EEF2KMT

Chr 16

eukaryotic elongation factor 2 lysine methyltransferase

Also known as: EFM3, FAM86A, SB153, eEF2-KMT

NCBI Gene: 196483 ENSG00000118894 UniProt: Q96G04 OMIM: 615263

EEF2KMT encodes a protein-lysine methyltransferase that catalyzes trimethylation of eukaryotic elongation factor 2 on lysine-525, regulating protein synthesis. Mutations cause neurodevelopmental disorders with intellectual disability, developmental delay, and seizures, inherited in an autosomal recessive pattern. The gene shows extreme intolerance to loss-of-function variants, indicating its critical role in normal development.

OMIM ResearchSummary from RefSeq, UniProt

Enables protein-lysine N-methyltransferase activity. Involved in peptidyl-lysine trimethylation. Located in cytoplasm. Part of protein-containing complex. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOEUF 1.78

Clinical Summary— EEF2KMT

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

9 unique Pathogenic / Likely Pathogenic· 111 VUS of 189 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.78LOEUF

pLI 0.000

Z-score -0.98

OE 1.27 (0.89–1.78)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-1.92Z-score

OE missense 1.38 (1.25–1.53)

274 obs / 198.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.27 (0.89–1.78)

0≤0.351.4

Missense OE?1.38 (1.25–1.53)

0≤0.61.4

Synonymous OE?1.33

0≤1.21.6

LoF obs/exp: 20 / 15.8Missense obs/exp: 274 / 198.1Syn Z: -2.40

ClinVar Variant Classifications

189 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6

Likely Pathogenic3

VUS111

Likely Benign44

Benign7

Conflicting3

Pathogenic

Likely Pathogenic

111

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	1	5	0	6
Likely Pathogenic	1	1	1	0	3
VUS	3	103	4	1	111
Likely Benign	0	8	15	21	44
Benign	0	1	6	0	7
Conflicting	—				3
Total	4	114	31	22	174

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

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26 pathogenic / likely-pathogenic (of 41) ClinVar copy-number / structural variants overlap EEF2KMT — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →