MAPK6

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

Basic information

Region (hg38): 15:51952105-52067375

Previous symbols: [ "PRKM6" ]

Links

ENSG00000069956 ∙ NCBI:5597 ∙ OMIM:602904 ∙ HGNC:6879 ∙ Uniprot:Q16659 ∙ 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 MAPK6 gene.

• Inborn genetic diseases (16 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MAPK6 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			15	1		16
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	15	1	0

Variants in MAPK6

This is a list of pathogenic ClinVar variants found in the MAPK6 region.

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

Position	Type	Phenotype	Significance	ClinVar
15-51953258-G-A		not specified	Uncertain significance (Mar 20, 2023)
15-51953266-G-A		LEO1-related disorder	Likely benign (Apr 11, 2019)
15-51954544-C-T		not specified	Uncertain significance (Aug 13, 2021)
15-51954547-C-G		not specified	Uncertain significance (May 24, 2023)
15-51954563-T-C		not specified	Uncertain significance (May 03, 2023)
15-51958747-A-G		LEO1-related disorder	Benign (May 20, 2019)
15-51959920-T-C		LEO1-related disorder	Uncertain significance (Mar 24, 2023)
15-51959946-G-A		LEO1-related disorder	Likely benign (Jun 24, 2019)
15-51959946-G-T		not specified	Uncertain significance (Jul 25, 2023)
15-51959969-T-C		not specified	Uncertain significance (Sep 26, 2022)
15-51960692-T-C		not specified	Uncertain significance (Aug 19, 2023)
15-51962414-C-T		LEO1-related disorder	Likely benign (Aug 21, 2019)
15-51962445-C-T		not specified	Uncertain significance (Nov 29, 2023)
15-51962485-T-C		LEO1-related disorder	Benign (Jan 14, 2020)
15-51965755-T-C		not specified	Uncertain significance (Feb 22, 2023)
15-51965799-T-C		not specified	Uncertain significance (Apr 25, 2022)
15-51965821-C-G		not specified	Uncertain significance (Jan 02, 2024)
15-51965874-T-A		not specified	Uncertain significance (Jan 16, 2024)
15-51965894-A-AT		LEO1-related disorder	Uncertain significance (Sep 08, 2022)
15-51965916-C-A		not specified	Uncertain significance (Dec 06, 2022)
15-51965917-G-A		not specified	Uncertain significance (Apr 07, 2022)
15-51965921-A-C		not specified	Uncertain significance (Aug 23, 2021)
15-51965939-T-G		not specified	Uncertain significance (Mar 07, 2024)
15-51965956-G-A		Male infertility with azoospermia or oligozoospermia due to single gene mutation	Likely pathogenic (Sep 01, 2023)
15-51965963-C-G		not specified	Uncertain significance (May 18, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MAPK6	protein_coding	protein_coding	ENST00000261845	5	114160

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.696	0.304	125722	0	24	125746	0.0000954

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.727	333	373	0.894	0.0000179	4825
Missense in Polyphen		56	101.98	0.54914		1406
Synonymous	-2.27	164	131	1.25	0.00000633	1303
Loss of Function	3.80	5	25.8	0.194	0.00000123	358

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000904	0.0000904
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000109	0.000109
Finnish	0.0000465	0.0000462
European (Non-Finnish)	0.000155	0.000123
Middle Eastern	0.000109	0.000109
South Asian	0.000131	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Atypical MAPK protein. Phosphorylates microtubule- associated protein 2 (MAP2) and MAPKAPK5. The precise role of the complex formed with MAPKAPK5 is still unclear, but the complex follows a complex set of phosphorylation events: upon interaction with atypical MAPKAPK5, ERK3/MAPK6 is phosphorylated at Ser-189 and then mediates phosphorylation and activation of MAPKAPK5, which in turn phosphorylates ERK3/MAPK6. May promote entry in the cell cycle (By similarity). {ECO:0000250}.
• Pathway: IL-17 signaling pathway - Homo sapiens (human);VEGF Signaling Pathway;Integrin-mediated Cell Adhesion;Signal Transduction of S1P Receptor;MAPK6-MAPK4 signaling;Angiopoietin Like Protein 8 Regulatory Pathway;ESC Pluripotency Pathways;Insulin Signaling;Regulation of Actin Cytoskeleton;Signal Transduction;MAPK6/MAPK4 signaling;MAPK family signaling cascades (Consensus)

Recessive Scores

• pRec: 0.271

Intolerance Scores

• loftool: 0.561
• rvis_EVS: -0.67
• rvis_percentile_EVS: 15.86

Haploinsufficiency Scores

• pHI: 0.744
• hipred: Y
• hipred_score: 0.518
• ghis: 0.596

Essentials

• essential_gene_CRISPR: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.993

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mapk6
• 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); growth/size/body region phenotype; homeostasis/metabolism 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); 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; respiratory system phenotype; skeleton phenotype

Gene ontology

• Biological process: MAPK cascade;protein phosphorylation;cell cycle;signal transduction;regulation of gene expression;intracellular signal transduction;positive regulation of dendritic spine development;cellular response to organic substance
• Cellular component: nucleus;nucleoplasm;cytoplasm;cytosol;septin cytoskeleton;protein-containing complex
• Molecular function: protein serine/threonine kinase activity;MAP kinase activity;protein binding;ATP binding;protein kinase binding;protein heterodimerization activity