EEF1AKMT1

Summary

EEF1AKMT1 (EEF1A lysine methyltransferase 1, HGNC:27351) is a protein-coding gene on chromosome 13q12.11, encoding EEF1A lysine methyltransferase 1 (Q8WVE0). Protein N-lysine methyltransferase that selectively catalyzes the trimethylation of EEF1A at ‘Lys-79’.

Enables protein-lysine N-methyltransferase activity. Involved in peptidyl-lysine methylation. Predicted to be located in cytosol.

Source: NCBI Gene 221143 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 6 total — 1 pathogenic
• MANE Select transcript: NM_001318939

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27351
Approved symbol	EEF1AKMT1
Name	EEF1A lysine methyltransferase 1
Location	13q12.11
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000150456
Ensembl biotype	protein_coding
OMIM	617793
Entrez	221143

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000382754, ENST00000382758, ENST00000460374, ENST00000905336, ENST00000905337

RefSeq mRNA: 2 — MANE Select: NM_001318939 NM_001318939, NM_174928

CCDS: CCDS9293

Canonical transcript exons

ENST00000382758 — 5 exons

Exon	Start	End
ENSE00000995004	20737723	20737805
ENSE00001493270	20773921	20773961
ENSE00003389500	20728731	20729216
ENSE00003423777	20731841	20732121
ENSE00003424548	20757455	20757617

Expression profiles

Bgee: expression breadth ubiquitous, 246 present calls, max score 90.50.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.3094 / max 243.7578, expressed in 1723 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
136359	6.5830	1699
136358	0.7264	348

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.50	gold quality
cardiac muscle of right atrium	UBERON:0003379	86.56	silver quality
islet of Langerhans	UBERON:0000006	86.34	gold quality
kidney epithelium	UBERON:0004819	85.84	gold quality
quadriceps femoris	UBERON:0001377	84.57	silver quality
tibialis anterior	UBERON:0001385	84.49	silver quality
deltoid	UBERON:0001476	84.39	gold quality
oocyte	CL:0000023	84.34	gold quality
myocardium	UBERON:0002349	84.24	silver quality
vastus lateralis	UBERON:0001379	84.12	gold quality
calcaneal tendon	UBERON:0003701	83.79	gold quality
bronchial epithelial cell	CL:0002328	83.70	gold quality
hindlimb stylopod muscle	UBERON:0004252	83.69	gold quality
right adrenal gland	UBERON:0001233	83.45	gold quality
hypothalamus	UBERON:0001898	83.27	gold quality
lower esophagus muscularis layer	UBERON:0035833	83.24	gold quality
lower esophagus	UBERON:0013473	83.20	gold quality
right adrenal gland cortex	UBERON:0035827	83.16	gold quality
bronchus	UBERON:0002185	83.06	gold quality
right coronary artery	UBERON:0001625	82.59	gold quality
anterior cingulate cortex	UBERON:0009835	82.57	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	82.56	gold quality
left uterine tube	UBERON:0001303	82.46	gold quality
muscle of leg	UBERON:0001383	82.40	gold quality
amygdala	UBERON:0001876	82.39	gold quality
endocervix	UBERON:0000458	82.38	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	82.38	gold quality
muscle tissue	UBERON:0002385	82.34	gold quality
prefrontal cortex	UBERON:0000451	82.31	gold quality
left coronary artery	UBERON:0001626	82.28	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.54

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

11 targeting EEF1AKMT1, 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-3667-3P	99.99	67.17	1636
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-7109-5P	99.18	66.13	1057
HSA-MIR-3125	99.14	68.49	2269
HSA-MIR-3916	98.99	68.04	2155
HSA-MIR-6859-5P	98.99	68.07	2049
HSA-MIR-583	98.71	67.44	1791
HSA-MIR-6887-5P	98.56	68.49	1295
HSA-MIR-6795-5P	98.52	68.51	1277

Literature-anchored findings (GeneRIF, showing 1)

• Data indicate that the methylation of lysine (Lys) in elongation factor 1A (eEF1A) by methyltransferase is conserved from yeast to human. (PMID:26545399)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	eef1akmt1	ENSDARG00000040584
mus_musculus	Eef1akmt1	ENSMUSG00000021951
rattus_norvegicus	Eef1akmt1	ENSRNOG00000009849
drosophila_melanogaster	CG9154	FBGN0031777
caenorhabditis_elegans		WBGENE00043057

Protein

Protein identifiers

EEF1A lysine methyltransferase 1 — Q8WVE0 (reviewed: Q8WVE0)

Alternative names: N(6)-adenine-specific DNA methyltransferase 2, Protein-lysine N-methyltransferase N6AMT2, eEF1A-KMT

All UniProt accessions (1): Q8WVE0

UniProt curated annotations — full annotation on UniProt →

Function. Protein N-lysine methyltransferase that selectively catalyzes the trimethylation of EEF1A at ‘Lys-79’.

Subcellular location. Cytoplasm.

Similarity. Belongs to the class I-like SAM-binding methyltransferase superfamily. EFM5 family.

RefSeq proteins (2): NP_001305868, NP_777588 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002052	DNA_methylase_N6_adenine_CS	Conserved_site
IPR019369	Efm5/EEF1AKMT1	Family
IPR029063	SAM-dependent_MTases_sf	Homologous_superfamily
IPR041370	Mlase_EEF1AKMT1/ZCCHC4	Family

Pfam: PF10237

Enzyme classification (BRENDA):

• EC 2.1.1.244 — protein N-terminal methyltransferase (BRENDA: 5 organisms, 114 substrates, 37 inhibitors, 30 Km, 20 kcat entries)

Substrate kinetics (BRENDA)

19 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
N-TERMINAL-SPKRIA-[RCC1]	0.0032–0.263	3
SSKRAKAKTTKKRP	0.0044–0.0156	3
N-TERMINAL-SPKRIAKRRSPP	0.0031–0.0049	2
N-TERMINAL-[RCC1]	0.002–0.0021	2
SPKRIAKRRSPPADA	0.0009–0.0011	2
(E)-HEX-2-EN-5-YNYL-S-ADENOSYL-L-METHIONINE	0.0014	1
APKRQSPLPP	0.002	1
APKRVVQLSL	0.0031	1
N-TERMINAL-DIMETHYL-SPKRIAKRRS	0.0043	1
N-TERMINAL-LPKRIA	0.0054	1
N-TERMINAL-METHYL-SPKRIAKRRS	0.0014	1
N-TERMINAL-PPKRIA	0.0003	1
N-TERMINAL-RPKRIA	0.004	1
N-TERMINAL-SPKRIAKRR	0.0014	1
N-TERMINAL-SPKRIAKRRS	0.0009	1

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 (5 total): modified residue 2, initiator methionine 1, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WVE0-F1	86.57	0.71

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, 2

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8876725	Protein methylation

MSigDB gene sets: 124 (showing top): TGCGCANK_UNKNOWN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_PEPTIDYL_LYSINE_MODIFICATION, BYSTRYKH_HEMATOPOIESIS_STEM_CELL_AND_BRAIN_QTL_CIS, GOBP_METHYLATION, GOBP_PEPTIDYL_LYSINE_METHYLATION, CHESLER_BRAIN_QTL_CIS, ZHENG_FOXP3_TARGETS_UP, 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

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

GO Molecular Function (4): nucleic acid binding (GO:0003676), methyltransferase activity (GO:0008168), protein-lysine N-methyltransferase activity (GO:0016279), transferase activity (GO:0016740)

GO Cellular Component (2): cytosol (GO:0005829), cytoplasm (GO:0005737)

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	2
protein methylation	1
peptidyl-lysine modification	1
metabolic process	1
binding	1
transferase activity, transferring one-carbon groups	1
protein methyltransferase activity	1
lysine N-methyltransferase activity	1
catalytic activity	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

494 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EEF1AKMT1	EEF1AKMT2	Q5JPI9	773
EEF1AKMT1	EEF1AKMT3	Q96AZ1	685
EEF1AKMT1	METTL21A	Q8WXB1	666
EEF1AKMT1	VCPKMT	Q9H867	627
EEF1AKMT1	ETFBKMT	Q8IXQ9	620
EEF1AKMT1	EEF2KMT	Q96G04	613
EEF1AKMT1	ZDHHC20	Q5W0Z9	578
EEF1AKMT1	METTL18	O95568	571
EEF1AKMT1	METTL23	Q86XA0	563
EEF1AKMT1	HEMK2	Q9Y5N5	556
EEF1AKMT1	METTL22	Q9BUU2	548
EEF1AKMT1	CAMKMT	Q7Z624	543
EEF1AKMT1	ANTKMT	Q9BQD7	528
EEF1AKMT1	METTL21C	Q5VZV1	527
EEF1AKMT1	MICU2	Q8IYU8	525
EEF1AKMT1	ATPSCKMT	Q6P4H8	525

IntAct

8 interactions, top by confidence:

A	B	Type	Score
	EEF1AKMT1	psi-mi:“MI:0915”(physical association)	0.560
EEF1AKMT1	EEF1A1	psi-mi:“MI:0914”(association)	0.530
EEF1AKMT1	TTLL12	psi-mi:“MI:0914”(association)	0.530
NDN	EEF1AKMT1	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (17): EEF1A2 (Affinity Capture-MS), TTLL12 (Affinity Capture-MS), EEF1A1 (Affinity Capture-MS), NFS1 (Affinity Capture-MS), EGLN1 (Affinity Capture-MS), N6AMT2 (Two-hybrid), N6AMT2 (Affinity Capture-MS), N6AMT2 (Synthetic Lethality), N6AMT2 (Synthetic Lethality), N6AMT2 (Positive Genetic), EEF1A2 (Affinity Capture-MS), EGLN1 (Affinity Capture-MS), TTLL12 (Affinity Capture-MS), EEF1A1 (Affinity Capture-MS), N6AMT2 (Negative Genetic)

ESM2 similar proteins: A6H767, A9CB27, O75312, P0C0V4, P24534, P28656, P29412, P29522, P34826, P55209, Q17QC0, Q17QF2, Q1EBV4, Q1LZC9, Q20168, Q21102, Q2TBX0, Q3E840, Q4I9U7, Q4P8G2, Q4R312, Q4WPU8, Q5E983, Q5R4D4, Q5R7N8, Q5RED0, Q5ZIN1, Q62384, Q6BTW5, Q6C0G3, Q6CMG4, Q6DET9, Q6FXS6, Q6GN98, Q6NPL9, Q6VUC1, Q74Z32, Q7SC15, Q7ZY81, Q8K0W9

Diamond homologs: P53200, Q17QF2, Q5WRN3, Q5ZKT6, Q6GN98, Q6NYP8, Q86A24, Q8WVE0, Q9CY45, Q9VMH7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	1
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
685307	GRCh37/hg19 13q11-12.11(chr13:19436286-23274540)x1	Pathogenic

SpliceAI

979 predictions. Top by Δscore:

Variant	Effect	Δscore
13:20731836:CCTA:C	donor_loss	1.0000
13:20731837:CTA:C	donor_loss	1.0000
13:20732117:CGATT:C	acceptor_gain	1.0000
13:20732120:TT:T	acceptor_gain	1.0000
13:20732122:C:CC	acceptor_gain	1.0000
13:20757449:ACTT:A	donor_loss	1.0000
13:20757450:CTT:C	donor_loss	1.0000
13:20757451:TT:T	donor_loss	1.0000
13:20757452:TAC:T	donor_loss	1.0000
13:20757453:AC:A	donor_gain	1.0000
13:20757454:CC:C	donor_gain	1.0000
13:20729217:C:CC	acceptor_gain	0.9900
13:20729218:T:A	acceptor_loss	0.9900
13:20731093:A:T	acceptor_gain	0.9900
13:20731839:A:AC	donor_gain	0.9900
13:20731840:C:CC	donor_gain	0.9900
13:20732118:GATT:G	acceptor_gain	0.9900
13:20732119:ATT:A	acceptor_gain	0.9900
13:20732121:TC:T	acceptor_loss	0.9900
13:20732122:C:G	acceptor_loss	0.9900
13:20732130:CAAAA:C	acceptor_loss	0.9900
13:20755915:C:CT	donor_gain	0.9900
13:20757453:A:AC	donor_gain	0.9900
13:20757454:C:CC	donor_gain	0.9900
13:20757454:CCCA:C	donor_gain	0.9900
13:20757454:CCCAA:C	donor_gain	0.9900
13:20757614:TAAC:T	acceptor_gain	0.9900
13:20757614:TAACC:T	acceptor_loss	0.9900
13:20757616:ACCT:A	acceptor_loss	0.9900
13:20757617:CCTGC:C	acceptor_loss	0.9900

AlphaMissense

1414 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:20737791:A:C	F53L	0.998
13:20737791:A:T	F53L	0.998
13:20737793:A:G	F53L	0.998
13:20729125:A:C	F200L	0.997
13:20729125:A:T	F200L	0.997
13:20729127:A:G	F200L	0.997
13:20732116:G:T	A78E	0.996
13:20732106:A:C	S81R	0.995
13:20732106:A:T	S81R	0.995
13:20732108:T:G	S81R	0.995
13:20732097:A:C	S84R	0.994
13:20732097:A:T	S84R	0.994
13:20732099:T:G	S84R	0.994
13:20732004:A:C	F115L	0.993
13:20732004:A:T	F115L	0.993
13:20732006:A:G	F115L	0.993
13:20737797:G:C	S51R	0.992
13:20737797:G:T	S51R	0.992
13:20737799:T:G	S51R	0.992
13:20732025:A:C	F108L	0.991
13:20732025:A:T	F108L	0.991
13:20732027:A:G	F108L	0.991
13:20732114:A:G	C79R	0.991
13:20737792:A:G	F53S	0.991
13:20729126:A:G	F200S	0.989
13:20731936:A:T	V138E	0.989
13:20729126:A:C	F200C	0.988
13:20757530:A:C	F23L	0.988
13:20757530:A:T	F23L	0.988
13:20757532:A:G	F23L	0.988

dbSNP variants (sampled 300 via entrez): RS1000006396 (13:20756331 T>C), RS1000118744 (13:20751621 G>C), RS1000220928 (13:20744702 C>T), RS1000239912 (13:20759675 G>A), RS1000273263 (13:20744911 A>G,T), RS1000469507 (13:20751384 A>G), RS1000502874 (13:20745954 A>T), RS1000514446 (13:20740260 G>A,C), RS1000558567 (13:20746247 G>A), RS1000582645 (13:20746297 T>C), RS1000675480 (13:20759453 A>G), RS1000741615 (13:20752596 C>G), RS1000894204 (13:20731283 T>C), RS1000924054 (13:20731088 A>T), RS1000985100 (13:20770857 A>G)

Disease associations

OMIM: gene MIM:617793 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST002456_1	PR segment duration	2.000000e-08
GCST010152_3	Neuroblastoma or malignant cutaneous melanoma	2.000000e-06
GCST010796_25	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-14
GCST010796_76	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-10
GCST010796_77	Electrocardiogram morphology (amplitude at temporal datapoints)	9.000000e-12
GCST010796_78	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-12
GCST010796_79	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-12

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005095	PR segment
EFO:0004327	electrocardiography

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance	2
Cyclosporine	decreases expression	2
FR900359	decreases phosphorylation	1
dicrotophos	decreases expression	1
4-aminophenylarsenoxide	decreases reaction, affects binding	1
K 7174	decreases expression	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Atrazine	decreases expression	1
Benzoates	decreases expression	1
Caffeine	increases phosphorylation	1
Dimethyl Sulfoxide	affects expression	1
Oxygen	decreases expression	1
Quercetin	decreases expression	1
Aflatoxin B1	decreases methylation	1
Copper Sulfate	decreases expression	1
Particulate Matter	increases abundance, decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SZ72	HAP1 N6AMT2 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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