ELP6

Summary

ELP6 (elongator acetyltransferase complex subunit 6, HGNC:25976) is a protein-coding gene on chromosome 3p21.31, encoding Elongator complex protein 6 (Q0PNE2). Component of the elongator complex which is required for multiple tRNA modifications, including mcm5U (5-methoxycarbonylmethyl uridine), mcm5s2U (5-methoxycarbonylmethyl-2-thiouridine), and ncm5U (5-carbamoylmethyl uridine). It is a common-essential gene (DepMap: required in 92.7% of cancer cell lines).

Predicted to be involved in positive regulation of cell migration. Predicted to act upstream of or within several processes, including autophagosome maturation; gene expression; and homeostasis of number of retina cells. Located in cytosol and nucleus. Part of elongator holoenzyme complex.

Source: NCBI Gene 54859 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 56 total — 1 likely-pathogenic
• Cancer dependency (DepMap): dependent in 92.7% of screened cell lines (common-essential)
• MANE Select transcript: NM_001031703

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25976
Approved symbol	ELP6
Name	elongator acetyltransferase complex subunit 6
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20211
Ensembl gene	ENSG00000163832
Ensembl biotype	protein_coding
OMIM	615020
Entrez	54859

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 15 protein_coding, 4 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000296149, ENST00000412761, ENST00000414236, ENST00000425291, ENST00000439305, ENST00000442215, ENST00000444760, ENST00000445044, ENST00000446787, ENST00000449409, ENST00000460502, ENST00000461208, ENST00000483205, ENST00000485029, ENST00000494161, ENST00000896657, ENST00000896658, ENST00000896659, ENST00000923767, ENST00000923768, ENST00000923769, ENST00000923770

RefSeq mRNA: 23 — MANE Select: NM_001031703 NM_001031703, NM_001363957, NM_001424210, NM_001424211, NM_001424212, NM_001424213, NM_001424214, NM_001424215, NM_001424216, NM_001424217, NM_001424218, NM_001424219, NM_001424220, NM_001424222, NM_001424223, NM_001424224, NM_001424225, NM_001424226, NM_001424227, NM_001424228, NM_001424229, NM_001424230, NM_001424231

CCDS: CCDS43082, CCDS87073

Canonical transcript exons

ENST00000296149 — 7 exons

Exon	Start	End
ENSE00001811169	47495640	47496197
ENSE00001820378	47513537	47513712
ENSE00003472764	47501650	47501851
ENSE00003550128	47510184	47510254
ENSE00003647031	47511148	47511226
ENSE00003647419	47504330	47504448
ENSE00003788426	47498286	47498432

Expression profiles

Bgee: expression breadth ubiquitous, 247 present calls, max score 93.50.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.4374 / max 107.5337, expressed in 1792 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
42046	11.3996	1781
42045	3.0378	1373

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right adrenal gland	UBERON:0001233	93.50	gold quality
right adrenal gland cortex	UBERON:0035827	93.48	gold quality
left adrenal gland	UBERON:0001234	92.85	gold quality
left adrenal gland cortex	UBERON:0035825	92.74	gold quality
apex of heart	UBERON:0002098	92.30	gold quality
adrenal gland	UBERON:0002369	91.80	gold quality
adrenal cortex	UBERON:0001235	91.70	gold quality
right testis	UBERON:0004534	91.35	gold quality
left testis	UBERON:0004533	91.22	gold quality
metanephros cortex	UBERON:0010533	90.96	gold quality
right ovary	UBERON:0002118	90.51	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	90.42	gold quality
islet of Langerhans	UBERON:0000006	90.41	gold quality
prefrontal cortex	UBERON:0000451	90.37	gold quality
left ovary	UBERON:0002119	90.34	gold quality
adrenal tissue	UBERON:0018303	90.15	gold quality
mucosa of transverse colon	UBERON:0004991	89.97	gold quality
testis	UBERON:0000473	89.90	gold quality
smooth muscle tissue	UBERON:0001135	89.67	gold quality
adenohypophysis	UBERON:0002196	89.64	gold quality
right lobe of thyroid gland	UBERON:0001119	89.55	gold quality
right lobe of liver	UBERON:0001114	89.41	gold quality
muscle of leg	UBERON:0001383	89.38	gold quality
gastrocnemius	UBERON:0001388	89.35	gold quality
Brodmann (1909) area 9	UBERON:0013540	89.33	gold quality
metanephros	UBERON:0000081	89.32	gold quality
hypothalamus	UBERON:0001898	89.30	gold quality
putamen	UBERON:0001874	89.23	gold quality
anterior cingulate cortex	UBERON:0009835	89.21	gold quality
stromal cell of endometrium	CL:0002255	89.18	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.24

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 92.7% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 2)

• data identify DERP6/ELP5 and C3ORF75/ELP6 as key players for migration, invasion and tumorigenicity of melanoma cells, as integral subunits of Elongator. (PMID:22854966)
• ELP6 is expressed intracellularly in developing and mature granulocytes and monocytes but not in lymphocytes and erythrocytes. (PMID:24284306)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	elp6	ENSDARG00000060445
mus_musculus	Elp6	ENSMUSG00000054836
rattus_norvegicus	Elp6	ENSRNOG00000020847

Protein

Protein identifiers

Elongator complex protein 6 — Q0PNE2 (reviewed: Q0PNE2)

Alternative names: Angiotonin-transactivated protein 1, Protein TMEM103

All UniProt accessions (9): C9IYN7, C9J2D6, C9J9N8, C9JA82, Q0PNE2, C9JEX8, C9JLH5, F8WE64, H7BZM9

UniProt curated annotations — full annotation on UniProt →

Function. Component of the elongator complex which is required for multiple tRNA modifications, including mcm5U (5-methoxycarbonylmethyl uridine), mcm5s2U (5-methoxycarbonylmethyl-2-thiouridine), and ncm5U (5-carbamoylmethyl uridine). The elongator complex catalyzes formation of carboxymethyluridine in the wobble base at position 34 in tRNAs. Involved in cell migration.

Subunit / interactions. Component of the elongator complex which consists of ELP1, ELP2, ELP3, ELP4, ELP5 and ELP6.

Subcellular location. Cytoplasm. Nucleus.

Pathway. tRNA modification; 5-methoxycarbonylmethyl-2-thiouridine-tRNA biosynthesis.

Similarity. Belongs to the ELP6 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q0PNE2-1	1	yes
Q0PNE2-2	2

RefSeq proteins (23): NP_001026873, NP_001350886, NP_001411139, NP_001411140, NP_001411141, NP_001411142, NP_001411143, NP_001411144, NP_001411145, NP_001411146, NP_001411147, NP_001411148, NP_001411149, NP_001411151, NP_001411152, NP_001411153, NP_001411154, NP_001411155, NP_001411156, NP_001411157, NP_001411158, NP_001411159, NP_001411160 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR018627	ELP6	Family
IPR027417	P-loop_NTPase	Homologous_superfamily

Pfam: PF09807

UniProt features (3 total): splice variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q0PNE2-F1	90.70	0.76

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-3214847	HATs acetylate histones

MSigDB gene sets: 131 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, GOBP_BEHAVIOR, GOBP_INFLAMMATORY_RESPONSE, GOBP_TRNA_METABOLIC_PROCESS, GOBP_NEUROGENESIS, GOBP_NEUROMUSCULAR_PROCESS_CONTROLLING_BALANCE, GOBP_MACROAUTOPHAGY, GOBP_TRANSLATION, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_PROTEIN_MATURATION, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, GOBP_RNA_MODIFICATION

GO Biological Process (21): tRNA wobble uridine modification (GO:0002098), translation (GO:0006412), regulation of translation (GO:0006417), protein folding (GO:0006457), response to unfolded protein (GO:0006986), locomotory behavior (GO:0007626), ubiquitin recycling (GO:0010992), positive regulation of cell migration (GO:0030335), cellular response to stress (GO:0033554), photoreceptor cell differentiation (GO:0046530), homeostasis of number of retina cells (GO:0048877), neuromuscular process controlling balance (GO:0050885), neuron apoptotic process (GO:0051402), retina development in camera-type eye (GO:0060041), motor behavior (GO:0061744), autophagosome maturation (GO:0097352), inflammasome-mediated signaling pathway (GO:0141084), autophagy (GO:0006914), apoptotic process (GO:0006915), tRNA processing (GO:0008033), neuromuscular process (GO:0050905)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (5): nucleus (GO:0005634), cytosol (GO:0005829), elongator holoenzyme complex (GO:0033588), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Chromatin modifying enzymes	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
behavior	2
tRNA wobble base modification	1
peptidyltransferase activity	1
translational initiation	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
translation	1
post-transcriptional regulation of gene expression	1
regulation of protein metabolic process	1
cellular process	1
protein maturation	1
response to topologically incorrect protein	1
cellular homeostasis	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
response to stress	1
cellular response to stimulus	1
neuron differentiation	1
retina homeostasis	1
homeostasis of number of cells within a tissue	1
musculoskeletal movement	1
neuromuscular process	1
apoptotic process	1
camera-type eye development	1
anatomical structure development	1
macroautophagy	1
protein-containing complex disassembly	1
cytoplasmic pattern recognition receptor signaling pathway	1
inflammatory response	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1

Protein interactions and networks

STRING

918 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ELP6	ELP4	Q96EB1	988
ELP6	ELP5	Q8TE02	980
ELP6	ELP3	Q9H9T3	939
ELP6	ELP2	Q6IA86	911
ELP6	ELP1	O95163	879
ELP6	ABCA5	Q8WWZ7	810
ELP6	ABCA7	Q8IZY2	761
ELP6	ABCA2	Q9BZC7	738
ELP6	MT-ATP6	P00846	727
ELP6	MT-ATP8	P03928	664
ELP6	ALKBH8	Q96BT7	643
ELP6	CTU1	Q7Z7A3	593
ELP6	TRMT112	Q9UI30	586
ELP6	CTU2	Q2VPK5	571
ELP6	PPP6R1	Q9UPN7	551

IntAct

20 interactions, top by confidence:

A	B	Type	Score
ELP4	ELP1	psi-mi:“MI:0914”(association)	0.600
ELP5	ELP6	psi-mi:“MI:0915”(physical association)	0.560
PIPOX	ZNF217	psi-mi:“MI:0914”(association)	0.530
DNAJB8	DNAJB6	psi-mi:“MI:0914”(association)	0.530
SLC8A1	ELP6	psi-mi:“MI:0915”(physical association)	0.400
MLH1	ELP6	psi-mi:“MI:0915”(physical association)	0.370
GATD1	MYO9A	psi-mi:“MI:0914”(association)	0.350
APBA1	KIF2A	psi-mi:“MI:0914”(association)	0.350
LYPD4	PIK3C2A	psi-mi:“MI:0914”(association)	0.350
ELP6	ZBTB25	psi-mi:“MI:0914”(association)	0.350
ELP3	ACACB	psi-mi:“MI:0914”(association)	0.350
ELP4	HSPA8	psi-mi:“MI:0914”(association)	0.350
ELP6	ELP2	psi-mi:“MI:0914”(association)	0.350
PIPOX	LALBA	psi-mi:“MI:0914”(association)	0.350
CAMK2D	PPM1D	psi-mi:“MI:0914”(association)	0.350
KLHL15	DNAJB5	psi-mi:“MI:0914”(association)	0.350
NIPA2	ELP6	psi-mi:“MI:0914”(association)	0.350

BioGRID (83): ELP4 (Affinity Capture-MS), ZBTB2 (Affinity Capture-MS), ZNF639 (Affinity Capture-MS), ELP5 (Affinity Capture-MS), ZBTB25 (Affinity Capture-MS), ELP6 (Affinity Capture-MS), ELP6 (Co-fractionation), ELP6 (Co-fractionation), ELP6 (Co-fractionation), ELP6 (Co-fractionation), ELP6 (Co-fractionation), ELP6 (Co-fractionation), ELP6 (Co-fractionation), ELP6 (Co-fractionation), ELP6 (Co-fractionation)

ESM2 similar proteins: A2AA28, A2RRH5, A2RT67, A2RUS2, B2RYG8, O09172, O75031, P0CL18, P11716, P41214, P48507, P48508, P48553, P50747, Q0IHA2, Q0PNE2, Q0V8R7, Q28CX0, Q2KHY5, Q2T9Y6, Q2TBH1, Q2TBN5, Q3SZD4, Q3T0J1, Q3TLI0, Q499N3, Q4VBE8, Q568M3, Q58CR3, Q5RA63, Q5RJL2, Q5TYQ1, Q6NYU2, Q8BK75, Q8BQX5, Q8CHQ0, Q8K2Q0, Q8VCX6, Q91W86, Q920N2

Diamond homologs: B2RYG8, Q0IHA2, Q0P424, Q0PNE2, Q28CX0, Q8BK75

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ELP6	“form complex”	“Elongator complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 26 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
HATs acetylate histones	5	18.9×	8e-04

GO biological processes:

GO term	Partners	Fold	FDR
regulation of translation	5	42.1×	1e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	36
Likely benign	8
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1676202	NM_001031703.3(ELP6):c.353T>G (p.Leu118Trp)	Likely pathogenic

SpliceAI

1093 predictions. Top by Δscore:

Variant	Effect	Δscore
3:47498281:CATA:C	donor_loss	1.0000
3:47498282:ATACC:A	donor_loss	1.0000
3:47498283:TAC:T	donor_loss	1.0000
3:47498284:A:C	donor_loss	1.0000
3:47498285:C:G	donor_loss	1.0000
3:47498300:C:A	donor_gain	1.0000
3:47501645:AGTAC:A	donor_loss	1.0000
3:47501646:GTA:G	donor_loss	1.0000
3:47501647:TACC:T	donor_loss	1.0000
3:47501648:A:T	donor_loss	1.0000
3:47501649:C:CA	donor_loss	1.0000
3:47501848:CTCC:C	acceptor_gain	1.0000
3:47501850:CC:C	acceptor_gain	1.0000
3:47501851:CC:C	acceptor_gain	1.0000
3:47501852:C:CC	acceptor_gain	1.0000
3:47504325:CTGA:C	donor_loss	1.0000
3:47504326:TGA:T	donor_loss	1.0000
3:47504327:GACC:G	donor_loss	1.0000
3:47504445:CACC:C	acceptor_gain	1.0000
3:47504446:ACC:A	acceptor_gain	1.0000
3:47504447:CC:C	acceptor_gain	1.0000
3:47504447:CCC:C	acceptor_gain	1.0000
3:47504448:CC:C	acceptor_gain	1.0000
3:47504449:C:CA	acceptor_loss	1.0000
3:47504449:C:CC	acceptor_gain	1.0000
3:47504449:C:T	acceptor_gain	1.0000
3:47504455:A:C	acceptor_gain	1.0000
3:47513531:TCTTA:T	donor_loss	1.0000
3:47513532:CTTAC:C	donor_loss	1.0000
3:47513534:TA:T	donor_loss	1.0000

AlphaMissense

1755 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:47496131:A:C	Y247D	0.992
3:47496130:T:G	Y247S	0.989
3:47511182:G:C	F33L	0.988
3:47511182:G:T	F33L	0.988
3:47511184:A:G	F33L	0.988
3:47496196:A:G	L225P	0.987
3:47498346:G:C	S204R	0.987
3:47498346:G:T	S204R	0.987
3:47498348:T:G	S204R	0.987
3:47498291:C:A	G223W	0.985
3:47498335:A:G	L208P	0.985
3:47498290:C:T	G223E	0.984
3:47496131:A:T	Y247N	0.982
3:47496131:A:G	Y247H	0.980
3:47496099:A:C	F257L	0.979
3:47496099:A:T	F257L	0.979
3:47496101:A:G	F257L	0.979
3:47504411:A:G	L81P	0.979
3:47511183:A:G	F33S	0.979
3:47501679:A:G	C166R	0.977
3:47498290:C:A	G223V	0.976
3:47511180:A:T	L34H	0.976
3:47510230:G:T	A53E	0.974
3:47511153:A:G	L43P	0.974
3:47511165:A:G	L39P	0.974
3:47511180:A:C	L34R	0.974
3:47498314:G:A	T215I	0.972
3:47498341:A:G	L206P	0.971
3:47510242:A:T	V49D	0.970
3:47511190:C:A	G31W	0.970

dbSNP variants (sampled 300 via entrez): RS1000006934 (3:47502207 G>A), RS1000370582 (3:47509934 G>T), RS1000510501 (3:47496947 G>C), RS1001030655 (3:47514436 A>G), RS1001145011 (3:47514673 C>T), RS1001365123 (3:47502183 T>C,G), RS1001396013 (3:47508208 A>C,T), RS1001616749 (3:47509193 C>A), RS1001677042 (3:47503628 C>T), RS1001788732 (3:47503549 G>A,T), RS1001994334 (3:47504952 C>T), RS1002108923 (3:47505172 C>T), RS1002190992 (3:47496483 A>G), RS1002866407 (3:47510482 T>C), RS1002867684 (3:47508449 G>A)

Disease associations

OMIM: gene MIM:615020 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002500_23	QT interval	3.000000e-08
GCST007268_10	Diastolic blood pressure	6.000000e-10
GCST010002_422	Refractive error	4.000000e-14

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004682	QT interval
EFO:0006336	diastolic blood pressure

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

44 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, decreases expression, affects cotreatment	3
Benzo(a)pyrene	increases mutagenesis, affects methylation	2
Hydrogen Peroxide	affects cotreatment, decreases expression, increases expression, affects expression	2
GSK-J4	decreases expression	1
bisphenol A	affects cotreatment, increases methylation	1
glycidyl methacrylate	decreases expression	1
trichostatin A	affects expression	1
beta-lapachone	decreases expression	1
sodium arsenite	increases abundance, decreases expression	1
zinc chromate	decreases expression, increases abundance	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	increases expression, affects cotreatment	1
butylparaben	increases expression	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	increases abundance, decreases expression	1
pentabromodiphenyl ether	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
NSC 689534	affects binding, decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	decreases expression, affects cotreatment	1
Fulvestrant	affects cotreatment, increases methylation	1
Leflunomide	decreases expression	1
Acetaminophen	increases expression	1
Ethanol	increases expression, affects cotreatment, increases abundance	1

Clinical trials (associated diseases)

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