MAP2K7

mitogen-activated protein kinase kinase 7, the group of Mitogen-activated protein kinase kinases

Basic information

Region (hg38): 19:7903842-7914478

Previous symbols: [ "PRKMK7" ]

Links

ENSG00000076984 ∙ NCBI:5609 ∙ OMIM:603014 ∙ HGNC:6847 ∙ Uniprot:O14733 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• schizophrenia (No Known Disease Relationship), mode of inheritance: Unknown

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MAP2K7 gene.

• Inborn genetic diseases (15 variants)
• not provided (13 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MAP2K7 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					7	7
missense			15			15
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1	1	2
non coding				1	3	4
Total	0	0	15	1	10

Variants in MAP2K7

This is a list of pathogenic ClinVar variants found in the MAP2K7 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-7903979-G-T		not specified	Uncertain significance (Jan 27, 2022)
19-7909785-G-T		not specified	Uncertain significance (Dec 01, 2022)
19-7909794-C-T		not specified	Uncertain significance (Jan 08, 2024)
19-7909830-C-T		not specified	Uncertain significance (Nov 08, 2022)
19-7909881-C-T		not specified	Uncertain significance (Feb 27, 2024)
19-7909883-C-T		not specified	Uncertain significance (Apr 17, 2023)
19-7910319-C-T			Benign (Dec 31, 2019)
19-7910344-C-T		not specified	Uncertain significance (Oct 28, 2023)
19-7910353-G-A		not specified	Uncertain significance (Jun 02, 2023)
19-7910571-A-G		not specified	Uncertain significance (Jul 20, 2021)
19-7910734-C-T			Benign (Jun 18, 2018)
19-7910754-G-A		not specified	Uncertain significance (Nov 22, 2021)
19-7910773-C-A			Benign (Dec 31, 2019)
19-7910773-C-T			Benign (Jan 11, 2018)
19-7910777-C-T		not specified	Uncertain significance (May 24, 2023)
19-7910778-G-A		not specified	Uncertain significance (Apr 25, 2022)
19-7911056-T-C		Neuroblastoma	other (May 01, 2016)
19-7911065-G-A		not specified	Uncertain significance (Sep 01, 2021)
19-7911099-C-T			Benign (Aug 08, 2018)
19-7911135-C-T			Benign (Aug 09, 2018)
19-7911169-G-C			Benign (Dec 31, 2019)
19-7911231-T-C			Benign (May 28, 2021)
19-7911241-C-G			Likely benign (Jun 13, 2018)
19-7911242-C-G			Benign (May 28, 2021)
19-7911322-A-G		not specified	Uncertain significance (Mar 23, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MAP2K7	protein_coding	protein_coding	ENST00000397979	11	10636

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.996	0.00448	120507	0	2	120509	0.00000830

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.80	146	277	0.527	0.0000190	2722
Missense in Polyphen		32	107.39	0.29799		970
Synonymous	-2.36	154	121	1.27	0.00000929	808
Loss of Function	3.98	1	20.4	0.0490	9.65e-7	242

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)	0.00000927	0.00000924
Middle Eastern	0.00	0.00
South Asian	0.0000331	0.0000331
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K4/MKK4, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4/MKK4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The monophosphorylation of JNKs on the Thr residue is sufficient to increase JNK activity indicating that MAP2K7/MKK7 is important to trigger JNK activity, while the additional phosphorylation of the Tyr residue by MAP2K4/MKK4 ensures optimal JNK activation. Has a specific role in JNK signal transduction pathway activated by proinflammatory cytokines. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis. {ECO:0000269|PubMed:9312068, ECO:0000269|PubMed:9372971, ECO:0000269|PubMed:9535930, ECO:0000269|Ref.5}.
• Pathway: Relaxin signaling pathway - Homo sapiens (human);T cell receptor signaling pathway - Homo sapiens (human);Fc epsilon RI signaling pathway - Homo sapiens (human);Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human);Neurotrophin signaling pathway - Homo sapiens (human);Tight junction - Homo sapiens (human);Influenza A - Homo sapiens (human);GnRH signaling pathway - Homo sapiens (human);ErbB signaling pathway - Homo sapiens (human);Protein processing in endoplasmic reticulum - Homo sapiens (human);TNF signaling pathway - Homo sapiens (human);Toll-like receptor signaling pathway - Homo sapiens (human);Fluid shear stress and atherosclerosis - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Osteoclast differentiation - Homo sapiens (human);Epstein-Barr virus infection - Homo sapiens (human);EGFR Inhibitor Pathway, Pharmacodynamics;Tacrolimus/Cyclosporine Pathway, Pharmacodynamics;VEGF Signaling Pathway;Intracellular Signalling Through Adenosine Receptor A2b and Adenosine;Intracellular Signalling Through Adenosine Receptor A2a and Adenosine;Fc Epsilon Receptor I Signaling in Mast Cells;EGF-Core;Regulation of toll-like receptor signaling pathway;MicroRNAs in cardiomyocyte hypertrophy;IL-1 signaling pathway;RANKL-RANK (Receptor activator of NFKB (ligand)) Signaling Pathway;Signaling Pathways in Glioblastoma;TNF alpha Signaling Pathway;Structural Pathway of Interleukin 1 (IL-1);Cardiac Hypertrophic Response;Photodynamic therapy-induced AP-1 survival signaling.;MAPK Signaling Pathway;ERK Pathway in Huntington,s Disease;T-Cell antigen Receptor (TCR) pathway during Staphylococcus aureus infection;VEGFA-VEGFR2 Signaling Pathway;Angiopoietin Like Protein 8 Regulatory Pathway;MAPK Cascade;Insulin Signaling;ErbB Signaling Pathway;Toll-like Receptor Signaling Pathway;Toll Like Receptor 7/8 (TLR7/8) Cascade;Interleukin-17 signaling;Disease;Signaling by Interleukins;hiv-1 nef: negative effector of fas and tnf;tnf/stress related signaling;keratinocyte differentiation;mapkinase signaling pathway;Cytokine Signaling in Immune system;Toll Like Receptor 9 (TLR9) Cascade;Oxidative Stress Induced Senescence;MyD88 cascade initiated on plasma membrane;Toll Like Receptor 10 (TLR10) Cascade;Toll Like Receptor 3 (TLR3) Cascade;Toll Like Receptor 5 (TLR5) Cascade;Toll-Like Receptors Cascades;Cellular Senescence;Fas;Cellular responses to stress;FCERI mediated MAPK activation;Uptake and actions of bacterial toxins;Fc epsilon receptor (FCERI) signaling;Uptake and function of anthrax toxins;Infectious disease;Innate Immune System;Immune System;IL-1 p38;IL-1 JNK;IL1;TLR p38;Cellular responses to external stimuli;IL-7 signaling;JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1;fc epsilon receptor i signaling in mast cells;EGFR1;MAP kinase activation;TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation;MyD88 dependent cascade initiated on endosome;JAK STAT pathway and regulation;EPO signaling;TLR ECSIT MEKK1 JNK;TLR ECSIT MEKK1 p38;TLR JNK;TRIF(TICAM1)-mediated TLR4 signaling ;MyD88-independent TLR4 cascade ;Toll Like Receptor 4 (TLR4) Cascade;TNF;VEGF;MyD88:Mal cascade initiated on plasma membrane;Toll Like Receptor TLR1:TLR2 Cascade;Toll Like Receptor TLR6:TLR2 Cascade;Toll Like Receptor 2 (TLR2) Cascade;HIV-1 Nef: Negative effector of Fas and TNF-alpha;RAC1 signaling pathway;TNF receptor signaling pathway ;CDC42 signaling events;Fc-epsilon receptor I signaling in mast cells;Reelin signaling pathway;FAS (CD95) signaling pathway;PDGFR-beta signaling pathway;Cellular roles of Anthrax toxin (Consensus)

Intolerance Scores

• loftool: 0.0231
• rvis_EVS: -0.51
• rvis_percentile_EVS: 21.41

Haploinsufficiency Scores

• pHI: 0.815
• hipred: Y
• hipred_score: 0.775
• ghis: 0.606

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 1.00

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Map2k7
• 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); vision/eye phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); hematopoietic system 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); normal phenotype; neoplasm; endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype; cellular phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: map2k7
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: decreased length

Gene ontology

• Biological process: activation of MAPK activity;apoptotic process;response to osmotic stress;signal transduction;activation of JUN kinase activity;response to heat;response to UV;peptidyl-tyrosine phosphorylation;signal transduction by protein phosphorylation;stress-activated protein kinase signaling cascade;activation of protein kinase activity;positive regulation of telomere maintenance via telomerase;response to tumor necrosis factor;positive regulation of transcription, DNA-templated;stress-activated MAPK cascade;positive regulation of telomerase activity;positive regulation of ERK1 and ERK2 cascade;positive regulation of telomere capping
• Cellular component: nucleus;cytoplasm;cytosol
• Molecular function: magnesium ion binding;protein serine/threonine kinase activity;MAP kinase kinase activity;protein tyrosine kinase activity;protein binding;ATP binding;JUN kinase kinase activity;enzyme binding;protein kinase binding;protein phosphatase binding