MAPK7

protein-coding

mitogen-activated protein kinase 7, the group of Mitogen-activated protein kinases|Armadillo like helical domain containing

Gene summary

The protein encoded by this gene is a member of the MAP kinase family. MAP kinases act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. This kinase is specifically activated by mitogen-activated protein kinase kinase 5 (MAP2K5/MEK5). It is involved in the downstream signaling processes of various receptor molecules including receptor type kinases, and G protein-coupled receptors. In response to extracelluar signals, this kinase translocates to cell nucleus, where it regulates gene expression by phosphorylating, and activating different transcription factors. Four alternatively spliced transcript variants of this gene encoding two distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

Previous symbols:

PRKM7

MANE transcript

NM_002749.4

Inheritance

—

ClinVar variants

P:3U:115B:5

Top phenotype

Scoliosis, isolated, susceptibility to, 1

gnomAD constraint

pLI —, LoF o/e 0.35

Max pathogenic AF

—

Genomic locus

chr17:19,377,721-19,383,544

External References & Databases

Ensembl (ENSG00000166484)

Transcript & Mutation Effects

hg38 • Region Span ~5.8 kb

Loading mutation effect viewer...

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 MAPK7 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 116

Scoliosis, isolated, susceptibility to, 1Total: 3

not providedTotal: 2

Type 2 diabetes mellitusTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002749.4. 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				2 clinvar		2
missense	3 clinvar		114 clinvar	3 clinvar		120
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	3	0	115	5	0	123

Highest pathogenic variant AF is 0.00022180972

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 38 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002749.4	RefSeq	NP_002740.2	6	MANE Select
ENST00000395604.8	Ensembl	ENSP00000378968.3	6	MANE Select
NM_139032.3	RefSeq	NP_620601.1	4	Standard
NM_139033.3	RefSeq	NP_620602.2	6	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
mapk7	Danio rerio	Structure: vertebra Quality: decreased occurrence abnormal

Gene / Model

Organism

Observed Phenotype

mapk7

Danio rerio

Structure: vertebra

Quality: decreased occurrence

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Oxytocin signaling pathway - Homo sapiens (human)
Neurotrophin signaling pathway - Homo sapiens (human)
GnRH signaling pathway - Homo sapiens (human)
Gap junction - Homo sapiens (human)
Fluid shear stress and atherosclerosis - Homo sapiens (human)

Biological Process

MAPK cascade
cell cycle
signal transduction
axon guidance
regulation of gene expression

Molecular Function

protein serine/threonine kinase activity
MAP kinase activity
protein binding
ATP binding
mitogen-activated protein kinase binding

Cellular Component

nucleus
nucleoplasm
cytoplasm
cytosol
PML body

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000308406
Coding exons: 6
Length: 5824
Individuals with no LoFs: 125736
Homozygous LoFs: 0
Heterozygous LoFs: 12
Defined: 125748
p: 0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.80	402	517	0.777	0.0000318	5195
Missense (PolyPhen)		36	57.051	0.63101		598
Synonymous	-1.61	242	212	1.14	0.0000126	1819
Loss of Function	3.07	9	25.8	0.349	0.00000133	280

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000063	0.000062	rare
South Asian	0.000038	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays a role in various cellular processes such as proliferation, differentiation and cell survival. The upstream activator of MAPK7 is the MAPK kinase MAP2K5. Upon activation, it translocates to the nucleus and phosphorylates various downstream targets including MEF2C. EGF activates MAPK7 through a Ras- independent and MAP2K5-dependent pathway. May have a role in muscle cell differentiation. May be important for endothelial function and maintenance of blood vessel integrity. MAP2K5 and MAPK7 interact specifically with one another and not with MEK1/ERK1 or MEK2/ERK2 pathways. Phosphorylates SGK1 at Ser-78 and this is required for growth factor-induced cell cycle progression. Involved in the regulation of p53/TP53 by disrupting the PML-MDM2 interaction. {ECO:0000269|PubMed:11254654, ECO:0000269|PubMed:11278431, ECO:0000269|PubMed:22869143, ECO:0000269|PubMed:9384584, ECO:0000269|PubMed:9790194}.;

Recessive Scores

pRec: 0.206

Intolerance Scores

LoFtool: 0.504
RVIS EVS: -1.31
RVIS percentile EVS: 4.89

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.996

Gene Damage Prediction

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