MAPK6

Chr 15

mitogen-activated protein kinase 6

Also known as: ERK3, HsT17250, PRKM6, p97MAPK

NCBI Gene: 5597 ENSG00000069956 UniProt: Q16659 OMIM: 602904

The protein encoded by this gene is a member of the Ser/Thr protein kinase family, and is most closely related to mitogen-activated protein kinases (MAP kinases). MAP kinases also known as extracellular signal-regulated kinases (ERKs), are activated through protein phosphorylation cascades and act as integration points for multiple biochemical signals. This kinase is localized in the nucleus, and has been reported to be activated in fibroblasts upon treatment with serum or phorbol esters. [provided by RefSeq, Jul 2008]

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

0.41

LOEUF

GOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.41LOEUF

pLI 0.696

Z-score 3.80

OE 0.19 (0.10–0.41)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.73Z-score

OE missense 0.89 (0.82–0.98)

333 obs / 372.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.19 (0.10–0.41)

0≤0.351.4

Missense OE?0.89 (0.82–0.98)

0≤0.61.4

Synonymous OE?1.25

0≤1.21.6

LoF obs/exp: 5 / 25.8Missense obs/exp: 333 / 372.5Syn Z: -2.27

Background carrier burden — how many people carry a rare variant somewhere in MAPK6?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 100

806 rare PASS variants

Rare truncating (LoF)

1 in 2,000

60 rare PASS variants

Rare synonymous (reference)

1 in 200

342 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MAPK6. 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 130	1 in 1,100
South Asian	~43k	1 in 62	≈ 1 in 11,000
Remaining (unassigned)	~30k	1 in 72	≈ 1 in 15,000
European (Finnish)	~27k	1 in 670	≈ 1 in 27,000
Admixed American	~22k	1 in 100	≈ 1 in 7,400
African / African American	~21k	1 in 98	1 in 2,300
East Asian	~20k	1 in 92	1 in 3,300
Ashkenazi Jewish	~13k	1 in 330	1 in 2,200
Middle Eastern	~2,884	1 in 110	≈ 1 in 1,000

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): All 5 coding exons well covered in gnomAD exomes and genomes.? see exons ↓