MAPK6

protein-coding

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

Gene summary

The protein encoded by this gene is a member of the Ser/Thr protein kinase family, and is most closely related to mitogen-activated protein kinases (MAP kinases). MAP kinases also known as extracellular signal-regulated kinases (ERKs), are activated through protein phosphorylation cascades and act as integration points for multiple biochemical signals. This kinase is localized in the nucleus, and has been reported to be activated in fibroblasts upon treatment with serum or phorbol esters. [provided by RefSeq, Jul 2008]

Previous symbols:

PRKM6

MANE transcript

NM_002748.4

Inheritance

—

ClinVar variants

U:74B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.19

Max pathogenic AF

—

Genomic locus

chr15:51,952,106-52,067,375

External References & Databases

Ensembl (ENSG00000069956)

Transcript & Mutation Effects

hg38 • Region Span ~115.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MAPK6 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 70

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002748.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar			1
missense			73 clinvar	1 clinvar		74
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	74	1	0	75

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 46 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002748.4	RefSeq	NP_002739.1	5	MANE Select
ENST00000261845.7	Ensembl	ENSP00000261845.5	5	MANE Select
ENST00000680066.1	Ensembl	ENSP00000505862.1	5	Standard
ENST00000680066.2	Ensembl	ENSP00000505862.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

IL-17 signaling pathway - Homo sapiens (human)
VEGF Signaling Pathway
Integrin-mediated Cell Adhesion
Signal Transduction of S1P Receptor
MAPK6-MAPK4 signaling

Biological Process

MAPK cascade
protein phosphorylation
cell cycle
signal transduction
regulation of gene expression

Molecular Function

protein serine/threonine kinase activity
MAP kinase activity
protein binding
ATP binding
protein kinase binding

Cellular Component

nucleus
nucleoplasm
cytoplasm
cytosol
septin cytoskeleton

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000261845
Coding exons: 5
Length: 114160
Individuals with no LoFs: 125722
Homozygous LoFs: 0
Heterozygous LoFs: 24
Defined: 125746
p: 0.0000954

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.727	333	373	0.894	0.0000179	4825
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00011	0.00011	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00015	0.00012	rare
South Asian	0.00013	0.00013	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.271

Intolerance Scores

LoFtool: 0.561
RVIS EVS: -0.67
RVIS percentile EVS: 15.86

Essentials

Essential (CRISPR): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.993

Gene Damage Prediction

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