MAP2K5

mitogen-activated protein kinase kinase 5, the group of Mitogen-activated protein kinase kinases

Basic information

Region (hg38): 15:67542702-67807117

Previous symbols: [ "PRKMK5" ]

Links

ENSG00000137764 ∙ NCBI:5607 ∙ OMIM:602520 ∙ HGNC:6845 ∙ Uniprot:Q13163 ∙ 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 MAP2K5 gene.

• Inborn genetic diseases (7 variants)
• not provided (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MAP2K5 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						0
missense			7			7
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					3	3
non coding						0
Total	0	0	7	0	0

Variants in MAP2K5

This is a list of pathogenic ClinVar variants found in the MAP2K5 region.

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

Position	Type	Phenotype	Significance	ClinVar
15-67543355-G-T		not specified	Uncertain significance (Jan 31, 2024)
15-67550089-C-T			Benign (Aug 16, 2018)
15-67563296-T-G		not specified	Uncertain significance (Dec 27, 2023)
15-67580796-A-G		not specified	Uncertain significance (Feb 21, 2024)
15-67586855-C-T		not specified	Uncertain significance (Feb 27, 2024)
15-67592963-G-A		not specified	Uncertain significance (Jun 06, 2023)
15-67646223-A-G			Benign (Jan 19, 2018)
15-67646403-A-G		not specified	Uncertain significance (Jun 12, 2023)
15-67646431-T-C		not specified	Uncertain significance (Mar 07, 2024)
15-67658571-A-G		not specified	Uncertain significance (Aug 12, 2022)
15-67658613-C-T		not specified	Uncertain significance (Nov 10, 2022)
15-67692480-C-T			Benign (Jul 31, 2018)
15-67703401-T-C		not specified	Uncertain significance (Apr 11, 2023)
15-67727946-G-A			Uncertain significance (Mar 01, 2024)
15-67806709-C-T		not specified	Uncertain significance (Dec 20, 2023)
15-67806734-A-G		not specified	Uncertain significance (Nov 19, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MAP2K5	protein_coding	protein_coding	ENST00000178640	22	264415

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00477	0.995	125728	0	20	125748	0.0000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.02	161	251	0.641	0.0000134	2916
Missense in Polyphen		41	88.882	0.46129		1057
Synonymous	0.0533	89	89.6	0.993	0.00000519	829
Loss of Function	3.84	11	35.8	0.308	0.00000177	421

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000185	0.000185
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000545	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000882	0.0000879
Middle Eastern	0.0000545	0.0000544
South Asian	0.000134	0.000131
Other	0.000329	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts as a scaffold for the formation of a ternary MAP3K2/MAP3K3-MAP3K5-MAPK7 signaling complex. Activation of this pathway appears to play a critical role in protecting cells from stress-induced apoptosis, neuronal survival and cardiac development and angiogenesis. {ECO:0000269|PubMed:7759517, ECO:0000269|PubMed:9384584}.
• Pathway: Oxytocin signaling pathway - Homo sapiens (human);Neurotrophin signaling pathway - Homo sapiens (human);Gap junction - Homo sapiens (human);Fluid shear stress and atherosclerosis - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);VEGF Signaling Pathway;EGF-Core;MicroRNAs in cardiomyocyte hypertrophy;Integrin-mediated Cell Adhesion;Signaling Pathways in Glioblastoma;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;Cardiac Hypertrophic Response;MAPK Signaling Pathway;Angiopoietin Like Protein 8 Regulatory Pathway;ESC Pluripotency Pathways;EGF-EGFR Signaling Pathway;Insulin Signaling;Signal Transduction;role of erk5 in neuronal survival pathway;mapkinase signaling pathway;IL-1 p38;IL-1 JNK;TLR p38;IL-7 signaling;Signaling by NTRK1 (TRKA);Signaling by NTRKs;EGFR1;ErbB1 downstream signaling;JAK STAT pathway and regulation;EPO signaling;Signalling to ERK5;TLR ECSIT MEKK1 JNK;TLR ECSIT MEKK1 p38;TNFalpha;TLR JNK;Signaling by Receptor Tyrosine Kinases;VEGF;Trk receptor signaling mediated by the MAPK pathway (Consensus)

Recessive Scores

• pRec: 0.219

Intolerance Scores

• loftool: 0.775
• rvis_EVS: -0.69
• rvis_percentile_EVS: 14.97

Haploinsufficiency Scores

• pHI: 0.384
• hipred: Y
• hipred_score: 0.651
• ghis: 0.621

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.999

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Map2k5
• Phenotype: embryo 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); normal 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); growth/size/body region phenotype; muscle phenotype; cellular phenotype

Zebrafish Information Network

• Gene name: map2k5
• Affected structure: optic tectum
• Phenotype tag: abnormal
• Phenotype quality: decreased size

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;activation of MAPK activity;signal transduction;heart development;peptidyl-tyrosine phosphorylation;signal transduction by protein phosphorylation;positive regulation of cell growth;stress-activated protein kinase signaling cascade;negative regulation of NF-kappaB transcription factor activity;activation of protein kinase activity;negative regulation of heterotypic cell-cell adhesion;negative regulation of cysteine-type endopeptidase activity involved in apoptotic process;negative regulation of interleukin-8 biosynthetic process;positive regulation of transcription by RNA polymerase II;positive regulation of epithelial cell proliferation;positive regulation of protein metabolic process;negative regulation of response to cytokine stimulus;ERK5 cascade;cellular response to growth factor stimulus;cellular response to laminar fluid shear stress;negative regulation of cell migration involved in sprouting angiogenesis;negative regulation of chemokine (C-X-C motif) ligand 2 production;negative regulation of extrinsic apoptotic signaling pathway in absence of ligand
• Cellular component: nucleus;cytoplasm;spindle;cytosol
• Molecular function: protein kinase activity;protein serine/threonine kinase activity;MAP kinase kinase activity;protein tyrosine kinase activity;protein binding;ATP binding;metal ion binding