MAP3K6

mitogen-activated protein kinase kinase kinase 6, the group of Mitogen-activated protein kinase kinase kinases

Basic information

Region (hg38): 1:27355184-27366961

Links

ENSG00000142733 ∙ NCBI:9064 ∙ OMIM:604468 ∙ HGNC:6858 ∙ Uniprot:O95382 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Transcripts

Transcript IDs starting with ENST are treated as Ensembl, all others as RefSeq. Showing 4 of 15.

Transcript ID	Protein ID	Coding exons	MANE Select	MANE Plus Clinical
NM_004672.5	NP_004663.3	29	yes	-
ENST00000357582.3	ENSP00000350195.2	29	yes	-
NM_001297609.2	NP_001284538.1	28	-	-
ENST00000374040.7	ENSP00000363152.2	28	-	-

Phenotypes

GenCC

Source: genCC

• hereditary diffuse gastric adenocarcinoma (Supportive), mode of inheritance: AD
• gastric cancer (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Familial gastric cancer	AD	Oncologic	Awareness of the risk of diffuse gastric cancer may allow preventive measures and early diagnosis and treatment	Oncologic	25340522

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MAP3K6 gene.

• not_specified (207 variants)
• MAP3K6-related_disorder (25 variants)
• not_provided (19 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MAP3K6 gene is commonly pathogenic or not. These statistics are base on transcript: NM_004672.5. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			7	10	3	20
missense			201	11	7	219
nonsense			1			1
start loss						0
frameshift		1	1			2
splice donor/acceptor (+/-2bp)			7	1		8
Total	0	1	217	22	10

Highest pathogenic variant AF is 0.000048335343

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MAP3K6	protein_coding	protein_coding	ENST00000493901	29	11709

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		124657	4	1087	125748	0.00435

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.24	651	746	0.872	0.0000478	8159
Missense in Polyphen		189	237.01	0.79743		2589
Synonymous	1.99	271	316	0.857	0.0000196	2765
Loss of Function	3.05	36	61.9	0.581	0.00000299	705

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00543	0.00539
Ashkenazi Jewish	0.00282	0.00268
East Asian	0.00132	0.00131
Finnish	0.0104	0.0102
European (Non-Finnish)	0.00506	0.00485
Middle Eastern	0.00132	0.00131
South Asian	0.00266	0.00255
Other	0.00421	0.00408

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of a protein kinase signal transduction cascade. Activates the JNK, but not ERK or p38 kinase pathways. {ECO:0000269|PubMed:17210579, ECO:0000269|PubMed:9875215}.
• Pathway: MAPK signaling pathway - Homo sapiens (human);EGF-Core;MAPK Signaling Pathway;Angiopoietin Like Protein 8 Regulatory Pathway;Insulin Signaling;p38 MAPK signaling pathway (Consensus)

Recessive Scores

• pRec: 0.108

Intolerance Scores

• loftool: 0.849
• rvis_EVS: 0.37
• rvis_percentile_EVS: 74.78

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.976

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium

Gene ontology

• Biological process: activation of MAPKK activity;protein phosphorylation;signal transduction;activation of JUN kinase activity
• Molecular function: magnesium ion binding;protein kinase activity;MAP kinase kinase kinase activity;ATP binding