MAPK8

Chr 10

mitogen-activated protein kinase 8

Also known as: JNK, JNK-46, JNK1, JNK1A2, JNK21B1/2, PRKM8, SAPK1, SAPK1c

MAPK8 encodes a serine/threonine kinase that phosphorylates transcription factors and regulatory proteins in response to cellular stress, controlling processes including apoptosis, cell proliferation, T-cell differentiation, and neuronal development. Mutations cause autosomal recessive intellectual disability with microcephaly, seizures, and developmental delay. This gene is highly constrained against loss-of-function variants in the general population.

Summary from RefSeq, UniProt
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0
Active trials
120
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.21
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical SummaryMAPK8
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.21LOEUF
pLI 0.998
Z-score 4.24
OE 0.04 (0.010.21)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.88Z-score
OE missense 0.46 (0.400.55)
106 obs / 228.3 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.04 (0.010.21)
00.351.4
Missense OE0.46 (0.400.55)
00.61.4
Synonymous OE0.92
01.21.6
LoF obs/exp: 1 / 22.9Missense obs/exp: 106 / 228.3Syn Z: 0.53
DN
0.4190th %ile
GOF
0.5170th %ile
LOF
0.67top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.21

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

MAPK8 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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