MAP3K2

mitogen-activated protein kinase kinase kinase 2, the group of Mitogen-activated protein kinase kinase kinases

Basic information

Region (hg38): 2:127298668-127388465

Previous symbols: [ "MEKK2" ]

Links

ENSG00000169967 ∙ NCBI:10746 ∙ OMIM:609487 ∙ HGNC:6854 ∙ Uniprot:Q9Y2U5 ∙ 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 MAP3K2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MAP3K2 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					2	2
missense			17			17
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	17	0	2

Variants in MAP3K2

This is a list of pathogenic ClinVar variants found in the MAP3K2 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-127307620-C-T		not specified	Uncertain significance (Sep 27, 2021)
2-127307653-G-A		not specified	Uncertain significance (May 02, 2024)
2-127307674-A-G		not specified	Uncertain significance (Oct 12, 2022)
2-127307698-T-C		not specified	Uncertain significance (Dec 04, 2024)
2-127307740-T-C		MAP3K2-related condition	Uncertain significance (Jun 27, 2024)
2-127308589-T-C		not specified	Uncertain significance (Jan 04, 2024)
2-127308665-C-G		not specified	Uncertain significance (Jul 25, 2023)
2-127308684-C-G		not specified	Uncertain significance (Nov 18, 2022)
2-127308687-A-C		not specified	Uncertain significance (May 30, 2024)
2-127308760-C-T		not specified	Uncertain significance (Mar 06, 2023)
2-127314883-C-T		not specified	Uncertain significance (Oct 29, 2021)
2-127317648-A-T		not specified	Uncertain significance (Dec 20, 2023)
2-127317689-A-G			Benign (Jul 17, 2018)
2-127318189-C-T		not specified	Uncertain significance (Mar 14, 2023)
2-127318240-C-T		not specified	Uncertain significance (Apr 11, 2023)
2-127318251-T-C		not specified	Uncertain significance (Aug 02, 2021)
2-127322108-C-T		not specified	Uncertain significance (Jul 08, 2024)
2-127322212-G-T			Benign (Mar 29, 2018)
2-127322234-C-A		not specified	Uncertain significance (Mar 07, 2024)
2-127326727-A-T		not specified	Uncertain significance (Dec 08, 2021)
2-127326751-G-A		not specified	Uncertain significance (May 20, 2024)
2-127329962-G-C		not specified	Uncertain significance (Oct 20, 2024)
2-127329996-C-T		not specified	Uncertain significance (Aug 28, 2024)
2-127329999-A-T		not specified	Uncertain significance (Jul 06, 2021)
2-127330412-C-A		not specified	Uncertain significance (Apr 12, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MAP3K2	protein_coding	protein_coding	ENST00000409947	16	89736

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.00000820	124638	0	3	124641	0.0000120

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.31	198	313	0.633	0.0000159	4011
Missense in Polyphen		67	134.69	0.49744		1720
Synonymous	0.190	104	106	0.977	0.00000518	1137
Loss of Function	5.31	0	32.9	0.00	0.00000188	436

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000288	0.0000265
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of a protein kinase signal transduction cascade. Regulates the JNK and ERK5 pathways by phosphorylating and activating MAP2K5 and MAP2K7 (By similarity). Plays a role in caveolae kiss-and-run dynamics. {ECO:0000250, ECO:0000269|PubMed:10713157, ECO:0000269|PubMed:16001074}.
• Pathway: GnRH signaling pathway - Homo sapiens (human);Gap junction - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);EGF-Core;IL-1 signaling pathway;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;MAPK Signaling Pathway;Angiopoietin Like Protein 8 Regulatory Pathway;MAPK Cascade;EGF-EGFR Signaling Pathway;Insulin Signaling;mapkinase signaling pathway;IL1;IL-7 signaling;EGFR1;ErbB1 downstream signaling;JAK STAT pathway and regulation;EPO signaling;TNFalpha;VEGF;Trk receptor signaling mediated by the MAPK pathway (Consensus)

Recessive Scores

• pRec: 0.170

Intolerance Scores

• rvis_EVS: -0.29
• rvis_percentile_EVS: 33.2

Haploinsufficiency Scores

• pHI: 0.612
• hipred: Y
• hipred_score: 0.786
• ghis: 0.597

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.941

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Map3k2
• Phenotype: homeostasis/metabolism phenotype; reproductive system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; immune system phenotype

Gene ontology

• Biological process: activation of MAPKK activity;activation of MAPK activity;protein phosphorylation;activation of JUN kinase activity;signal transduction by protein phosphorylation;stress-activated protein kinase signaling cascade;activation of protein kinase activity;positive regulation of transcription, DNA-templated;cellular response to mechanical stimulus
• Cellular component: nucleoplasm;cytoplasm;cytosol
• Molecular function: protein kinase activity;protein serine/threonine kinase activity;MAP kinase kinase kinase activity;protein binding;ATP binding;protein kinase binding;metal ion binding