6 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 23.3 +279.2 279212 10.1 HDGF PKNOX1 CLOCK FOXA2 SMAD1 ARNT ZFP64 ARID4B SIN3A ZNF2 RARG MAP3K12 ZNF740 LOC105378250 ITGB7 ENSG00000257500 CSAD NPFF AAAS ENSG00000257605
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around MAP3K12 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the MAP3K12 gene promoter:
  • AP-1
  • Sp1

Genomic Locations for MAP3K12 Gene

Genomic Locations for MAP3K12 Gene
20,468 bases
Minus strand
19,574 bases
Minus strand

Genomic View for MAP3K12 Gene

Genes around MAP3K12 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
MAP3K12 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for MAP3K12 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for MAP3K12 Gene

Proteins for MAP3K12 Gene

  • Protein details for MAP3K12 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Mitogen-activated protein kinase kinase kinase 12
    Protein Accession:
    Secondary Accessions:
    • B3KSS9
    • G3V1Y2
    • Q86VQ5
    • Q8WY25

    Protein attributes for MAP3K12 Gene

    859 amino acids
    Molecular mass:
    93219 Da
    Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
    Quaternary structure:
    • Interacts with MBIP.

    Three dimensional structures from OCA and Proteopedia for MAP3K12 Gene

    Alternative splice isoforms for MAP3K12 Gene


neXtProt entry for MAP3K12 Gene

Post-translational modifications for MAP3K12 Gene

  • Autophosphorylated on Ser/Thr. Phosphorylated in cytosol under basal conditions and dephosphorylated when membrane-associated (By similarity).
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for MAP3K12 Gene

Domains & Families for MAP3K12 Gene

Gene Families for MAP3K12 Gene

Suggested Antigen Peptide Sequences for MAP3K12 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry



  • Interacts with MBIP through the leucine-zipper motif.
  • Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.
  • Interacts with MBIP through the leucine-zipper motif.
  • Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.
genes like me logo Genes that share domains with MAP3K12: view

Function for MAP3K12 Gene

Molecular function for MAP3K12 Gene

UniProtKB/Swiss-Prot Function:
May be an activator of the JNK/SAPK pathway. Phosphorylates beta-casein, histone 1 and myelin basic protein in vitro.
UniProtKB/Swiss-Prot CatalyticActivity:
ATP + a protein = ADP + a phosphoprotein.
GENATLAS Biochemistry:
mitogen activated protein (MAP/ERK) kinase kinase kinase 12,expressed in brain,interacting with the GTP bound form of RAC and CDC42,regulators of JNK pathway

Enzyme Numbers (IUBMB) for MAP3K12 Gene

Phenotypes From GWAS Catalog for MAP3K12 Gene

Gene Ontology (GO) - Molecular Function for MAP3K12 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000166 nucleotide binding IEA --
GO:0004672 protein kinase activity TAS,IEA 8637721
GO:0004674 protein serine/threonine kinase activity ISS,IBA 9353328
GO:0004709 MAP kinase kinase kinase activity IEA --
GO:0004871 obsolete signal transducer activity IBA --
genes like me logo Genes that share ontologies with MAP3K12: view
genes like me logo Genes that share phenotypes with MAP3K12: view

Animal Models for MAP3K12 Gene

MGI Knock Outs for MAP3K12:

Animal Model Products

Clone Products

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for MAP3K12 Gene

Localization for MAP3K12 Gene

Subcellular locations from UniProtKB/Swiss-Prot for MAP3K12 Gene

Cytoplasm. Membrane; Peripheral membrane protein.

Subcellular locations from

Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for MAP3K12 gene
Compartment Confidence
cytosol 5
plasma membrane 4
nucleus 3
cytoskeleton 1
mitochondrion 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cell Junctions (2)
  • Nucleus (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for MAP3K12 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005622 intracellular IEA --
GO:0005737 cytoplasm TAS 8663324
GO:0005829 cytosol ISS,IEA --
GO:0005886 plasma membrane IEA,ISS --
GO:0016020 membrane ISS 9353328
genes like me logo Genes that share ontologies with MAP3K12: view

Pathways & Interactions for MAP3K12 Gene

genes like me logo Genes that share pathways with MAP3K12: view

Pathways by source for MAP3K12 Gene

SIGNOR curated interactions for MAP3K12 Gene

Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for MAP3K12 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000165 MAPK cascade IBA --
GO:0000186 activation of MAPKK activity IEA --
GO:0006468 protein phosphorylation ISS,IEA --
GO:0007254 JNK cascade TAS,ISS 9353328
GO:0016310 phosphorylation IEA --
genes like me logo Genes that share ontologies with MAP3K12: view

Drugs & Compounds for MAP3K12 Gene

(10) Drugs for MAP3K12 Gene - From: DrugBank, ApexBio, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
fostamatinib Approved, Investigational Pharma Target, inhibitor Kinase Inhibitors 0
Magnesium Approved Nutra 0
ATP Investigational Nutra Agonist, Activator, Full agonist, Antagonist, Potentiation, Pore Blocker 0
URMC-099 Pharma 0

(2) Additional Compounds for MAP3K12 Gene - From: HMDB and Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
  • 5'-Adenylphosphoric acid
  • Adenosine 5'-diphosphate
  • ADENOSINE-5'-diphosphATE
  • H3ADP
  • 5'-Adenylphosphate
Full agonist, Agonist, Partial agonist, Antagonist, Gating inhibitor 58-64-0
genes like me logo Genes that share compounds with MAP3K12: view

Transcripts for MAP3K12 Gene

Unigene Clusters for MAP3K12 Gene

Mitogen-activated protein kinase kinase kinase 12:
Representative Sequences:

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for MAP3K12 Gene

ExUns: 1a · 1b ^ 2 ^ 3a · 3b ^ 4a · 4b · 4c ^ 5 ^ 6 ^ 7a · 7b ^ 8a · 8b ^ 9 ^ 10 ^ 11 ^ 12a · 12b ^ 13a · 13b ^ 14 ^ 15 ^ 16
SP1: - - - - -
SP2: - - -
SP3: - - - -
SP4: - - -
SP6: -

Relevant External Links for MAP3K12 Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for MAP3K12 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for MAP3K12 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for MAP3K12 Gene

This gene is overexpressed in Brain - Cerebellum (x4.4).

Protein differential expression in normal tissues from HIPED for MAP3K12 Gene

This gene is overexpressed in Cervix (50.6) and Plasma (10.5).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for MAP3K12 Gene

NURSA nuclear receptor signaling pathways regulating expression of MAP3K12 Gene:


SOURCE GeneReport for Unigene cluster for MAP3K12 Gene:


mRNA Expression by UniProt/SwissProt for MAP3K12 Gene:

Tissue specificity: Highly expressed in brain and kidney.

Evidence on tissue expression from TISSUES for MAP3K12 Gene

  • Nervous system(2.8)
genes like me logo Genes that share expression patterns with MAP3K12: view

No data available for Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for MAP3K12 Gene

Orthologs for MAP3K12 Gene

This gene was present in the common ancestor of animals.

Orthologs for MAP3K12 Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia MAP3K12 34 33
  • 99.77 (n)
(Bos Taurus)
Mammalia MAP3K12 34 33
  • 92.36 (n)
(Canis familiaris)
Mammalia MAP3K12 34 33
  • 91.37 (n)
(Mus musculus)
Mammalia Map3k12 16 34 33
  • 90.69 (n)
(Rattus norvegicus)
Mammalia Map3k12 33
  • 90.17 (n)
(Ornithorhynchus anatinus)
Mammalia MAP3K12 34
  • 78 (a)
(Gallus gallus)
Aves MAP3K12 34
  • 86 (a)
(Anolis carolinensis)
Reptilia MAP3K12 34
  • 76 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia map3k12 33
  • 67.55 (n)
(Danio rerio)
Actinopterygii map3k12 33
  • 71.59 (n)
MAP3K12 34
  • 64 (a)
fruit fly
(Drosophila melanogaster)
Insecta CG8789 35
  • 60 (a)
wnd 34
  • 32 (a)
(Caenorhabditis elegans)
Secernentea dlk-1 34
  • 27 (a)
Species where no ortholog for MAP3K12 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • oppossum (Monodelphis domestica)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for MAP3K12 Gene

Gene Tree for MAP3K12 (if available)
Gene Tree for MAP3K12 (if available)
Evolutionary constrained regions (ECRs) for MAP3K12: view image

Paralogs for MAP3K12 Gene

(9) SIMAP similar genes for MAP3K12 Gene using alignment to 3 proteins:

  • M3K12_HUMAN
genes like me logo Genes that share paralogs with MAP3K12: view

Variants for MAP3K12 Gene

Sequence variations from dbSNP and Humsavar for MAP3K12 Gene

SNP ID Clin Chr 12 pos Variation AA Info Type
VAR_040705 A breast pleomorphic lobular carcinoma sample p.Glu409Lys
rs1000055065 -- 53,489,920(-) G/A intron_variant
rs1000304068 -- 53,497,057(-) C/T genic_upstream_transcript_variant, intron_variant
rs1000310038 -- 53,502,657(-) C/A/G upstream_transcript_variant
rs1000619064 -- 53,488,714(-) C/T intron_variant

Structural Variations from Database of Genomic Variants (DGV) for MAP3K12 Gene

Variant ID Type Subtype PubMed ID
esv1293318 CNV deletion 17803354
esv2289574 CNV deletion 18987734
esv2745906 CNV deletion 23290073
esv2745908 CNV deletion 23290073
esv992595 CNV deletion 20482838
nsv714 CNV insertion 18451855

Variation tolerance for MAP3K12 Gene

Residual Variation Intolerance Score: 6.51% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.70; 46.25% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for MAP3K12 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for MAP3K12 Gene

Disorders for MAP3K12 Gene

Additional Disease Information for MAP3K12

Genetic Association Database
Human Genome Epidemiology Navigator
ATLAS of Genetics and Cytogenetics in Oncology and Haematology

No disorders were found for MAP3K12 Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for MAP3K12 Gene

Publications for MAP3K12 Gene

  1. Cloning of a novel putative protein kinase having a leucine zipper domain from human brain. (PMID: 8037767) Reddy UR … Pleasure D (Biochemical and biophysical research communications 1994) 2 3 4 22 58
  2. SP3 acts as a positive regulator on the core promoter of human ZPK gene. (PMID: 14697235) Itoh A … Itoh T (Biochemical and biophysical research communications 2004) 3 4 22 58
  3. Genetic variation in MicroRNA genes and risk of oral premalignant lesions. (PMID: 19851984) Clague J … Wu X (Molecular carcinogenesis 2010) 3 44 58
  4. The small heat-shock protein Hsp27 undergoes ERK-dependent phosphorylation and redistribution to the cytoskeleton in response to dual leucine zipper-bearing kinase expression. (PMID: 19675578) Robitaille H … Germain L (The Journal of investigative dermatology 2010) 3 22 58
  5. The variant rs1867277 in FOXE1 gene confers thyroid cancer susceptibility through the recruitment of USF1/USF2 transcription factors. (PMID: 19730683) Landa I … Robledo M (PLoS genetics 2009) 3 44 58

Products for MAP3K12 Gene

Sources for MAP3K12 Gene

  • (44) GAD
  • (45)