EXO1

Summary

EXO1 (exonuclease 1, HGNC:3511) is a protein-coding gene on chromosome 1q43, encoding Exonuclease 1 (Q9UQ84). 5’->3’ double-stranded DNA exonuclease which may also possess a cryptic 3’->5’ double-stranded DNA exonuclease activity.

This gene encodes a protein with 5’ to 3’ exonuclease activity as well as an RNase H activity. It is similar to the Saccharomyces cerevisiae protein Exo1 which interacts with Msh2 and which is involved in mismatch repair and recombination. Alternative splicing of this gene results in three transcript variants encoding two different isoforms.

Source: NCBI Gene 9156 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Lynch syndrome (Refuted, ClinGen)
• GWAS associations: 12
• Clinical variants (ClinVar): 160 total — 1 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_130398

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3511
Approved symbol	EXO1
Name	exonuclease 1
Location	1q43
Locus type	gene with protein product
Status	Approved
Aliases	HEX1, hExoI
Ensembl gene	ENSG00000174371
Ensembl biotype	protein_coding
OMIM	606063
Entrez	9156

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 15 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000348581, ENST00000366548, ENST00000423131, ENST00000437497, ENST00000450748, ENST00000469419, ENST00000493702, ENST00000518483, ENST00000518741, ENST00000519225, ENST00000521202, ENST00000523590, ENST00000926748, ENST00000926749, ENST00000926750, ENST00000926751, ENST00000926752, ENST00000926753

RefSeq mRNA: 4 — MANE Select: NM_130398 NM_001319224, NM_003686, NM_006027, NM_130398

CCDS: CCDS1620, CCDS44336

Canonical transcript exons

ENST00000366548 — 16 exons

Exon	Start	End
ENSE00001236038	241848731	241849027
ENSE00001236120	241849112	241849216
ENSE00001738146	241889465	241889939
ENSE00001936226	241848204	241848353
ENSE00002329387	241861406	241861502
ENSE00002354384	241878749	241879343
ENSE00002366151	241872032	241872278
ENSE00002380510	241885314	241885507
ENSE00002398962	241866830	241867055
ENSE00002423792	241881916	241882017
ENSE00003511202	241852292	241852411
ENSE00003588593	241850409	241850586
ENSE00003602156	241858506	241858718
ENSE00003624766	241857345	241857482
ENSE00003666280	241860517	241860704
ENSE00003784222	241853358	241853481

Expression profiles

Bgee: expression breadth ubiquitous, 168 present calls, max score 89.36.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.7209 / max 215.3484, expressed in 1278 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
9391	12.4225	1212
9390	0.7179	390
9389	0.4480	200
9395	0.0601	21
9392	0.0399	11
9394	0.0238	4
9393	0.0086	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
type B pancreatic cell	CL:0000169	89.36	gold quality
ventricular zone	UBERON:0003053	89.10	gold quality
olfactory bulb	UBERON:0002264	89.06	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.79	gold quality
ganglionic eminence	UBERON:0004023	87.59	gold quality
embryo	UBERON:0000922	85.19	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.10	gold quality
trabecular bone tissue	UBERON:0002483	80.70	gold quality
diaphragm	UBERON:0001103	80.64	gold quality
bone marrow	UBERON:0002371	80.34	gold quality
bone marrow cell	CL:0002092	79.13	gold quality
cervix squamous epithelium	UBERON:0006922	75.35	gold quality
hair follicle	UBERON:0002073	74.82	gold quality
stromal cell of endometrium	CL:0002255	74.26	gold quality
secondary oocyte	CL:0000655	73.98	gold quality
epithelial cell of pancreas	CL:0000083	73.10	gold quality
mucosa of transverse colon	UBERON:0004991	72.68	gold quality
rectum	UBERON:0001052	72.07	gold quality
lymph node	UBERON:0000029	72.03	gold quality
adrenal tissue	UBERON:0018303	71.35	gold quality
cervix epithelium	UBERON:0004801	70.65	gold quality
thymus	UBERON:0002370	70.19	silver quality
male germ cell	CL:0000015	70.16	gold quality
vermiform appendix	UBERON:0001154	69.48	gold quality
placenta	UBERON:0001987	69.19	gold quality
oocyte	CL:0000023	68.92	silver quality
smooth muscle tissue	UBERON:0001135	68.89	gold quality
decidua	UBERON:0002450	68.78	gold quality
caecum	UBERON:0001153	68.30	gold quality
sperm	CL:0000019	68.07	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ENAD-20	yes	338.57
E-ANND-3	yes	5.78
E-MTAB-6911	no	219.68

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB1, SP1, SP3, TCF3

miRNA regulators (miRDB)

50 targeting EXO1, 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-340-5P	100.00	72.50	4437
HSA-MIR-3163	100.00	77.23	8605
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-323A-3P	99.79	70.30	1739
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-5197-5P	99.64	69.08	1494
HSA-MIR-4663	99.62	65.33	957

Literature-anchored findings (GeneRIF, showing 40)

• requirement for in 5’ and 3’ mismatch repair (PMID:11809771)
• structural analysis of interactions of Exo1 with DNA (PMID:11842105)
• Functional alterations of human exonuclease 1 mutants identified in atypical hereditary nonpolyposis colorectal cancer syndrome. (PMID:12414623)
• Several EXO1 variants observed in patients were also observed in controls with similar frequencies, including the truncating variant proposed previously to be a disease-causing mutation (PMID:12517792)
• The functional interaction between WRN and EXO-1 is mediated by a protein domain of WRN which interacts with flap endonuclease 1. (PMID:12704184)
• hPMS2 accounts for a small proportion of Hereditary non-polyposis colorectal cancer families, and none were deemed to be associated with hEXO1 (PMID:14756672)
• REVIEW: role in cancer? (PMID:15328369)
• there is an association of EXO1 gene polymorphisms with colorectal cancer risk. (PMID:15550454)
• hEXO1, hMLH1 and hMSH2 form complexes and are imported to the nucleus together, and that redundant nuclear localization signals in the proteins may safeguard nuclear import and thereby mismatch repair activity. (PMID:17426132)
• MLH3 and EXO1 alterations in familial colorectal cancer patients not fulfilling Amsterdam criteria. (PMID:17656264)
• EXO1 stability is dependent on phosphorylation by an ATR kinase pathway. (PMID:18048416)
• single nucleotide polymorphisms are associated with risk of lung cancer in chinese population (PMID:18079015)
• robust cleavage by human exonuclease 1 of transcribed G-rich DNA sequences with potential to form G loops and G4 DNA; Predicted Ig switch recombination intermediates are substrates for both exonucleolytic and 5’ flap endonucleolytic cleavage (PMID:18940926)
• Stimulation of DNA resection by hExo1 is independent of BLM helicase activity and is, instead, mediated by an interaction between the 2 proteins (PMID:18971343)
• The site S2 in Mlh1 mediates Exo1 recruitment in order to optimize mismatch repair-dependent mutation avoidance. (PMID:19015241)
• Results provide evidence that the A allele of Exo1 K589E may be associated with the development of lung cancer. (PMID:19331228)
• Gene-environment interactions with smoking were significant for Exo1 K589E polymorphism (OR=2.509, 95% CI=1.914-3.287) and results provide evidence that the A allele of the Exo1 K589E may be associated with the development of oral cancer. (PMID:19515603)
• A functional EXO1 promoter variant is associated with prolonged life expectancy in centenarians. (PMID:19698732)
• Results provide evidence that the A allele of EXO1 K589E may be associated with the development of breast cancer and may be a useful biomarker for breast cancer detection and primary prevention. (PMID:19846925)
• Exo1 is phosphorylated after DNA damage and this event is required for the subsequent recruitment of other DNA repair proteins and homologous recombination (PMID:20019063)
• results suggest that EXO1 may act at transcription-induced telomeric structures to promote telomere recombination while FEN1 has a dominant role in lagging strand replication at telomeres (PMID:20126648)
• The A allele of the Exo1 K589E may be associated with the development of gastric cancer and may be a novel and useful marker for primary prevention and anticancer intervention. (PMID:20337148)
• study found in gastric and colorectal cancers that EXO1 gene harbored somatic frameshift mutations within the mononucleotide repeats in the coding sequences; these mutations were found in the cancers with microsatellite instability (PMID:20429728)
• WRN helicase operates in an EXO1-dependent pathway to help cells survive replicational stress. (PMID:20447876)
• FEN1 and EXO1 can eliminate structures formed by trinucleotide repeats in the course of replication, relying on endonucleolytic and exonucleolytic activities, respectively. (PMID:20643645)
• The EXO1 polymorphism, P757L, was analyzed by PCR-RFLP. Patients with the Leu/Leu genotype have a reduced risk of colorectal cancer. (PMID:20854105)
• This study identifies new functions of CtIP and EXO1 in DNA end resection and provides new information on the regulation of DNA double-strand breaks repair pathways, which is a key factor in the maintenance of genome integrity. (PMID:21052091)
• BLM increases the affinity of EXO1 for ends, and MRN recruits and enhances the processivity of EXO1. (PMID:21325134)
• Exo1 induces a sharp bend in the DNA at nicks or gaps. Frayed 5’ ends of nicked duplexes resemble flap junctions, unifying the mechanisms of endo- and exonucleolytic processing. (PMID:21496642)
• a key role for hEXO1 in the UV-induced DNA damage response linking nucleotide excision repair to checkpoint activation in human cells. (PMID:21808022)
• Gene expression intensity of exonuclease 1 as related to Aicardi- Goutie;res syndrome mutations. (PMID:21862834)
• In this study, we have chosen 2 common SNPs of EXO1 and investigated the association between these 2 SNPs and the risk for cervical cancer in Chinese population by PCR-RFLP. (PMID:22146767)
• Human Ku70/80 protein blocks exonuclease 1-mediated DNA resection in the presence of human Mre11 or Mre11/Rad50 protein complex. (PMID:22179609)
• The Lys/Lys homozygote genotype of Exo 1 K589E polymorphism may be a genetic susceptibility factor for hepatocellular carcinoma in the Turkish population. (PMID:22205538)
• direct and robust interaction between hEXO1 and six of the seven 14-3-3 isoforms, is demonstrated. (PMID:22222486)
• A promoter region SNP in the editing and processing nucleases gene EXO1 was associated with decreased expression of EXO1 and decreased melanoma risk. (PMID:22230721)
• No statistically significant differences were found in the allele or genotype distributions of the Exo 1 T439M polymorphism among HCC and cancer-free control subjects (P>0.05). (PMID:22296401)
• Exo1 as a key mediator of DNA end resection and DSB repair and damage signaling decisions in human cells (PMID:22326273)
• EXO1 deficiency leads to ICL sensitivity but does not increase ICL sensitivity in the absence of FANCD2. (PMID:22987153)
• This mouse transgene line carries an Exo1-null knockout mutation leading to the complete loss of EXO1 protein expression (termed Exo1(null); Exo1-mutant lines show defects in DNA damage response. (PMID:23754438)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	exo1	ENSDARG00000056832
mus_musculus	Exo1	ENSMUSG00000039748
rattus_norvegicus	Exo1	ENSRNOG00000056209
drosophila_melanogaster	tos	FBGN0015553
caenorhabditis_elegans		WBGENE00009731

Paralogs (2): FEN1 (ENSG00000168496), GEN1 (ENSG00000178295)

Protein

Protein identifiers

Exonuclease 1 — Q9UQ84 (reviewed: Q9UQ84)

Alternative names: Exonuclease I

All UniProt accessions (7): Q9UQ84, E5RGY3, E5RHK1, H0YAZ2, Q5T397, Q5T398, Q5T399

UniProt curated annotations — full annotation on UniProt →

Function. 5’->3’ double-stranded DNA exonuclease which may also possess a cryptic 3’->5’ double-stranded DNA exonuclease activity. Functions in DNA mismatch repair (MMR) to excise mismatch-containing DNA tracts directed by strand breaks located either 5’ or 3’ to the mismatch. Also exhibits endonuclease activity against 5’-overhanging flap structures similar to those generated by displacement synthesis when DNA polymerase encounters the 5’-end of a downstream Okazaki fragment. Required for somatic hypermutation (SHM) and class switch recombination (CSR) of immunoglobulin genes. Essential for male and female meiosis.

Subunit / interactions. Interacts with the MLH1-PMS2 heterodimer via MLH1. Interacts with MSH3. Interacts with the MSH2-MSH6 heterodimer via MSH2, and this interaction may increase the processivity of the 5’->3’ exonuclease activity. Interacts with PCNA, and this interaction may both stimulate the cryptic 3’->5’ exonuclease activity and suppress the 5’->3’ exonuclease activity. Interacts with WRN, and this interaction stimulates both the 5’->3’ exonuclease activity and cleavage of 5’-overhanging flap structures. Interacts with RECQL/RECQ1, and this interaction stimulates cleavage of 5’-overhanging flap structures. Interacts with DNA helicase ZGRF1; the interaction is increased following DNA damage induction.

Subcellular location. Nucleus.

Tissue specificity. Highly expressed in bone marrow, testis and thymus. Expressed at lower levels in colon, lymph nodes, ovary, placenta, prostate, small intestine, spleen and stomach.

Post-translational modifications. Phosphorylated upon DNA damage and in response to agents stalling DNA replication, probably by ATM or ATR. Phosphorylation at Ser-454, Thr-621 and Ser-714 is induced upon DNA-damage caused by treatment with hydroxyurea (HU) but not upon IR treatment. The HU-induced EXO1 triple phosphorylation facilitates destabilization/degradation of the protein.

Cofactor. Binds 2 magnesium ions per subunit. They probably participate in the reaction catalyzed by the enzyme. May bind an additional third magnesium ion after substrate binding.

Polymorphism. Most naturally occurring variants in this protein are not associated with familial disposition to hereditary non-polyposis colorectal cancer (HNPCC). Furthermore, germline deletions involving this locus are not associated with clinically manifested colorectal tumors.

Similarity. Belongs to the XPG/RAD2 endonuclease family. EXO1 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UQ84-1	1, B	yes
Q9UQ84-4	2, A

RefSeq proteins (4): NP_001306153, NP_003677, NP_006018, NP_569082* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006084	XPG/Rad2	Family
IPR006085	XPG_DNA_repair_N	Domain
IPR006086	XPG-I_dom	Domain
IPR008918	HhH2	Conserved_site
IPR019974	XPG_CS	Conserved_site
IPR029060	PIN-like_dom_sf	Homologous_superfamily
IPR036279	5-3_exonuclease_C_sf	Homologous_superfamily
IPR037315	EXO1_H3TH	Domain
IPR044752	PIN-like_EXO1	Domain

Pfam: PF00752, PF00867

Enzyme classification (BRENDA):

• EC 3.1.11.1 — exodeoxyribonuclease I (BRENDA: 12 organisms, 162 substrates, 12 inhibitors, 19 Km, 16 kcat entries)

Substrate kinetics (BRENDA)

13 substrates with measured Km, best-characterized 13. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
SSDNA 10 MER	0.28–0.48	2
SSDNA 21 MER	0.35–0.44	2
SSDNA 28 MER	0.26–0.29	2
SSDNA 40 MER	0.24–0.32	2
SSDNA 50 MER	0.13–0.16	2
3’-END 6-FLUORESCEIN-LABELED POLY(DT)10	0.0002	1
3’-END 6-FLUORESCEIN-LABELED POLY(DT)10-5’-PHOSP	0.0002	1
3’-END 6-FLUORESCEIN-LABELED POLY(DT)20	0.0001	1
5’-END 6-FLUORESCEIN-LABELED POLY(DT)10	—	1
5’-END 6-FLUORESCEIN-LABELED POLY(DT)20	0.0001	1
OLIGONUCLEOTIDE (POLYDA)4	0.1	1
OLIGONUCLEOTIDE (POLYDT)(POLYDA)(POLYDT)(POLYDA)	0.04	1
SINGLE-STRANDED DNA	0.016	1

UniProt features (117 total): sequence variant 29, helix 22, modified residue 14, strand 13, region of interest 8, binding site 8, mutagenesis site 8, compositionally biased region 7, turn 4, splice variant 2, chain 1, short sequence motif 1

Structure

Experimental structures (PDB)

25 structures.

PDB	Method	Resolution (Å)
9SEB	X-RAY DIFFRACTION	1.9
5V07	X-RAY DIFFRACTION	2.15
9SMO	X-RAY DIFFRACTION	2.2
7MXV	X-RAY DIFFRACTION	2.21
5V0A	X-RAY DIFFRACTION	2.38
5UZV	X-RAY DIFFRACTION	2.45
3QE9	X-RAY DIFFRACTION	2.51
5V0C	X-RAY DIFFRACTION	2.58
5V0B	X-RAY DIFFRACTION	2.63
5V0D	X-RAY DIFFRACTION	2.63
5V04	X-RAY DIFFRACTION	2.65
5V0E	X-RAY DIFFRACTION	2.74
5V06	X-RAY DIFFRACTION	2.75
5V09	X-RAY DIFFRACTION	2.75
7MXS	X-RAY DIFFRACTION	2.8
5V08	X-RAY DIFFRACTION	2.81
7MXW	X-RAY DIFFRACTION	2.84
7MXX	X-RAY DIFFRACTION	2.85
5V05	X-RAY DIFFRACTION	2.9
3QEB	X-RAY DIFFRACTION	3
7MXU	X-RAY DIFFRACTION	3.04
7MXT	X-RAY DIFFRACTION	3.05
3QEA	X-RAY DIFFRACTION	3.1
7MXR	X-RAY DIFFRACTION	3.1
7MXQ	X-RAY DIFFRACTION	3.23

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UQ84-F1	63.80	0.39

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 (8): 30; 78; 150; 152; 171; 173; 225; 270

Post-translational modifications (14): 376, 422, 454, 482, 581, 598, 610, 621, 623, 639, 660, 674, 714, 746

Mutagenesis-validated functional residues (8):

Position	Phenotype
78	abrogates double-stranded dna exonuclease activity and endonuclease activity against 5’-overhanging flap structures. als
173	abrogates double-stranded dna exonuclease activity and endonuclease activity against 5’-overhanging flap structures. no
225	abrogates double-stranded dna exonuclease activity and endonuclease activity against 5’-overhanging flap structures. als
418	complete loss of nuclear localization.
419	complete loss of nuclear localization.
454	no rescue of hu-induced degradation. no rescue of hu-induced degradation; when associated with a-714. loss of hu-sensiti
621	no rescue of hu-induced degradation. no rescue of hu-induced degradation; when associated with a-714. loss of hu-sensiti
714	no rescue of hu-induced degradation and loss of hu-induced increase of phosphorylation. no rescue of hu-induced degradat

Function

Pathways and Gene Ontology

Reactome pathways

16 pathways

ID	Pathway
R-HSA-5358565	Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha)
R-HSA-5358606	Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta)
R-HSA-5685938	HDR through Single Strand Annealing (SSA)
R-HSA-5685942	HDR through Homologous Recombination (HRR)
R-HSA-5693554	Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)
R-HSA-5693568	Resolution of D-loop Structures through Holliday Junction Intermediates
R-HSA-5693579	Homologous DNA Pairing and Strand Exchange
R-HSA-5693607	Processing of DNA double-strand break ends
R-HSA-5693616	Presynaptic phase of homologous DNA pairing and strand exchange
R-HSA-6804756	Regulation of TP53 Activity through Phosphorylation
R-HSA-69473	G2/M DNA damage checkpoint
R-HSA-9701192	Defective homologous recombination repair (HRR) due to BRCA1 loss of function
R-HSA-9704331	Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function
R-HSA-9704646	Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function
R-HSA-9709570	Impaired BRCA2 binding to RAD51
R-HSA-9709603	Impaired BRCA2 binding to PALB2

MSigDB gene sets: 317 (showing top): GOBP_DNA_TEMPLATED_DNA_REPLICATION_MAINTENANCE_OF_FIDELITY, GOBP_CHROMOSOME_ORGANIZATION, WU_APOPTOSIS_BY_CDKN1A_VIA_TP53, GOMF_ENDONUCLEASE_ACTIVITY, GOMF_RNA_NUCLEASE_ACTIVITY, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_B_CELL_ACTIVATION, FISCHER_G1_S_CELL_CYCLE, GOMF_NUCLEASE_ACTIVITY, REACTOME_G2_M_DNA_DAMAGE_CHECKPOINT, RIZ_ERYTHROID_DIFFERENTIATION_CCNE1, GOBP_TELOMERE_ORGANIZATION, KAUFFMANN_DNA_REPAIR_GENES, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY, AACWWCAANK_UNKNOWN

GO Biological Process (11): humoral immune response mediated by circulating immunoglobulin (GO:0002455), DNA repair (GO:0006281), mismatch repair (GO:0006298), DNA recombination (GO:0006310), somatic hypermutation of immunoglobulin genes (GO:0016446), isotype switching (GO:0045190), meiotic cell cycle (GO:0051321), t-circle formation (GO:0090656), DNA strand resection involved in replication fork processing (GO:0110025), immune system process (GO:0002376), DNA damage response (GO:0006974)

GO Molecular Function (18): DNA binding (GO:0003677), chromatin binding (GO:0003682), RNA-DNA hybrid ribonuclease activity (GO:0004523), exonuclease activity (GO:0004527), 5’-3’ exonuclease activity (GO:0008409), 5’-flap endonuclease activity (GO:0017108), 5’-3’ DNA exonuclease activity (GO:0035312), single-stranded DNA 5’-3’ DNA exonuclease activity (GO:0045145), metal ion binding (GO:0046872), flap endonuclease activity (GO:0048256), double-stranded DNA 5’-3’ DNA exonuclease activity (GO:0051908), catalytic activity (GO:0003824), nuclease activity (GO:0004518), endonuclease activity (GO:0004519), DNA endonuclease activity (GO:0004520), protein binding (GO:0005515), hydrolase activity (GO:0016787), hydrolase activity, acting on ester bonds (GO:0016788)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), plasma membrane (GO:0005886), nuclear body (GO:0016604)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	3
Mismatch Repair	2
Resolution of D-Loop Structures	2
Defective homologous recombination repair (HRR) due to PALB2 loss of function	2
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	2
HDR through Homologous Recombination (HRR)	1
Homologous DNA Pairing and Strand Exchange	1
Regulation of TP53 Activity	1
G2/M Checkpoints	1
Diseases of DNA Double-Strand Break Repair	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA metabolic process	3
5’-3’ DNA exonuclease activity	3
binding	2
nuclease activity	2
hydrolase activity, acting on ester bonds	2
humoral immune response	1
immunoglobulin mediated immune response	1
DNA damage response	1
DNA repair	1
somatic diversification of immune receptors via somatic mutation	1
somatic diversification of immunoglobulins	1
somatic recombination of immunoglobulin genes involved in immune response	1
B cell activation involved in immune response	1
cell cycle	1
sexual reproduction	1
reproductive process	1
meiotic nuclear division	1
formation of extrachromosomal circular DNA	1
telomere maintenance via telomere trimming	1
replication fork processing	1
biological_process	1
cellular response to stress	1
nucleic acid binding	1
RNA endonuclease activity producing 5’-phosphomonoesters, hydrolytic mechanism	1
exonuclease activity	1
DNA endonuclease activity, producing 5’-phosphomonoesters	1
flap endonuclease activity	1
5’-3’ exonuclease activity	1
DNA exonuclease activity, producing 5’-phosphomonoesters	1
single-stranded DNA exodeoxyribonuclease activity	1
cation binding	1
DNA endonuclease activity	1
double-stranded DNA exodeoxyribonuclease activity	1
molecular_function	1
catalytic activity, acting on a nucleic acid	1
endonuclease activity	1
DNA nuclease activity	1
catalytic activity	1
hydrolase activity	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

4048 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EXO1	MLH1	P40692	998
EXO1	MSH2	P43246	996
EXO1	MLH3	P49751	993
EXO1	DNA2	P51530	988
EXO1	WRN	Q14191	986
EXO1	RBBP8	Q99708	974
EXO1	MSH6	P52701	973
EXO1	PMS2	P54278	972
EXO1	MSH3	P20585	957
EXO1	RAD51	Q06609	954
EXO1	RECQL	P46063	931
EXO1	BLM	P54132	915
EXO1	BRCA1	P38398	898
EXO1	RAD52	P43351	897
EXO1	PMS1	P54277	896

IntAct

50 interactions, top by confidence:

A	B	Type	Score
MSH2	MSH3	psi-mi:“MI:0914”(association)	0.920
YWHAQ	WDR62	psi-mi:“MI:0914”(association)	0.830
RBBP8	MRE11	psi-mi:“MI:0914”(association)	0.670
RBBP8	EXO1	psi-mi:“MI:0915”(physical association)	0.660
EXO1	RBBP8	psi-mi:“MI:0915”(physical association)	0.660
RBBP8	EXO1	psi-mi:“MI:0407”(direct interaction)	0.660
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
YWHAB	BLTP3B	psi-mi:“MI:2364”(proximity)	0.610
YWHAB	BLTP3B	psi-mi:“MI:0914”(association)	0.610
ZGRF1	BRCA1	psi-mi:“MI:0914”(association)	0.580
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
ZGRF1	EXO1	psi-mi:“MI:0915”(physical association)	0.560
MSH6	PCNA	psi-mi:“MI:0914”(association)	0.530
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
WDR83	SH2B2	psi-mi:“MI:0914”(association)	0.530
EXO1	BLM	psi-mi:“MI:0407”(direct interaction)	0.440
EXO1	PLEC	psi-mi:“MI:0915”(physical association)	0.400
SLC46A1	EXO1	psi-mi:“MI:0915”(physical association)	0.400
EXO1	MLH1	psi-mi:“MI:0915”(physical association)	0.370
LLGL2	RBBP6	psi-mi:“MI:0914”(association)	0.350
Tmem109	ASXL2	psi-mi:“MI:0914”(association)	0.350
MYEF2	PRMT5	psi-mi:“MI:0914”(association)	0.350
COMT		psi-mi:“MI:0914”(association)	0.350
CD14	PHF20L1	psi-mi:“MI:0914”(association)	0.350
KLC3	KLC1	psi-mi:“MI:0914”(association)	0.350
ACTR5	TBRG1	psi-mi:“MI:0914”(association)	0.350
CFTR	SNHG32	psi-mi:“MI:0914”(association)	0.350
YWHAG	C1orf226	psi-mi:“MI:0914”(association)	0.350

BioGRID (128): EXO1 (Affinity Capture-MS), EXO1 (Affinity Capture-MS), EXO1 (Affinity Capture-MS), EXO1 (Affinity Capture-MS), EXO1 (Affinity Capture-MS), EXO1 (Affinity Capture-MS), EXO1 (Affinity Capture-MS), EXO1 (Affinity Capture-MS), EXO1 (Affinity Capture-MS), EXO1 (Biochemical Activity), SENP6 (Affinity Capture-Western), SENP6 (Reconstituted Complex), EXO1 (Affinity Capture-MS), EXO1 (Phenotypic Enhancement), EXO1 (Affinity Capture-RNA)

ESM2 similar proteins: A0A0G2L7I0, A2VDP0, A2YX04, A5D979, B4FM28, B6SLJ0, D3ZVU1, F4I8S3, F4KFC7, F6UH96, G3X912, O01835, Q0J9J6, Q22557, Q24595, Q2HJG4, Q32LR5, Q38796, Q4KM91, Q53WJ1, Q5U3H2, Q65Z40, Q680Q4, Q6E3D5, Q6PI47, Q6Z8M8, Q700C2, Q7KW09, Q7XC57, Q7Y1C4, Q7Y1C5, Q7Z5K2, Q7ZXG4, Q801E2, Q8L840, Q8RY95, Q91W18, Q91ZX6, Q941B6, Q9BVC5

Diamond homologs: A0B9M7, A1RSC7, A1RWY2, A3CWV2, A3DMG2, A3FPN7, A3MY15, A4HFE4, A4I2L4, A4S1G4, A4WNC4, A5KAL1, A5UL52, A6UX46, A7AX58, A7IA59, A7RRJ0, A8AAC1, A8B672, A8M9L3, A8NQC2, B0E412, B0EN90, B0UXL7, B1YC46, B3MDA3, B3NP61, B4GIM3, B4HTA1, B4J6M4, B4LM90, B4MR84, B4P5U9, B4QIG6, B5DUR8, B6AFP1, B6JYI7, B7XHS8, B8C6S5, B8GIA0

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
ATM	up-regulates	EXO1	phosphorylation
CHEK2	“down-regulates activity”	EXO1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 59 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
Activation of BAD and translocation to mitochondria	6	99.3×	1e-09
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	6	87.6×	2e-09
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	6	87.6×	2e-09
Diseases of DNA repair	7	86.9×	1e-10
Activation of BH3-only proteins	6	64.8×	1e-08
RHO GTPases activate PKNs	6	41.4×	1e-07
Intrinsic Pathway for Apoptosis	6	38.2×	2e-07
Impaired BRCA2 binding to RAD51	5	33.5×	5e-06

GO biological processes:

GO term	Partners	Fold	FDR
mismatch repair	6	69.5×	1e-07
protein targeting	5	32.7×	4e-05
double-strand break repair	6	21.8×	3e-05
DNA replication	6	17.7×	8e-05
intracellular protein localization	8	14.9×	1e-05
double-strand break repair via homologous recombination	5	13.9×	1e-03
DNA repair	8	9.1×	1e-04
chromatin remodeling	6	7.8×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	93
Likely benign	25
Benign	16

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
546633	NM_130398.4(EXO1):c.136del (p.Lys45_Leu46insTer)	Likely pathogenic

SpliceAI

2832 predictions. Top by Δscore:

Variant	Effect	Δscore
1:241852412:G:GG	donor_gain	1.0000
1:241853356:A:AG	acceptor_gain	1.0000
1:241853357:G:GG	acceptor_gain	1.0000
1:241853473:G:GG	donor_gain	1.0000
1:241853482:G:GG	donor_gain	1.0000
1:241857342:TA:T	acceptor_loss	1.0000
1:241857343:A:AC	acceptor_loss	1.0000
1:241857343:A:AG	acceptor_gain	1.0000
1:241857343:AG:A	acceptor_gain	1.0000
1:241857343:AGGCT:A	acceptor_gain	1.0000
1:241857344:G:GT	acceptor_gain	1.0000
1:241857344:GG:G	acceptor_gain	1.0000
1:241857344:GGC:G	acceptor_gain	1.0000
1:241857344:GGCT:G	acceptor_gain	1.0000
1:241857344:GGCTG:G	acceptor_gain	1.0000
1:241857478:AAAAG:A	donor_gain	1.0000
1:241857483:GT:G	donor_loss	1.0000
1:241857484:T:A	donor_loss	1.0000
1:241858714:TAAAG:T	donor_loss	1.0000
1:241858715:AAAGG:A	donor_loss	1.0000
1:241858716:AAGG:A	donor_loss	1.0000
1:241858717:AGGTA:A	donor_loss	1.0000
1:241858719:G:C	donor_loss	1.0000
1:241858720:T:G	donor_loss	1.0000
1:241860688:C:CG	donor_gain	1.0000
1:241860693:C:G	donor_gain	1.0000
1:241860702:G:GT	donor_gain	1.0000
1:241860702:G:T	donor_gain	1.0000
1:241860722:GAATG:G	donor_gain	1.0000
1:241872031:GCA:G	acceptor_gain	1.0000

AlphaMissense

5578 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:241852384:A:T	K85I	0.999
1:241852385:A:C	K85N	0.999
1:241852385:A:T	K85N	0.999
1:241857451:A:C	D171A	0.999
1:241857468:T:C	F177L	0.999
1:241857470:T:A	F177L	0.999
1:241857470:T:G	F177L	0.999
1:241860604:T:C	F282L	0.999
1:241860606:C:A	F282L	0.999
1:241860606:C:G	F282L	0.999
1:241850429:G:A	G2R	0.998
1:241850429:G:C	G2R	0.998
1:241850508:C:A	A28D	0.998
1:241850514:A:T	D30V	0.998
1:241850525:T:A	W34R	0.998
1:241850525:T:C	W34R	0.998
1:241852366:G:A	G79E	0.998
1:241852405:G:C	R92T	0.998
1:241852406:A:C	R92S	0.998
1:241852406:A:T	R92S	0.998
1:241853363:G:C	R96P	0.998
1:241853383:G:A	G103R	0.998
1:241853383:G:C	G103R	0.998
1:241853384:G:A	G103E	0.998
1:241853393:T:C	L106P	0.998
1:241857451:A:T	D171V	0.998
1:241857457:A:G	D173G	0.998
1:241857460:T:C	L174P	0.998
1:241858537:G:A	G192E	0.998
1:241858617:T:C	C219R	0.998

dbSNP variants (sampled 300 via entrez): RS1000197298 (1:241847739 G>T), RS1000214712 (1:241853728 C>T), RS1000283551 (1:241878392 G>T), RS1000287789 (1:241857440 A>G), RS1000440710 (1:241848105 G>A,C,T), RS1000462358 (1:241877234 G>A), RS1000486911 (1:241885043 T>G), RS1000500670 (1:241888942 G>GT), RS1000552221 (1:241854941 G>A,C), RS1000617114 (1:241884603 TTAAG>T), RS1000681167 (1:241868849 A>G), RS1000729813 (1:241884816 A>G), RS1000732983 (1:241869091 T>A), RS1000837966 (1:241884807 C>G,T), RS1000863486 (1:241863226 C>A)

Disease associations

OMIM: gene MIM:606063 | disease phenotypes: MIM:613659

GenCC curated gene-disease

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Lynch syndrome	Refuted	AD

Mondo (2): gastric cancer (MONDO:0001056), hereditary breast ovarian cancer syndrome (MONDO:0003582)

Orphanet (1): Hereditary breast and/or ovarian cancer syndrome (Orphanet:145)

HPO phenotypes

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

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST001381_10	Menopause (age at onset)	8.000000e-10
GCST004950_30	Breast cancer	2.000000e-08
GCST004988_263	Breast cancer	2.000000e-14
GCST005312_4	Menopause (age at onset)	8.000000e-14
GCST007236_65	Breast cancer	3.000000e-07
GCST008870_76	Keratinocyte cancer (MTAG)	2.000000e-09
GCST008871_14	Basal cell carcinoma	1.000000e-08
GCST010396_52	Gut microbiota (bacterial taxa, hurdle binary method)	7.000000e-06
GCST90002381_20	Eosinophil count	1.000000e-10
GCST90002382_30	Eosinophil percentage of white cells	5.000000e-12
GCST90002390_344	Mean corpuscular hemoglobin	3.000000e-10
GCST90002392_259	Mean corpuscular volume	2.000000e-10

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004704	age at menopause
EFO:0010176	keratinocyte carcinoma
EFO:0007874	gut microbiome measurement
EFO:0004842	eosinophil count
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004527	mean corpuscular hemoglobin

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D061325	Hereditary Breast and Ovarian Cancer Syndrome	C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523496 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1047840	Efficacy	3	capecitabine;fluorouracil	Metastatic neoplasm

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1047840	EXO1	3	0.00	1	capecitabine;fluorouracil

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, decreases methylation, increases expression	6
Cyclosporine	decreases expression	4
Tetrachlorodibenzodioxin	affects cotreatment, increases expression, decreases expression	3
sodium arsenite	affects expression, decreases expression	2
Endosulfan	affects cotreatment, increases expression	2
Ozone	affects cotreatment, increases oxidation, increases abundance, increases expression	2
Rotenone	decreases expression, increases expression	2
Testosterone	affects cotreatment, decreases expression, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression, increases expression	2
Aflatoxin B1	affects expression, increases expression	2
afuresertib	decreases expression	1
FR900359	affects phosphorylation	1
TAK-243	increases sumoylation	1
pradimicin-IRD	decreases expression, affects expression, affects response to substance	1
lasiocarpine	increases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
4-biphenylamine	decreases expression	1
bisphenol A	affects cotreatment, decreases methylation	1
VX-agent	increases expression	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
perfluorooctanoic acid	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
fludarabine	affects cotreatment, decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
coumarin	affects phosphorylation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
beta-methylcholine	affects expression	1
chromium hexavalent ion	decreases expression, increases abundance	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4418092	Binding	Inhibition of nuclease activity of EXO1 (unknown origin) up to 125 uM using DNA substrate	DNA2 inhibitors for cancer treatment

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B7X8	Abcam Raji EXO1 KO	Cancer cell line	Male
CVCL_B9XV	Abcam THP-1 EXO1 KO	Cancer cell line	Male
CVCL_C6ZQ	Abcam PC-3 EXO1 KO	Cancer cell line	Male
CVCL_SM58	HAP1 EXO1 (-) 1	Cancer cell line	Male
CVCL_XN57	HAP1 EXO1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00365508	PHASE4	COMPLETED	Counseling and Nicotine Replacement Therapy in Helping Adult Smokers Quit Smoking
NCT00558155	PHASE4	COMPLETED	The Impact of Immunostimulating Nutrition on the Outcome of Surgery
NCT00576940	PHASE4	COMPLETED	Standard and Immunostimulating Enteral Nutrition in Surgical Patients
NCT00666978	PHASE4	COMPLETED	Health Education Counseling With or Without Bupropion in Helping African Americans Stop Smoking
NCT01038154	PHASE4	UNKNOWN	Study to Evaluate the Efficacy of Pravastatin on Survival and Recurrence of Advanced Gastroesophageal Cancer
NCT01234272	PHASE4	COMPLETED	Comparison of the Analgesic Effect Between Intrathecal Morphine and IV-fentanyl Patient Controlled Analgesia (ITM-IVPCA) and Epidural PCA (PCEA) in Patients Undergoing Gastrectomy -Randomized Allocation Study-
NCT01260194	PHASE4	TERMINATED	A Study of Herceptin (Trastuzumab) in Combination With Standard Chemotherapy in Patients With HER Positive Metastatic Gastric Cancer
NCT01271582	PHASE4	UNKNOWN	Investigation of Association Between UGT1A1 Polymorphisms and Irinotecan Toxicity in Korean Patients
NCT01401075	PHASE4	COMPLETED	RCT With Adjuvant Mistletoe Treatment in Gastric Cancer Patients
NCT01471756	PHASE4	COMPLETED	Improving Complete Endoscopic Mucosal Resection (EMR) of Colorectal Neoplasia
NCT01766765	PHASE4	UNKNOWN	Early Jejunostomy Nutrition Minimizes Time to Chemotherapy
NCT01910948	PHASE4	UNKNOWN	Perioperative Application of Omega-3 Polyunsaturated Fatty Acids in Gastric Cancer Patients
NCT01927328	PHASE4	UNKNOWN	Iron Replacement in Oesophagogastric Neoplasia
NCT01962272	PHASE4	COMPLETED	The Effect of Nutritional Counseling for Cancer Patients
NCT01962376	PHASE4	UNKNOWN	Preoperative Chemotherapy With Bevacizumab For Potentially Resectable Gastric Cancer With Liver Metastasis
NCT02047994	PHASE4	RECRUITING	Multicentric Randomized Study of H. Pylori Eradication and Pepsinogen Testing for Prevention of Gastric Cancer Mortality
NCT02235246	PHASE4	COMPLETED	The Effect of Perioperative Intravenous Magnesium on Pain After Endoscopic Submucosal Dissection for Gastric Neoplasm: Prospective Randomized Double-blind Placebo Controlled Study
NCT02366819	PHASE4	SUSPENDED	Genetic Analysis-Guided Irinotecan Hydrochloride Dosing of mFOLFIRINOX in Treating Patients With Locally Advanced Gastroesophageal or Stomach Cancer
NCT02401971	PHASE4	UNKNOWN	Irinotecan Plus Thalidomide in Second Line Advanced Gastric Cancer
NCT02458573	PHASE4	COMPLETED	Comparison of the Effects of Continuous Epidural Analgesia and Continuous Intravenous Analgesia on Postoperative Bowel Movement in Patients Undergoing Laparoscopic Gastrectomy
NCT02638584	PHASE4	COMPLETED	Effects of Ilaprazole on Ulcer Healing Rate and Prevention of Gastrointestinal Bleeding in the Patients Undergone ESD.
NCT02776527	PHASE4	UNKNOWN	A Clinical Trial of Maintenance Treatment of Apatinib in Advanced Gastric Cancer Patients Have Completed Postoprative Adjuvant Chemotherapy
NCT03384511	PHASE4	COMPLETED	The Use of 18F-ALF-NOTA-PRGD2 PET/CT Scan to Predict the Efficacy and Adverse Events of Apatinib in Malignancies.
NCT03550482	PHASE4	COMPLETED	Oncoxin® and Quality of Life in Cancer Patients
NCT03609892	PHASE4	COMPLETED	Helicobacter Rescue Therapy With Berberine Plus Amoxicillin Quadruple Therapy Versus Tetracycline Plus Furazolidone Quadruple Therapy
NCT03642093	PHASE4	UNKNOWN	HOPE - A Study to Evaluate the Effect of a Prehabilitation Program on GI Cancer Patients Planning to Undergo Surgery
NCT03733639	PHASE4	UNKNOWN	Tisseel® as a Reinforcement of Esophagojejunal Anastomoses
NCT04168346	PHASE4	NOT_YET_RECRUITING	Preoperative Intravenous Iron Therapy in Patients With Gastric Cancer
NCT04209933	PHASE4	COMPLETED	Helicobacter Pylori Eradication With Different Bismuth Quadruple Therapies
NCT04591028	PHASE4	WITHDRAWN	A Study to Evaluate Indocyanine Green Lymphangiography to Improve Lymphadenectomy in Gastric Cancer Patients
NCT04607057	PHASE4	UNKNOWN	Supplemental Parenteral Nutrition During Postgastrectomy in Nutritionally at Risk Patient
NCT04660123	PHASE4	COMPLETED	A Real World Study of Bismuth Colloidal Pectin Granules Quadruple Therapy for H. Pylori Eradication
NCT04678492	PHASE4	COMPLETED	Helicobacter Rescue Therapy With High-dose Esomeprazole and Amoxicillin Dual Therapy Versus Bismuth-containing Quadruple Therapy
NCT04697186	PHASE4	COMPLETED	Helicobacter Pylori Eradication With Berberine Plus Amoxicillin Triple Therapy Versus Bismuth-containing Quadruple Therapy
NCT05029453	PHASE4	UNKNOWN	Apatinib Combined With Chemotherapy Versus Chemotherapy in Second-line Gastric Cancer Receiving Prior Anti-PD-1 Therapy
NCT05183126	PHASE4	RECRUITING	Pharmacokinetic Study of Skeletal Muscle Area-based Paclitaxel Infusion in Patients With Cancer
NCT05354856	PHASE4	TERMINATED	The Effect of Chemoradiotherapy on Gastric Perfusion in Patients With Gastric Cancer.
NCT05410535	PHASE4	COMPLETED	To Evaluate Efficacy of Ursodeoxycholic Acid (UDCA) for the Prevention of Gallstone Formation After Gasterectomy
NCT05498766	PHASE4	NOT_YET_RECRUITING	Effect and Safety of Huaier Granule Versus SOX Regimen in Gastric Cancer Patients
NCT05518929	PHASE4	COMPLETED	Hypoxia During Gastroenterological Endoscope Procedures Sedated With Ciprofol In Overweight Or Obesity Patients