ABCE1

Summary

ABCE1 (ATP binding cassette subfamily E member 1, HGNC:69) is a protein-coding gene on chromosome 4q31.21, encoding ATP-binding cassette sub-family E member 1 (P61221). Nucleoside-triphosphatase (NTPase) involved in ribosome recycling by mediating ribosome disassembly. It is a common-essential gene (DepMap: required in 99.8% of cancer cell lines).

The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the OABP subfamily. Alternatively referred to as the RNase L inhibitor, this protein functions to block the activity of ribonuclease L. Activation of ribonuclease L leads to inhibition of protein synthesis in the 2-5A/RNase L system, the central pathway for viral interferon action. Two transcript variants encoding the same protein have been found for this gene.

Source: NCBI Gene 6059 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 59 total — 4 pathogenic, 1 likely-pathogenic
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 99.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_002940

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:69
Approved symbol	ABCE1
Name	ATP binding cassette subfamily E member 1
Location	4q31.21
Locus type	gene with protein product
Status	Approved
Aliases	RLI, OABP, RLI1
Ensembl gene	ENSG00000164163
Ensembl biotype	protein_coding
OMIM	601213
Entrez	6059

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 10 protein_coding, 4 retained_intron, 2 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000296577, ENST00000502586, ENST00000502803, ENST00000504292, ENST00000504683, ENST00000506506, ENST00000507193, ENST00000509593, ENST00000510321, ENST00000515678, ENST00000877691, ENST00000877692, ENST00000877693, ENST00000877694, ENST00000877695, ENST00000877696, ENST00000936065, ENST00000936066

RefSeq mRNA: 2 — MANE Select: NM_002940 NM_001040876, NM_002940

CCDS: CCDS34071

Canonical transcript exons

ENST00000296577 — 18 exons

Exon	Start	End
ENSE00001081967	145110968	145111064
ENSE00001081970	145108015	145108112
ENSE00001081972	145117293	145117414
ENSE00001081973	145110103	145110240
ENSE00001081976	145110375	145110444
ENSE00001081977	145105605	145105690
ENSE00001081978	145109132	145109249
ENSE00002021363	145127526	145129524
ENSE00002024138	145098311	145098419
ENSE00003470684	145123215	145123357
ENSE00003568172	145123021	145123131
ENSE00003568431	145121174	145121233
ENSE00003583975	145121333	145121391
ENSE00003592817	145104386	145104515
ENSE00003601134	145119932	145120153
ENSE00003636730	145124990	145125101
ENSE00003642019	145123478	145123600
ENSE00003653728	145112239	145112328

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 95.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 46.7103 / max 975.0310, expressed in 1813 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
49893	46.7103	1813

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	95.52	gold quality
adrenal tissue	UBERON:0018303	95.46	gold quality
islet of Langerhans	UBERON:0000006	94.52	gold quality
ventricular zone	UBERON:0003053	94.36	gold quality
cortical plate	UBERON:0005343	93.41	gold quality
calcaneal tendon	UBERON:0003701	93.36	gold quality
stromal cell of endometrium	CL:0002255	93.24	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	93.21	gold quality
ganglionic eminence	UBERON:0004023	92.95	gold quality
pancreas	UBERON:0001264	92.84	gold quality
secondary oocyte	CL:0000655	92.69	gold quality
body of pancreas	UBERON:0001150	92.61	gold quality
rectum	UBERON:0001052	92.32	gold quality
vermiform appendix	UBERON:0001154	92.02	gold quality
tonsil	UBERON:0002372	91.89	gold quality
gall bladder	UBERON:0002110	91.00	gold quality
colonic epithelium	UBERON:0000397	90.85	gold quality
embryo	UBERON:0000922	90.77	gold quality
lymph node	UBERON:0000029	90.74	gold quality
gastrocnemius	UBERON:0001388	90.69	gold quality
ovary	UBERON:0000992	90.66	gold quality
left ovary	UBERON:0002119	90.65	gold quality
endometrium	UBERON:0001295	90.47	gold quality
peritoneum	UBERON:0002358	90.44	gold quality
omental fat pad	UBERON:0010414	90.44	gold quality
caecum	UBERON:0001153	90.30	gold quality
tendon	UBERON:0000043	90.29	gold quality
monocyte	CL:0000576	90.28	gold quality
muscle of leg	UBERON:0001383	90.28	gold quality
mononuclear cell	CL:0000842	90.17	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	8.84
E-ANND-3	yes	6.38
E-MTAB-7008	no	334.19

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR

miRNA regulators (miRDB)

159 targeting ABCE1, 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-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• During assembly of an immature HIV-1 capsid, HIV-1 Gag progresses through a pathway of sequential assembly intermediates that contain ABCE1, a cellular ATPase that was found to facilitate capsid formation. (PMID:11780123)
• host protein essential for assembly of immature HIV-1 capsids (PMID:11780123)
• HIV-1, HIV-2, SIV mac239, and SIVagm Gag proteins form ABCE1-containing assembly intermediates during immature capsid formation, indicating that Gag proteins of these diverse retroviruses bind to ABCE1 despite the limited homology between these Gags. (PMID:14747530)
• HIV-2 Gag associates with human HP68 in a cell-free system and that Gag proteins of HIV-2, simian immunodeficiency virus SIVmac239, and SIVagm associate with endogenous HP68 in primate cells, as is seen for HIV-1. (PMID:14747530)
• overexpression in a permissive cell line had no significant effect on varicella zoster virus replication (PMID:15107989)
• ABCE1 and its peptides could be target molecules in specific immunotherapy for HLA-A2(+) colon cancer patients. (PMID:15809757)
• For binding of WT HIV-1 Gag to the cellular ATPase ABCE1, which facilitates HIV-1 capsid assembly, the basic residues in the nucleocapsid domain of Gag are required but the cysteine and histidine residues in the nucleocapsid domain are dispensable. (PMID:16275648)
• Pulse chase experiments and immunoelectron microscopy shows that HIV-1 Gag associates transiently with ABCE1 during HIV-1 capsid assembly, including at the plasma membrane where assembly is completed. (PMID:17233757)
• The primary role of ABCE-1 in the effect of TULA appears to be the recruitment of TULA to the sites of HIV-1 assembly where TULA interferes with the late steps of the HIV-1 life cycle. (PMID:18006034)
• common variation in the putative prostate cancer susceptibility gene, RNASEL, or its inhibitor does not contribute significantly to prostate cancer risk in Tobago Afro-Caribbean population (PMID:18189233)
• were able to confirm the excess of rare genetic variation among HIV-1-positive African-American individuals (n=53; Tajima’s D=-2.34). These results highlight the potential importance of ABCE1’s role in infectious diseases such as HIV-1. (PMID:19657357)
• NTP hydrolysis by ABCE1 is stimulated by posttermination complexes and is required for its ribosomal recycling activity. (PMID:20122402)
• Results suggest that ABCE1 plays an important role in the pathogenesis of human small cell lung cancer cell. (PMID:20372810)
• Pelota/Hbs1 induced dissociation of elongation complexes from ribosomes and release of peptidyl-tRNA, but only in the presence of ABCE1. (PMID:21448132)
• Report high expression level of ABCE1 mRNA and protein in human lung adenocarcinoma tissues and metastatic lymph nodes, which was also correlated with clinical stages. (PMID:22267055)
• To form HIV-1 capsid assembly intermediates, HIV-1 Gag co-opts a complex found in infected and uninfected cells that contains the cellular ATPase ABCE1 and the RNA helicase DDX6, both of which facilitate HIV-1 capsid assembly. (PMID:22851315)
• ABCE1 protein regulates a broad range of biological functions including viral infection, tumor cell proliferation, and antiapoptosis. (Review) (PMID:23008114)
• Studies indicate a strong sequence conservation of ABC-type ATPase ABCE1 in eukaryotes and archaea. (PMID:23266104)
• ABCE1 is closely connected with the pathogenesis and development of esophageal carcinoma, which act through the cellular pathways of 2-5A/RNase L. (PMID:24551278)
• ABCE1 is closely connected with the pathogenesis and development of oral cancer, which acts through the cellular pathways of 2-5A/RNase L. (PMID:25337191)
• ABCE1 is able to suppress RNA silencing in Nicotiana benthamiana plants, in mammalian HEK293 cells and in the worm Caenorhabditis elegans. (PMID:25659154)
• Downregulation of ABCE1 via siRNA affects the sensitivity of lung cancer cells against chemotherapeutic agents. (PMID:25744244)
• ABCE1 is closely associated with cell proliferation, invasion and migration in esophageal cancer and silencing the ABCE1 gene by electroporation can significantly reduce the proliferation, invasion and migration capacity (PMID:25815591)
• Expression of the ABCE1-silencing gene, transfected by electrotransfer, could inhibit the proliferation, invasion, and migration of thyroid cancer cells. (PMID:26600528)
• miR-299-3p promotes the sensibility of lung cancer to doxorubicin through suppression of ABCE1, at least partly. Therefore, the disordered decreased of miR-299-3p and resulting ABCE1 up-expression may contribute to chemoresistance of lung cancer (PMID:26617714)
• ABCE1 plays an essential role in the progression and metastasis of lung cancers and may represent a valuable therapeutic target for the management of lung tumor (PMID:26733164)
• ABCE1 is involved in histone biosynthesis and DNA replication and therefore is essential for normal S phase progression. (PMID:26985706)
• The present study reported on the effects of ABCE1 overexpression on lung adenocarcinoma cells in vitro, demonstrating its enhancing effect on cell proliferation and invasiveness with simultaneous downregulation of p27 protein expression. (PMID:27314749)
• Induction of ribosome rescue factors PELO and HBS1L is required to support protein synthesis when ABCE1 levels fall in platelets, including for hemoglobin production during blood cell development. (PMID:27681415)
• Damage-induced ubiquitination of ABCE1 protein by NOT4 generates poly-ubiquitin signals that attract autophagy receptors to mitochondrial outer membrane to initiate mitophagy. (PMID:29861391)
• This study demonstrated that ABCE1 was up-regulated in glioma tissues and cell lines. Down-regulation of ABCE1 inhibited temozolomide resistance of glioma cells in vitro and in vivo. The PI3K/Akt/NF-kappaB pathway was involved in ABCE1-mediated chemoresistance of glioma cells. (PMID:30455394)
• This study highlights the role of ABCE1 as a host factor required for efficient paramyxovirus and pneumovirus translation. (PMID:31088929)
• Ribosome recycling in mRNA translation, quality control, and homeostasis. (PMID:31665102)
• ABCE1 Acts as a Positive Regulator of Exogenous RNA Decay. (PMID:32033097)
• Suppression of ABCE1-Mediated mRNA Translation Limits N-MYC-Driven Cancer Progression. (PMID:32651259)
• Ribosome Recycling by ABCE1 Links Lysosomal Function and Iron Homeostasis to 3’ UTR-Directed Regulation and Nonsense-Mediated Decay. (PMID:32668236)
• FOXO3a-dependent Parkin regulates the development of gastric cancer by targeting ATP-binding cassette transporter E1. (PMID:32914432)
• Readthrough of stop codons under limiting ABCE1 concentration involves frameshifting and inhibits nonsense-mediated mRNA decay. (PMID:32941650)
• MicroRNA145 promotes the apoptosis of leukemic stem cells and enhances drugresistant K562/ADM cell sensitivity to adriamycin via the regulation of ABCE1. (PMID:32945355)
• A structural inventory of native ribosomal ABCE1-43S pre-initiation complexes. (PMID:33289941)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	abce1	ENSDARG00000007216
mus_musculus	Abce1	ENSMUSG00000058355
rattus_norvegicus	Abce1	ENSRNOG00000018345
drosophila_melanogaster	pix	FBGN0086706
caenorhabditis_elegans		WBGENE00012714

Protein

Protein identifiers

ATP-binding cassette sub-family E member 1 — P61221 (reviewed: P61221)

Alternative names: 2’-5’-oligoadenylate-binding protein, HuHP68, RNase L inhibitor, Ribonuclease 4 inhibitor

All UniProt accessions (4): D6R9I9, D6RGF4, P61221, H0Y990

UniProt curated annotations — full annotation on UniProt →

Function. Nucleoside-triphosphatase (NTPase) involved in ribosome recycling by mediating ribosome disassembly. Able to hydrolyze ATP, GTP, UTP and CTP. Splits ribosomes into free 60S subunits and tRNA- and mRNA-bound 40S subunits. Acts either after canonical termination facilitated by release factors (ETF1/eRF1) or after recognition of stalled and vacant ribosomes by mRNA surveillance factors (PELO/Pelota). Involved in the No-Go Decay (NGD) pathway: recruited to stalled ribosomes by the Pelota-HBS1L complex, and drives the disassembly of stalled ribosomes, followed by degradation of damaged mRNAs as part of the NGD pathway. Also plays a role in quality control of translation of mitochondrial outer membrane-localized mRNA. As part of the PINK1-regulated signaling, ubiquitinated by CNOT4 upon mitochondria damage; this modification generates polyubiquitin signals that recruit autophagy receptors to the mitochondrial outer membrane and initiate mitophagy. RNASEL-specific protein inhibitor which antagonizes the binding of 2-5A (5’-phosphorylated 2’,5’-linked oligoadenylates) to RNASEL. Negative regulator of the anti-viral effect of the interferon-regulated 2-5A/RNASEL pathway. (Microbial infection) May act as a chaperone for post-translational events during HIV-1 capsid assembly. (Microbial infection) Plays a role in the down-regulation of the 2-5A/RNASEL pathway during encephalomyocarditis virus (EMCV) and HIV-1 infections.

Subunit / interactions. (Microbial infection) Interacts with Chandipura virus matrix protein. Interacts with PINK1. Interacts with CNOT4. Interacts with PELO. Probably heterodimerizes with RNASEL; this interaction inhibits RNASEL. (Microbial infection) Interacts with HIV-1 proteins Vif and Gag. (Microbial infection) Interacts with HIV-2 protein Gag.

Subcellular location. Cytoplasm. Mitochondrion.

Post-translational modifications. Ubiquitinated by CNOT4. Ubiquitination mediates the recruitment of autophagy receptors to the mitochondrial outer membrane and initiates mitophagy.

Induction. Activated by encephalomyocarditis virus (EMCV) and HIV-1.

Miscellaneous. The ABC transporter domains seem not to be functional.

Similarity. Belongs to the ABC transporter superfamily. ABCE family.

RefSeq proteins (2): NP_001035809, NP_002931* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003439	ABC_transporter-like_ATP-bd	Domain
IPR003593	AAA+_ATPase	Domain
IPR007209	RNaseL-inhib-like_metal-bd_dom	Domain
IPR013283	RLI1	Family
IPR017871	ABC_transporter-like_CS	Conserved_site
IPR017896	4Fe4S_Fe-S-bd	Domain
IPR017900	4Fe4S_Fe_S_CS	Conserved_site
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR034348	RLI_dom_1	Domain

Pfam: PF00005, PF00037, PF04068

Catalyzed reactions (Rhea), 4 shown:

• ATP + H2O = ADP + phosphate + H(+) (RHEA:13065)
• GTP + H2O = GDP + phosphate + H(+) (RHEA:19669)
• CTP + H2O = CDP + phosphate + H(+) (RHEA:29387)
• UTP + H2O = UDP + phosphate + H(+) (RHEA:64900)

UniProt features (15 total): domain 4, sequence conflict 3, binding site 2, modified residue 2, chain 1, sequence variant 1, mutagenesis site 1, cross-link 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
6ZME	ELECTRON MICROSCOPY	3
7A09	ELECTRON MICROSCOPY	3.5
6ZVJ	ELECTRON MICROSCOPY	3.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P61221-F1	86.76	0.38

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 (2): 110–117; 379–386

Post-translational modifications (3): 417, 550, 20

Mutagenesis-validated functional residues (1):

Position	Phenotype
20	abolishes ubiquitination by cnot4 and diminished the ability to recruit autophagy receptors to damaged mitochondria and

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-8983711	OAS antiviral response
R-HSA-909733	Interferon alpha/beta signaling
R-HSA-9954714	PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA
R-HSA-1169410	Antimicrobial mechanism of IFN-stimulated genes
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-168256	Immune System
R-HSA-913531	Interferon Signaling

MSigDB gene sets: 262 (showing top): ATF_B, TGGTGCT_MIR29A_MIR29B_MIR29C, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, DACOSTA_UV_RESPONSE_VIA_ERCC3_XPCS_DN, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, MATTIOLI_MGUS_VS_PCL, AAGCCAT_MIR135A_MIR135B, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_TRANSLATIONAL_INITIATION, GOBP_TRANSLATIONAL_TERMINATION, CAGCTG_AP4_Q5, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, PUJANA_CHEK2_PCC_NETWORK, GOBP_TRANSLATION

GO Biological Process (11): translational initiation (GO:0006413), translational termination (GO:0006415), regulation of translation (GO:0006417), ribosome disassembly (GO:0032790), negative regulation of endoribonuclease activity (GO:0060702), rescue of stalled cytosolic ribosome (GO:0072344), translation (GO:0006412), regulation of macromolecule metabolic process (GO:0060255), protein ufmylation (GO:0071569), CAT tailing (GO:0140708), ribosome-associated ubiquitin-dependent protein catabolic process (GO:1990116)

GO Molecular Function (14): GTPase activity (GO:0003924), iron ion binding (GO:0005506), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), ribonucleoside triphosphate phosphatase activity (GO:0017111), ribosomal small subunit binding (GO:0043024), CTPase activity (GO:0043273), 4 iron, 4 sulfur cluster binding (GO:0051539), endoribonuclease inhibitor activity (GO:0060698), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787), metal ion binding (GO:0046872), iron-sulfur cluster binding (GO:0051536)

GO Cellular Component (6): cytoplasm (GO:0005737), mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), cytosol (GO:0005829), membrane (GO:0016020), cytosolic ribosome (GO:0022626)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Interferon Signaling	2
Antimicrobial mechanism of IFN-stimulated genes	1
Ribosome-associated quality control	1
Immune System	1
Cytokine Signaling in Immune system	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
translation	3
ribonucleoside triphosphate phosphatase activity	3
cellular anatomical structure	3
RNA endonuclease activity	2
cytoplasmic translational elongation	2
cytoplasm	2
formation of translation initiation ternary complex	1
metabolic process	1
protein-containing complex disassembly	1
post-transcriptional regulation of gene expression	1
regulation of protein metabolic process	1
organelle disassembly	1
negative regulation of catalytic activity	1
regulation of endoribonuclease activity	1
ribosome disassembly	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
regulation of metabolic process	1
macromolecule metabolic process	1
protein modification by small protein conjugation	1
rescue of stalled cytosolic ribosome	1
ribosome-associated ubiquitin-dependent protein catabolic process	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
transition metal ion binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ATP-dependent activity	1
pyrophosphatase activity	1
ribosome binding	1
iron-sulfur cluster binding	1
ribonuclease inhibitor activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1

Protein interactions and networks

STRING

3663 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ABCE1	HBS1L	Q9Y450	928
ABCE1	RNASEL	Q05823	918
ABCE1	EIF5	P55010	882
ABCE1	ETF1	P46055	843
ABCE1	EIF1	P41567	826
ABCE1	MRRF	Q96E11	811
ABCE1	LTN1	O94822	762
ABCE1	NEMF	O60524	731
ABCE1	ABCF1	Q8NE71	727
ABCE1	PELO	Q9BRX2	719
ABCE1	EIF2D	P41214	715
ABCE1	ABCF2	Q9UG63	714
ABCE1	EIF5B	O60841	702
ABCE1	ZNF598	Q86UK7	699
ABCE1	EEF2	P13639	695

IntAct

126 interactions, top by confidence:

A	B	Type	Score
EGFR	HSP90AA1	psi-mi:“MI:0914”(association)	0.820
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
EIF3J	ABCE1	psi-mi:“MI:0915”(physical association)	0.670
ATXN10	PPP1R12A	psi-mi:“MI:0914”(association)	0.670
EIF3M	EIF3CL	psi-mi:“MI:0914”(association)	0.640
LTO1	ABCE1	psi-mi:“MI:0914”(association)	0.640
ABCE1	gag	psi-mi:“MI:0915”(physical association)	0.590
gag	ABCE1	psi-mi:“MI:0915”(physical association)	0.590
M	ABCE1	psi-mi:“MI:0915”(physical association)	0.580
ABCE1	EIF3H	psi-mi:“MI:0914”(association)	0.530
ILK	ILVBL	psi-mi:“MI:0914”(association)	0.530
P	ABCE1	psi-mi:“MI:0915”(physical association)	0.500
LTK	PIK3R2	psi-mi:“MI:0914”(association)	0.420
Cdc6		psi-mi:“MI:0914”(association)	0.350
Kif13b	TCF3	psi-mi:“MI:0914”(association)	0.350
XRCC5	BACC1	psi-mi:“MI:0914”(association)	0.350
Sidt2	PRSS1	psi-mi:“MI:0914”(association)	0.350
Brca1	SMCHD1	psi-mi:“MI:0914”(association)	0.350
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
RIPK4	VWA8	psi-mi:“MI:0914”(association)	0.350
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
DNM1L		psi-mi:“MI:0914”(association)	0.350

BioGRID (476): ABCE1 (Affinity Capture-MS), ABCF1 (Affinity Capture-MS), FUBP3 (Affinity Capture-MS), CBX3 (Affinity Capture-MS), PDHA1 (Affinity Capture-MS), ABLIM1 (Affinity Capture-MS), CNIH4 (Affinity Capture-MS), NAA10 (Affinity Capture-MS), PSMD4 (Affinity Capture-MS), CORO1C (Affinity Capture-MS), MAPK1 (Affinity Capture-MS), SRP9 (Affinity Capture-MS), TIMM21 (Affinity Capture-MS), SNAP23 (Affinity Capture-MS), HIST1H1C (Affinity Capture-MS)

ESM2 similar proteins: A0CDD4, A1Z6E0, A2VE01, A8IU92, B0R0D7, O22715, O97555, P21856, P31150, P35602, P48455, P50396, P60028, P61221, P61222, Q09130, Q0G819, Q16HW7, Q23651, Q24208, Q29NT9, Q2PG46, Q2TBQ0, Q499T7, Q4R7R3, Q5PQL4, Q5R4V9, Q5ZHP3, Q5ZMA6, Q61JK7, Q6B857, Q6GL74, Q6GPY6, Q6P4W8, Q6PBJ2, Q711T7, Q7YQM0, Q811P6, Q86D25, Q8BTU1

Diamond homologs: A0K3S5, A1B9Q7, B4TGI0, B5BA33, B5FJ99, B5QVV9, G0SEV9, O30144, O32188, O57896, O60102, P18813, P19566, P47425, P55453, P61221, P61222, P63351, P63352, Q01937, Q02QT6, Q03195, Q035B2, Q03I83, Q05596, Q07LQ4, Q0RKH4, Q0S0X2, Q0SIB7, Q1BRZ8, Q1BWI2, Q1CC21, Q1CNR8, Q1QTX6, Q21XJ9, Q2J3T0, Q2K4V4, Q2NIT5, Q2YJB5, Q2YKZ7

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ABCE1	“down-regulates quantity by destabilization”	80S_cytosolic_ribosome	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 151 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
Ribosomal scanning and start codon recognition	12	21.8×	4e-11
Formation of the ternary complex, and subsequently, the 43S complex	10	20.5×	4e-09
Translation initiation complex formation	11	19.9×	7e-10
GTP hydrolysis and joining of the 60S ribosomal subunit	17	16.2×	1e-13
L13a-mediated translational silencing of Ceruloplasmin expression	16	15.4×	1e-12
Formation of a pool of free 40S subunits	14	14.9×	6e-11
SRP-dependent cotranslational protein targeting to membrane	12	11.4×	5e-08
Eukaryotic Translation Termination	9	10.3×	1e-05

GO biological processes:

GO term	Partners	Fold	FDR
formation of cytoplasmic translation initiation complex	8	72.5×	2e-11
translational initiation	11	31.8×	2e-11
regulation of translational initiation	5	18.9×	1e-03
cytoplasmic translation	10	14.9×	4e-07
translation	9	7.5×	9e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	1
Uncertain significance	25
Likely benign	2
Benign	4

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
147586	GRCh38/hg38 4q31.21(chr4:143738209-145870474)x1	Pathogenic
2685986	GRCh37/hg19 4q26-32.3(chr4:117518683-168174703)x3	Pathogenic
58044	GRCh38/hg38 4q31.21-31.3(chr4:140876253-152186578)x3	Pathogenic
59479	GRCh38/hg38 4q26-31.21(chr4:116630862-145429900)x1	Pathogenic
153878	GRCh38/hg38 4q31.21-31.23(chr4:144742003-148490914)x1	Likely pathogenic

SpliceAI

2080 predictions. Top by Δscore:

Variant	Effect	Δscore
4:145104380:TCATA:T	acceptor_loss	1.0000
4:145104381:CATA:C	acceptor_loss	1.0000
4:145104382:A:AG	acceptor_gain	1.0000
4:145104382:ATAG:A	acceptor_loss	1.0000
4:145104383:T:G	acceptor_gain	1.0000
4:145104383:TA:T	acceptor_loss	1.0000
4:145104384:A:AG	acceptor_gain	1.0000
4:145104384:A:AT	acceptor_loss	1.0000
4:145104385:G:A	acceptor_loss	1.0000
4:145104385:G:GC	acceptor_gain	1.0000
4:145104385:GA:G	acceptor_gain	1.0000
4:145104385:GAA:G	acceptor_gain	1.0000
4:145104385:GAAGA:G	acceptor_gain	1.0000
4:145104512:ATGGG:A	donor_loss	1.0000
4:145104514:GG:G	donor_gain	1.0000
4:145104514:GGGTA:G	donor_loss	1.0000
4:145104515:GG:G	donor_gain	1.0000
4:145104515:GGT:G	donor_loss	1.0000
4:145104516:G:GG	donor_gain	1.0000
4:145104517:T:A	donor_loss	1.0000
4:145105602:CAGG:C	acceptor_loss	1.0000
4:145105603:A:AG	acceptor_gain	1.0000
4:145105604:G:GG	acceptor_gain	1.0000
4:145105604:G:GT	acceptor_loss	1.0000
4:145105604:GGAAA:G	acceptor_gain	1.0000
4:145105689:AGGT:A	donor_loss	1.0000
4:145105691:GTA:G	donor_loss	1.0000
4:145105692:T:A	donor_loss	1.0000
4:145108006:A:AG	acceptor_gain	1.0000
4:145108007:A:AG	acceptor_gain	1.0000

AlphaMissense

3937 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:145104438:C:A	A9D	1.000
4:145104458:T:A	C16S	1.000
4:145104458:T:C	C16R	1.000
4:145104459:G:C	C16S	1.000
4:145104473:T:C	C21R	1.000
4:145104485:T:C	C25R	1.000
4:145104497:T:C	C29R	1.000
4:145104498:G:A	C29Y	1.000
4:145104498:G:T	C29F	1.000
4:145104499:T:G	C29W	1.000
4:145105613:T:C	C38R	1.000
4:145105614:G:A	C38Y	1.000
4:145105615:C:G	C38W	1.000
4:145105664:T:A	C55S	1.000
4:145105664:T:C	C55R	1.000
4:145105665:G:A	C55Y	1.000
4:145105665:G:C	C55S	1.000
4:145105665:G:T	C55F	1.000
4:145105666:T:G	C55W	1.000
4:145105674:G:A	C58Y	1.000
4:145105682:T:C	C61R	1.000
4:145105683:G:A	C61Y	1.000
4:145105684:T:G	C61W	1.000
4:145108018:T:C	C65R	1.000
4:145108082:G:C	R86P	1.000
4:145108099:T:C	F92L	1.000
4:145108101:C:A	F92L	1.000
4:145108101:C:G	F92L	1.000
4:145108106:T:A	L94H	1.000
4:145108106:T:C	L94P	1.000

dbSNP variants (sampled 300 via entrez): RS1000092242 (4:145099584 GGA>G), RS1000123345 (4:145099878 C>T), RS1000128514 (4:145115293 G>C), RS1000239363 (4:145122332 A>C,G), RS1000240669 (4:145105903 C>G,T), RS1000289991 (4:145121929 A>C), RS1000415472 (4:145109559 A>G,T), RS1000425532 (4:145112029 G>A), RS1000626520 (4:145114975 A>G), RS1000659597 (4:145104697 A>G), RS1000709916 (4:145117031 T>C), RS1000761781 (4:145110754 G>A), RS1000776002 (4:145118622 C>T), RS1000845930 (4:145111731 T>C), RS1000925792 (4:145103599 C>T)

Disease associations

OMIM: gene MIM:601213 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): prostate cancer (MONDO:0008315)

Orphanet (1): Familial prostate cancer (Orphanet:1331)

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST005956_60	Waist-to-hip ratio adjusted for BMI	2.000000e-08
GCST005962_45	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	2.000000e-06
GCST010701_94	Cortical surface area (MOSTest)	2.000000e-13
GCST010702_38	Subcortical volume (MOSTest)	1.000000e-10
GCST010703_203	Brain morphology (MOSTest)	1.000000e-11
GCST010725_4	Malaria	4.000000e-10
GCST010725_84	Malaria	7.000000e-11
GCST010725_89	Malaria	7.000000e-11
GCST012227_1326	Hip circumference adjusted for BMI	1.000000e-28

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0004346	neuroimaging measurement
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067318 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.44	Kd	0.362	nM	CHEMBL5653589
9.44	ED50	0.362	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 4 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147769: Binding affinity to human ABCE1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0004	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	increases abundance, increases oxidation, decreases expression, affects cotreatment	3
Tretinoin	decreases expression, increases reaction	3
bisphenol F	increases expression, increases methylation	2
bisphenol A	decreases expression	2
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	2
Acetaminophen	decreases expression	2
Estradiol	increases reaction, increases expression	2
Valproic Acid	decreases expression	2
Cadmium Chloride	decreases expression	2
beta-Naphthoflavone	increases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
sodium arsenate	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression	1
decabromobiphenyl ether	decreases expression	1
methylparaben	decreases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
potassium chromate(VI)	decreases expression, affects cotreatment	1
1-nitropyrene	increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
pinosylvin	decreases expression	1
perfluoro-n-nonanoic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5650811	Binding	Binding affinity to human ABCE1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer