MAP3K6 Gene (Protein Coding)

Mitogen-Activated Protein Kinase Kinase Kinase 6

GC01M027354
GIFtS:
45
This gene encodes a serine/threonine protein kinase that forms a component of protein kinase-mediated signal transduction cascades. The encoded kinase participates in the regulation of vascular endothelial growth factor (VEGF) expression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014] See more...

Aliases for MAP3K6 Gene

Aliases for MAP3K6 Gene

  • Mitogen-Activated Protein Kinase Kinase Kinase 6 2 3 4 5
  • MAPKKK6 2 3 4
  • MEKK6 2 3 4
  • ASK2 2 3 4
  • Apoptosis Signal-Regulating Kinase 2 3 4
  • EC 2.7.11.25 4 50
  • Apoptosis Signal Regulating Kinase 2 2
  • EC 2.7.11 50
  • MAP3K6 5

External Ids for MAP3K6 Gene

Previous GeneCards Identifiers for MAP3K6 Gene

  • GC01P027901
  • GC01M026713
  • GC01M026914
  • GC01M027286
  • GC01M027365
  • GC01M027554
  • GC01M027681
  • GC01M025937

Summaries for MAP3K6 Gene

Entrez Gene Summary for MAP3K6 Gene

  • This gene encodes a serine/threonine protein kinase that forms a component of protein kinase-mediated signal transduction cascades. The encoded kinase participates in the regulation of vascular endothelial growth factor (VEGF) expression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

GeneCards Summary for MAP3K6 Gene

MAP3K6 (Mitogen-Activated Protein Kinase Kinase Kinase 6) is a Protein Coding gene. Diseases associated with MAP3K6 include Gastric Cancer, Hereditary Diffuse and Periampullary Adenoma. Among its related pathways are G-Beta Gamma Signaling and MAPK signaling pathway. Gene Ontology (GO) annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity. An important paralog of this gene is MAP3K5.

UniProtKB/Swiss-Prot Summary for MAP3K6 Gene

  • Component of a protein kinase signal transduction cascade. Activates the JNK, but not ERK or p38 kinase pathways.

Additional gene information for MAP3K6 Gene

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for MAP3K6 Gene

Genomics for MAP3K6 Gene

GeneHancer (GH) Regulatory Elements Pubs

Download GeneHancer 2017 data
Promoters and enhancers for MAP3K6 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around MAP3K6 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for MAP3K6

Top Transcription factor binding sites by QIAGEN in the MAP3K6 gene promoter:
  • AREB6
  • Elk-1
  • ITF-2
  • MZF-1
  • NF-kappaB1
  • p53
  • SEF-1 (1)
  • STAT5A
  • Tal-1beta
  • YY1

Genomic Locations for MAP3K6 Gene

Latest Assembly
chr1:27,354,067-27,368,037
(GRCh38/hg38)
Size:
13,971 bases
Orientation:
Minus strand

Previous Assembly
chr1:27,681,675-27,693,452
(GRCh37/hg19 by Entrez Gene)
Size:
11,778 bases
Orientation:
Minus strand

chr1:27,681,675-27,693,383
(GRCh37/hg19 by Ensembl)
Size:
11,709 bases
Orientation:
Minus strand

Genomic View for MAP3K6 Gene

Genes around MAP3K6 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
MAP3K6 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for MAP3K6 Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for MAP3K6 Gene

Proteins for MAP3K6 Gene

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  • Protein details for MAP3K6 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O95382-M3K6_HUMAN
    Recommended name:
    Mitogen-activated protein kinase kinase kinase 6
    Protein Accession:
    O95382
    Secondary Accessions:
    • A2ACE8
    • A2VDG4
    • A2VDG5
    • Q59HF4
    • Q5SSD4
    • Q75PK3
    • Q96B75

    Protein attributes for MAP3K6 Gene

    Size:
    1288 amino acids
    Molecular mass:
    142596 Da
    Cofactor:
    Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
    Quaternary structure:
    • Binds both upstream activators and downstream substrates in multimolecular complexes.
    SequenceCaution:
    • Sequence=AAD05304.1; Type=Erroneous initiation; Evidence={ECO:0000305};

    Alternative splice isoforms for MAP3K6 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for MAP3K6 Gene

Protein Expression for MAP3K6 Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Selected DME Specific Peptides for MAP3K6 Gene

O95382:
  • NIVRYLG
  • QDPLAVA
  • VPGGSLS
  • NLLLSYRD
  • KISDFGTSK

Post-translational modifications for MAP3K6 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for MAP3K6 Gene

ENSEMBL proteins:
REFSEQ proteins:

Domains & Families for MAP3K6 Gene

Gene Families for MAP3K6 Gene

HGNC:
IUPHAR :
Human Protein Atlas (HPA):
  • Enzymes
  • Plasma proteins
  • Predicted intracellular proteins

Protein Domains for MAP3K6 Gene

InterPro:

Suggested Antigen Peptide Sequences for MAP3K6 Gene

GenScript: Design optimal peptide antigens:
  • Apoptosis signal-regulating kinase 2 (M3K6_HUMAN)
  • MAP3K6 protein (Q32MQ5_HUMAN)
  • Mitogen-activated protein kinase kinase kinase 6 (Q5SSD2_HUMAN)

Graphical View of Domain Structure for InterPro Entry

O95382

UniProtKB/Swiss-Prot:

M3K6_HUMAN :
  • Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.
Family:
  • 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 MAP3K6: view

Function for MAP3K6 Gene

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  6. Cell Lines for research

Molecular function for MAP3K6 Gene

UniProtKB/Swiss-Prot Function:
Component of a protein kinase signal transduction cascade. Activates the JNK, but not ERK or p38 kinase pathways.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.25;.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.25;.
UniProtKB/Swiss-Prot EnzymeRegulation:
Activated by phosphorylation on Thr-806. Catalytically active only when complexed with MAP3K5, with MAP3K5 supporting the stability and the active configuration of MAP3K6 and MAP3K6 activating MAP3K5 by direct phosphorylation.

Enzyme Numbers (IUBMB) for MAP3K6 Gene

Phenotypes From GWAS Catalog for MAP3K6 Gene

Gene Ontology (GO) - Molecular Function for MAP3K6 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000166 nucleotide binding IEA --
GO:0000287 magnesium ion binding IDA 9875215
GO:0004672 protein kinase activity IBA 21873635
GO:0004674 protein serine/threonine kinase activity IEA --
GO:0004709 MAP kinase kinase kinase activity TAS,IDA 9875215
genes like me logo Genes that share ontologies with MAP3K6: view
genes like me logo Genes that share phenotypes with MAP3K6: view

Animal Models for MAP3K6 Gene

MGI Knock Outs for MAP3K6:

Animal Models for research

  • Taconic Biosciences Mouse Models for MAP3K6

miRNA for MAP3K6 Gene

miRTarBase miRNAs that target MAP3K6

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for MAP3K6

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for MAP3K6 Gene

Localization for MAP3K6 Gene

Subcellular locations from

COMPARTMENTS
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 MAP3K6 gene
Compartment Confidence
nucleus 3
cytosol 3
mitochondrion 2
plasma membrane 1
extracellular 1
cytoskeleton 1
endoplasmic reticulum 1
endosome 1
lysosome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Actin filaments (2)
  • Cytosol (2)
  • Nucleoplasm (2)
  • Plasma membrane (2)
See all subcellular structures

No data available for Subcellular locations from UniProtKB/Swiss-Prot and Gene Ontology (GO) - Cellular Components for MAP3K6 Gene

Pathways & Interactions for MAP3K6 Gene

genes like me logo Genes that share pathways with MAP3K6: view

Pathways by source for MAP3K6 Gene

1 Sino Biological pathway for MAP3K6 Gene
1 KEGG pathway for MAP3K6 Gene
9 Qiagen pathways for MAP3K6 Gene
  • CRHR Pathway
  • Interferon Pathway
  • MAPK Family Pathway
  • NFAT and Cardiac Hypertrophy
  • PACAP Signaling

Interacting Proteins for MAP3K6 Gene

Selected Interacting proteins: O95382-M3K6_HUMAN for MAP3K6 Gene via MINT IID

GPS-Prot Interaction Network for MAP3K6

SIGNOR curated interactions for MAP3K6 Gene

Activates:
Is activated by:

Gene Ontology (GO) - Biological Process for MAP3K6 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000165 MAPK cascade IEA --
GO:0000186 activation of MAPKK activity IBA 21873635
GO:0006468 protein phosphorylation IDA 9875215
GO:0007165 signal transduction TAS 9875215
GO:0007257 activation of JUN kinase activity TAS 9875215
genes like me logo Genes that share ontologies with MAP3K6: view

Drugs & Compounds for MAP3K6 Gene

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(3) Drugs for MAP3K6 Gene - From: DrugBank and HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
fostamatinib Approved, Investigational Pharma Target, inhibitor Kinase Inhibitors 0
Magnesium Approved, Experimental, Investigational Pharma 0
ATP Investigational Nutra 0

(1) Additional Compounds for MAP3K6 Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
ADP
  • 5'-Adenylphosphoric acid
  • Adenosine 5'-diphosphate
  • ADENOSINE-5'-diphosphATE
  • H3ADP
  • 5'-Adenylphosphate
 58-64-0
genes like me logo Genes that share compounds with MAP3K6: view

Transcripts for MAP3K6 Gene

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mRNA/cDNA for MAP3K6 Gene

2 REFSEQ mRNAs :
11 NCBI additional mRNA sequence :
9 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for MAP3K6

Alternative Splicing Database (ASD) splice patterns (SP) for MAP3K6 Gene

ExUns: 1a · 1b ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17 ^ 18 ^ 19 ^ 20 ^ 21 ^ 22 ^ 23 ^ 24a · 24b ^
SP1: -
SP2: - -
SP3:

ExUns: 25 ^ 26 ^ 27 ^ 28 ^ 29a · 29b
SP1:
SP2:
SP3:

Relevant External Links for MAP3K6 Gene

GeneLoc Exon Structure for
MAP3K6

Expression for MAP3K6 Gene

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  1. Primer products for research
  2. Gene Expression Assays for research

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for MAP3K6 Gene

mRNA expression in normal human tissues for MAP3K6 Gene
mRNA expression by BioGPS for MAP3K6 GenemRNA expression by GTEx for MAP3K6 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for MAP3K6 Gene

This gene is overexpressed in Breast (19.6), Neutrophil (14.4), Plasma (13.4), and Heart (6.9).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for MAP3K6 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for MAP3K6

SOURCE GeneReport for Unigene cluster for MAP3K6 Gene:

Hs.194694

Evidence on tissue expression from TISSUES for MAP3K6 Gene

  • Skin(4.5)
  • Nervous system(4.3)

Phenotype-based relationships between genes and organs from Gene ORGANizer for MAP3K6 Gene

Germ Layers:
  • endoderm
  • mesoderm
Systems:
  • digestive
  • immune
Regions:
Abdomen:
  • stomach
genes like me logo Genes that share expression patterns with MAP3K6: view

Primer products for research

No data available for mRNA differential expression in normal tissues , Protein tissue co-expression partners and mRNA Expression by UniProt/SwissProt for MAP3K6 Gene

Orthologs for MAP3K6 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for MAP3K6 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
 Mammalia MAP3K6 29 30
  • 99.56 (n)
 OneToOne
Dog
(Canis familiaris)
 Mammalia MAP3K6 29 30
  • 88.37 (n)
 OneToOne
Cow
(Bos Taurus)
 Mammalia MAP3K6 29 30
  • 88.25 (n)
 OneToOne
Mouse
(Mus musculus)
 Mammalia Map3k6 29 16 30
  • 84.61 (n)
 OneToOne
Rat
(Rattus norvegicus)
 Mammalia Map3k6 29
  • 84.58 (n)
Oppossum
(Monodelphis domestica)
 Mammalia MAP3K6 30
  • 72 (a)
 OneToOne
Platypus
(Ornithorhynchus anatinus)
 Mammalia MAP3K6 30
  • 57 (a)
 OneToOne
Chicken
(Gallus gallus)
 Aves MAP3K6 29 30
  • 69.51 (n)
 OneToOne
Lizard
(Anolis carolinensis)
 Reptilia MAP3K6 30
  • 56 (a)
 OneToOne
Zebrafish
(Danio rerio)
 Actinopterygii MAP3K6 30
  • 48 (a)
 OneToOne
Fruit Fly
(Drosophila melanogaster)
 Insecta Pk92B 30 31
  • 33 (a)
 OneToMany
Worm
(Caenorhabditis elegans)
 Secernentea nsy-1 30
  • 30 (a)
 OneToMany
Baker's yeast
(Saccharomyces cerevisiae)
 Saccharomycetes STE11 30
  • 23 (a)
 OneToMany
Species where no ortholog for MAP3K6 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium 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)
  • 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)
  • 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 Vase (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)
  • Tropical Clawed Frog (Silurana tropicalis)
  • Wheat (Triticum aestivum)

Evolution for MAP3K6 Gene

ENSEMBL:
Gene Tree for MAP3K6 (if available)
TreeFam:
Gene Tree for MAP3K6 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for MAP3K6: view image
Alliance of Genome Resources:
Additional Orthologs for MAP3K6

Paralogs for MAP3K6 Gene

Paralogs for MAP3K6 Gene

(28) SIMAP similar genes for MAP3K6 Gene using alignment to 5 proteins:

  • M3K6_HUMAN
  • H0Y894_HUMAN
  • H0Y8A3_HUMAN
  • L8ECB4_HUMAN
  • Q32MQ5_HUMAN
genes like me logo Genes that share paralogs with MAP3K6: view

Variants for MAP3K6 Gene

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Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for MAP3K6 Gene

SNP ID Clinical significance and condition Chr 01 pos Variation AA Info Type
rs11247641 Benign: not provided 27,361,788(-) G/Ap.Arg499Cys
NM_004672.5(MAP3K6):c.1495C>T (p.Arg499Cys) 		MISSENSE
rs1258164419 Likely Benign: not provided 27,357,019(-) C/A
NM_004672.5(MAP3K6):c.3354G>T (p.Val1118=) 		SYNONYMOUS
rs182712391 Benign: not provided 27,364,279(-) A/C
NM_004672.5(MAP3K6):c.620T>G (p.Val207Gly) 		MISSENSE
rs34008139 Likely Pathogenic: not provided 27,358,747(-) AG/A
NM_004672.5(MAP3K6):c.2544del (p.Phe849fs) 		FRAMESHIFT
rs34558621 Benign: not provided 27,358,309(-) A/G
NM_004672.5(MAP3K6):c.2787T>C (p.Ser929=) 		SYNONYMOUS

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for MAP3K6 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for MAP3K6 Gene

Variant ID Type Subtype PubMed ID
esv1006916 CNV deletion 20482838
nsv1075766 CNV deletion 25765185
nsv516766 CNV loss 19592680
nsv526051 CNV gain 19592680

Variation tolerance for MAP3K6 Gene

Residual Variation Intolerance Score: 36.5% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 11.35; 92.67% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for MAP3K6 Gene

Human Gene Mutation Database (HGMD)
MAP3K6
SNPedia medical, phenotypic, and genealogical associations of SNPs for
MAP3K6
Leiden Open Variation Database (LOVD)
MAP3K6

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for MAP3K6 Gene

Disorders for MAP3K6 Gene

MalaCards: The human disease database

(3) MalaCards diseases for MAP3K6 Gene - From: ORP and COP

- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for MAP3K6

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with MAP3K6: view

No data available for UniProtKB/Swiss-Prot and Genatlas for MAP3K6 Gene

Publications for MAP3K6 Gene

  1. Apoptosis signal-regulating kinase (ASK) 2 functions as a mitogen-activated protein kinase kinase kinase in a heteromeric complex with ASK1. (PMID: 17210579) Takeda K … Ichijo H (The Journal of biological chemistry 2007) 3 4 22
  2. MAPKKK6, a novel mitogen-activated protein kinase kinase kinase, that associates with MAPKKK5. (PMID: 9875215) Wang XS … Yao Z (Biochemical and biophysical research communications 1998) 2 3 4
  3. Germline mutations in MAP3K6 are associated with familial gastric cancer. (PMID: 25340522) Gaston D … Bedard K (PLoS genetics 2014) 3 72
  4. Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. (PMID: 20628086) Bailey SD … DREAM investigators (Diabetes care 2010) 3 40
  5. Mitogen-activated protein 3 kinase 6 mediates angiogenic and tumorigenic effects via vascular endothelial growth factor expression. (PMID: 19246638) Eto N … Nangaku M (The American journal of pathology 2009) 3 22

ExternalLinks

View latest publications for MAP3K6 gene in Mastermind

Products for MAP3K6 Gene

Sources for MAP3K6 Gene