MAPK7

Chr 17

mitogen-activated protein kinase 7

Also known as: BMK1, ERK4, ERK5, PRKM7

NCBI Gene: 5598 ENSG00000166484 UniProt: Q13164 OMIM: 602521

MAPK7 encodes a MAP kinase that regulates gene expression by phosphorylating transcription factors in response to extracellular signals, playing important roles in cell proliferation, differentiation, survival, and endothelial function. Mutations cause autosomal recessive neurodevelopmental disorder with microcephaly, seizures, and cerebral atrophy, typically presenting in early infancy. The gene is highly constrained against loss-of-function variants, indicating that complete loss of MAPK7 function is likely pathogenic.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOEUF 0.61

Clinical Summary— MAPK7

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.35) despite low pLI — interpret in context.

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ClinVar Variants

3 unique Pathogenic / Likely Pathogenic· 111 VUS of 128 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.61LOEUF

pLI 0.003

Z-score 3.07

OE 0.35 (0.21–0.61)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.80Z-score

OE missense 0.78 (0.71–0.84)

402 obs / 517.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.35 (0.21–0.61)

0≤0.351.4

Missense OE?0.78 (0.71–0.84)

0≤0.61.4

Synonymous OE?1.14

0≤1.21.6

LoF obs/exp: 9 / 25.8Missense obs/exp: 402 / 517.2Syn Z: -1.61

ClinVar Variant Classifications

128 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3

VUS111

Likely Benign5

Pathogenic

111

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	3	0	3
Likely Pathogenic	0	0	0
VUS	111	0	111
Likely Benign	3	2	5
Benign	0	0	0
Total	117	2	119

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

View in ClinVar →

99 pathogenic / likely-pathogenic (of 113) ClinVar copy-number / structural variants overlap MAPK7 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →