MAPK7

Chr 17

mitogen-activated protein kinase 7

Also known as: BMK1, ERK4, ERK5, PRKM7

NCBI Gene: 5598ENSG00000166484UniProt: Q13164

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]

230
ClinVar variants
102
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— MAPK7
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.35) despite low pLI — interpret in context.
📋
ClinVar Variants
102 Pathogenic / Likely Pathogenic· 123 VUS of 230 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.61LOEUF
pLI 0.003
Z-score 3.07
OE 0.35 (0.21–0.61)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.80Z-score
OE missense 0.78 (0.71–0.84)
402 obs / 517.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.35 (0.21–0.61)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.78 (0.71–0.84)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.14
0≤1.21.6
LoF obs/exp: 9 / 25.8Missense obs/exp: 402 / 517.2Syn Z: -1.61

ClinVar Variant Classifications

230 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic100
Likely Pathogenic2
VUS123
Likely Benign5
100
Pathogenic
2
Likely Pathogenic
123
VUS
5
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
3
97
0
100
Likely Pathogenic
0
0
2
0
2
VUS
0
110
13
0
123
Likely Benign
0
3
0
2
5
Benign
0
0
0
0
0
Total01161122230

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

MAPK7 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Proteomic Characterization Identifies Clinically Relevant Subgroups of Gastrointestinal Stromal Tumors.
Sun M et al.·Gastroenterology
2024
Reciprocal regulation of endothelial-mesenchymal transition by MAPK7 and EZH2 in intimal hyperplasia and coronary artery disease.
Vanchin B et al.·Sci Rep
2021
Mutant MAPK7-Induced Idiopathic Scoliosis is Linked to Impaired Osteogenesis.
Zhou T et al.·Cell Physiol Biochem
2018
The Investigation of MAPK7 Gene Variations in Colorectal Cancer Risk.
Cacina C et al.·In Vivo
2023
Targeting the MAPK7/MMP9 axis for metastasis in primary bone cancer.
Green D et al.·Oncogene
2020
Role of MAPK7 in cell proliferation and metastasis in ovarian cancer.
Dai J et al.·Int J Clin Exp Pathol
2015
MAPK7 variants related to prognosis and chemotherapy response in osteosarcoma.
Tesser-Gamba F et al.·Ann Diagn Pathol
2020
MAPK7 gene controls proliferation, migration and cell invasion in osteosarcoma.
Tesser-Gamba F et al.·Mol Carcinog
2016
Identification of De Novo JAK2 and MAPK7 Mutations Related to Autism Spectrum Disorder Using Whole-Exome Sequencing in a Chinese Child and Adolescent Trio-Based Sample.
Jiao J et al.·J Mol Neurosci
2020
Rare coding variants in MAPK7 predispose to adolescent idiopathic scoliosis.
Gao W et al.·Hum Mutat
2017
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Machine learning-guided discovery of mitogen-activated protein kinase 7 (MAPK7 inhibitors): integrating virtual screening, docking, and molecular dynamics simulations.
Hayat C et al.·In Silico Pharmacol
2026
Mapk7 enhances osteogenesis and suppresses adipogenesis by activating Lrp6/β-catenin signaling axis in mesenchymal stem cells.
Li C et al.·Commun Biol
2025🔓 Open Access
Macrophage MAPK7/AhR/STAT3 Signaling Mediates Mitochondrial ROS Burst and Enterohepatic Inflammatory Responses Induced by Deoxynivalenol Relevant to Low-Dose Exposure in Children.
Zhang Q et al.·Environ Sci Technol
2024
Identification of a Novel ERK5 (MAPK7) Inhibitor, MHJ-627, and Verification of Its Potent Anticancer Efficacy in Cervical Cancer HeLa Cells.
Hwang J et al.·Curr Issues Mol Biol
2023🔓 Open Access
Mapk7 deletion in chondrocytes causes vertebral defects by reducing MEF2C/PTEN/AKT signaling.
Wu C et al.·Genes Dis
2024🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Cavernous Malformation, Cerebral

Daratumumab for Familial Cerebral Cavernous Malformations: A Single-Arm Safety and Efficacy Study

NOT YET RECRUITING
NCT07026604Phase EARLY_PHASE1Beijing Tiantan HospitalStarted 2025-07-01
Daratumumab

External Resources

Links to major genomics databases and tools