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MAP3K6 mitogen-activated protein kinase kinase kinase 6 [ Homo sapiens (human) ]

Gene ID: 9064, updated on 6-Jul-2025
Official Symbol
MAP3K6provided by HGNC
Official Full Name
mitogen-activated protein kinase kinase kinase 6provided by HGNC
Primary source
HGNC:HGNC:6858
See related
Ensembl:ENSG00000142733 MIM:604468; AllianceGenome:HGNC:6858
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
ASK2; MEKK6; MAPKKK6
Summary
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]
Expression
Broad expression in skin (RPKM 18.7), fat (RPKM 11.6) and 21 other tissues See more
Orthologs
mouse all
NEW
Try the new Gene table
Try the new Transcript table
See MAP3K6 in Genome Data Viewer
Location:
1p36.11
Exon count:
30
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (27355184..27366961, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (27196422..27208199, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (27681675..27693452, complement)

Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene transmembrane protein 222 Neighboring gene actin gamma 1 pseudogene 20 Neighboring gene RNA, U6 small nuclear 48, pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid active region 543 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 544 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:27669148-27669765 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 545 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:27673548-27674088 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:27674089-27674627 Neighboring gene synaptotagmin like 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 508 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 509 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:27685945-27686480 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:27686481-27687016 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 546 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 510 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 511 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:27692433-27693376 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:27693377-27694318 Neighboring gene ficolin 3 Neighboring gene CD164 molecule like 2

Go to nucleotide: Graphics FASTA GenBank

  • Project title: Tissue-specific circular RNA induction during human fetal development
  • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
  • BioProject: PRJNA270632
  • Publication: PMID 26076956
  • Analysis date: Mon Apr 2 22:54:59 2018

Related articles in PubMed

  1. Heteromeric complex formation of ASK2 and ASK1 regulates stress-induced signaling. Ortner E, et al. Biochem Biophys Res Commun, 2007 Oct 19. PMID 17714688
  2. Germline mutations in MAP3K6 are associated with familial gastric cancer. Gaston D, et al. PLoS Genet, 2014 Oct. PMID 25340522, Free PMC Article
  3. MAPKKK6, a novel mitogen-activated protein kinase kinase kinase, that associates with MAPKKK5. Wang XS, et al. Biochem Biophys Res Commun, 1998 Dec 9. PMID 9875215
  4. ASK1 and ASK2 differentially regulate the counteracting roles of apoptosis and inflammation in tumorigenesis. Iriyama T, et al. EMBO J, 2009 Apr 8. PMID 19214184, Free PMC Article
  5. Mitogen-activated protein 3 kinase 6 mediates angiogenic and tumorigenic effects via vascular endothelial growth factor expression. Eto N, et al. Am J Pathol, 2009 Apr. PMID 19246638, Free PMC Article

See all (35) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Structure-based mechanism of preferential complex formation by apoptosis signal-regulating kinases.
    Title: Structure-based mechanism of preferential complex formation by apoptosis signal-regulating kinases.
  2. MAP3K6 should no longer be considered a gastric cancer (GC) predisposition gene, whereas deleterious CTNNA1 variants are confirmed as an infrequent cause of GC susceptibility. Biallelic MYD88 germline mutations are at most a very rare cause of GC susceptibility.
    Title: Role of germline aberrations affecting CTNNA1, MAP3K6 and MYD88 in gastric cancer susceptibility.
  3. Data show that the MAPKKK6 ASK2, a modulator of MAPKKK5 ASK1 signaling, was essential for ASK1-dependent apoptosis, but not for inducing interferon-beta (IFNB) expression.
    Title: The ASK family kinases differentially mediate induction of type I interferon and apoptosis during the antiviral response.
  4. MAP3K6 acts as a tumor suppressor, and studies showing the presence of somatic mutations in MAP3K6 in non-hereditary gastric cancers and gastric cancer cell lines, point towards MAP3K6 variants as a predisposing factor for familial gastric cancer
    Title: Germline mutations in MAP3K6 are associated with familial gastric cancer.
  5. Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
    Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
  6. regulation of VEGF by MAP3K6 may play a crucial role in both angiogenesis and tumorigenesis.
    Title: Mitogen-activated protein 3 kinase 6 mediates angiogenic and tumorigenic effects via vascular endothelial growth factor expression.
  7. Observational study of gene-disease association. (HuGE Navigator)
    Title: Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.
  8. Apoptosis signal-regulating kinase (ASK) 2 functions as a mitogen-activated protein kinase kinase kinase in a heteromeric complex with ASK1.
    Title: Apoptosis signal-regulating kinase (ASK) 2 functions as a mitogen-activated protein kinase kinase kinase in a heteromeric complex with ASK1.
Submit: New GeneRIF Correction

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Clone Names

  • MGC20114, MGC125653

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables ATP binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables ATP binding IEA
Inferred from Electronic Annotation
more info
  
enables MAP kinase kinase kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables MAP kinase kinase kinase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables MAP kinase kinase kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables MAP kinase kinase kinase activity TAS
Traceable Author Statement
more info
 PubMed 
enables kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables magnesium ion binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables metal ion binding IEA
Inferred from Electronic Annotation
more info
  
enables nucleotide binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables protein serine kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables protein serine/threonine kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables transferase activity IEA
Inferred from Electronic Annotation
more info
  
Process Evidence Code Pubs
involved_in JNK cascade IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in MAPK cascade IEA
Inferred from Electronic Annotation
more info
  
involved_in p38MAPK cascade IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in protein phosphorylation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in signal transduction TAS
Traceable Author Statement
more info
 PubMed 
Preferred Names
mitogen-activated protein kinase kinase kinase 6
Names
apoptosis signal-regulating kinase 2
NP_001284538.1
NP_004663.3
XP_016858261.1
XP_047289645.1
XP_047289648.1
XP_047289651.1
XP_054195489.1
XP_054195490.1
XP_054195491.1
XP_054195492.1

NEW Try the new Transcript table

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_051309.1 RefSeqGene

    Range
    6077..17854
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_1086

mRNA and Protein(s)

  1. NM_001297609.2 → NP_001284538.1  mitogen-activated protein kinase kinase kinase 6 isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an alternate in-frame exon in the 5' coding region, compared to variant 1. The encoded isoform (2) is shorter than isoform 1.
    Source sequence(s)
    AB208805, AI658745, AW771625, FO393419
    Consensus CDS
    CCDS72738.1
    UniProtKB/Swiss-Prot
    O95382
    Related
    ENSP00000363152.2, ENST00000374040.7
    Conserved Domains (3) summary
    smart00220
    Location:645 → 898
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    cd06624
    Location:631 → 898
    STKc_ASK; Catalytic domain of the Serine/Threonine Kinase, Apoptosis signal-regulating kinase
    pfam13281
    Location:129 → 498
    DUF4071; Domain of unknown function (DUF4071)

  2. NM_004672.5 → NP_004663.3  mitogen-activated protein kinase kinase kinase 6 isoform 1

    See identical proteins and their annotated locations for NP_004663.3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
    Source sequence(s)
    AB167411, AF100318, AW771625, FO393419
    Consensus CDS
    CCDS299.1
    UniProtKB/Swiss-Prot
    A2ACE8, A2VDG4, A2VDG5, O95382, Q59HF4, Q5SSD4, Q75PK3, Q96B75
    Related
    ENSP00000350195.2, ENST00000357582.3
    Conserved Domains (3) summary
    smart00220
    Location:653 → 906
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    cd06624
    Location:639 → 906
    STKc_ASK; Catalytic domain of the Serine/Threonine Kinase, Apoptosis signal-regulating kinase
    pfam13281
    Location:129 → 506
    DUF4071; Domain of unknown function (DUF4071)

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000001.11 Reference GRCh38.p14 Primary Assembly

    Range
    27355184..27366961 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047433689.1 → XP_047289645.1  mitogen-activated protein kinase kinase kinase 6 isoform X1

    Related
    ENST00000493901.6

  2. XM_047433695.1 → XP_047289651.1  mitogen-activated protein kinase kinase kinase 6 isoform X3

  3. XM_047433692.1 → XP_047289648.1  mitogen-activated protein kinase kinase kinase 6 isoform X2

  4. XM_017002772.2 → XP_016858261.1  mitogen-activated protein kinase kinase kinase 6 isoform X4

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060925.1 Alternate T2T-CHM13v2.0

    Range
    27196422..27208199 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054339514.1 → XP_054195489.1  mitogen-activated protein kinase kinase kinase 6 isoform X1

  2. XM_054339516.1 → XP_054195491.1  mitogen-activated protein kinase kinase kinase 6 isoform X3

  3. XM_054339515.1 → XP_054195490.1  mitogen-activated protein kinase kinase kinase 6 isoform X2

  4. XM_054339517.1 → XP_054195492.1  mitogen-activated protein kinase kinase kinase 6 isoform X4

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_145319.1: Suppressed sequence

    Description
    NM_145319.1: This RefSeq record was removed by NCBI staff. Contact info@ncbi.nlm.nih.gov for further information.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
O95382.3 GenPept UniProtKB/Swiss-Prot:O95382

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