LTO1

Summary

LTO1 (LTO1 maturation factor of ABCE1, HGNC:17589) is a protein-coding gene on chromosome 11q13.2, encoding Protein LTO1 homolog (Q8WV07). The complex LTO1:YAE1 functions as a target specific adapter that probably recruits apo-ABCE1 to the cytosolic iron-sulfur protein assembly (CIA) complex machinery. It is a common-essential gene (DepMap: required in 99.6% of cancer cell lines).

Involved in ribosomal large subunit biogenesis and translational initiation. Predicted to be located in nucleus.

Source: NCBI Gene 220064 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 28 total
• Cancer dependency (DepMap): dependent in 99.6% of screened cell lines (common-essential)
• MANE Select transcript: NM_153451

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17589
Approved symbol	LTO1
Name	LTO1 maturation factor of ABCE1
Location	11q13.2
Locus type	gene with protein product
Status	Approved
Aliases	TAOS1, CIAB1
Ensembl gene	ENSG00000149716
Ensembl biotype	protein_coding
OMIM	607224
Entrez	220064

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 9 protein_coding, 4 retained_intron, 4 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay

ENST00000279147, ENST00000355486, ENST00000441922, ENST00000535542, ENST00000535657, ENST00000536870, ENST00000537272, ENST00000537324, ENST00000538554, ENST00000539414, ENST00000542341, ENST00000542470, ENST00000542515, ENST00000543023, ENST00000543562, ENST00000543863, ENST00000544096, ENST00000569105, ENST00000857305, ENST00000941637

RefSeq mRNA: 1 — MANE Select: NM_153451 NM_153451

CCDS: CCDS8192

Canonical transcript exons

ENST00000279147 — 5 exons

Exon	Start	End
ENSE00001758089	69675190	69675353
ENSE00002255217	69665563	69667587
ENSE00003468185	69673216	69673321
ENSE00003520239	69667895	69668012
ENSE00003606266	69671749	69671819

Expression profiles

Bgee: expression breadth ubiquitous, 180 present calls, max score 90.31.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.5518 / max 173.0874, expressed in 1810 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
121048	16.4345	1809
121049	0.9070	563
121047	0.2103	106

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	90.31	gold quality
cerebellar hemisphere	UBERON:0002245	90.00	gold quality
granulocyte	CL:0000094	89.81	gold quality
cerebellar cortex	UBERON:0002129	89.78	gold quality
lower esophagus mucosa	UBERON:0035834	89.19	gold quality
skin of leg	UBERON:0001511	88.71	gold quality
right frontal lobe	UBERON:0002810	88.66	gold quality
Brodmann (1909) area 9	UBERON:0013540	88.43	gold quality
apex of heart	UBERON:0002098	88.41	gold quality
adenohypophysis	UBERON:0002196	88.39	gold quality
body of uterus	UBERON:0009853	88.15	gold quality
right ovary	UBERON:0002118	88.14	gold quality
cerebellum	UBERON:0002037	88.08	gold quality
mucosa of transverse colon	UBERON:0004991	88.06	gold quality
stromal cell of endometrium	CL:0002255	88.00	gold quality
body of pancreas	UBERON:0001150	87.82	gold quality
left ovary	UBERON:0002119	87.82	gold quality
anterior cingulate cortex	UBERON:0009835	87.65	gold quality
right uterine tube	UBERON:0001302	87.64	gold quality
skin of abdomen	UBERON:0001416	87.62	gold quality
right lobe of thyroid gland	UBERON:0001119	87.54	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	87.49	gold quality
left uterine tube	UBERON:0001303	87.47	gold quality
muscle layer of sigmoid colon	UBERON:0035805	87.42	gold quality
left lobe of thyroid gland	UBERON:0001120	87.36	gold quality
ectocervix	UBERON:0012249	87.30	gold quality
lower esophagus	UBERON:0013473	87.26	gold quality
lower esophagus muscularis layer	UBERON:0035833	87.26	gold quality
putamen	UBERON:0001874	87.25	gold quality
small intestine Peyer’s patch	UBERON:0003454	87.17	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.78

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

27 targeting LTO1, 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-7110-3P	100.00	73.18	2486
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-5582-5P	99.27	71.42	1879
HSA-MIR-593-3P	99.22	67.28	1327
HSA-MIR-4784	99.15	67.41	1733
HSA-MIR-3190-5P	98.87	64.89	1345
HSA-MIR-3150B-3P	98.81	67.21	1728
HSA-MIR-4297	98.77	66.95	2013
HSA-MIR-12114	98.70	63.45	730
HSA-MIR-7977	98.65	66.18	2590
HSA-MIR-224-5P	98.33	70.12	1256
HSA-MIR-6771-3P	98.20	66.53	971
HSA-MIR-4690-3P	97.02	64.72	981
HSA-MIR-5685	97.02	64.34	1004
HSA-MIR-6823-3P	95.45	66.14	704
HSA-MIR-2114-3P	95.45	66.11	579
HSA-MIR-1268A	87.06	61.46	145
HSA-MIR-1268B	87.06	61.46	145

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.6% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 13)

• High-resolution mapping of the 11q13 amplicon and identification of a gene that is amplified and overexpressed in oral cancer cells (PMID:12172009)
• data suggested potential roles in oral carcinogenesis and that TAOS1 might be involved earlier than EMS1. Both genes might be candidate biomarkers for diagnosis and prognosis in OSCC (PMID:17005439)
• ORAOV1 plays pivotal roles in the growth and angiogenesis of oral squamous cell carcinoma. (PMID:18688849)
• In OSCC tissue samples, the expression frequency of ORAOV1-A (51.1%) was much higher than that in normal samples (10.5%). ORAOV1-A may play a functional role in the tumorigenesis of OSCC. (PMID:19493886)
• ORAOV1 has an important role in regulating cell growth of cervical cancer HeLa cells through regulating the cell cycle and apoptosis. (PMID:20105337)
• overexpression of ORAOV1 in non-tumoral margin samples can occur in absence of amplification. weak correlation between ORAOV1 amplification and expression in OSSC suggests ORAOV1 expression can be regulated by mechanisms other than gene amplification. (PMID:21623924)
• An oral cancer overexpressed 1 (ORAOV1) gene was identified as a probable target within the 11q13 amplicon in lymph node metastases from gastric adenocarcinoma. (PMID:21993861)
• The ORAOV1 complex could prevent ROS-induced ribosomal damage, explaining why overexpression of ORAOV1 is so common in solid tumours (PMID:23318452)
• the ORAOV1 gene is frequently amplified in esophageal squamous cell cancer (PMID:24930674)
• provides the first evidence of ORAOV1 overexpression in esophageal squamous cell cancer and esophageal squamous intraepithelial neoplasia (PMID:25732110)
• Validation of ORAOV1 as a new treatment target in hepatocellular carcinoma. (PMID:33161447)
• ORAOV1-B Promotes OSCC Metastasis via the NF-kappaB-TNFalpha Loop. (PMID:33655785)
• ORAOV1, CCND1, and MIR548K Are the Driver Oncogenes of the 11q13 Amplicon in Squamous Cell Carcinoma. (PMID:37930255)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	LTO1	ENSMUSG00000031072
rattus_norvegicus	Lto1	ENSRNOG00000020903

Protein

Protein identifiers

Protein LTO1 homolog — Q8WV07 (reviewed: Q8WV07)

Alternative names: Oral cancer-overexpressed protein 1, Tumor-amplified and overexpressed sequence 1

All UniProt accessions (9): Q8WV07, A6YPU5, B4DFA5, F5GWS9, F5GZY6, F5H179, F5H6T8, F5H8D9, H3BPK6

UniProt curated annotations — full annotation on UniProt →

Function. The complex LTO1:YAE1 functions as a target specific adapter that probably recruits apo-ABCE1 to the cytosolic iron-sulfur protein assembly (CIA) complex machinery. May be required for biogenesis of the large ribosomal subunit and initiation of translation. May play a role in the regulation of proline metabolism and ROS production.

Subunit / interactions. Forms a complex with YAE1. Interacts with PYCR1 and PYCR2.

Subcellular location. Nucleus.

Tissue specificity. Widely expressed. Highly expressed in placenta, kidney and skeletal muscle.

Miscellaneous. Amplified and overexpressed in oral cancer cells.

Similarity. Belongs to the LTO1 family.

RefSeq proteins (1): NP_703152* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019191	Essential_protein_Yae1_N	Domain
IPR052436	LTO1_adapter	Family

Pfam: PF09811

UniProt features (6 total): modified residue 2, initiator methionine 1, chain 1, region of interest 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WV07-F1	85.08	0.52

Functional residue map

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

Post-translational modifications (2): 2, 4

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 85 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, GSE45365_NK_CELL_VS_CD8A_DC_UP, GOBP_CHROMOSOME_ORGANIZATION, GOBP_RIBOSOME_BIOGENESIS, GOBP_TELOMERE_ORGANIZATION, GOBP_TRANSLATIONAL_INITIATION, chr11q13, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, GOBP_TRANSLATION, GOBP_PROTEIN_MATURATION, RICKMAN_HEAD_AND_NECK_CANCER_A, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, NIKOLSKY_BREAST_CANCER_11Q12_Q14_AMPLICON, GOBP_RIBONUCLEOPROTEIN_COMPLEX_BIOGENESIS

GO Biological Process (4): telomere maintenance (GO:0000723), translational initiation (GO:0006413), ribosomal large subunit biogenesis (GO:0042273), protein maturation (GO:0051604)

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

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA metabolic process	1
telomere organization	1
formation of translation initiation ternary complex	1
translation	1
metabolic process	1
ribonucleoprotein complex biogenesis	1
ribosome biogenesis	1
gene expression	1
protein metabolic process	1
binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

396 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LTO1	FGF19	O95750	908
LTO1	FGF4	P08620	761
LTO1	FGF3	P11487	757
LTO1	PYCR1	P32322	757
LTO1	YAE1	Q9NRH1	745
LTO1	PPFIA1	Q13136	741
LTO1	CCND1	P24385	695
LTO1	MYEOV	Q96EZ4	670
LTO1	CTTN	Q14247	587
LTO1	ANO1	Q5XXA6	578
LTO1	MMS19	Q96T76	539
LTO1	CIAPIN1	Q6FI81	504
LTO1	NUBP1	P53384	489
LTO1	CIAO3	Q9H6Q4	488
LTO1	FADD	Q13158	487

IntAct

18 interactions, top by confidence:

A	B	Type	Score
LTO1	ABCE1	psi-mi:“MI:0914”(association)	0.640
LTO1	YAE1	psi-mi:“MI:0915”(physical association)	0.560
GSC2	LTO1	psi-mi:“MI:0915”(physical association)	0.560
ABCE1	EIF3H	psi-mi:“MI:0914”(association)	0.530
BEND6	LTO1	psi-mi:“MI:0915”(physical association)	0.400
CAND1	GTPBP10	psi-mi:“MI:0914”(association)	0.350
OR13G1	VPS26C	psi-mi:“MI:0914”(association)	0.350
LTO1	USP11	psi-mi:“MI:0914”(association)	0.350
YAE1	LTO1	psi-mi:“MI:0915”(physical association)	0.000
LTO1	YAE1	psi-mi:“MI:0915”(physical association)	0.000
LTO1	GSC2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (27): ORAOV1 (Affinity Capture-MS), ORAOV1 (Affinity Capture-RNA), ORAOV1 (Negative Genetic), ORAOV1 (Negative Genetic), ORAOV1 (Negative Genetic), ORAOV1 (Negative Genetic), RPL36A (Negative Genetic), SNAPC1 (Positive Genetic), WDR61 (Negative Genetic), ORAOV1 (Synthetic Growth Defect), ORAOV1 (Two-hybrid), YAE1D1 (Two-hybrid), TGFBRAP1 (Affinity Capture-MS), ORAOV1 (Affinity Capture-MS), ABCE1 (Affinity Capture-MS)

ESM2 similar proteins: A0JN27, D3K5L7, E2R222, F1LTR1, G1SPK4, O43504, O62657, P05388, P14869, P19945, P20821, P22234, P23434, P35268, P40224, P48061, Q0VCQ4, Q13888, Q15645, Q1JQE6, Q29214, Q2KJ29, Q2TBV5, Q2VIR3, Q3KNV8, Q3MHF7, Q3SZ68, Q3UA06, Q5R8Y5, Q5RKI9, Q5SP67, Q5XHZ9, Q66X52, Q6P1K8, Q6PIU2, Q7RTP6, Q8BTQ0, Q8NHW5, Q8WV07, Q91ZH7

Diamond homologs: Q8CH62, Q8WV07

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	21
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

936 predictions. Top by Δscore:

Variant	Effect	Δscore
11:69668008:TTCTG:T	acceptor_gain	1.0000
11:69668010:CTG:C	acceptor_gain	1.0000
11:69668011:TG:T	acceptor_gain	1.0000
11:69668013:C:CC	acceptor_gain	1.0000
11:69667583:CAAAA:C	acceptor_gain	0.9900
11:69667890:CGCA:C	donor_loss	0.9900
11:69667891:GCA:G	donor_loss	0.9900
11:69667892:CA:C	donor_loss	0.9900
11:69667893:A:AT	donor_loss	0.9900
11:69667894:C:CT	donor_loss	0.9900
11:69668009:TCTG:T	acceptor_loss	0.9900
11:69668013:C:CG	acceptor_loss	0.9900
11:69668014:T:A	acceptor_loss	0.9900
11:69675185:CCCA:C	donor_loss	0.9900
11:69675186:CCA:C	donor_loss	0.9900
11:69675187:CAC:C	donor_loss	0.9900
11:69675188:A:AT	donor_loss	0.9900
11:69675189:C:CT	donor_loss	0.9900
11:69675189:CCT:C	donor_gain	0.9900
11:69671736:TCTCC:T	donor_gain	0.9800
11:69673320:ACC:A	acceptor_loss	0.9800
11:69673321:CCT:C	acceptor_loss	0.9800
11:69673323:T:G	acceptor_loss	0.9800
11:69675223:T:TA	donor_gain	0.9800
11:69667588:C:CC	acceptor_gain	0.9700
11:69668015:G:GC	acceptor_gain	0.9700
11:69673211:CTTA:C	donor_loss	0.9700
11:69673212:TTA:T	donor_loss	0.9700
11:69673213:T:TG	donor_loss	0.9700
11:69673214:ACCTC:A	donor_loss	0.9700

AlphaMissense

916 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:69667901:A:C	F113L	0.966
11:69667901:A:T	F113L	0.966
11:69667903:A:G	F113L	0.966
11:69667898:T:A	K114N	0.960
11:69667898:T:G	K114N	0.960
11:69673235:C:T	G46E	0.954
11:69667522:A:C	F137L	0.953
11:69667522:A:T	F137L	0.953
11:69667524:A:G	F137L	0.953
11:69671803:C:T	G58D	0.950
11:69673247:C:T	G42D	0.950
11:69671804:C:G	G58R	0.949
11:69673296:C:G	G26R	0.947
11:69671799:A:C	F59L	0.941
11:69671799:A:T	F59L	0.941
11:69671801:A:G	F59L	0.941
11:69673260:C:G	G38R	0.941
11:69673260:C:T	G38R	0.941
11:69667910:T:A	R110S	0.936
11:69667910:T:G	R110S	0.936
11:69675200:C:G	A14P	0.934
11:69667902:A:G	F113S	0.933
11:69667964:G:C	F92L	0.933
11:69667964:G:T	F92L	0.933
11:69667966:A:G	F92L	0.933
11:69673223:C:T	G50E	0.933
11:69671797:G:T	A60D	0.931
11:69673295:C:T	G26D	0.929
11:69673318:A:C	F18L	0.928
11:69673318:A:T	F18L	0.928

dbSNP variants (sampled 300 via entrez): RS1000343924 (11:69674364 G>A), RS1000375301 (11:69674632 G>A), RS1000493325 (11:69668129 C>T), RS1000858545 (11:69669745 G>A), RS1000993565 (11:69665242 A>C), RS1001531217 (11:69667391 C>T), RS1001896335 (11:69669223 C>A,T), RS1001982666 (11:69675249 C>CA), RS1002079764 (11:69675080 C>A,T), RS1002454231 (11:69671978 A>C), RS1002506466 (11:69671649 T>A,C), RS1002546948 (11:69675864 A>C,G), RS1002682797 (11:69666736 C>T), RS1002690369 (11:69670110 C>G), RS1002924587 (11:69675621 A>G)

Disease associations

OMIM: gene MIM:607224 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST000678_13	Breast cancer	3.000000e-15
GCST004412_6	Craniofacial microsomia	4.000000e-17
GCST005231_20	Major depressive disorder	6.000000e-06
GCST006986_11	Red vs. brown/black hair color	6.000000e-10
GCST007293_120	Body fat distribution (arm fat ratio)	4.000000e-06
GCST007293_22	Body fat distribution (arm fat ratio)	5.000000e-09
GCST007293_48	Body fat distribution (arm fat ratio)	5.000000e-12
GCST010989_29	Body size at age 10	7.000000e-15
GCST012228_541	Waist-hip index	4.000000e-08
GCST012230_34	Waist-to-hip ratio adjusted for BMI	4.000000e-08
GCST90000025_167	Appendicular lean mass	4.000000e-13

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0003924	hair color
EFO:0004341	body fat distribution
EFO:0009819	comparative body size at age 10, self-reported
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0004980	appendicular lean mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, decreases methylation	2
Cyclosporine	increases expression	2
aristolochic acid I	increases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
trichostatin A	decreases expression	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
2-palmitoylglycerol	increases expression	1
ICG 001	increases expression	1
abrine	increases 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
Arsenic	affects cotreatment, increases abundance, increases expression	1
Atrazine	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Methyl Methanesulfonate	decreases expression	1
Silver	increases expression	1
Smoke	decreases expression	1
Vincristine	decreases expression	1
Antirheumatic Agents	decreases expression	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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