MAP3K4

mitogen-activated protein kinase kinase kinase 4, the group of Mitogen-activated protein kinase kinase kinases

Basic information

Region (hg38): 6:160991726-161117385

Previous symbols: [ "MEKK4" ]

Links

ENSG00000085511 ∙ NCBI:4216 ∙ OMIM:602425 ∙ HGNC:6856 ∙ Uniprot:Q9Y6R4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MAP3K4 gene.

• Inborn genetic diseases (58 variants)
• not provided (7 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MAP3K4 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1		1
missense			57	2	1	60
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1	1	2
non coding						0
Total	0	0	57	3	1

Variants in MAP3K4

This is a list of pathogenic ClinVar variants found in the MAP3K4 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
6-160991962-C-T		not specified	Uncertain significance (Oct 05, 2023)
6-160992010-C-T		not specified	Uncertain significance (Sep 29, 2023)
6-160992025-C-T		not specified	Uncertain significance (Dec 13, 2023)
6-160992032-C-T		not specified	Uncertain significance (Mar 29, 2022)
6-160992046-G-A		not specified	Uncertain significance (Apr 26, 2023)
6-160992068-G-T		not specified	Uncertain significance (Dec 16, 2022)
6-160992070-T-C		not specified	Uncertain significance (Sep 28, 2022)
6-160992070-T-G		not specified	Uncertain significance (May 31, 2023)
6-161034273-T-G		not specified	Uncertain significance (Aug 08, 2023)
6-161034293-A-G		not specified	Uncertain significance (Sep 26, 2022)
6-161034340-G-C		not specified	Uncertain significance (Mar 02, 2023)
6-161034363-C-G		not specified	Uncertain significance (Apr 14, 2022)
6-161034381-T-G		not specified	Uncertain significance (Dec 06, 2022)
6-161034387-G-A		not specified	Uncertain significance (May 18, 2023)
6-161048646-A-G		not specified	Uncertain significance (Jul 19, 2023)
6-161048649-A-C		not specified	Uncertain significance (Dec 27, 2023)
6-161048684-T-C		not specified	Uncertain significance (Jul 08, 2022)
6-161048736-G-A		not specified	Uncertain significance (Dec 21, 2023)
6-161048787-G-T		not specified	Uncertain significance (Jul 20, 2021)
6-161048820-A-C		not specified	Uncertain significance (May 26, 2023)
6-161048867-C-G		not specified	Uncertain significance (Aug 08, 2023)
6-161048884-G-A		not specified	Uncertain significance (Aug 21, 2023)
6-161048886-C-T		not specified	Uncertain significance (Jan 23, 2024)
6-161048888-A-G		not specified	Uncertain significance (Sep 27, 2021)
6-161048895-G-A		not specified	Uncertain significance (May 24, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MAP3K4	protein_coding	protein_coding	ENST00000392142	27	125659

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	7.25e-8	125715	0	33	125748	0.000131

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.87	653	895	0.730	0.0000485	10583
Missense in Polyphen		153	353.08	0.43333		4230
Synonymous	-0.643	343	328	1.05	0.0000188	3043
Loss of Function	7.65	9	85.2	0.106	0.00000479	998

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000290	0.0000290
Ashkenazi Jewish	0.00	0.00
East Asian	0.000222	0.000217
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000212	0.000202
Middle Eastern	0.000222	0.000217
South Asian	0.0000655	0.0000653
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of a protein kinase signal transduction cascade. Activates the CSBP2, P38 and JNK MAPK pathways, but not the ERK pathway. Specifically phosphorylates and activates MAP2K4 and MAP2K6. {ECO:0000269|PubMed:12052864, ECO:0000269|PubMed:9305639}.
• Pathway: GnRH signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Intracellular Signalling Through Adenosine Receptor A2b and Adenosine;Intracellular Signalling Through Adenosine Receptor A2a and Adenosine;EGF-Core;MAPK Signaling Pathway;Angiopoietin Like Protein 8 Regulatory Pathway;EGF-EGFR Signaling Pathway;Insulin Signaling;G13 Signaling Pathway;DNA Damage Response (only ATM dependent);mapkinase signaling pathway;EGFR1;IL6;p38 MAPK signaling pathway (Consensus)

Recessive Scores

• pRec: 0.114

Intolerance Scores

• loftool: 0.579
• rvis_EVS: -1.08
• rvis_percentile_EVS: 7.32

Haploinsufficiency Scores

• pHI: 0.747
• hipred: Y
• hipred_score: 0.704
• ghis: 0.600

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.986

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Map3k4
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; skeleton phenotype; immune system phenotype; embryo phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; growth/size/body region phenotype; hematopoietic system phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype

Gene ontology

• Biological process: MAPK cascade;activation of MAPKK activity;placenta development;response to UV-C;regulation of gene expression;male germ-line sex determination;signal transduction by protein phosphorylation;stress-activated protein kinase signaling cascade;activation of protein kinase activity;positive regulation of telomere maintenance via telomerase;intracellular signal transduction;positive regulation of JUN kinase activity;positive regulation of telomerase activity;chorionic trophoblast cell differentiation;positive regulation of p38MAPK cascade;positive regulation of telomere capping
• Cellular component: cytoplasm;perinuclear region of cytoplasm
• Molecular function: protein serine/threonine kinase activity;MAP kinase kinase kinase activity;protein binding;ATP binding;metal ion binding