LIG1

Summary

LIG1 (DNA ligase 1, HGNC:6598) is a protein-coding gene on chromosome 19q13.33, encoding DNA ligase 1 (P18858). DNA ligase that seals nicks in double-stranded during DNA repair. It is a selective cancer dependency (DepMap: 18.0% of cell lines).

This gene encodes a member of the ATP-dependent DNA ligase protein family. The encoded protein functions in DNA replication, recombination, and the base excision repair process. Mutations in this gene that lead to DNA ligase I deficiency result in immunodeficiency and increased sensitivity to DNA-damaging agents. Disruption of this gene may also be associated with a variety of cancers. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 3978 — RefSeq curated summary.

At a glance

• Gene–disease (curated): immunodeficiency 96 (Definitive, ClinGen)
• Clinical variants (ClinVar): 857 total — 2 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 18
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 18.0% of screened cell lines
• MANE Select transcript: NM_000234

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6598
Approved symbol	LIG1
Name	DNA ligase 1
Location	19q13.33
Locus type	gene with protein product
Status	Approved
Aliases	LIGI, hLig1
Ensembl gene	ENSG00000105486
Ensembl biotype	protein_coding
OMIM	126391
Entrez	3978

Gene structure

Transcript identifiers

Ensembl transcripts: 66 — 39 protein_coding, 14 retained_intron, 9 nonsense_mediated_decay, 4 protein_coding_CDS_not_defined

ENST00000263274, ENST00000427526, ENST00000542460, ENST00000593425, ENST00000594067, ENST00000594759, ENST00000595758, ENST00000596104, ENST00000596332, ENST00000596457, ENST00000596549, ENST00000596672, ENST00000597146, ENST00000597901, ENST00000598938, ENST00000599165, ENST00000599322, ENST00000600055, ENST00000601091, ENST00000699865, ENST00000699866, ENST00000699867, ENST00000699868, ENST00000699869, ENST00000699870, ENST00000699871, ENST00000699872, ENST00000699873, ENST00000699874, ENST00000699875, ENST00000699876, ENST00000699877, ENST00000699878, ENST00000699879, ENST00000699880, ENST00000699881, ENST00000884156, ENST00000884157, ENST00000884158, ENST00000884159, ENST00000884160, ENST00000884161, ENST00000884162, ENST00000884164, ENST00000916664, ENST00000916665, ENST00000916666, ENST00000916667, ENST00000916668, ENST00000916669, ENST00000916670, ENST00000916671, ENST00000916672, ENST00000916673, ENST00000916674, ENST00000916675, ENST00000916676, ENST00000916677, ENST00000916678, ENST00000916679, ENST00000916680, ENST00000916681, ENST00000968336, ENST00000968337, ENST00000968338, ENST00000968339

RefSeq mRNA: 5 — MANE Select: NM_000234 NM_000234, NM_001289063, NM_001289064, NM_001320970, NM_001320971

CCDS: CCDS12711, CCDS74409, CCDS74410, CCDS92657, CCDS92658

Canonical transcript exons

ENST00000263274 — 28 exons

Exon	Start	End
ENSE00000953171	48161372	48161507
ENSE00000953172	48157014	48157140
ENSE00002246723	48170241	48170344
ENSE00003021368	48115445	48115732
ENSE00003465309	48137008	48137084
ENSE00003467036	48143883	48143963
ENSE00003467223	48122934	48123016
ENSE00003473795	48127277	48127348
ENSE00003475529	48123174	48123318
ENSE00003476493	48115873	48115965
ENSE00003480395	48162262	48162351
ENSE00003483456	48132982	48133097
ENSE00003499308	48135680	48135779
ENSE00003521923	48136034	48136125
ENSE00003525353	48117638	48117781
ENSE00003529081	48137522	48137688
ENSE00003530152	48121170	48121322
ENSE00003549446	48151232	48151339
ENSE00003550714	48131076	48131171
ENSE00003557072	48127910	48128020
ENSE00003569746	48150088	48150210
ENSE00003601954	48119137	48119190
ENSE00003612011	48165550	48165623
ENSE00003614812	48133981	48134066
ENSE00003635842	48153872	48153967
ENSE00003660169	48143543	48143599
ENSE00003673487	48149763	48149841
ENSE00003675368	48139971	48140143

Expression profiles

Bgee: expression breadth ubiquitous, 198 present calls, max score 94.99.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.0695 / max 349.3423, expressed in 1790 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
181819	19.8862	1758
181818	7.2015	1448
181817	0.9818	591

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	94.99	gold quality
ventricular zone	UBERON:0003053	94.93	gold quality
ganglionic eminence	UBERON:0004023	93.81	gold quality
sural nerve	UBERON:0015488	92.13	gold quality
mucosa of transverse colon	UBERON:0004991	91.41	gold quality
left testis	UBERON:0004533	91.20	gold quality
granulocyte	CL:0000094	91.04	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.99	gold quality
right testis	UBERON:0004534	90.64	gold quality
embryo	UBERON:0000922	89.92	gold quality
lower esophagus mucosa	UBERON:0035834	89.06	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.93	gold quality
skin of abdomen	UBERON:0001416	88.93	gold quality
testis	UBERON:0000473	88.46	gold quality
skin of leg	UBERON:0001511	88.42	gold quality
right hemisphere of cerebellum	UBERON:0014890	87.82	gold quality
cerebellar hemisphere	UBERON:0002245	87.56	gold quality
lymph node	UBERON:0000029	87.51	gold quality
spleen	UBERON:0002106	87.48	gold quality
cerebellar cortex	UBERON:0002129	87.37	gold quality
rectum	UBERON:0001052	87.12	gold quality
endometrium epithelium	UBERON:0004811	86.89	gold quality
small intestine Peyer’s patch	UBERON:0003454	86.86	gold quality
left lobe of thyroid gland	UBERON:0001120	86.71	gold quality
body of pancreas	UBERON:0001150	86.67	gold quality
bone marrow cell	CL:0002092	86.56	gold quality
right lobe of thyroid gland	UBERON:0001119	86.56	gold quality
adenohypophysis	UBERON:0002196	86.28	gold quality
esophagus mucosa	UBERON:0002469	86.25	gold quality
thyroid gland	UBERON:0002046	85.99	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.76
E-MTAB-6911	no	295.94

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): APEX1, PARP1, TP53

miRNA regulators (miRDB)

4 targeting LIG1, 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-5680	99.91	69.83	3421
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-488-3P	99.61	68.79	1731
HSA-MIR-4763-5P	98.75	63.89	854

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 18.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• DNA ligase I competes with FEN1 to expand repetitive DNA sequences in vitro. (PMID:11948189)
• stimulated by APE1 for progression through the base excision repair pathway (PMID:12200445)
• phosphorylation of DNA ligase I and possibly other replicative enzymes is part of the mechanism that directs the disassembly of the replication machinery at the completion of S-phase. (PMID:12851383)
• majority of single-strand DNA interruptions produced during the repair of alkylated DNA bases are repaired by the pathway mediated by Pol beta and either Lig I or Lig III (PMID:14627836)
• crystal structure of human DNA ligase I (residues 233 to 919) in complex with a nicked, 5’ adenylated DNA intermediate (PMID:15565146)
• The human checkpoint sensor and alternative clamp Rad9-Rad1-Hus1 can interact with and specifically stimulate DNA ligase I (PMID:15871698)
• LIG1-deficiency reduces recombinational repair of DNA double-strand beaks. (PMID:15907772)
• human DNA ligase I is stimulated by the Rad9-rad1-Hus1 checkpoint complex (PMID:16731526)
• siRNA mediated down-regulation of DNA ligase I in human HTD114 cells led to impaired end joining that was mediated by 2-, 3- or 10-bp microhomology. (PMID:18440984)
• The LIG1 SNP 5’UTR showed a significant association with glioma risk. (PMID:19124499)
• drastically reduced replicative LigI activity in 46BR.1G1 cells results in the accumulation of both single-stranded and double-stranded DNA breaks. (PMID:19223467)
• a mutant version of hLigI, which mimics the hyperphosphorylated M-phase form of hLigI, does not interact with and is not inhibited by RFC, demonstrating that inhibition of ligation is dependent upon the interaction between hLigI and RFC (PMID:19223468)
• The DNA binding domain (DBD) within the hLigI catalytic fragment interacts with both PCNA and the heterotrimeric cell-cycle checkpoint clamp, hRad9-hRad1-hHus1 (9-1-1). (PMID:19523882)
• Data support the notion that DNA ligase I participates in homology dependent pathways that deal with replication-associated lesions generated when replication fork encounters DNA damage. (PMID:19597347)
• Data show that disruption of LigI and PCNA interactions influences trinucleotide repeat instability. (PMID:19628465)
• RNA silencing of human DNA ligase I expression severely reduced replication of viral DNA in cells infected with vaccinia virus ligase-deficient mutants. (PMID:20006844)
• Kinetic mechanism of human DNA ligase I reveals magnesium-dependent changes in the rate-limiting step that compromise ligation efficiency. (PMID:21561855)
• Data show that association of study-wide significance (P < 8.2 x 10(-5)) was identified for single-nucleotide polymorphisms (SNP) in TP53, LIG1, and BIK. (PMID:22139380)
• DNA ligase I also interacts with replication factor C, the factor that loads the PCNA trimeric ring onto DNA. (PMID:22918593)
• phosphorylation of serine 51 on hLigI plays a critical role in regulating the interaction between hLigI and RFC, which is required for efficient DNA replication and repair. (PMID:22952233)
• Single nucleotide polymorphisms in LIG1 are associated with myelodysplastic syndromes. (PMID:23339595)
• Data indicate that Ku70/Ku80 facilitates the cooperative binding of multiple XRCC4/Ligase IV (XL) and XLF molecules to DNA. (PMID:23620595)
• there is no association between LIGI polymorphisms and cervical cancer risk. However, they may be playing an important role in modulating the risk of cervical adenocarcinoma in North Indian women (PMID:24084463)
• Ppolymorphisms in LIG1 affect its expression and may therefore change its function. (PMID:25189241)
• A novel method for monitoring functional lesion-specific recruitment of repair proteins in live cells. (PMID:25879709)
• The LIG1 CC genotype was associated with susceptibility to non-small cell lung cancer, and the AA genotype demonstrated increased radiosensitivity compared to the AC and CC genotypes. (PMID:26125914)
• Data suggest that DNA ligase I (LigI)-deficient 46BR.1G1 cells represent a model to investigate the biological effects of sub-lethal levels of DNA insults. (PMID:26151554)
• The rs156641 polymorphism of DNA ligase 1 (LIG1) was significantly associated with lung cancer risk, whereas no association was found between rs3730931/rs439132/rs20579 polymorphisms and lung cancer. (PMID:27352326)
• single-stranded break repair by human DNA ligase III isoforms reveal biochemical differences from DNA ligase (PMID:28751376)
• A histone H3K9-like mimic within LIG1 is methylated by G9a and GLP and avidly binds UHRF1. Interaction with methylated LIG1 promotes the recruitment of UHRF1 to DNA replication sites and is required for DNA methylation maintenance. (PMID:28803780)
• LIG1 is regulated by the oncoprotein SRSF1 and plays a relevant role in lung cancer cell proliferation and progression. (PMID:30181552)
• In the current study, we have demonstrated that the combination of miRNA-mediated targeting of RAD51, PRKDC, LIG1 genes and ionizing radiation is effective to enhance cytotoxic effect of therapeutic doses of gamma-radiation in NSCLC A549 cells (PMID:30389599)
• These data suggest that different forms of autosomal recessive, partial DNA ligase 1 deficiency underlie an immunodeficiency of variable severity. (PMID:30395541)
• We have resolved an essential and non-redundant role for DNA ligase 1 in the fusion of sister chromatids bearing targeted double strand DNA breaks that is entirely uncoupled from its requisite engagement in DNA replication. (PMID:30590694)
• The crystal structure of UHRF1 tandem tudor domain (TTD) domain bound to the LIG1K126me3 showed that Arg121 of LIG1 is a key residue for high-affinity binding to TTD. Its phosphorylation negatively regulates the interaction with UHRF1. LIG1K126me3 binding changes UHRF1 structure from closed to open. (PMID:30639225)
• Altered DNA ligase activity in human disease. (PMID:31630206)
• Results support a model whereby LIG1 fidelity is governed by a high-fidelity (HiFi) interface between LIG1, Mg(2+), and the DNA substrate that tunes the enzyme to release pro-mutagenic DNA nicks. In a second tier of protection, LIG1 activity is surveilled by Aprataxin (APTX), which suppresses mutagenic and abortive ligation at sites of oxidative DNA damage. (PMID:31780661)
• Radio-adaptive response, individual radio-sensitivity and correlation of base excision repair gene polymorphism (hOGG1, APE1, XRCC1, and LIGASE1) in human peripheral blood mononuclear cells exposed to gamma radiation. (PMID:32324932)
• Serine 298 Phosphorylation in Linker 2 of UHRF1 Regulates Ligand-Binding Property of Its Tandem Tudor Domain. (PMID:32428527)
• DNA ligase I variants fail in the ligation of mutagenic repair intermediates with mismatches and oxidative DNA damage. (PMID:32914844)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	lig1	ENSDARG00000060041
mus_musculus	Lig1	ENSMUSG00000056394
rattus_norvegicus	Lig1	ENSRNOG00000014193
drosophila_melanogaster	DNAlig1	FBGN0262619
caenorhabditis_elegans		WBGENE00002985

Paralogs (2): LIG3 (ENSG00000005156), LIG4 (ENSG00000174405)

Protein

Protein identifiers

DNA ligase 1 — P18858 (reviewed: P18858)

Alternative names: DNA ligase I, Polydeoxyribonucleotide synthase [ATP] 1

All UniProt accessions (15): P18858, A0A8V8TNZ9, A0A8V8TP03, A0A8V8TPA5, A0A8V8TPB0, A0A8V8TPH4, A0A8V8TPH8, A0A8V8TQC4, A0A8V8TQC8, A0A8V8TQQ3, A0A8V8TQQ7, B4E135, F5GZ28, M0R0Q7, M0R254

UniProt curated annotations — full annotation on UniProt →

Function. DNA ligase that seals nicks in double-stranded during DNA repair. Also involved in DNA replication and DNA recombination.

Subunit / interactions. Interacts with PCNA. Interacts with POLB.

Subcellular location. Nucleus.

Disease relevance. Immunodeficiency 96 (IMD96) [MIM:619774] An autosomal recessive disorder characterized by onset of recurrent, usually viral, respiratory infections in infancy or early childhood. Other infections, including gastrointestinal and urinary tract infections, may also occur. Laboratory studies show hypogammaglobulinemia, lymphopenia with increased gamma/delta T cells, and erythrocyte macrocytosis. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the ATP-dependent DNA ligase family.

Isoforms (3)

UniProt ID	Names	Canonical?
P18858-1	1	yes
P18858-2	2
P18858-3	3

RefSeq proteins (5): NP_000225, NP_001275992, NP_001275993, NP_001307899, NP_001307900 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000977	DNA_ligase_ATP-dep	Family
IPR012308	DNA_ligase_ATP-dep_N	Domain
IPR012309	DNA_ligase_ATP-dep_C	Domain
IPR012310	DNA_ligase_ATP-dep_cent	Domain
IPR012340	NA-bd_OB-fold	Homologous_superfamily
IPR016059	DNA_ligase_ATP-dep_CS	Conserved_site
IPR036599	DNA_ligase_N_sf	Homologous_superfamily
IPR050191	ATP-dep_DNA_ligase	Family

Pfam: PF01068, PF04675, PF04679

Enzyme classification (BRENDA):

• EC 6.5.1.1 — DNA ligase (ATP) (BRENDA: 129 organisms, 228 substrates, 149 inhibitors, 70 Km, 29 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
ATP	—	33
DNA	—	7
DATP	0.0016–0.004	3
NICKED DNA	—	2
(2E,6E)-FARNESYL TRIPHOSPHATE	0.15	1
(DEOXYRIBONUCLEOTIDE)20	—	1
(DT)20	0.0001	1
(NICKED DOUBLE-STRANDED DNA)N	0.0001	1
(SINGLE-STRANDED DNA SPLINTED BY RNA)M	—	1
CLODRONATE	0.08	1
DIMETHYLALLYL DIPHOSPHATE	4	1
ETIDRONATE	0.73	1
FARNESYL DIPHOSPHATE	0.05	1
GERANYL DIPHOSPHATE	0.21	1
GERANYL TRIPHOSPHATE	0.31	1

UniProt features (135 total): helix 31, strand 25, modified residue 19, sequence variant 19, turn 10, binding site 7, mutagenesis site 6, compositionally biased region 5, site 4, splice variant 4, region of interest 3, chain 1, active site 1

Structure

Experimental structures (PDB)

35 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
6P0C	X-RAY DIFFRACTION	1.55
6P0D	X-RAY DIFFRACTION	1.75
6P0E	X-RAY DIFFRACTION	1.85
6Q1V	X-RAY DIFFRACTION	1.85
7L34	X-RAY DIFFRACTION	1.9
9YHU	X-RAY DIFFRACTION	1.96
7L35	X-RAY DIFFRACTION	2
8V1U	X-RAY DIFFRACTION	2
6P0A	X-RAY DIFFRACTION	2.05
6P09	X-RAY DIFFRACTION	2.05
7KR4	X-RAY DIFFRACTION	2.2
8V1W	X-RAY DIFFRACTION	2.2
6P0B	X-RAY DIFFRACTION	2.2
8V1V	X-RAY DIFFRACTION	2.3
8VDN	X-RAY DIFFRACTION	2.39
9BS4	X-RAY DIFFRACTION	2.4
8VZL	X-RAY DIFFRACTION	2.41
8VZM	X-RAY DIFFRACTION	2.51
9YHW	X-RAY DIFFRACTION	2.56
9NYS	X-RAY DIFFRACTION	2.64
5YY9	X-RAY DIFFRACTION	2.65
9BS3	X-RAY DIFFRACTION	2.69
9YHY	X-RAY DIFFRACTION	2.76
7KR3	X-RAY DIFFRACTION	2.78
8VDT	X-RAY DIFFRACTION	2.78
8VDS	X-RAY DIFFRACTION	2.79
7SX5	X-RAY DIFFRACTION	2.8
9YHV	X-RAY DIFFRACTION	2.81
7SUM	X-RAY DIFFRACTION	2.9
9YHX	X-RAY DIFFRACTION	2.96

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P18858-F1	77.05	0.62

Functional residue map

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

Catalytic / active sites (5): 305 (interaction with target dna); 590 (interaction with target dna); 770 (interaction with target dna); 795 (interaction with target dna); 568 (n6-amp-lysine intermediate)

Ligand- & substrate-binding residues (7): 566; 573; 621; 621; 720; 725; 744

Post-translational modifications (19): 47, 49, 51, 66, 76, 141, 195, 199, 201, 207, 226, 229, 230, 233, 798, 801, 819, 911, 913

Mutagenesis-validated functional residues (6):

Position	Phenotype
568	loss of dna ligase activity.
600	severely reduced dna ligase activity.
641	severely reduced dna ligase activity.
642	no effect on dna ligase activity.
643	no effect on dna ligase activity.
644	no effect on dna ligase activity.

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-110362	POLB-Dependent Long Patch Base Excision Repair
R-HSA-162594	Early Phase of HIV Life Cycle
R-HSA-174414	Processive synthesis on the C-strand of the telomere
R-HSA-5358565	Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha)
R-HSA-5358606	Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta)
R-HSA-5651801	PCNA-Dependent Long Patch Base Excision Repair
R-HSA-5685938	HDR through Single Strand Annealing (SSA)
R-HSA-5696397	Gap-filling DNA repair synthesis and ligation in GG-NER
R-HSA-6782210	Gap-filling DNA repair synthesis and ligation in TC-NER
R-HSA-69183	Processive synthesis on the lagging strand
R-HSA-9825895	Regulation of MITF-M-dependent genes involved in DNA replication, damage repair and senescence

MSigDB gene sets: 375 (showing top): GOBP_CHROMOSOME_ORGANIZATION, REACTOME_DNA_REPLICATION, GNF2_MSH2, E2F4DP1_01, GOBP_CELL_CYCLE_DNA_REPLICATION, ENK_UV_RESPONSE_KERATINOCYTE_UP, GOBP_DNA_STRAND_ELONGATION_INVOLVED_IN_DNA_REPLICATION, GOBP_TELOMERE_ORGANIZATION, KAUFFMANN_DNA_REPAIR_GENES, SHIPP_DLBCL_CURED_VS_FATAL_DN, SHEPARD_BMYB_MORPHOLINO_DN, GOLDRATH_ANTIGEN_RESPONSE, PUJANA_CHEK2_PCC_NETWORK, KRASNOSELSKAYA_ILF3_TARGETS_DN, REACTOME_HIV_INFECTION

GO Biological Process (13): lagging strand elongation (GO:0006273), DNA repair (GO:0006281), base-excision repair (GO:0006284), base-excision repair, gap-filling (GO:0006287), mismatch repair (GO:0006298), DNA recombination (GO:0006310), anatomical structure morphogenesis (GO:0009653), telomere maintenance via semi-conservative replication (GO:0032201), cell division (GO:0051301), DNA biosynthetic process (GO:0071897), Okazaki fragment processing involved in mitotic DNA replication (GO:1903461), DNA replication (GO:0006260), DNA damage response (GO:0006974)

GO Molecular Function (8): DNA binding (GO:0003677), DNA ligase activity (GO:0003909), DNA ligase (ATP) activity (GO:0003910), ATP binding (GO:0005524), metal ion binding (GO:0046872), nucleotide binding (GO:0000166), protein binding (GO:0005515), ligase activity (GO:0016874)

GO Cellular Component (2): nucleus (GO:0005634), nucleoplasm (GO:0005654)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Resolution of AP sites via the multiple-nucleotide patch replacement pathway	2
Mismatch Repair	2
HIV Life Cycle	1
Telomere C-strand (Lagging Strand) Synthesis	1
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	1
Global Genome Nucleotide Excision Repair (GG-NER)	1
Transcription-Coupled Nucleotide Excision Repair (TC-NER)	1
Lagging Strand Synthesis	1
MITF-M-dependent gene expression	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA metabolic process	5
DNA repair	2
DNA replication, synthesis of primer	1
DNA strand elongation involved in DNA replication	1
DNA replication, removal of RNA primer	1
DNA damage response	1
base-excision repair	1
developmental process	1
anatomical structure development	1
telomere maintenance	1
cell cycle process	1
nuclear DNA replication	1
cellular process	1
nucleic acid biosynthetic process	1
DNA replication, Okazaki fragment processing	1
mitotic DNA replication	1
mitotic cell cycle process	1
DNA biosynthetic process	1
cellular response to stress	1
nucleic acid binding	1
ligase activity, forming phosphoric ester bonds	1
catalytic activity, acting on DNA	1
DNA ligase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
cation binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1

Protein interactions and networks

STRING

2130 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LIG1	XRCC1	P18887	995
LIG1	APEX1	P27695	978
LIG1	FEN1	P39748	973
LIG1	POLB	P06746	964
LIG1	UNG	P13051	942
LIG1	ERCC1	P07992	890
LIG1	WRN	Q14191	867
LIG1	OGG1	P78554	858
LIG1	DNA2	P51530	856
LIG1	EXO1	Q9UQ84	854
LIG1	XRCC4	Q13426	839
LIG1	POLL	Q9UGP5	839
LIG1	ERCC2	P18074	835
LIG1	XPA	P23025	814
LIG1	POLM	Q9NP87	797

IntAct

24 interactions, top by confidence:

A	B	Type	Score
RNF166	MPDZ	psi-mi:“MI:0914”(association)	0.530
BAG2	HGS	psi-mi:“MI:0914”(association)	0.530
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
LIG1	H1-2	psi-mi:“MI:0915”(physical association)	0.400
LIG1	UBE3B	psi-mi:“MI:0915”(physical association)	0.400
HSPB1	LIG1	psi-mi:“MI:0915”(physical association)	0.370
LIG1	HSPB1	psi-mi:“MI:0915”(physical association)	0.370
LIG1	RGS2	psi-mi:“MI:0915”(physical association)	0.370
AURKA	CTNNB1	psi-mi:“MI:0914”(association)	0.350
Lyplal1	PARP10	psi-mi:“MI:0914”(association)	0.350
Tgs1	EFCAB5	psi-mi:“MI:0914”(association)	0.350
hspa1a_hspa1b_human-1	SHTN1	psi-mi:“MI:0914”(association)	0.350
S100A6	VWA8	psi-mi:“MI:0914”(association)	0.350
SPANXN5	USP1	psi-mi:“MI:0914”(association)	0.350
BBS1	SHTN1	psi-mi:“MI:0914”(association)	0.350
ZBTB2	SHTN1	psi-mi:“MI:0914”(association)	0.350
SYT6	SUPT5H	psi-mi:“MI:0914”(association)	0.350
B3GALT2	LIG1	psi-mi:“MI:0914”(association)	0.350
SUPV3L1	BLTP3B	psi-mi:“MI:2364”(proximity)	0.270
UTP3	NACA	psi-mi:“MI:2364”(proximity)	0.270
NPM1	SBNO1	psi-mi:“MI:2364”(proximity)	0.270
INPP1	LIG1	psi-mi:“MI:0915”(physical association)	0.000
TUBB4A	LIG1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (151): LIG1 (Affinity Capture-RNA), LIG1 (Affinity Capture-MS), LIG1 (Two-hybrid), CHTF18 (Co-fractionation), FEN1 (Co-fractionation), LIG1 (Co-fractionation), LIG1 (Co-fractionation), STKLD1 (Co-fractionation), LIG1 (Affinity Capture-MS), LIG1 (Affinity Capture-MS), LIG1 (Affinity Capture-MS), LIG1 (Affinity Capture-MS), LIG1 (Affinity Capture-MS), LIG1 (Affinity Capture-MS), LIG1 (Affinity Capture-Western)

ESM2 similar proteins: A0A0G2JV04, D4A1F2, F1MF74, F1QWK4, O54935, O75038, O94851, P18858, P18887, P37913, P41111, P49916, P51432, P51892, P58404, P78563, P97386, Q01970, Q12851, Q1HFZ0, Q3T058, Q3TX08, Q58DG1, Q5HZH2, Q5REM3, Q60596, Q61211, Q61749, Q63186, Q641W2, Q7ZU92, Q8BMI3, Q8BML1, Q8CG07, Q91YU8, Q92918, Q96T60, Q99JE6, Q9D2Q2, Q9ESZ0

Diamond homologs: A0A7H0DNE6, A0RWD6, A4WH24, C0QSL7, D2CJS7, O57250, P04819, P0DOO3, P0DOO4, P12000, P16272, P18858, P20492, P37913, P49916, P51892, P97386, Q42572, Q4JAM1, Q54QM4, Q67480, Q869E1, Q976G4, Q9C1W9, Q9JHY8, Q9W1H4, Q9YD18, Q9YMV2, A0B7F9, A0PTC0, A0QJL0, A0QUP1, A0R3R7, A1KN60, A1RTK4, A1RXA6, A1RY72, A1SKL2, A1T6P2, A1UDY9

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
CDK1	“up-regulates activity”	LIG1	phosphorylation
CDK2	“up-regulates activity”	LIG1	phosphorylation
CSNK2A1	“up-regulates activity”	LIG1	phosphorylation
miR-325	“down-regulates quantity by destabilization”	LIG1	“post transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	319
Likely benign	429
Benign	62

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
1343095	NM_000234.3(LIG1):c.1244del (p.Thr415fs)	Pathogenic
16775	NM_000234.3(LIG1):c.1696G>A (p.Glu566Lys)	Pathogenic
2504596	NM_000234.3(LIG1):c.2444del (p.Leu815fs)	Likely pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

5969 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:48121279:A:G	L759P	0.999
19:48122942:A:G	W742R	0.999
19:48122942:A:T	W742R	0.999
19:48122991:C:A	K725N	0.999
19:48122991:C:G	K725N	0.999
19:48123001:A:G	L722P	0.999
19:48123005:C:G	G721R	0.999
19:48123005:C:T	G721R	0.999
19:48127929:A:G	L638P	0.999
19:48127937:G:C	F635L	0.999
19:48127937:G:T	F635L	0.999
19:48127939:A:G	F635L	0.999
19:48127971:G:T	A624D	0.999
19:48131131:C:A	R589M	0.999
19:48132995:C:A	G571V	0.999
19:48132995:C:T	G571E	0.999
19:48132996:C:A	G571W	0.999
19:48132997:G:C	D570E	0.999
19:48132997:G:T	D570E	0.999
19:48132998:T:A	D570V	0.999
19:48133003:T:A	K568N	0.999
19:48133003:T:G	K568N	0.999
19:48115933:G:C	F872L	0.998
19:48115933:G:T	F872L	0.998
19:48115935:A:G	F872L	0.998
19:48115940:A:T	L870H	0.998
19:48117697:A:G	W842R	0.998
19:48117697:A:T	W842R	0.998
19:48121317:C:A	K746N	0.998
19:48121317:C:G	K746N	0.998

dbSNP variants (sampled 300 via entrez): RS1000048604 (19:48171696 G>A,T), RS1000157919 (19:48139861 C>A,G,T), RS1000163183 (19:48170734 A>G), RS1000203076 (19:48148788 C>T), RS1000329711 (19:48120593 C>A,T), RS1000366309 (19:48134208 C>T), RS1000444781 (19:48139488 T>C), RS1000471732 (19:48114999 T>C), RS1000474645 (19:48143775 C>T), RS1000542001 (19:48147696 T>C), RS1000596485 (19:48143543 C>G,T), RS1000783947 (19:48147417 A>C,G), RS1000807515 (19:48157779 T>C), RS1000853504 (19:48124000 T>C), RS1000870553 (19:48149738 T>C)

Disease associations

OMIM: gene MIM:126391 | disease phenotypes: MIM:619774

GenCC curated gene-disease

Disease	Classification	Inheritance
immunodeficiency 96	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
immunodeficiency 96	Definitive	AR

Mondo (1): immunodeficiency 96 (MONDO:0030693)

Orphanet (0):

HPO phenotypes

18 total (18 of 18 shown, HPO-id order):

HPO	Term
HP:0000003	Multicystic kidney dysplasia
HP:0000007	Autosomal recessive inheritance
HP:0000403	Recurrent otitis media
HP:0000524	Conjunctival telangiectasia
HP:0000964	Eczematoid dermatitis
HP:0001249	Intellectual disability
HP:0001270	Motor delay
HP:0001510	Growth delay
HP:0002719	Recurrent infections
HP:0002720	Decreased circulating IgA concentration
HP:0002783	Recurrent lower respiratory tract infections
HP:0002850	Decreased circulating total IgM
HP:0003593	Infantile onset
HP:0004315	Decreased circulating IgG concentration
HP:0005518	Increased mean corpuscular volume
HP:0011463	Childhood onset
HP:0031379	Abnormal T cell proliferation
HP:0500270	Increased gamma-delta T cell proportion

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5694 (SINGLE PROTEIN)

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

Binding affinities (BindingDB)

106 measured of 115 human assays (115 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
tert-butyl N-(3-{7-oxo-7-[5-(pyridin-2-yl)-1,3-oxazol-2-yl]heptyl}phenyl)carbamate	KI	2.4 nM
6-(phenylsulfanyl)-1-[5-(pyridin-2-yl)-1,3-oxazol-2-yl]hexan-1-one	KI	3 nM
7-(3-fluorophenyl)-1-[5-(pyridin-2-yl)-1,3-oxazol-2-yl]hept-6-yn-1-one	KI	3.2 nM
2-[(4-phenylbutyl)sulfanyl]-1-[5-(pyridin-2-yl)-1,3-oxazol-2-yl]ethan-1-one	KI	4 nM
7-(3-nitrophenyl)-1-[5-(pyridin-2-yl)-1,3-oxazol-2-yl]hept-6-yn-1-one	KI	4.8 nM
7-(2,3-dichlorophenyl)-1-[5-(pyridin-2-yl)-1,3-oxazol-2-yl]hept-6-yn-1-one	KI	5 nM
tert-butyl N-(4-{7-oxo-7-[5-(pyridin-2-yl)-1,3-oxazol-2-yl]heptyl}phenyl)carbamate	KI	5.6 nM
7-(3-chlorophenyl)-1-[5-(pyridin-2-yl)-1,3-oxazol-2-yl]hept-6-yn-1-one	KI	7 nM
7-(2-fluorophenyl)-1-[5-(pyridin-2-yl)-1,3-oxazol-2-yl]hept-6-yn-1-one	KI	8 nM
2-hydroxy-7-phenyl-1-[5-(pyridin-2-yl)-1,3-oxazol-2-yl]heptan-1-one	KI	8 nM
1-[5-(pyridin-2-yl)-1,3-oxazol-2-yl]-7-[3-(trifluoromethyl)phenyl]hept-6-yn-1-one	KI	10 nM
tert-butyl N-(3-{7-oxo-7-[5-(pyridin-2-yl)-1,3-oxazol-2-yl]hept-1-yn-1-yl}phenyl)carbamate	KI	12 nM
7-(2-chlorophenyl)-1-[5-(pyridin-2-yl)-1,3-oxazol-2-yl]hept-6-yn-1-one	KI	13 nM
6-phenoxy-1-[5-(pyridin-2-yl)-1,3-oxazol-2-yl]hexan-1-one	KI	14 nM
1-[5-(pyridin-2-yl)-1,3-oxazol-2-yl]-7-[2-(trifluoromethyl)phenyl]hept-6-yn-1-one	KI	16 nM
7-(2-nitrophenyl)-1-[5-(pyridin-2-yl)-1,3-oxazol-2-yl]hept-6-yn-1-one	KI	17 nM
7-(naphthalen-2-yl)-1-[5-(pyridin-2-yl)-1,3-oxazol-2-yl]heptan-1-one	IC50	20 nM
7-(4-chlorophenyl)-1-[5-(pyridin-2-yl)-1,3-oxazol-2-yl]hept-6-yn-1-one	KI	20 nM
tert-butyl N-(4-{7-oxo-7-[5-(pyridin-2-yl)-1,3-oxazol-2-yl]hept-1-yn-1-yl}phenyl)carbamate	KI	23 nM
7-phenyl-1-[5-(pyridin-2-yl)-1,3-oxazol-2-yl]hept-6-yn-1-one	KI	25 nM
methyl 4-{7-oxo-7-[5-(pyridin-2-yl)-1,3-oxazol-2-yl]hept-1-yn-1-yl}benzoate	KI	25 nM
5-(benzylsulfanyl)-1-[5-(pyridin-2-yl)-1,3-oxazol-2-yl]pentan-1-one	KI	25 nM
7-(3-aminophenyl)-1-[5-(pyridin-2-yl)-1,3-oxazol-2-yl]heptan-1-one	KI	30 nM
methyl 3-{7-oxo-7-[5-(pyridin-2-yl)-1,3-oxazol-2-yl]hept-1-yn-1-yl}benzoate	KI	30 nM
7-(4-nitrophenyl)-1-[5-(pyridin-2-yl)-1,3-oxazol-2-yl]hept-6-yn-1-one	KI	31 nM
methyl 2-{7-oxo-7-[5-(pyridin-2-yl)-1,3-oxazol-2-yl]hept-1-yn-1-yl}benzoate	KI	34 nM
3-hydroxy-7-phenyl-1-[5-(pyridin-2-yl)-1,3-oxazol-2-yl]heptan-1-one	KI	35 nM
7-hydroxy-7-phenyl-1-[5-(pyridin-2-yl)-1,3-oxazol-2-yl]heptan-1-one	KI	35 nM
7-(4-fluorophenyl)-1-[5-(pyridin-2-yl)-1,3-oxazol-2-yl]hept-6-yn-1-one	KI	36 nM
3-[4-(benzyloxy)phenyl]-1-{pyrido[2,3-d][1,3]oxazol-2-yl}propan-1-one	IC50	40 nM
6-[methyl(phenyl)amino]-1-[5-(pyridin-2-yl)-1,3-oxazol-2-yl]hexan-1-one	KI	40 nM
5-(benzyloxy)-1-[5-(pyridin-2-yl)-1,3-oxazol-2-yl]pentan-1-one	KI	55 nM
4-(2-phenylethoxy)-1-[5-(pyridin-2-yl)-1,3-oxazol-2-yl]butan-1-one	KI	63 nM
1-[5-(pyridin-2-yl)-1,3-oxazol-2-yl]-7-[4-(trifluoromethyl)phenyl]hept-6-yn-1-one	KI	75 nM
3-[4-(phenylsulfanyl)phenyl]-1-[5-(pyridin-2-yl)-1,3-oxazol-2-yl]propan-1-one	IC50	90 nM
3-(3-phenylpropoxy)-1-[5-(pyridin-2-yl)-1,3-oxazol-2-yl]propan-1-one	KI	90 nM
1-[5-(pyridin-2-yl)-1,3-oxazol-2-yl]-7-(pyridin-4-yl)hept-6-yn-1-one	KI	150 nM
1-[5-(pyridin-2-yl)-1,3-oxazol-2-yl]-7-[3-(trifluoromethyl)phenyl]heptan-1-one	IC50	200 nM
1-[5-(pyridin-2-yl)-1,3-oxazol-2-yl]-7-[4-(trifluoromethyl)phenyl]heptan-1-one	IC50	200 nM
3-(4-phenoxyphenyl)-1-[5-(pyridin-2-yl)-1,3-oxazol-2-yl]propan-1-one	IC50	200 nM
3-[methyl(3-phenylpropyl)amino]-1-[5-(pyridin-2-yl)-1,3-oxazol-2-yl]propan-1-one	KI	200 nM
5-[benzyl(methyl)amino]-1-[5-(pyridin-2-yl)-1,3-oxazol-2-yl]pentan-1-one	KI	200 nM
6-hydroxy-7-phenyl-1-[5-(pyridin-2-yl)-1,3-oxazol-2-yl]heptan-1-one	KI	200 nM
7-(pyridin-2-yl)-1-[5-(pyridin-2-yl)-1,3-oxazol-2-yl]hept-6-yn-1-one	KI	280 nM
7-(naphthalen-1-yl)-1-[5-(pyridin-2-yl)-1,3-oxazol-2-yl]heptan-1-one	IC50	300 nM
7-[3-(methylsulfanyl)phenyl]-1-[5-(pyridin-2-yl)-1,3-oxazol-2-yl]heptan-1-one	IC50	300 nM
1-[5-(pyridin-2-yl)-1,3-oxazol-2-yl]-7-(pyridin-3-yl)hept-6-yn-1-one	KI	300 nM
2-(4-phenylbutoxy)-1-[5-(pyridin-2-yl)-1,3-oxazol-2-yl]ethan-1-one	IC50	340 nM
7-(2-fluorophenyl)-1-[5-(pyridin-2-yl)-1,3-oxazol-2-yl]heptan-1-one	IC50	500 nM
7-(3-chlorophenyl)-1-[5-(pyridin-2-yl)-1,3-oxazol-2-yl]heptan-1-one	IC50	500 nM

ChEMBL bioactivities

10 potent at pChembl≥5 of 31 total, top 10 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.22	IC50	600	nM	CHEMBL468590
6.00	IC50	1000	nM	CHEMBL2348305
5.40	Ki	4000	nM	CHEMBL375078
5.40	IC50	4000	nM	CHEMBL468589
5.40	IC50	4000	nM	CHEMBL375078
5.30	IC50	5000	nM	CHEMBL4458668
5.10	IC50	8000	nM	CHEMBL467192
5.10	IC50	8000	nM	CHEMBL467373
5.00	IC50	1e+04	nM	CHEMBL4461698
5.00	IC50	1e+04	nM	CHEMBL450866

PubChem BioAssay actives

110 with measured affinity, of 321 total; 50 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
1-([1,3]oxazolo[4,5-b]pyridin-2-yl)-3-(4-phenylmethoxyphenyl)propan-1-one	1798285: FAAH Inhibition Assay from Article 10.1021/jm061414r: “Structure-activity relationships of alpha-ketooxazole inhibitors of fatty acid amide hydrolase.”	ki	0.0004	uM
3-(4-phenylphenyl)-1-(5-pyridin-2-yl-1,3-oxazol-2-yl)propan-1-one	1798285: FAAH Inhibition Assay from Article 10.1021/jm061414r: “Structure-activity relationships of alpha-ketooxazole inhibitors of fatty acid amide hydrolase.”	ki	0.0008	uM
7-(2,3-dichlorophenyl)-1-(5-pyridin-2-yl-1,3-oxazol-2-yl)heptan-1-one	1798285: FAAH Inhibition Assay from Article 10.1021/jm061414r: “Structure-activity relationships of alpha-ketooxazole inhibitors of fatty acid amide hydrolase.”	ki	0.0009	uM
7-(3-chlorophenyl)-1-(5-pyridin-2-yl-1,3-oxazol-2-yl)heptan-1-one	1798285: FAAH Inhibition Assay from Article 10.1021/jm061414r: “Structure-activity relationships of alpha-ketooxazole inhibitors of fatty acid amide hydrolase.”	ki	0.0009	uM
1-(5-pyridin-2-yl-1,3-oxazol-2-yl)-7-[3-(trifluoromethyl)phenyl]heptan-1-one	1798285: FAAH Inhibition Assay from Article 10.1021/jm061414r: “Structure-activity relationships of alpha-ketooxazole inhibitors of fatty acid amide hydrolase.”	ki	0.0010	uM
methyl 2-[7-oxo-7-(5-pyridin-2-yl-1,3-oxazol-2-yl)heptyl]benzoate	1798285: FAAH Inhibition Assay from Article 10.1021/jm061414r: “Structure-activity relationships of alpha-ketooxazole inhibitors of fatty acid amide hydrolase.”	ki	0.0010	uM
3-[4-(phenoxymethyl)phenyl]-1-(5-pyridin-2-yl-1,3-oxazol-2-yl)propan-1-one	1798285: FAAH Inhibition Assay from Article 10.1021/jm061414r: “Structure-activity relationships of alpha-ketooxazole inhibitors of fatty acid amide hydrolase.”	ki	0.0010	uM
3-(4-phenylmethoxyphenyl)-1-(5-pyridin-2-yl-1,3-oxazol-2-yl)propan-1-one	1798285: FAAH Inhibition Assay from Article 10.1021/jm061414r: “Structure-activity relationships of alpha-ketooxazole inhibitors of fatty acid amide hydrolase.”	ki	0.0013	uM
7-(3-methylsulfonylphenyl)-1-(5-pyridin-2-yl-1,3-oxazol-2-yl)heptan-1-one	1798285: FAAH Inhibition Assay from Article 10.1021/jm061414r: “Structure-activity relationships of alpha-ketooxazole inhibitors of fatty acid amide hydrolase.”	ki	0.0013	uM
methyl 4-[7-oxo-7-(5-pyridin-2-yl-1,3-oxazol-2-yl)heptyl]benzoate	1798285: FAAH Inhibition Assay from Article 10.1021/jm061414r: “Structure-activity relationships of alpha-ketooxazole inhibitors of fatty acid amide hydrolase.”	ki	0.0015	uM
7-(2-fluorophenyl)-1-(5-pyridin-2-yl-1,3-oxazol-2-yl)heptan-1-one	1798285: FAAH Inhibition Assay from Article 10.1021/jm061414r: “Structure-activity relationships of alpha-ketooxazole inhibitors of fatty acid amide hydrolase.”	ki	0.0017	uM
7-(2-chlorophenyl)-1-(5-pyridin-2-yl-1,3-oxazol-2-yl)heptan-1-one	1798285: FAAH Inhibition Assay from Article 10.1021/jm061414r: “Structure-activity relationships of alpha-ketooxazole inhibitors of fatty acid amide hydrolase.”	ki	0.0019	uM
methyl 3-[7-oxo-7-(5-pyridin-2-yl-1,3-oxazol-2-yl)heptyl]benzoate	1798285: FAAH Inhibition Assay from Article 10.1021/jm061414r: “Structure-activity relationships of alpha-ketooxazole inhibitors of fatty acid amide hydrolase.”	ki	0.0019	uM
3-(4-anilinophenyl)-1-(5-pyridin-2-yl-1,3-oxazol-2-yl)propan-1-one	1798285: FAAH Inhibition Assay from Article 10.1021/jm061414r: “Structure-activity relationships of alpha-ketooxazole inhibitors of fatty acid amide hydrolase.”	ki	0.0020	uM
7-(3-fluorophenyl)-1-(5-pyridin-2-yl-1,3-oxazol-2-yl)heptan-1-one	1798285: FAAH Inhibition Assay from Article 10.1021/jm061414r: “Structure-activity relationships of alpha-ketooxazole inhibitors of fatty acid amide hydrolase.”	ki	0.0022	uM
3-(4-phenylsulfanylphenyl)-1-(5-pyridin-2-yl-1,3-oxazol-2-yl)propan-1-one	1798285: FAAH Inhibition Assay from Article 10.1021/jm061414r: “Structure-activity relationships of alpha-ketooxazole inhibitors of fatty acid amide hydrolase.”	ki	0.0022	uM
tert-butyl N-[3-[7-oxo-7-(5-pyridin-2-yl-1,3-oxazol-2-yl)heptyl]phenyl]carbamate	1798285: FAAH Inhibition Assay from Article 10.1021/jm061414r: “Structure-activity relationships of alpha-ketooxazole inhibitors of fatty acid amide hydrolase.”	ki	0.0024	uM
7-(3-methoxyphenyl)-1-(5-pyridin-2-yl-1,3-oxazol-2-yl)heptan-1-one	1798285: FAAH Inhibition Assay from Article 10.1021/jm061414r: “Structure-activity relationships of alpha-ketooxazole inhibitors of fatty acid amide hydrolase.”	ki	0.0025	uM
7-(4-methylsulfanylphenyl)-1-(5-pyridin-2-yl-1,3-oxazol-2-yl)heptan-1-one	1798285: FAAH Inhibition Assay from Article 10.1021/jm061414r: “Structure-activity relationships of alpha-ketooxazole inhibitors of fatty acid amide hydrolase.”	ki	0.0025	uM
7-naphthalen-1-yl-1-(5-pyridin-2-yl-1,3-oxazol-2-yl)heptan-1-one	1798285: FAAH Inhibition Assay from Article 10.1021/jm061414r: “Structure-activity relationships of alpha-ketooxazole inhibitors of fatty acid amide hydrolase.”	ki	0.0026	uM
7-(4-chlorophenyl)-1-(5-pyridin-2-yl-1,3-oxazol-2-yl)heptan-1-one	1798285: FAAH Inhibition Assay from Article 10.1021/jm061414r: “Structure-activity relationships of alpha-ketooxazole inhibitors of fatty acid amide hydrolase.”	ki	0.0027	uM
7-(4-methylphenyl)-1-(5-pyridin-2-yl-1,3-oxazol-2-yl)heptan-1-one	1798285: FAAH Inhibition Assay from Article 10.1021/jm061414r: “Structure-activity relationships of alpha-ketooxazole inhibitors of fatty acid amide hydrolase.”	ki	0.0028	uM
7-(2-methylphenyl)-1-(5-pyridin-2-yl-1,3-oxazol-2-yl)heptan-1-one	1798285: FAAH Inhibition Assay from Article 10.1021/jm061414r: “Structure-activity relationships of alpha-ketooxazole inhibitors of fatty acid amide hydrolase.”	ki	0.0030	uM
7-(4-aminophenyl)-1-(5-pyridin-2-yl-1,3-oxazol-2-yl)heptan-1-one	1798285: FAAH Inhibition Assay from Article 10.1021/jm061414r: “Structure-activity relationships of alpha-ketooxazole inhibitors of fatty acid amide hydrolase.”	ki	0.0030	uM
6-phenylsulfanyl-1-(5-pyridin-2-yl-1,3-oxazol-2-yl)hexan-1-one	1798285: FAAH Inhibition Assay from Article 10.1021/jm061414r: “Structure-activity relationships of alpha-ketooxazole inhibitors of fatty acid amide hydrolase.”	ki	0.0030	uM
3-(4-benzylphenyl)-1-(5-pyridin-2-yl-1,3-oxazol-2-yl)propan-1-one	1798285: FAAH Inhibition Assay from Article 10.1021/jm061414r: “Structure-activity relationships of alpha-ketooxazole inhibitors of fatty acid amide hydrolase.”	ki	0.0032	uM
7-(3-fluorophenyl)-1-(5-pyridin-2-yl-1,3-oxazol-2-yl)hept-6-yn-1-one	1798285: FAAH Inhibition Assay from Article 10.1021/jm061414r: “Structure-activity relationships of alpha-ketooxazole inhibitors of fatty acid amide hydrolase.”	ki	0.0032	uM
7-(4-fluorophenyl)-1-(5-pyridin-2-yl-1,3-oxazol-2-yl)heptan-1-one	1798285: FAAH Inhibition Assay from Article 10.1021/jm061414r: “Structure-activity relationships of alpha-ketooxazole inhibitors of fatty acid amide hydrolase.”	ki	0.0032	uM
7-(3-methylphenyl)-1-(5-pyridin-2-yl-1,3-oxazol-2-yl)heptan-1-one	1798285: FAAH Inhibition Assay from Article 10.1021/jm061414r: “Structure-activity relationships of alpha-ketooxazole inhibitors of fatty acid amide hydrolase.”	ki	0.0033	uM
7-(2-methylsulfanylphenyl)-1-(5-pyridin-2-yl-1,3-oxazol-2-yl)heptan-1-one	1798285: FAAH Inhibition Assay from Article 10.1021/jm061414r: “Structure-activity relationships of alpha-ketooxazole inhibitors of fatty acid amide hydrolase.”	ki	0.0033	uM
3-(4-phenoxyphenyl)-1-(5-pyridin-2-yl-1,3-oxazol-2-yl)propan-1-one	1798285: FAAH Inhibition Assay from Article 10.1021/jm061414r: “Structure-activity relationships of alpha-ketooxazole inhibitors of fatty acid amide hydrolase.”	ki	0.0034	uM
2-(4-phenylbutylsulfanyl)-1-(5-pyridin-2-yl-1,3-oxazol-2-yl)ethanone	1798285: FAAH Inhibition Assay from Article 10.1021/jm061414r: “Structure-activity relationships of alpha-ketooxazole inhibitors of fatty acid amide hydrolase.”	ki	0.0040	uM
1-(5-pyridin-2-yl-1,3-oxazol-2-yl)-7-[2-(trifluoromethyl)phenyl]heptan-1-one	1798285: FAAH Inhibition Assay from Article 10.1021/jm061414r: “Structure-activity relationships of alpha-ketooxazole inhibitors of fatty acid amide hydrolase.”	ki	0.0040	uM
1-(5-pyridin-2-yl-1,3-oxazol-2-yl)-7-[4-(trifluoromethyl)phenyl]heptan-1-one	1798285: FAAH Inhibition Assay from Article 10.1021/jm061414r: “Structure-activity relationships of alpha-ketooxazole inhibitors of fatty acid amide hydrolase.”	ki	0.0040	uM
7-(3-methylsulfanylphenyl)-1-(5-pyridin-2-yl-1,3-oxazol-2-yl)heptan-1-one	1798285: FAAH Inhibition Assay from Article 10.1021/jm061414r: “Structure-activity relationships of alpha-ketooxazole inhibitors of fatty acid amide hydrolase.”	ki	0.0042	uM
1-(5-pyridin-2-yl-1,3-oxazol-2-yl)-7-thiophen-2-ylheptan-1-one	1798285: FAAH Inhibition Assay from Article 10.1021/jm061414r: “Structure-activity relationships of alpha-ketooxazole inhibitors of fatty acid amide hydrolase.”	ki	0.0043	uM
7-phenyl-1-(5-pyridin-2-yl-1,3-oxazol-2-yl)heptan-1-one	1798285: FAAH Inhibition Assay from Article 10.1021/jm061414r: “Structure-activity relationships of alpha-ketooxazole inhibitors of fatty acid amide hydrolase.”	ki	0.0047	uM
7-(3-nitrophenyl)-1-(5-pyridin-2-yl-1,3-oxazol-2-yl)hept-6-yn-1-one	1798285: FAAH Inhibition Assay from Article 10.1021/jm061414r: “Structure-activity relationships of alpha-ketooxazole inhibitors of fatty acid amide hydrolase.”	ki	0.0048	uM
7-(2,3-dichlorophenyl)-1-(5-pyridin-2-yl-1,3-oxazol-2-yl)hept-6-yn-1-one	1798285: FAAH Inhibition Assay from Article 10.1021/jm061414r: “Structure-activity relationships of alpha-ketooxazole inhibitors of fatty acid amide hydrolase.”	ki	0.0050	uM
1-(5-pyridin-2-yl-1,3-oxazol-2-yl)-7-thiophen-3-ylheptan-1-one	1798285: FAAH Inhibition Assay from Article 10.1021/jm061414r: “Structure-activity relationships of alpha-ketooxazole inhibitors of fatty acid amide hydrolase.”	ki	0.0051	uM
tert-butyl N-[4-[7-oxo-7-(5-pyridin-2-yl-1,3-oxazol-2-yl)heptyl]phenyl]carbamate	1798285: FAAH Inhibition Assay from Article 10.1021/jm061414r: “Structure-activity relationships of alpha-ketooxazole inhibitors of fatty acid amide hydrolase.”	ki	0.0056	uM
7-(2-methoxyphenyl)-1-(5-pyridin-2-yl-1,3-oxazol-2-yl)heptan-1-one	1798285: FAAH Inhibition Assay from Article 10.1021/jm061414r: “Structure-activity relationships of alpha-ketooxazole inhibitors of fatty acid amide hydrolase.”	ki	0.0058	uM
7-(4-methoxyphenyl)-1-(5-pyridin-2-yl-1,3-oxazol-2-yl)heptan-1-one	1798285: FAAH Inhibition Assay from Article 10.1021/jm061414r: “Structure-activity relationships of alpha-ketooxazole inhibitors of fatty acid amide hydrolase.”	ki	0.0062	uM
7-(4-nitrophenyl)-1-(5-pyridin-2-yl-1,3-oxazol-2-yl)heptan-1-one	1798285: FAAH Inhibition Assay from Article 10.1021/jm061414r: “Structure-activity relationships of alpha-ketooxazole inhibitors of fatty acid amide hydrolase.”	ki	0.0065	uM
7-(4-hexylphenyl)-1-(5-pyridin-2-yl-1,3-oxazol-2-yl)heptan-1-one	1798285: FAAH Inhibition Assay from Article 10.1021/jm061414r: “Structure-activity relationships of alpha-ketooxazole inhibitors of fatty acid amide hydrolase.”	ki	0.0067	uM
7-(3-chlorophenyl)-1-(5-pyridin-2-yl-1,3-oxazol-2-yl)hept-6-yn-1-one	1798285: FAAH Inhibition Assay from Article 10.1021/jm061414r: “Structure-activity relationships of alpha-ketooxazole inhibitors of fatty acid amide hydrolase.”	ki	0.0070	uM
7-(2-fluorophenyl)-1-(5-pyridin-2-yl-1,3-oxazol-2-yl)hept-6-yn-1-one	1798285: FAAH Inhibition Assay from Article 10.1021/jm061414r: “Structure-activity relationships of alpha-ketooxazole inhibitors of fatty acid amide hydrolase.”	ki	0.0080	uM
2-hydroxy-7-phenyl-1-(5-pyridin-2-yl-1,3-oxazol-2-yl)heptan-1-one	1798285: FAAH Inhibition Assay from Article 10.1021/jm061414r: “Structure-activity relationships of alpha-ketooxazole inhibitors of fatty acid amide hydrolase.”	ki	0.0080	uM
1-(5-pyridin-2-yl-1,3-oxazol-2-yl)-7-[3-(trifluoromethyl)phenyl]hept-6-yn-1-one	1798285: FAAH Inhibition Assay from Article 10.1021/jm061414r: “Structure-activity relationships of alpha-ketooxazole inhibitors of fatty acid amide hydrolase.”	ki	0.0100	uM
7-naphthalen-2-yl-1-(5-pyridin-2-yl-1,3-oxazol-2-yl)heptan-1-one	1798285: FAAH Inhibition Assay from Article 10.1021/jm061414r: “Structure-activity relationships of alpha-ketooxazole inhibitors of fatty acid amide hydrolase.”	ki	0.0110	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression, decreases expression, increases abundance, increases expression	6
bisphenol A	affects expression, decreases expression, affects cotreatment, decreases reaction	5
Benzo(a)pyrene	increases expression, affects methylation, decreases methylation	3
Mustard Gas	affects reaction, increases phosphorylation, increases activity	3
Cyclosporine	decreases expression	3
Arsenic	affects methylation, decreases expression, increases abundance	2
Cisplatin	affects cotreatment, increases expression	2
Doxorubicin	decreases expression, affects expression, affects response to substance	2
Tretinoin	decreases expression	2
Aflatoxin B1	affects expression, increases methylation	2
tert-Butylhydroperoxide	increases methylation, decreases expression	2
FR900359	affects phosphorylation	1
pradimicin-IRD	decreases expression, affects expression, affects response to substance	1
dicrotophos	increases expression	1
N(6),N(6)-dimethyladenine	decreases reaction, increases phosphorylation	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
4-biphenylamine	decreases expression	1
2,2’-methylenebis(4-methyl-6-tert-butylphenol)	affects expression, affects response to substance	1
arsenite	increases expression	1
bromoacetate	decreases expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
quinoline yellow	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
cupric oxide	increases expression	1
2-chloroethyl ethyl sulfide	increases activity, increases phosphorylation, decreases reaction	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1

ChEMBL screening assays

32 unique, capped per target: 32 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1810900	Binding	Inhibition of human DNA Ligase I by FRET-based assay	Discovery of bacterial NAD+-dependent DNA ligase inhibitors: optimization of antibacterial activity. — Bioorg Med Chem Lett

Cellosaurus cell lines

5 cell lines: 3 transformed cell line, 1 cancer cell line, 1 finite cell line

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

Cellosaurus	Name	Category	Sex
CVCL_2288	46BR.1G1	Transformed cell line	Female
CVCL_2289	46BR.1N	Transformed cell line	Female
CVCL_KT70	HeLa SilenciX LigI	Cancer cell line	Female
CVCL_L943	46BR	Finite cell line	Female
CVCL_L950	46BRLigI	Transformed cell line	Female

Clinical trials (associated diseases)

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