MAPK12

Chr 22

mitogen-activated protein kinase 12

Also known as: ERK-6, ERK3, ERK6, MAPK 12, P38GAMMA, PRKM12, SAPK-3, SAPK3

NCBI Gene: 6300ENSG00000188130UniProt: P53778

Activation of members of the mitogen-activated protein kinase family is a major mechanism for transduction of extracellular signals. Stress-activated protein kinases are one subclass of MAP kinases. The protein encoded by this gene functions as a signal transducer during differentiation of myoblasts to myotubes. [provided by RefSeq, Jul 2008]

235
ClinVar variants
141
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— MAPK12
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
141 Pathogenic / Likely Pathogenic· 82 VUS of 235 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.
0.99LOEUF
pLI 0.000
Z-score 1.59
OE 0.62 (0.41–0.99)
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.
-0.47Z-score
OE missense 1.09 (0.98–1.21)
234 obs / 214.8 exp
Tolerant

Tolerant to missense variation

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.0.62 (0.41–0.99)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.09 (0.98–1.21)
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.1.21
0≤1.21.6
LoF obs/exp: 13 / 20.8Missense obs/exp: 234 / 214.8Syn Z: -1.60

ClinVar Variant Classifications

235 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic140
Likely Pathogenic1
VUS82
Likely Benign1
Benign1
Conflicting1
140
Pathogenic
1
Likely Pathogenic
82
VUS
1
Likely Benign
1
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
140
0
140
Likely Pathogenic
0
0
1
0
1
VUS
0
71
11
0
82
Likely Benign
0
1
0
0
1
Benign
0
0
1
0
1
Conflicting
—1
Total0721530226

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

View in ClinVar →

Protein Context — Lollipop Plot

MAPK12 · 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
A retrospective analysis of the clinicopathological features and prognostic value of MAPK12 protein expression in diffuse large B-cell lymphoma.
Liu Y et al.·Clin Transl Oncol
2024
Activation of P38 MAPK Signaling Cascade is Linked with Clinical Outcomes and Therapeutic Responses in Human Cancers.
Emelyanova A et al.·Biochemistry (Mosc)
2024
Oncogenes in melanoma: an update.
Kunz M·Eur J Cell Biol
2014Review
The Role of p38γ in Cancer: From review to outlook.
Xu W et al.·Int J Biol Sci
2021Review
Loss-of-function RNAi screens in breast cancer cells identify AURKB, PLK1, PIK3R1, MAPK12, PRKD2, and PTK6 as sensitizing targets of rapamycin activity.
Ou O et al.·Cancer Lett
2014
Comprehensive characterization of clonality of driver genes revealing their clinical relevance in colorectal cancer.
Shi J et al.·J Transl Med
2022
Transcriptomic Analysis of mRNA Expression Profiles in the Microglia of Mouse Brains Infected with Rabies Viruses of Varying Virulence.
Liu J et al.·Viruses
2023Functional
p38 MAPK regulates the Wnt inhibitor Dickkopf-1 in osteotropic prostate cancer cells.
Browne AJ et al.·Cell Death Dis
2016
Chronic stress and impaired glutamate function elicit a depressive-like phenotype and common changes in gene expression in the mouse frontal cortex.
Tordera RM et al.·Eur Neuropsychopharmacol
2011Functional
CD47 expression in classic follicular lymphoma is associated with event-free survival.
Kume A et al.·Hum Pathol
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Metastatic Thyroid Gland CarcinomaUnresectable Thyroid Gland Carcinoma

Dabrafenib and Lapatinib in Treating Patients With Refractory Thyroid Cancer That Cannot Be Removed by Surgery

ACTIVE NOT RECRUITING
NCT01947023Phase PHASE1National Cancer Institute (NCI)Started 2013-09-27
Biopsy ProcedureBiospecimen CollectionComputed Tomography

External Resources

Links to major genomics databases and tools