EEF1AKMT2

Summary

EEF1AKMT2 (EEF1A lysine methyltransferase 2, HGNC:33787) is a protein-coding gene on chromosome 10q26.13, encoding EEF1A lysine methyltransferase 2 (Q5JPI9). Protein-lysine methyltransferase that selectively catalyzes the trimethylation of EEF1A at ‘Lys-318’.

Enables protein-lysine N-methyltransferase activity. Involved in peptidyl-lysine methylation. Located in cytosol and nucleoplasm.

Source: NCBI Gene 399818 — RefSeq curated summary.

At a glance

• GWAS associations: 23
• Clinical variants (ClinVar): 45 total
• MANE Select transcript: NM_212554

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33787
Approved symbol	EEF1AKMT2
Name	EEF1A lysine methyltransferase 2
Location	10q26.13
Locus type	gene with protein product
Status	Approved
Aliases	Efm4
Ensembl gene	ENSG00000203791
Ensembl biotype	protein_coding
OMIM	617794
Entrez	399818

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 8 protein_coding, 3 nonsense_mediated_decay, 2 retained_intron

ENST00000368836, ENST00000464099, ENST00000466270, ENST00000468738, ENST00000495711, ENST00000498770, ENST00000652548, ENST00000906050, ENST00000906051, ENST00000929128, ENST00000929129, ENST00000948224, ENST00000948225

RefSeq mRNA: 4 — MANE Select: NM_212554 NM_001304467, NM_001304468, NM_001416243, NM_212554

CCDS: CCDS31307

Canonical transcript exons

ENST00000368836 — 7 exons

Exon	Start	End
ENSE00001448079	124791724	124791887
ENSE00001900716	124757834	124760503
ENSE00003587138	124774675	124774782
ENSE00003614437	124765392	124765608
ENSE00003622947	124790273	124790338
ENSE00003625974	124762300	124762558
ENSE00003661761	124789043	124789157

Expression profiles

Bgee: expression breadth ubiquitous, 240 present calls, max score 93.60.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.3903 / max 182.1816, expressed in 1815 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
111859	24.3634	1815
111860	0.0268	10

Top tissues by expression

251 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	93.60	gold quality
calcaneal tendon	UBERON:0003701	92.82	gold quality
ganglionic eminence	UBERON:0004023	92.17	gold quality
left testis	UBERON:0004533	92.06	gold quality
right testis	UBERON:0004534	92.02	gold quality
testis	UBERON:0000473	90.57	gold quality
cortical plate	UBERON:0005343	90.03	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.92	gold quality
adrenal tissue	UBERON:0018303	88.45	gold quality
tendon	UBERON:0000043	88.28	gold quality
oviduct epithelium	UBERON:0004804	88.09	gold quality
cerebellar hemisphere	UBERON:0002245	86.91	gold quality
cerebellar cortex	UBERON:0002129	86.83	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.72	gold quality
left ovary	UBERON:0002119	86.67	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	86.56	gold quality
ovary	UBERON:0000992	86.25	gold quality
right ovary	UBERON:0002118	86.22	gold quality
right hemisphere of cerebellum	UBERON:0014890	86.16	gold quality
prefrontal cortex	UBERON:0000451	85.88	gold quality
rectum	UBERON:0001052	85.84	gold quality
cerebellum	UBERON:0002037	85.69	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	85.52	gold quality
bone marrow cell	CL:0002092	85.44	gold quality
nucleus accumbens	UBERON:0001882	85.38	gold quality
ectocervix	UBERON:0012249	85.33	gold quality
anterior cingulate cortex	UBERON:0009835	85.31	gold quality
endocervix	UBERON:0000458	85.28	gold quality
left lobe of thyroid gland	UBERON:0001120	85.28	gold quality
hindlimb stylopod muscle	UBERON:0004252	85.05	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.58

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

82 targeting EEF1AKMT2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-139-5P	99.80	69.50	1399
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-8084	99.73	69.57	1760
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-548M	99.70	68.87	1749
HSA-MIR-379-3P	99.69	69.60	1524
HSA-MIR-411-3P	99.69	69.63	1524

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	eef1akmt2	ENSDARG00000102144
mus_musculus	Eef1akmt2	ENSMUSG00000030960
rattus_norvegicus	Eef1akmt2	ENSRNOG00000017137
drosophila_melanogaster	CG9643	FBGN0031485
caenorhabditis_elegans		WBGENE00017919

Protein

Protein identifiers

EEF1A lysine methyltransferase 2 — Q5JPI9 (reviewed: Q5JPI9)

Alternative names: Methyltransferase-like protein 10, Protein-lysine N-methyltransferase METTL10

All UniProt accessions (3): G3V238, M0QZ67, Q5JPI9

UniProt curated annotations — full annotation on UniProt →

Function. Protein-lysine methyltransferase that selectively catalyzes the trimethylation of EEF1A at ‘Lys-318’.

Subcellular location. Cytoplasm. Nucleus.

Miscellaneous. Isoform 2 is the predominantly expressed isoform, as indicated by ribosome footprint sequencing data and mass spectrometry. Additionally, isoform 2 catalyzes eEF1A1/2 ‘Lys-318’ methylation in vitro, while isoform 1 could not.

Similarity. Belongs to the class I-like SAM-binding methyltransferase superfamily. EFM4 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q5JPI9-2	2, eEF1A-KMT2-207	yes
Q5JPI9-1	1, eEF1A-KMT2-201

RefSeq proteins (4): NP_001291396, NP_001291397, NP_001403172, NP_997719* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR025714	Methyltranfer_dom	Domain
IPR026635	Efm4/METTL10	Family
IPR029063	SAM-dependent_MTases_sf	Homologous_superfamily

Pfam: PF13847

Catalyzed reactions (Rhea), 1 shown:

• L-lysyl-[protein] + 3 S-adenosyl-L-methionine = N(6),N(6),N(6)-trimethyl-L-lysyl-[protein] + 3 S-adenosyl-L-homocysteine + 3 H(+) (RHEA:54192)

UniProt features (13 total): mutagenesis site 3, sequence conflict 2, modified residue 2, initiator methionine 1, chain 1, region of interest 1, compositionally biased region 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5JPI9-F1	91.22	0.83

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 2, 21

Mutagenesis-validated functional residues (3):

Position	Phenotype
220	reduces elongation factor 1-alpha ’lys-318’ methylation.
85–91	highly reduces methylation activity toward eef1a1.
218	no effect on elongation factor 1-alpha.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8876725	Protein methylation

MSigDB gene sets: 82 (showing top): GOBP_PEPTIDYL_LYSINE_MODIFICATION, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, CHANG_IMMORTALIZED_BY_HPV31_UP, GOBP_METHYLATION, GOBP_PEPTIDYL_LYSINE_METHYLATION, CAGCTTT_MIR320, NUYTTEN_NIPP1_TARGETS_DN, GOMF_N_METHYLTRANSFERASE_ACTIVITY, GOMF_PROTEIN_METHYLTRANSFERASE_ACTIVITY, GOMF_S_ADENOSYLMETHIONINE_DEPENDENT_METHYLTRANSFERASE_ACTIVITY, GOMF_TRANSFERASE_ACTIVITY_TRANSFERRING_ONE_CARBON_GROUPS, GOMF_LYSINE_N_METHYLTRANSFERASE_ACTIVITY, REACTOME_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_PROTEIN_METHYLATION, GOBERT_OLIGODENDROCYTE_DIFFERENTIATION_DN

GO Biological Process (2): peptidyl-lysine methylation (GO:0018022), methylation (GO:0032259)

GO Molecular Function (3): methyltransferase activity (GO:0008168), protein-lysine N-methyltransferase activity (GO:0016279), transferase activity (GO:0016740)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
protein methylation	1
peptidyl-lysine modification	1
metabolic process	1
transferase activity, transferring one-carbon groups	1
protein methyltransferase activity	1
lysine N-methyltransferase activity	1
catalytic activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

682 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EEF1AKMT2	METTL13	Q8N6R0	818
EEF1AKMT2	EEF2KMT	Q96G04	806
EEF1AKMT2	METTL25	Q8N6Q8	800
EEF1AKMT2	EEF1AKMT1	Q8WVE0	773
EEF1AKMT2	METTL21C	Q5VZV1	757
EEF1AKMT2	METTL21A	Q8WXB1	735
EEF1AKMT2	EEF1AKMT4	P0DPD7	734
EEF1AKMT2	ETFBKMT	Q8IXQ9	723
EEF1AKMT2	VCPKMT	Q9H867	718
EEF1AKMT2	CSKMT	A8MUP2	717
EEF1AKMT2	EEF1AKMT3	Q96AZ1	664
EEF1AKMT2	METTL24	Q5JXM2	599
EEF1AKMT2	TMT1B	Q6UX53	594
EEF1AKMT2	NTMT1	Q9BV86	590
EEF1AKMT2	METTL18	O95568	589

IntAct

3 interactions, top by confidence:

A	B	Type	Score
EEF1AKMT2	IFT56	psi-mi:“MI:0914”(association)	0.350
EEF1AKMT2	PAK3	psi-mi:“MI:0914”(association)	0.350

BioGRID (37): ZNF318 (Affinity Capture-MS), SMG7 (Affinity Capture-MS), TTC26 (Affinity Capture-MS), RAD17 (Affinity Capture-MS), SMCR8 (Affinity Capture-MS), STXBP4 (Affinity Capture-MS), PRR14 (Affinity Capture-MS), PTPN13 (Affinity Capture-MS), SPG11 (Affinity Capture-MS), TBL1XR1 (Affinity Capture-MS), PEX1 (Affinity Capture-MS), RGPD8 (Affinity Capture-MS), BRCA2 (Affinity Capture-MS), CAMK2B (Affinity Capture-MS), GSE1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0F7U1Z8, A0A1E1FFN5, A2XMJ1, A8WVR2, B1H2P7, B8JM82, C8YTM5, O13748, O74386, O74529, P34254, P38074, P38340, P40516, Q0C8A3, Q10224, Q29LW1, Q4KL94, Q4KLE6, Q54I98, Q55DH6, Q5D013, Q5JPI9, Q5PP70, Q5RDV8, Q60YU0, Q61E36, Q66I74, Q6AWU6, Q6AXU8, Q6C3K2, Q6NN40, Q6NWG4, Q6NWX7, Q86BS6, Q8BVH9, Q8SR66, Q8TCB7, Q8VY08, Q93V78

Diamond homologs: P40516, Q5D013, Q5JPI9, Q9D853, Q9P7Z3, C0QLV7, Q7SHI7, A8ZW25, Q9VIK9, A7GSD9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

45 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	32
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1851 predictions. Top by Δscore:

Variant	Effect	Δscore
10:124760316:A:AC	donor_gain	1.0000
10:124760317:C:CC	donor_gain	1.0000
10:124760317:CTAAG:C	donor_gain	1.0000
10:124763676:CTA:C	donor_gain	1.0000
10:124765387:CTTA:C	donor_loss	1.0000
10:124765388:TTA:T	donor_loss	1.0000
10:124765389:TA:T	donor_loss	1.0000
10:124765390:A:AC	donor_gain	1.0000
10:124765391:C:CC	donor_gain	1.0000
10:124765391:C:CT	donor_loss	1.0000
10:124765391:CCTT:C	donor_gain	1.0000
10:124789041:A:AC	donor_gain	1.0000
10:124789042:C:CC	donor_gain	1.0000
10:124789067:T:TA	donor_gain	1.0000
10:124790339:C:CC	acceptor_gain	1.0000
10:124790341:A:C	acceptor_gain	1.0000
10:124790348:CAA:C	acceptor_gain	1.0000
10:124790350:A:C	acceptor_gain	1.0000
10:124791722:A:AC	donor_gain	1.0000
10:124791722:ACTG:A	donor_gain	1.0000
10:124791723:C:CT	donor_gain	1.0000
10:124791723:CTG:C	donor_gain	1.0000
10:124791723:CTGC:C	donor_gain	1.0000
10:124791723:CTGCT:C	donor_gain	1.0000
10:124760500:AATCC:A	acceptor_loss	0.9900
10:124760501:ATCC:A	acceptor_loss	0.9900
10:124760502:TC:T	acceptor_gain	0.9900
10:124760503:CC:C	acceptor_gain	0.9900
10:124760503:CCT:C	acceptor_loss	0.9900
10:124760503:CCTGT:C	acceptor_loss	0.9900

AlphaMissense

1890 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:124789154:A:C	F60L	0.996
10:124789154:A:T	F60L	0.996
10:124789156:A:G	F60L	0.996
10:124790335:C:A	W38C	0.992
10:124790335:C:G	W38C	0.992
10:124765528:G:C	S160R	0.988
10:124765528:G:T	S160R	0.988
10:124765530:T:G	S160R	0.988
10:124765537:A:C	D157E	0.988
10:124765537:A:T	D157E	0.988
10:124790337:A:G	W38R	0.988
10:124790337:A:T	W38R	0.988
10:124765550:T:A	K153I	0.987
10:124765532:A:T	I159K	0.986
10:124765548:C:G	G154R	0.985
10:124765548:C:T	G154R	0.985
10:124765549:T:A	K153N	0.985
10:124765549:T:G	K153N	0.985
10:124789074:C:T	G87E	0.985
10:124765560:A:G	C150R	0.984
10:124765538:T:C	D157G	0.983
10:124774724:A:G	L117P	0.983
10:124765536:C:G	A158P	0.982
10:124765538:T:A	D157V	0.982
10:124765548:C:A	G154W	0.982
10:124765567:A:C	F147L	0.982
10:124765567:A:T	F147L	0.982
10:124765569:A:G	F147L	0.982
10:124765558:A:C	C150W	0.981
10:124765554:C:G	D152H	0.980

dbSNP variants (sampled 300 via entrez): RS1000076263 (10:124779541 T>A), RS1000125071 (10:124779285 C>A,T), RS1000140343 (10:124787341 G>A,C), RS1000150604 (10:124778197 T>C), RS1000203396 (10:124778492 G>A), RS1000223501 (10:124784883 A>G), RS1000264693 (10:124773212 T>C), RS1000508691 (10:124790689 G>A), RS1000630173 (10:124784136 T>C), RS1000690163 (10:124785953 G>A), RS1000975241 (10:124768758 A>G), RS1000990292 (10:124768527 C>T), RS1001028964 (10:124773680 T>A,C), RS1001106520 (10:124768784 C>T), RS1001189874 (10:124791620 G>A,C)

Disease associations

OMIM: gene MIM:617794 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

23 associations (top):

Study	Trait	p-value
GCST001762_342	Obesity-related traits	8.000000e-06
GCST004131_12	Inflammatory bowel disease	1.000000e-09
GCST004132_94	Crohn’s disease	3.000000e-06
GCST004133_33	Ulcerative colitis	1.000000e-06
GCST005116_14	Male-pattern baldness	3.000000e-17
GCST006661_312	Male-pattern baldness	6.000000e-21
GCST006870_6	Hippocampal tail volume	3.000000e-14
GCST006871_8	Total hippocampal volume	1.000000e-15
GCST006878_1	Dentate gyrus molecular layer volume (corrected for total hippocampal volume)	4.000000e-12
GCST006887_2	Hippocampal subfield CA1 volume	1.000000e-09
GCST006888_1	Hippocampal subfield CA3 volume	3.000000e-12
GCST006889_4	Hippocampal subfield CA4 volume	6.000000e-15
GCST006890_3	Dentate gyrus granule cell layer volume	9.000000e-15
GCST006891_2	Dentate gyrus molecular layer volume	2.000000e-10
GCST007876_116	Estimated glomerular filtration rate	3.000000e-11
GCST008058_95	Estimated glomerular filtration rate	2.000000e-20
GCST008059_95	Estimated glomerular filtration rate	5.000000e-19
GCST008839_69	Height	9.000000e-17
GCST008971_25	Urate levels	6.000000e-07
GCST008972_71	Urate levels	2.000000e-08
GCST010703_92	Brain morphology (MOSTest)	4.000000e-63
GCST90002383_496	Hematocrit	5.000000e-10
GCST90002401_173	Platelet distribution width	7.000000e-09

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0005035	hippocampal volume
EFO:0009394	hippocampal CA1 volume
EFO:0009395	hippocampal CA3 volume
EFO:0009396	hippocampal CA4 volume
EFO:0004531	urate measurement
EFO:0004346	neuroimaging measurement
EFO:0004348	hematocrit
EFO:0007984	platelet component distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, increases expression	3
Cyclosporine	increases expression	3
bisphenol A	decreases expression, increases methylation	2
mercuric bromide	decreases expression, affects cotreatment	2
Benzo(a)pyrene	affects methylation, decreases expression	2
Nickel	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
p-Chloromercuribenzoic Acid	decreases expression, affects cotreatment	2
methylparaben	decreases expression	1
sodium arsenite	decreases expression	1
coumarin	decreases phosphorylation	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
NSC 689534	affects binding, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Acetaminophen	decreases expression	1
Caffeine	increases phosphorylation	1
Copper	affects binding, decreases expression	1
Methyl Methanesulfonate	decreases expression	1
N-Nitrosopyrrolidine	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Quercetin	decreases expression	1
Silicon Dioxide	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Copper Sulfate	decreases expression	1
Acrylamide	decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_SX87	HAP1 METTL10 (-) 1	Cancer cell line	Male
CVCL_XQ43	HAP1 METTL10 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.