MAP2K5

Chr 15

mitogen-activated protein kinase kinase 5

Also known as: HsT17454, MAPKK5, MEK5, PRKMK5

NCBI Gene: 5607 ENSG00000137764 UniProt: Q13163 OMIM: 602520

The protein encoded by this gene is a dual specificity protein kinase that belongs to the MAP kinase kinase family. This kinase specifically interacts with and activates MAPK7/ERK5. This kinase itself can be phosphorylated and activated by MAP3K3/MEKK3, as well as by atypical protein kinase C isoforms (aPKCs). The signal cascade mediated by this kinase is involved in growth factor stimulated cell proliferation and muscle cell differentiation. Three alternatively spliced transcript variants of this gene encoding distinct isoforms have been described. [provided by RefSeq, May 2011]

OMIM Research

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.51

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.51LOEUF

pLI 0.005

Z-score 3.84

OE 0.31 (0.19–0.51)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.02Z-score

OE missense 0.64 (0.56–0.73)

161 obs / 251.1 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.31 (0.19–0.51)

0≤0.351.4

Missense OE?0.64 (0.56–0.73)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 11 / 35.8Missense obs/exp: 161 / 251.1Syn Z: 0.05

Background carrier burden — how many people carry a rare variant somewhere in MAP2K5?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 210

513 rare PASS variants

Rare truncating (LoF)

1 in 1,400

115 rare PASS variants

Rare synonymous (reference)

1 in 340

222 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MAP2K5. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 280	1 in 2,100
South Asian	~43k	1 in 110	1 in 2,100
Remaining (unassigned)	~30k	1 in 140	1 in 1,100
European (Finnish)	~27k	1 in 680	≈ 1 in 7,700
Admixed American	~22k	1 in 200	1 in 990
African / African American	~21k	1 in 170	1 in 1,400
East Asian	~20k	1 in 99	1 in 1,400
Ashkenazi Jewish	~13k	1 in 820	none seen
Middle Eastern	~2,884	1 in 180	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 16 of 22 coding exons well covered in gnomAD exomes; exons 4, 7, 9, 10, 11, 13 marginal. Genomes: all 22.? see exons ↓