MAP3K6 (mitogen-activated protein kinase kinase kinase 6)

Gene

• Entrez ID: 9064
• Gene name: Mitogen-activated protein kinase kinase kinase 6
• Gene symbol: MAP3K6
• Synonyms (NCBI Gene): ASK2, MAPKKK6, MEKK6
• Chromosome: 1
• Chromosome location: 1p36.11
• 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 spli

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs34008139	G>-,GG	Likely-pathogenic	Non coding transcript variant, coding sequence variant, frameshift variant, genic downstream transcript variant
rs768616209	G>-	Likely-pathogenic	Non coding transcript variant, coding sequence variant, frameshift variant, genic downstream transcript variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT049479	hsa-miR-92a-3p	CLASH	23622248
MIRT736712	hsa-miR-4492	RNA-seq, qRT-PCR, Flow cytometry	32620026
MIRT2036729	hsa-miR-1273g	CLIP-seq
MIRT2036730	hsa-miR-4768-5p	CLIP-seq
MIRT2390578	hsa-miR-4691-5p	CLIP-seq
MIRT2390579	hsa-miR-516a-3p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000165	Process	MAPK cascade	IEA
GO:0000166	Function	Nucleotide binding	IEA
GO:0000287	Function	Magnesium ion binding	IDA	9875215
GO:0004672	Function	Protein kinase activity	IEA
GO:0004674	Function	Protein serine/threonine kinase activity	IEA
GO:0004709	Function	MAP kinase kinase kinase activity	IBA
GO:0004709	Function	MAP kinase kinase kinase activity	IDA	9875215
GO:0004709	Function	MAP kinase kinase kinase activity	IEA
GO:0004709	Function	MAP kinase kinase kinase activity	TAS	9875215
GO:0005515	Function	Protein binding	IPI	19935702, 28514442, 32707033, 33961781, 36931259
GO:0005524	Function	ATP binding	IDA	9875215
GO:0005524	Function	ATP binding	IEA
GO:0006468	Process	Protein phosphorylation	IDA	9875215
GO:0007165	Process	Signal transduction	TAS	9875215
GO:0007254	Process	JNK cascade	IBA
GO:0016301	Function	Kinase activity	IEA
GO:0016740	Function	Transferase activity	IEA
GO:0038066	Process	P38MAPK cascade	IBA
GO:0046872	Function	Metal ion binding	IEA
GO:0106310	Function	Protein serine kinase activity	IEA

Other IDs

• MIM: 604468
• HGNC: 6858
• e!Ensembl: ENSG00000142733

Protein

• UniProt ID: O95382
• Protein name: Mitogen-activated protein kinase kinase kinase 6 (EC 2.7.11.25) (Apoptosis signal-regulating kinase 2)
• Protein function: Component of a protein kinase signal transduction cascade. Activates the JNK, but not ERK or p38 kinase pathways.
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF13281	DUF4071	129 → 507	Domain of unknown function (DUF4071)	Family
  PF19039	ASK_PH	521 → 620	ASK kinase PH domain	Domain
  PF00069	Pkinase	649 → 906	Protein kinase domain	Domain

• Sequence:

  MAGPCPRSGAERAGSCWQDPLAVALSRGRQLAAPPGRGCARSRPLSVVYVLTREPQPGLE
  PREGTEAEPLPLRCLREACAQVPRPRPPPQLRSLPFGTLELGDTAALDAFYNADVVVLEV
  SSSLVQPSLFYHLGVRESFSMTNNVLLCSQADLPDLQALREDVFQKNSDCVGSYTLIPYV
  VTATGRVLCGDAGLLRGLADGLVQAGVGTEALLTPLVGRLARLLEATPTDSCGYFRETIR
  RDIRQARERFSGPQLRQELARLQRRLDSVELLSPDIIMNLLLSYRDVQDYSAIIELVETL
  QALPTCDVAEQHNVCFHYTFALNRRNRPGDRAKALSVLLPLVQLEGSVAPDLYCMCGRIY
  KDMFFSSGFQDAGHREQAYHWYRKAFDVEPSLHSGINAAVLLIAAGQHFEDSKELRLIGM
  KLGCLLARKGCVEKMQYYWDVGFYLGAQILANDPTQVVLAAEQLYKLNAPIWYLVSVMET
  FLLYQHFRPTPEPPGGPPRRAHFWLHFLLQSCQPFKTACAQGDQCLVLVLEMNKVLLPAK
  LEVRGTDPVSTVTLSLLEPETQDIPSSWTFPVASICGVSASKRDERCCFLYALPPAQDVQ
  LCFPSVGHCQWFCGLIQAWVTNPDSTAPAEEAEGAGEMLEFDYEYTETGERLVLGKGTYG
  VVYAGRDRHTRVRIAIKEIPERDSRFSQPLHEEIALHRRLRHKNIVRYLGSASQGGYLKI
  FMEEVPGGSLSSLLRSVWGPLKDNESTISFYTRQILQGLGYLHDNHIVHRDIKGDNVLIN
  TFSGLLKISDFGTSKRLAGITPCTETFTGTLQYMAPEIIDQGPRGYGKAADIWSLGCTVI
  EMATGRPPFHELGSPQAAMFQVGMYKVHPPMPSSLSAEAQAFLLRTFEPDPRLRASAQTL
  LGDPFLQPGKRSRSPSSPRHAPRPSDAPSASPTPSANSTTQSQTFPCPQAPSQHPPSPPK
  RCLSYGGTSQLRVPEEPAAEEPASPEESSGLSLLHQESKRRAMLAAVLEQELPALAENLH
  QEQKQEQGARLGRNHVEELLRCLGAHIHTPNRRQLAQELRALQGRLRAQGLGPALLHRPL
  FAFPDAVKQILRKRQIRPHWMFVLDSLLSRAVRAALGVLGPEVEKEAVSPRSEELSNEGD
  SQQSPGQQSPLPVEPEQGPAPLMVQLSLLRAETDRLREILAGKEREYQALVQRALQRLNE
  EARTYVLAPEPPTALSTDQGLVQWLQELNVDSGTIQMLLNHSFTLHTLLTYATRDDLIYT
  RIRGGMVCRIWRAILAQRAGSTPVTSGP

• Sequence length: 1288

Pathways

KEGG:

MAPK signaling pathway

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cholangiocarcinoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Chronic lymphocytic leukemia/small lymphocytic lymphoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Clear cell carcinoma of kidney	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GASTRIC CANCER	—	GenCC	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lymphoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of urinary bladder	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MAP3K6-related disorder	Benign; Likely benign; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Melanoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Nonpapillary renal cell carcinoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Squamous cell carcinoma of the head and neck	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyroid cancer, nonmedullary, 1	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uveal melanoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Breast Neoplasms	Breast neoplasm	Pubtator	33517263	Associate	★☆☆☆☆ Found in Text Mining only
Endometrioid carcinoma ovary	Ovarian endometrioid carcinoma	UNIPROT_DG			★☆☆☆☆ Found in Text Mining only
Hereditary Diffuse Gastric Cancer	Gastric Cancer	BEFREE	25340522		★☆☆☆☆ Found in Text Mining only
Hereditary Diffuse Gastric Cancer	Gastric Cancer	ORPHANET_DG	25340522		★☆☆☆☆ Found in Text Mining only
Hereditary diffuse gastric cancer	Gastric Cancer	Orphanet			★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	UNIPROT_DG			★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	19246638, 21097718, 25340522		★☆☆☆☆ Found in Text Mining only
Prostatic Intraepithelial Neoplasia	Prostatic intraepithelial neoplasia	Pubtator	32740981	Associate	★☆☆☆☆ Found in Text Mining only
Stomach Neoplasms	Stomach neoplasms	Pubtator	21097718, 25340522, 29330337	Associate	★☆☆☆☆ Found in Text Mining only