KDM4E

Chr 11

lysine demethylase 4E

Also known as: JMJD2E, KDM4DL, KDM5E

NCBI Gene: 390245 ENSG00000235268 UniProt: B2RXH2 OMIM: 616581

The protein encoded by this intronless gene is a member of a large family of histone lysine demethylases, which use oxygen and 2-oxoglutarate to demethylate di- and trimethylated lys9 of histone H3. Derepression of genes by demethylases is sometimes involved in viral infection or carcinogenesis, so inhibitors of these enzymes are desired. [provided by RefSeq, Dec 2016]

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

1.32

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

1.32LOEUF

pLI 0.513

Z-score 1.33

OE 0.00 (0.00–1.32)

Moderately constrained

Highly tolerant — LoF variants common in population

Missense Constraint?

0.17Z-score

OE missense 0.97 (0.88–1.07)

282 obs / 289.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–1.32)

0≤0.351.4

Missense OE?0.97 (0.88–1.07)

0≤0.61.4

Synonymous OE?1.15

0≤1.21.6

LoF obs/exp: 0 / 2.1Missense obs/exp: 282 / 289.9Syn Z: -1.21

Background carrier burden — how many people carry a rare variant somewhere in KDM4E?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 65

633 rare PASS variants

Rare truncating (LoF)

1 in 1,600

72 rare PASS variants

Rare synonymous (reference)

1 in 210

252 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for KDM4E. 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 71	1 in 2,300
South Asian	~43k	1 in 83	1 in 2,000
Remaining (unassigned)	~30k	1 in 79	1 in 700
European (Finnish)	~27k	1 in 120	1 in 5,200
Admixed American	~22k	1 in 71	1 in 980
African / African American	~21k	1 in 39	1 in 560
East Asian	~20k	1 in 68	1 in 450
Ashkenazi Jewish	~13k	1 in 170	none seen
Middle Eastern	~2,884	1 in 96	≈ 1 in 1,400

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 1 coding exons well covered in gnomAD exomes and genomes.? see exons ↓