EEF1AKMT4

Summary

EEF1AKMT4 (EEF1A lysine methyltransferase 4, HGNC:53611) is a protein-coding gene on chromosome 3q27.1, encoding EEF1A lysine methyltransferase 4 (P0DPD7). Protein-lysine methyltransferase that efficiently catalyzes three successive methylations on ‘Lys-36’ in eukaryotic translation elongation factor 1 alpha (EEF1A1 or EEF1A2).

This gene encodes a member of the lysine-specific methyltransferase (KMT) family. The encoded enzyme catalyzes the methylation of lysine-36 of the eukaryotic translation elongation factor 1 alpha. Methylation by this enzyme may affect endoplasmic reticulum-related processes.

Source: NCBI Gene 110599564 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 5 total
• MANE Select transcript: NM_032331

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:53611
Approved symbol	EEF1AKMT4
Name	EEF1A lysine methyltransferase 4
Location	3q27.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000284753
Ensembl biotype	protein_coding
Entrez	110599564

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000324557, ENST00000931939, ENST00000931940

RefSeq mRNA: 1 — MANE Select: NM_032331 NM_032331

CCDS: CCDS3255

Canonical transcript exons

ENST00000324557 — 3 exons

Exon	Start	End
ENSE00001266410	184258288	184258759
ENSE00001829254	184249672	184249890
ENSE00003818997	184257473	184257756

Expression profiles

Bgee: expression breadth ubiquitous, 163 present calls, max score 86.02.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.4795 / max 59.3413, expressed in 1665 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
40154	8.4795	1665
40153	0.0153	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	86.02	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.72	gold quality
right testis	UBERON:0004534	85.67	gold quality
mucosa of transverse colon	UBERON:0004991	85.59	gold quality
right lobe of liver	UBERON:0001114	84.12	gold quality
testis	UBERON:0000473	83.50	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.00	gold quality
body of pancreas	UBERON:0001150	81.69	gold quality
gastrocnemius	UBERON:0001388	80.46	gold quality
stromal cell of endometrium	CL:0002255	79.06	gold quality
esophagus mucosa	UBERON:0002469	78.77	gold quality
pancreas	UBERON:0001264	78.25	gold quality
lower esophagus mucosa	UBERON:0035834	78.00	gold quality
muscle of leg	UBERON:0001383	77.78	gold quality
granulocyte	CL:0000094	77.31	gold quality
leukocyte	CL:0000738	77.16	gold quality
monocyte	CL:0000576	77.11	gold quality
islet of Langerhans	UBERON:0000006	76.64	gold quality
right adrenal gland	UBERON:0001233	76.45	gold quality
right lobe of thyroid gland	UBERON:0001119	76.43	gold quality
left lobe of thyroid gland	UBERON:0001120	76.32	gold quality
left adrenal gland	UBERON:0001234	76.18	gold quality
skin of abdomen	UBERON:0001416	75.99	gold quality
left adrenal gland cortex	UBERON:0035825	75.86	gold quality
skin of leg	UBERON:0001511	75.84	gold quality
right adrenal gland cortex	UBERON:0035827	75.18	gold quality
body of stomach	UBERON:0001161	75.11	gold quality
liver	UBERON:0002107	74.96	gold quality
minor salivary gland	UBERON:0001830	74.38	gold quality
thyroid gland	UBERON:0002046	74.18	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

7 targeting EEF1AKMT4, 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-498-3P	99.91	71.27	1114
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-7150	99.62	66.80	1322
HSA-MIR-5008-5P	98.42	65.87	1019
HSA-MIR-4675	97.69	64.82	774
HSA-MIR-4741	97.69	64.14	883

Literature-anchored findings (GeneRIF, showing 1)

• Methylation of lysine (K36) in eukaryotic elongation factor alpha (eEF1A) proteins is dependent on EEF1A lysine methyltransferase 4 (eEF1A-KMT4) in vivo. (PMID:28520920)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ece2a	ENSDARG00000068021
mus_musculus	Eef1akmt4	ENSMUSG00000115219
rattus_norvegicus	Eef1akmt4	ENSRNOG00000029529
caenorhabditis_elegans	C17E4.11	WBGENE00044236

Paralogs (2): METTL13 (ENSG00000010165), CSKMT (ENSG00000214756)

Protein

Protein identifiers

EEF1A lysine methyltransferase 4 — P0DPD7 (reviewed: P0DPD7)

All UniProt accessions (1): P0DPD7

UniProt curated annotations — full annotation on UniProt →

Function. Protein-lysine methyltransferase that efficiently catalyzes three successive methylations on ‘Lys-36’ in eukaryotic translation elongation factor 1 alpha (EEF1A1 or EEF1A2).

Similarity. Belongs to the methyltransferase superfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P0DPD7-4	EEF1AKMT4-1	yes
P0DPD8-1	EEF1AKMT4-ECE2-1, ECE-2A

RefSeq proteins (1): NP_115707* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013216	Methyltransf_11	Domain
IPR029063	SAM-dependent_MTases_sf	Homologous_superfamily
IPR051419	Lys/N-term_MeTrsfase_sf	Family

Pfam: PF08241

Catalyzed reactions (Rhea), 3 shown:

• L-lysyl-[protein] + S-adenosyl-L-methionine = N(6)-methyl-L-lysyl-[protein] + S-adenosyl-L-homocysteine + H(+) (RHEA:51736)
• N(6)-methyl-L-lysyl-[protein] + S-adenosyl-L-methionine = N(6),N(6)-dimethyl-L-lysyl-[protein] + S-adenosyl-L-homocysteine + H(+) (RHEA:54196)
• N(6),N(6)-dimethyl-L-lysyl-[protein] + S-adenosyl-L-methionine = N(6),N(6),N(6)-trimethyl-L-lysyl-[protein] + S-adenosyl-L-homocysteine + H(+) (RHEA:54200)

UniProt features (40 total): helix 12, binding site 7, strand 7, mutagenesis site 6, turn 4, chain 1, short sequence motif 1, sequence variant 1, modified residue 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2PXX	X-RAY DIFFRACTION	1.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0DPD7-F1	90.53	0.80

Functional residue map

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

Ligand- & substrate-binding residues (7): 26; 30; 41; 66; 88–89; 113–114; 130

Post-translational modifications (1): 39

Mutagenesis-validated functional residues (6):

Position	Phenotype
88	abolishes methyltransferase activity.
129	abolishes protein-lysine n-methyltransferase activity.
130	abolishes protein-lysine n-methyltransferase activity.
132	reduces protein-lysine n-methyltransferase activity.
133	reduces protein-lysine n-methyltransferase activity.
134	abolishes protein-lysine n-methyltransferase activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 17 (showing top): BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_UP, GOBP_METHYLATION, CUI_TCF21_TARGETS_2_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, KRIGE_RESPONSE_TO_TOSEDOSTAT_6HR_DN, BILD_MYC_ONCOGENIC_SIGNATURE, chr3q27, MIR4741, MIR4675, LOCKWOOD_AMPLIFIED_IN_LUNG_CANCER, GENES_CORRELATED_WITH_COL1A1_DELETION

GO Biological Process (1): methylation (GO:0032259)

GO Molecular Function (4): methyltransferase activity (GO:0008168), protein-lysine N-methyltransferase activity (GO:0016279), S-adenosylmethionine-dependent methyltransferase activity (GO:0008757), transferase activity (GO:0016740)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
metabolic process	1
transferase activity, transferring one-carbon groups	1
protein methyltransferase activity	1
lysine N-methyltransferase activity	1
methyltransferase activity	1
catalytic activity	1

Protein interactions and networks

STRING

180 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EEF1AKMT4	EEF1AKMT2	Q5JPI9	734
EEF1AKMT4	VCPKMT	Q9H867	561
EEF1AKMT4	EEF1AKMT3	Q96AZ1	513
EEF1AKMT4	METTL21A	Q8WXB1	500
EEF1AKMT4	HSF2BP	O75031	466
EEF1AKMT4	ECE2	P0DPD6	464
EEF1AKMT4	HSPB9	Q9BQS6	391
EEF1AKMT4	HSF4	Q9ULV5	371
EEF1AKMT4	ANTKMT	Q9BQD7	360
EEF1AKMT4	EEF1AKMT1	Q8WVE0	333
EEF1AKMT4	EEF1A1	P04719	323
EEF1AKMT4	CAMKMT	Q7Z624	321
EEF1AKMT4	METTL18	O95568	320
EEF1AKMT4	EEF2KMT	Q96G04	317
EEF1AKMT4	MYSM1	Q5VVJ2	308

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A5F8AH41, A0AVI4, A0JMH2, A1Y9I9, A5WVX1, B0X4N1, B4P925, D3ZX08, O55171, O88512, O95050, O97972, P0DPD7, P0DPE0, P0DPE1, P10937, P10938, P11086, P40935, P40936, Q06AU9, Q08DK0, Q14CH7, Q32PE2, Q32Q92, Q3SZG9, Q3URQ7, Q568P9, Q5E9L5, Q5JTZ9, Q5RCH4, Q5RFR7, Q6NTR1, Q6NZB1, Q7QIL2, Q7TMC8, Q80YU0, Q8HY87, Q8K304, Q8NFF5

Diamond homologs: A5PK19, A5WVX1, P0DPD7, P0DPD8, P0DPD9, P0DPE0, P0DPE1, P0DPE2, Q29LW1, Q6NTR1, Q7MF74, Q7NQK7, Q8D3Q3, Q8N6R0, Q91YR5, Q9VIK9, A8MUP2, Q5RCI5, A0A0B4K692, B2RQR8, F1N476, O16796, O44857, O95672, P07861, P08049, P08473, P0C1T0, P0DPD6, P23276, P42891, P42892, P42893, P70669, P78562, P97739, Q18673, Q22523, Q495T6, Q4PZA2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

615 predictions. Top by Δscore:

Variant	Effect	Δscore
3:184249889:AG:A	donor_loss	1.0000
3:184249890:GG:G	donor_loss	1.0000
3:184249891:G:A	donor_loss	1.0000
3:184255068:T:TA	acceptor_gain	1.0000
3:184257466:A:AG	acceptor_gain	1.0000
3:184257471:A:AG	acceptor_gain	1.0000
3:184257471:AG:A	acceptor_gain	1.0000
3:184257471:AGGTT:A	acceptor_gain	1.0000
3:184257472:G:GG	acceptor_gain	1.0000
3:184257472:GG:G	acceptor_gain	1.0000
3:184257472:GGT:G	acceptor_gain	1.0000
3:184257472:GGTT:G	acceptor_gain	1.0000
3:184257472:GGTTG:G	acceptor_gain	1.0000
3:184257752:GTGAG:G	donor_gain	1.0000
3:184257756:GGT:G	donor_loss	1.0000
3:184257757:G:A	donor_loss	1.0000
3:184249872:G:GT	donor_gain	0.9900
3:184249873:A:T	donor_gain	0.9900
3:184255064:C:G	acceptor_gain	0.9900
3:184257457:T:G	acceptor_gain	0.9900
3:184257467:C:G	acceptor_gain	0.9900
3:184257468:CCCAG:C	acceptor_gain	0.9900
3:184257469:CCAGG:C	acceptor_gain	0.9900
3:184257470:CA:C	acceptor_gain	0.9900
3:184257471:AGG:A	acceptor_gain	0.9900
3:184257472:G:T	acceptor_gain	0.9900
3:184257621:G:GT	donor_gain	0.9900
3:184257751:A:AG	donor_gain	0.9900
3:184257757:G:T	donor_gain	0.9900
3:184257762:G:GT	donor_gain	0.9900

AlphaMissense

1643 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:184257532:A:C	S86R	0.990
3:184257534:T:A	S86R	0.990
3:184257534:T:G	S86R	0.990
3:184257493:A:C	S73R	0.986
3:184257495:C:A	S73R	0.986
3:184257495:C:G	S73R	0.986
3:184257646:T:C	F124L	0.983
3:184257648:T:A	F124L	0.983
3:184257648:T:G	F124L	0.983
3:184258384:T:A	W193R	0.979
3:184258384:T:C	W193R	0.979
3:184249772:G:C	W26C	0.976
3:184249772:G:T	W26C	0.976
3:184258318:T:C	F171L	0.970
3:184258319:T:C	F171S	0.970
3:184258320:T:A	F171L	0.970
3:184258320:T:G	F171L	0.970
3:184257479:G:T	G68V	0.967
3:184257601:T:A	W109R	0.966
3:184257601:T:C	W109R	0.966
3:184257666:G:C	K130N	0.965
3:184257666:G:T	K130N	0.965
3:184257484:A:C	S70R	0.964
3:184257486:T:A	S70R	0.964
3:184257486:T:G	S70R	0.964
3:184257662:A:T	E129V	0.963
3:184257656:T:A	V127E	0.957
3:184258301:T:A	L165H	0.957
3:184258386:G:C	W193C	0.957
3:184258386:G:T	W193C	0.957

dbSNP variants (sampled 300 via entrez): RS1000109911 (3:184251773 A>G), RS1000113898 (3:184248463 A>G), RS1000528091 (3:184248123 G>A), RS1000807655 (3:184250007 G>C,T), RS1001109841 (3:184250251 G>A), RS1001724942 (3:184252444 G>A), RS1002270184 (3:184256835 T>A), RS1002435023 (3:184250385 G>GA), RS1002463467 (3:184249498 G>A,C,T), RS1002992206 (3:184253972 T>C), RS1003129033 (3:184252680 C>A,T), RS1003278081 (3:184257957 A>G), RS1003327188 (3:184257734 C>G,T), RS1003452855 (3:184251330 C>T), RS1003523651 (3:184253032 A>C,G)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression, decreases expression	2
Dichlorodiphenyl Dichloroethylene	increases expression	1
Ivermectin	decreases expression	1
Smoke	decreases expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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