ELP3

Summary

ELP3 (elongator acetyltransferase complex subunit 3, HGNC:20696) is a protein-coding gene on chromosome 8p21.1, encoding Elongator complex protein 3 (Q9H9T3). Catalytic tRNA acetyltransferase subunit 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 91.1% of cancer cell lines).

Enables acetyltransferase activity and phosphorylase kinase regulator activity. Involved in regulation of transcription by RNA polymerase II and tRNA wobble uridine modification. Located in cytosol and nucleolus. Part of elongator holoenzyme complex.

Source: NCBI Gene 55140 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 90 total
• Phenotypes (HPO): 1
• Cancer dependency (DepMap): dependent in 91.1% of screened cell lines (common-essential)
• MANE Select transcript: NM_018091

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20696
Approved symbol	ELP3
Name	elongator acetyltransferase complex subunit 3
Location	8p21.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10422, KAT9
Ensembl gene	ENSG00000134014
Ensembl biotype	protein_coding
OMIM	612722
Entrez	55140

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 16 protein_coding, 3 nonsense_mediated_decay, 3 retained_intron, 3 protein_coding_CDS_not_defined

ENST00000256398, ENST00000517975, ENST00000518112, ENST00000519261, ENST00000520011, ENST00000520110, ENST00000520270, ENST00000520288, ENST00000521015, ENST00000521099, ENST00000521570, ENST00000521938, ENST00000522063, ENST00000523357, ENST00000523687, ENST00000523760, ENST00000524103, ENST00000537665, ENST00000697968, ENST00000900016, ENST00000900017, ENST00000900018, ENST00000924638, ENST00000924639, ENST00000924640

RefSeq mRNA: 6 — MANE Select: NM_018091 NM_001284220, NM_001284222, NM_001284224, NM_001284225, NM_001284226, NM_018091

CCDS: CCDS6065, CCDS64861, CCDS75717, CCDS75718

Canonical transcript exons

ENST00000256398 — 15 exons

Exon	Start	End
ENSE00002092374	28093139	28093233
ENSE00003465508	28097219	28097318
ENSE00003467377	28099828	28099966
ENSE00003472584	28155942	28156032
ENSE00003496910	28129502	28129663
ENSE00003505804	28106713	28106783
ENSE00003509044	28160229	28160456
ENSE00003515452	28161997	28162078
ENSE00003521905	28158568	28158633
ENSE00003612855	28137698	28137891
ENSE00003614181	28132278	28132404
ENSE00003667343	28110370	28110438
ENSE00003668799	28107913	28107976
ENSE00003791547	28113019	28113173
ENSE00003842926	28189649	28191153

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 97.46.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.3962 / max 332.3969, expressed in 1814 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
88187	27.2060	1814
88186	0.0983	11
205140	0.0920	67

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	97.46	gold quality
Brodmann (1909) area 23	UBERON:0013554	95.50	gold quality
middle temporal gyrus	UBERON:0002771	94.75	gold quality
endometrium	UBERON:0001295	93.95	gold quality
calcaneal tendon	UBERON:0003701	92.99	gold quality
tendon	UBERON:0000043	92.43	gold quality
colonic epithelium	UBERON:0000397	92.29	gold quality
adrenal tissue	UBERON:0018303	92.05	gold quality
germinal epithelium of ovary	UBERON:0001304	91.79	gold quality
medial globus pallidus	UBERON:0002477	91.66	gold quality
primary visual cortex	UBERON:0002436	91.50	gold quality
seminal vesicle	UBERON:0000998	91.18	gold quality
islet of Langerhans	UBERON:0000006	90.79	gold quality
globus pallidus	UBERON:0001875	90.41	gold quality
lateral nuclear group of thalamus	UBERON:0002736	90.41	gold quality
occipital lobe	UBERON:0002021	90.33	gold quality
muscle of leg	UBERON:0001383	90.03	gold quality
gastrocnemius	UBERON:0001388	89.95	gold quality
parietal pleura	UBERON:0002400	89.95	gold quality
hindlimb stylopod muscle	UBERON:0004252	89.75	gold quality
cortical plate	UBERON:0005343	89.74	gold quality
corpus callosum	UBERON:0002336	89.69	gold quality
muscle organ	UBERON:0001630	89.27	gold quality
skeletal muscle organ	UBERON:0014892	89.27	gold quality
superior vestibular nucleus	UBERON:0007227	89.05	gold quality
triceps brachii	UBERON:0001509	88.92	gold quality
visceral pleura	UBERON:0002401	88.84	gold quality
amniotic fluid	UBERON:0000173	88.77	gold quality
uterus	UBERON:0000995	88.66	gold quality
tendon of biceps brachii	UBERON:0008188	88.66	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.36

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): STAT1, TAF1

miRNA regulators (miRDB)

53 targeting ELP3, 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-548C-3P	99.99	74.01	7587
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-548AU-3P	99.70	68.22	1373
HSA-MIR-7161-5P	99.68	68.92	1592
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-548U	99.65	67.78	1463
HSA-MIR-567	99.63	68.57	1219
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-6126	99.62	68.09	996
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-6832-5P	99.58	64.82	1132
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-136-5P	99.50	67.26	1153
HSA-MIR-217-5P	99.49	69.93	1419
HSA-MIR-519D-5P	99.41	69.30	2057
HSA-MIR-297	99.40	69.58	1418
HSA-MIR-6828-5P	99.31	69.21	1433
HSA-MIR-6815-3P	99.13	68.98	1530
HSA-MIR-4424	98.91	70.33	1145
HSA-MIR-6894-5P	98.70	63.78	809
HSA-MIR-496	98.66	69.80	931
HSA-MIR-7155-5P	98.65	66.14	1290

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 91.1% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 13)

• We used hELP3 antisense oligonucl. to knock down hELP3 gene. The results showed that reduction of hELP3 mRNA and protein caused a suppression of HSP70-2 and histone H3 hypoacetylation. (PMID:17558451)
• Allelic variants of ELP3 were associated with amyotrophic lateral sclerosis in three populations comprising 1483 people. (PMID:18996918)
• ELP3 localises to mitochondria in HeLa cells, actin-like filaments, and actin-rich sites at the edges of spreading cells. This suggests that ELP3 and the ELONGATOR complex may play a role in mitochondrial function, actin organisation, and cell motility. (PMID:19429107)
• Elp3 promotes the acetylation of alpha-tubulin in microtubules in neurological disorders. (PMID:20036197)
• The results of this study uncover a novel role for Elp3 in the regulation of synaptic bouton expansion during neurogenesis that may be linked with a requirement for sleep. (PMID:20626565)
• data suggest that hElp3 can regulate the transcription of HSP70 gene, and the HAT domain of hElp3 is essential for this function (PMID:22216241)
• Regulation of G6PD acetylation by SIRT2 and KAT9 modulates NADPH homeostasis and cell survival during oxidative stress. (PMID:24769394)
• Promoter hypermethylation is an important mechanism of the transcriptional inactivation of ELP3 in invasive ductal breast carcinoma. (PMID:25148870)
• and CTU1/2, partner enzymes in U34 methoxycarbonylmethyl-2-thio tRNA modification, are up-regulated in human breast cancers and sustain metastasis. (PMID:27811057)
• Elongator activated migration and invasion of hepatocellular carcinoma cells by promoting the expression of MMP-2 and MMP-9 through the PI3K/AKT signaling pathway (PMID:29805303)
• study reveals a novel regulatory mechanism for ELP3, provides an example that acetyltransferase itself can be regulated by PTM, and suggests a potential target for ALK-positive cancer therapies. (PMID:31341009)
• Relation between the circular and linear form of the Elongator Acetyltransferase Complex Subunit 3 in the progression of triple-negative breast cancer. (PMID:35722999)
• Amyloid pathology reduces ELP3 expression and tRNA modifications leading to impaired proteostasis. (PMID:37640114)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	elp3	ENSDARG00000042005
mus_musculus	Elp3	ENSMUSG00000022031
rattus_norvegicus	Elp3	ENSRNOG00000014291
drosophila_melanogaster	Elp3	FBGN0031604
caenorhabditis_elegans		WBGENE00014123

Protein

Protein identifiers

Elongator complex protein 3 — Q9H9T3 (reviewed: Q9H9T3)

Alternative names: tRNA uridine(34) acetyltransferase

All UniProt accessions (10): B4DKA4, Q9H9T3, E5RG26, E5RHR2, E5RHY2, E5RIC0, E5RIU1, E5RIZ7, H0YAP7, H0YC54

UniProt curated annotations — full annotation on UniProt →

Function. Catalytic tRNA acetyltransferase subunit 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). In the elongator complex, acts as a tRNA uridine(34) acetyltransferase by mediating formation of carboxymethyluridine in the wobble base at position 34 in tRNAs. May also act as a protein lysine acetyltransferase by mediating acetylation of target proteins; such activity is however unclear in vivo and recent evidences suggest that ELP3 primarily acts as a tRNA acetyltransferase. Not a major acetyltransferase of tubulin. Involved in neurogenesis: regulates the migration and branching of projection neurons in the developing cerebral cortex, through a process depending on alpha-tubulin acetylation. Required for acetylation of GJA1 in the developing cerebral cortex.

Subunit / interactions. Component of the elongator complex which consists of ELP1, ELP2, ELP3, ELP4, ELP5 and ELP6. ELP1, ELP2 and ELP3 form the elongator core complex. Interacts with alpha-tubulin.

Subcellular location. Cytoplasm. Nucleus Nucleus Cytoplasm. Nucleus.

Tissue specificity. Expressed in the cerebellum and spinal motor neurons.

Post-translational modifications. Tyrosine-phosphorylated; phosphorylation on Tyr-202 does not affect elongator complex integrity or ELP3 protein stability. Also serine/threonine-phosphorylated.

Disease relevance. Amyotrophic lateral sclerosis (ALS) [MIM:105400] A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases. The gene represented in this entry may act as a disease modifier.

Cofactor. Binds 1 [4Fe-4S] cluster. The cluster is coordinated with 3 cysteines and an exchangeable S-adenosyl-L-methionine.

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

Similarity. Belongs to the ELP3 family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9H9T3-1	1	yes
Q9H9T3-2	2
Q9H9T3-4	3
Q9H9T3-5	4

RefSeq proteins (6): NP_001271149, NP_001271151, NP_001271153, NP_001271154, NP_001271155, NP_060561* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000182	GNAT_dom	Domain
IPR006638	Elp3/MiaA/NifB-like_rSAM	Domain
IPR007197	rSAM	Domain
IPR016181	Acyl_CoA_acyltransferase	Homologous_superfamily
IPR032432	Radical_SAM_C	Domain
IPR034687	ELP3-like	Family
IPR039661	ELP3	Family
IPR056591	ELP3-like_N	Domain
IPR058240	rSAM_sf	Homologous_superfamily

Pfam: PF04055, PF16199, PF23613

Enzyme classification (BRENDA):

• EC 2.3.1.48 — histone acetyltransferase (BRENDA: 41 organisms, 681 substrates, 1134 inhibitors, 140 Km, 96 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
ACETYL-COA	0.0002–0.046	51
HISTONE H3	0.007–2.09	23
HISTONE H4	—	11
HISTONE H4 PEPTIDE	0.0208–0.197	7
HISTONE	0.075–1.4	6
HISTONE H3 TAIL PEPTIDE	0.044–0.112	4
PICCOLONUA4 PEPTIDE	0.135–0.372	4
3-AZIDOPROPIONYL-COA	0.0002–0.0086	3
4-PENTYNOYL-COA	0.0009–0.0859	3
SPERMIDINE	0.18–0.27	3
5-HEXYNOYL-COA	0.0006–0.0117	2
6-HEPTYNOYL-COA	0.0003–0.0237	2
HISTONE H3-PEPTIDE	0.05–0.49	2
PROTEIN P53	1.28–4.63	2
3-AZIDOPROPANOYL-COA	0.0103	1

Catalyzed reactions (Rhea), 1 shown:

• uridine(34) in tRNA + acetyl-CoA + S-adenosyl-L-methionine + H2O = 5-(carboxymethyl)uridine(34) in tRNA + 5’-deoxyadenosine + L-methionine + CoA + 2 H(+) (RHEA:61020)

UniProt features (78 total): helix 26, strand 19, binding site 7, mutagenesis site 6, turn 5, modified residue 4, splice variant 4, sequence conflict 4, domain 2, chain 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
8PTX	ELECTRON MICROSCOPY	2.87
8PTZ	ELECTRON MICROSCOPY	3.35
8PTY	ELECTRON MICROSCOPY	3.58
8PU0	ELECTRON MICROSCOPY	4.25

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H9T3-F1	92.03	0.78

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): 99; 109; 112; 164; 474–477; 497–499; 530

Post-translational modifications (4): 161, 202, 229, 251

Mutagenesis-validated functional residues (6):

Position	Phenotype
202	substantial reduction in tyrosine phosphorylation.
207	no effect on tyrosine phosphorylation.
251	small reduction in tyrosine phosphorylation.
318	no effect on tyrosine phosphorylation.
329	no effect on tyrosine phosphorylation.
427	no effect on tyrosine phosphorylation.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-3214847	HATs acetylate histones

MSigDB gene sets: 186 (showing top): GOBP_TRNA_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_NEUROGENESIS, GOBP_TRANSLATION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOBP_RNA_MODIFICATION, chr8p21, GOBP_NEURON_MIGRATION, DODD_NASOPHARYNGEAL_CARCINOMA_UP, IVANOVA_HEMATOPOIESIS_EARLY_PROGENITOR, GOBP_TRNA_PROCESSING, GOBP_TRNA_MODIFICATION, GOBP_REGULATION_OF_TRANSLATION, MARSON_BOUND_BY_FOXP3_UNSTIMULATED, GOCC_NUCLEOLUS

GO Biological Process (9): neuron migration (GO:0001764), tRNA wobble uridine modification (GO:0002098), tRNA wobble base 5-methoxycarbonylmethyl-2-thiouridinylation (GO:0002926), regulation of transcription by RNA polymerase II (GO:0006357), regulation of translation (GO:0006417), central nervous system development (GO:0007417), positive regulation of cell migration (GO:0030335), nervous system development (GO:0007399), tRNA processing (GO:0008033)

GO Molecular Function (13): tRNA binding (GO:0000049), acetyltransferase activity (GO:0016407), metal ion binding (GO:0046872), 4 iron, 4 sulfur cluster binding (GO:0051539), tRNA uridine(34) acetyltransferase activity (GO:0106261), RNA binding (GO:0003723), catalytic activity (GO:0003824), protein binding (GO:0005515), phosphorylase kinase regulator activity (GO:0008607), transferase activity (GO:0016740), acyltransferase activity (GO:0016746), acyltransferase activity, transferring groups other than amino-acyl groups (GO:0016747), iron-sulfur cluster binding (GO:0051536)

GO Cellular Component (5): nucleus (GO:0005634), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), elongator holoenzyme complex (GO:0033588)

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
cell migration	2
system development	2
cellular anatomical structure	2
generation of neurons	1
tRNA wobble base modification	1
tRNA wobble uridine modification	1
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
translation	1
post-transcriptional regulation of gene expression	1
regulation of protein metabolic process	1
nervous system development	1
regulation of cell migration	1
positive regulation of cell motility	1
RNA processing	1
tRNA metabolic process	1
RNA binding	1
acyltransferase activity, transferring groups other than amino-acyl groups	1
cation binding	1
iron-sulfur cluster binding	1
acetyltransferase activity	1
catalytic activity, acting on a tRNA	1
nucleic acid binding	1
molecular_function	1
binding	1
phosphorylase kinase activity	1
protein kinase regulator activity	1
catalytic activity	1
transferase activity	1
acyltransferase activity	1
metal cluster binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
cytoplasm	1
intracellular protein-containing complex	1
catalytic complex	1

Protein interactions and networks

STRING

2880 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ELP3	ELP1	O95163	986
ELP3	ELP4	Q96EB1	972
ELP3	ELP2	Q6IA86	970
ELP3	ELP6	Q0PNE2	939
ELP3	ELP5	Q8TE02	914
ELP3	CTU1	Q7Z7A3	879
ELP3	DPH3	Q96FX2	835
ELP3	KTI12	Q96EK9	805
ELP3	KAT2A	Q92830	739
ELP3	ALKBH8	Q96BT7	736
ELP3	KAT2B	Q92831	730
ELP3	URM1	Q9BTM9	718
ELP3	CTU2	Q2VPK5	709
ELP3	FGGY	Q96C11	693
ELP3	MOCS3	O95396	665

IntAct

63 interactions, top by confidence:

A	B	Type	Score
ELP1	ELP3	psi-mi:“MI:0915”(physical association)	0.840
ELP3	ELP1	psi-mi:“MI:0915”(physical association)	0.840
PRPS1	PRPSAP2	psi-mi:“MI:0914”(association)	0.840
ELP3	ELP1	psi-mi:“MI:0914”(association)	0.840
ELP2	ELP1	psi-mi:“MI:0914”(association)	0.620
ELP1	ELP2	psi-mi:“MI:0914”(association)	0.620
ELP1	ELP2	psi-mi:“MI:0915”(physical association)	0.620
ELP4	ELP1	psi-mi:“MI:0914”(association)	0.600
FOXP3	FOXP2	psi-mi:“MI:0914”(association)	0.530
SLC31A1	C2orf72	psi-mi:“MI:0914”(association)	0.530
PSME1	POLR3A	psi-mi:“MI:0914”(association)	0.530
KPTN	EIF4G3	psi-mi:“MI:0914”(association)	0.530
IFI30	PRC1	psi-mi:“MI:0914”(association)	0.530
PLEKHN1	ELP1	psi-mi:“MI:0914”(association)	0.530
ELP1	ELP5	psi-mi:“MI:0914”(association)	0.460
ELP5	ELP1	psi-mi:“MI:0914”(association)	0.460
PGK1	ELP3	psi-mi:“MI:0915”(physical association)	0.400
ELP3	GJA1	psi-mi:“MI:0915”(physical association)	0.400
ELP3	POLR2A	psi-mi:“MI:0915”(physical association)	0.400
PPP5C	SNRNP200	psi-mi:“MI:0914”(association)	0.350
ATXN7L1	ELP1	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350

BioGRID (181): ELP3 (Affinity Capture-MS), ELP3 (Affinity Capture-MS), ELP3 (Affinity Capture-MS), ELP3 (Affinity Capture-MS), ELP3 (Affinity Capture-MS), ELP3 (Affinity Capture-MS), ELP3 (Affinity Capture-MS), ELP3 (Affinity Capture-MS), ELP3 (Affinity Capture-MS), ELP2 (Co-fractionation), ELP3 (Co-fractionation), WDR36 (Co-fractionation), ELP3 (Affinity Capture-MS), ELP3 (Affinity Capture-MS), ELP3 (Affinity Capture-MS)

ESM2 similar proteins: A0A365, A0QHM5, A0QX51, A1KIW9, A4FIS6, B1W5F4, B8ZR76, O88956, P00165, P16298, P20651, P31350, P37273, P48452, P48453, P63328, P63329, P65263, P9WK98, P9WK99, Q06GW7, Q06RA2, Q08209, Q0G9I9, Q0G9T2, Q0ZIY9, Q1KXS9, Q2KJ61, Q2PMQ5, Q332U7, Q33C02, Q3C1M5, Q4R7Q7, Q4VZI6, Q5HZM6, Q5RIC0, Q5ZHS1, Q68RX7, Q6ENT4, Q6EW22

Diamond homologs: A0A1C7D1B7, D5VRB9, O14023, P0ADW6, P0ADW7, Q02908, Q1ZXC6, Q23651, Q2KJ61, Q58536, Q5HZM6, Q5RIC0, Q5ZHS1, Q60LW7, Q6NVL5, Q7X7L3, Q93ZR1, Q9CZX0, Q9H9T3, Q9VQZ6, Q57910, Q58882

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ELP3	“form complex”	“Elongator complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	61
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

2283 predictions. Top by Δscore:

Variant	Effect	Δscore
8:28097215:CCAG:C	acceptor_loss	1.0000
8:28097217:A:AG	acceptor_gain	1.0000
8:28097217:A:C	acceptor_loss	1.0000
8:28097217:AG:A	acceptor_gain	1.0000
8:28097218:G:GA	acceptor_gain	1.0000
8:28097218:G:GT	acceptor_loss	1.0000
8:28097218:GG:G	acceptor_gain	1.0000
8:28097218:GGA:G	acceptor_gain	1.0000
8:28097314:AATAA:A	donor_gain	1.0000
8:28097315:A:G	donor_gain	1.0000
8:28097315:ATAA:A	donor_gain	1.0000
8:28097316:TAA:T	donor_gain	1.0000
8:28097316:TAAG:T	donor_loss	1.0000
8:28097317:AA:A	donor_gain	1.0000
8:28097317:AAGTA:A	donor_loss	1.0000
8:28097318:AGT:A	donor_loss	1.0000
8:28097319:G:GG	donor_gain	1.0000
8:28097320:T:A	donor_loss	1.0000
8:28099824:TCA:T	acceptor_loss	1.0000
8:28099825:CA:C	acceptor_loss	1.0000
8:28099826:A:AG	acceptor_gain	1.0000
8:28099826:A:T	acceptor_loss	1.0000
8:28099826:AG:A	acceptor_gain	1.0000
8:28099826:AGGGT:A	acceptor_gain	1.0000
8:28099827:G:GT	acceptor_gain	1.0000
8:28099827:GG:G	acceptor_gain	1.0000
8:28099827:GGGT:G	acceptor_gain	1.0000
8:28099827:GGGTG:G	acceptor_gain	1.0000
8:28099962:GTGGG:G	donor_gain	1.0000
8:28099964:GGG:G	donor_gain	1.0000

AlphaMissense

3562 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:28099953:G:C	R82T	1.000
8:28099954:A:C	R82S	1.000
8:28099954:A:T	R82S	1.000
8:28099961:A:C	S85R	1.000
8:28099963:T:A	S85R	1.000
8:28099963:T:G	S85R	1.000
8:28099964:G:T	G86W	1.000
8:28099965:G:A	G86E	1.000
8:28106726:C:A	A91D	1.000
8:28106732:T:A	M93K	1.000
8:28106732:T:G	M93R	1.000
8:28106749:T:A	C99S	1.000
8:28106749:T:C	C99R	1.000
8:28106750:G:A	C99Y	1.000
8:28106750:G:C	C99S	1.000
8:28106751:T:G	C99W	1.000
8:28106779:T:C	C109R	1.000
8:28106780:G:A	C109Y	1.000
8:28106781:T:G	C109W	1.000
8:28107917:T:C	C112R	1.000
8:28107918:G:A	C112Y	1.000
8:28107919:C:G	C112W	1.000
8:28107924:G:A	G114D	1.000
8:28107927:G:A	G115E	1.000
8:28107941:T:C	F120L	1.000
8:28107943:T:A	F120L	1.000
8:28107943:T:G	F120L	1.000
8:28107951:C:T	S123F	1.000
8:28107962:T:C	Y127H	1.000
8:28107969:G:A	G129D	1.000

dbSNP variants (sampled 300 via entrez): RS1000018571 (8:28158419 T>C,G), RS1000045837 (8:28175364 C>T), RS1000054473 (8:28108218 A>C), RS1000084961 (8:28145780 C>T), RS1000090768 (8:28150980 G>T), RS1000098660 (8:28088911 C>T), RS1000106927 (8:28130072 A>T), RS1000114060 (8:28140559 G>C), RS1000121765 (8:28182138 G>A), RS1000137731 (8:28131715 C>G,T), RS1000248534 (8:28188926 C>T), RS1000254401 (8:28125418 A>G), RS1000274 (8:28127661 A>G,T), RS1000275 (8:28127412 A>G), RS1000283200 (8:28112641 T>A,C)

Disease associations

OMIM: gene MIM:612722 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): amyotrophic lateral sclerosis (MONDO:0004976)

Orphanet (1): Amyotrophic lateral sclerosis (Orphanet:803)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0007354	Amyotrophic lateral sclerosis

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST003177_15	Childhood body mass index	5.000000e-09
GCST004904_78	Body mass index	4.000000e-08
GCST007400_64	Systemic lupus erythematosus	4.000000e-06
GCST010725_67	Malaria	1.000000e-06
GCST010988_291	Adult body size	4.000000e-08
GCST010989_137	Body size at age 10	8.000000e-12
GCST90002409_18	Childhood body mass index	7.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0009819	comparative body size at age 10, self-reported

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D000690	Amyotrophic Lateral Sclerosis	C10.228.854.139; C10.574.562.250; C10.574.950.050; C10.668.467.250; C18.452.845.800.050

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — 2.3.1.48 Histone acetyltransferases (HATs)

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	2
Acrolein	affects cotreatment, increases oxidation, increases abundance	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	2
Nickel	decreases expression, increases expression	2
Ozone	affects cotreatment, increases oxidation, increases abundance	2
Valproic Acid	affects expression, decreases expression	2
bufotalin	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	increases expression	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
di-n-butylphosphoric acid	affects expression	1
Acetaminophen	decreases expression	1
Air Pollutants, Occupational	decreases expression	1
Caffeine	affects phosphorylation	1
Doxorubicin	decreases expression	1
Ivermectin	decreases expression	1
Lead	decreases expression	1
Tetrachlorodibenzodioxin	decreases expression, increases expression	1
Sodium Selenite	increases expression	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1
Volatile Organic Compounds	increases oxidation, affects cotreatment	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00542412	PHASE4	COMPLETED	CARE Canadian ALS Riluzole Evaluation
NCT00560287	PHASE4	UNKNOWN	Non-Invasive Ventilation in Amyotrophic Lateral Sclerosis
NCT00613899	PHASE4	COMPLETED	Feasibility of Telesurveillance and Home Cough Assistance for Amyotrophic Lateral Patients (ALS)
NCT04997954	PHASE4	UNKNOWN	EMERALD TRIAL Open Label Extension Study
NCT06849115	PHASE4	COMPLETED	Effects of L-Carnitine in Amyotrophic Lateral Sclerosis Patients With CHCHD10 Mutations
NCT07223723	PHASE4	RECRUITING	A Study to Learn More About the Long-Term Safety of Tofersen (Qalsody) in Chinese Participants With SOD-1 Amyotrophic Lateral Sclerosis (ALS)
NCT00021697	PHASE3	COMPLETED	Safety/Efficacy of AVP-923 in the Treatment of Emotional Lability (Uncontrolled Crying & Laughing) in Patients With ALS
NCT00035815	PHASE3	COMPLETED	Insulin-like Growth Factor-1 in Amyotrophic Lateral Sclerosis (ALS) Trial
NCT00047723	PHASE3	COMPLETED	Minocycline to Treat Amyotrophic Lateral Sclerosis
NCT00069186	PHASE3	UNKNOWN	Study of Creatine Monohydrate in Patients With Amyotrophic Lateral Sclerosis
NCT00136110	PHASE3	COMPLETED	Trial of Sodium Valproate in Amyotrophic Lateral Sclerosis
NCT00330681	PHASE3	COMPLETED	Efficacy and Safety Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis (ALS)
NCT00349622	PHASE3	COMPLETED	Clinical Trial Ceftriaxone in Subjects With ALS
NCT00372879	PHASE3	COMPLETED	Clinical Trial of Vitamin E to Treat Muscular Cramps in Patients With ALS
NCT00415519	PHASE3	COMPLETED	Efficacy and Safety Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis (ALS) Who Met Severity Classification III
NCT00424463	PHASE3	COMPLETED	Expanded Controlled Study of Safety and Efficacy of MCI-186 in Patients With Amyotrophic Lateral Sclerosis (ALS)
NCT00839033	PHASE3	TERMINATED	Evaluation of a Mechanical Device During Acute Respiratory Failure in Patients With Neuromuscular Disorders
NCT00868166	PHASE3	COMPLETED	Safety and Efficacy of TRO19622 as add-on Therapy to Riluzole Versus Placebo in Treatment of Patients Suffering From ALS
NCT00965497	PHASE3	COMPLETED	Escitalopram (Lexapro) for Depression MS or ALS
NCT01016522	PHASE3	TERMINATED	Safety and Tolerability of the Ketogenic Diet in Amyotrophic Lateral Sclerosis (ALS)
NCT01160263	PHASE3	COMPLETED	Study of Dopamine and Serotonin Transporters in Patients With Amyotrophic Lateral Sclerosis and Controls
NCT01281189	PHASE3	COMPLETED	Phase 3 Study of Dexpramipexole in ALS
NCT01492686	PHASE3	COMPLETED	Phase 3 Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis
NCT01583088	PHASE3	TERMINATED	Early Stage Amyotrophic Lateral Sclerosis Phrenic Stimulation
NCT01622088	PHASE3	TERMINATED	Phase 3 Extension Study of Dexpramipexole in ALS
NCT02496767	PHASE3	COMPLETED	Ventilatory Investigation of Tirasemtiv and Assessment of Longitudinal Indices After Treatment for a Year
NCT02623699	PHASE3	COMPLETED	An Efficacy, Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of BIIB067 (Tofersen) in Adults With Inherited Amyotrophic Lateral Sclerosis (ALS)
NCT02936635	PHASE3	COMPLETED	A Study for Patients Who Completed VITALITY-ALS (CY 4031)
NCT03127267	PHASE3	RECRUITING	Efficacy and Safety of Masitinib Versus Placebo in the Treatment of ALS Patients
NCT03280056	PHASE3	COMPLETED	Safety and Efficacy of Repeated Administrations of NurOwn® in ALS Patients
NCT03491462	PHASE3	COMPLETED	Arimoclomol in Amyotropic Lateral Sclerosis
NCT03505021	PHASE3	COMPLETED	Effects of Oral Levosimendan (ODM-109) on Respiratory Function in Patients With ALS
NCT03548311	PHASE3	COMPLETED	Clinical Trial of Ultra-high Dose Methylcobalamin for ALS
NCT03690791	PHASE3	UNKNOWN	Efficacy of Cannabinoids in Amyotrophic Lateral Sclerosis or Motor Neurone Disease
NCT03800524	PHASE3	UNKNOWN	Safety and Efficacy of TUDCA as add-on Treatment in Patients Affected by ALS
NCT03836716	PHASE3	TERMINATED	Arimoclomol in Amyotropic Lateral Sclerosis - Open Label Extension Trial
NCT03948178	PHASE3	TERMINATED	Effects of Oral Levosimendan on Respiratory Function in Patients With Amyotrophic Lateral Sclerosis (ALS): Open-Label Extension
NCT04165824	PHASE3	COMPLETED	Safety Study of Oral Edaravone Administered in Subjects With ALS
NCT04248465	PHASE3	TERMINATED	An Efficacy and Safety Study of Ravulizumab in ALS Participants
NCT04569084	PHASE3	TERMINATED	Efficacy and Safety Study of Oral Edaravone Administered in Subjects With ALS