LIG4

Summary

LIG4 (DNA ligase 4, HGNC:6601) is a protein-coding gene on chromosome 13q33.3, encoding DNA ligase 4 (P49917). DNA ligase involved in DNA non-homologous end joining (NHEJ); required for double-strand break (DSB) repair and V(D)J recombination.

The protein encoded by this gene is a DNA ligase that joins single-strand breaks in a double-stranded polydeoxynucleotide in an ATP-dependent reaction. This protein is essential for V(D)J recombination and DNA double-strand break (DSB) repair through nonhomologous end joining (NHEJ). This protein forms a complex with the X-ray repair cross complementing protein 4 (XRCC4), and further interacts with the DNA-dependent protein kinase (DNA-PK). Both XRCC4 and DNA-PK are known to be required for NHEJ. The crystal structure of the complex formed by this protein and XRCC4 has been resolved. Defects in this gene are the cause of LIG4 syndrome. Alternatively spliced transcript variants encoding the same protein have been observed.

Source: NCBI Gene 3981 — RefSeq curated summary.

At a glance

• Gene–disease (curated): DNA ligase IV deficiency (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 809 total — 87 pathogenic, 16 likely-pathogenic
• Phenotypes (HPO): 164
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_206937

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6601
Approved symbol	LIG4
Name	DNA ligase 4
Location	13q33.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000174405
Ensembl biotype	protein_coding
OMIM	601837
Entrez	3981

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 28 protein_coding

ENST00000405925, ENST00000442234, ENST00000611712, ENST00000614526, ENST00000685338, ENST00000686095, ENST00000686204, ENST00000686913, ENST00000686926, ENST00000687164, ENST00000687822, ENST00000688396, ENST00000688455, ENST00000688529, ENST00000688595, ENST00000689762, ENST00000690127, ENST00000692222, ENST00000693040, ENST00000857200, ENST00000857201, ENST00000857202, ENST00000857203, ENST00000935507, ENST00000935508, ENST00000935509, ENST00000935510, ENST00000958174

RefSeq mRNA: 12 — MANE Select: NM_206937 NM_001098268, NM_001330595, NM_001352598, NM_001352599, NM_001352600, NM_001352601, NM_001352602, NM_001352603, NM_001352604, NM_001379095, NM_002312, NM_206937

CCDS: CCDS81779, CCDS9508

Canonical transcript exons

ENST00000442234 — 3 exons

Exon	Start	End
ENSE00001192809	108207442	108211296
ENSE00001766472	108215484	108215536
ENSE00003717287	108214538	108214610

Expression profiles

Bgee: expression breadth ubiquitous, 275 present calls, max score 88.49.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.1105 / max 217.0966, expressed in 1689 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
138172	4.3148	1439
138173	2.6036	1267
138171	0.1604	63
138170	0.0317	15

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	88.49	silver quality
oocyte	CL:0000023	88.04	gold quality
secondary oocyte	CL:0000655	87.83	gold quality
mucosa of paranasal sinus	UBERON:0005030	87.80	gold quality
pigmented layer of retina	UBERON:0001782	86.74	gold quality
Brodmann (1909) area 23	UBERON:0013554	86.25	gold quality
islet of Langerhans	UBERON:0000006	86.20	gold quality
jejunal mucosa	UBERON:0000399	84.50	gold quality
primary visual cortex	UBERON:0002436	83.69	gold quality
lower lobe of lung	UBERON:0008949	83.40	gold quality
right lobe of liver	UBERON:0001114	83.34	gold quality
right adrenal gland cortex	UBERON:0035827	82.83	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	82.79	gold quality
right adrenal gland	UBERON:0001233	82.78	gold quality
seminal vesicle	UBERON:0000998	82.53	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	82.33	gold quality
prefrontal cortex	UBERON:0000451	82.04	gold quality
left adrenal gland	UBERON:0001234	81.72	gold quality
left adrenal gland cortex	UBERON:0035825	81.50	gold quality
right frontal lobe	UBERON:0002810	81.49	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.11	gold quality
adenohypophysis	UBERON:0002196	81.10	gold quality
middle temporal gyrus	UBERON:0002771	80.96	gold quality
Brodmann (1909) area 9	UBERON:0013540	80.91	gold quality
spinal cord	UBERON:0002240	80.89	gold quality
right hemisphere of cerebellum	UBERON:0014890	80.83	gold quality
adrenal cortex	UBERON:0001235	80.75	gold quality
adrenal gland	UBERON:0002369	80.67	gold quality
monocyte	CL:0000576	80.59	gold quality
cerebellar cortex	UBERON:0002129	80.55	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-7303	no	339.31
E-ANND-3	no	3.73

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1, GABPA

miRNA regulators (miRDB)

63 targeting LIG4, 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-4262	100.00	73.26	3931
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-4671-3P	99.88	72.46	1045
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• crystal structure of an Xrcc4-DNA ligase IV complex (PMID:11702069)
• mutations identified in patients exhibiting developmental delay and immunodeficiency (PMID:11779494)
• Association of DNA polymerase mu (pol mu) with Ku and ligase IV: role for pol mu in end-joining double-strand break repair. (PMID:12077346)
• Genetic variants of NHEJ DNA ligase IV can affect the risk of developing multiple myeloma, a tumour characterised by aberrant class switch recombination (PMID:12471202)
• Coordinated assembly of Ku and p460 subunits of the DNA-dependent protein kinase on DNA ends is necessary for XRCC4-ligase IV recruitment (PMID:12547193)
• DNA ligase IV has a role in binding with a subunit of the condensin complex (PMID:12589063)
• stability is regulated by multiple factors, including interaction with XRCC4, phosphorylation status, and possibly Lig4 conformation (PMID:15194694)
• Examination of recombinant mutant DNA ligase IV shows that the severity of LIG4 syndrome correlates with the level of residual ligase activity. (PMID:15333585)
• interactions between BLM and DNA ligase IV play a role in DNA repair in human cells (PMID:15509577)
• DNAPK was physically required for the mobilization of the XRCC4-ligase IV complex, and for stable recruitment of XRCC4; phosphorylation of either H2AX or XRCC4 was unnecessary for DNAPK or XRCC4-ligase IV recruitment (PMID:15520013)
• LIG4 mutations can result in either a developmental defect with immunological abnormalities or a severe combined immunodeficiency picture with normal development. (PMID:16357942)
• We confirmed that DNA ligase IV is unstable in the absence of XRCC4, with a half-life of approximately 30-90 min. (PMID:16412978)
• Cernunnos physically interacts with the XRCC4 x DNA-ligase IV complex (PMID:16571728)
• residues 470-476 function as part of a molecular pincer that maintains the DNA in a conformation that is required for ligation (PMID:16735143)
• DNA-PK kinase activity results in disassembly of the Ku/DNA ligase IV/Xrcc4 complex (PMID:17241822)
• XRCC4:DNA ligase IV can ligate incompatible DNA ends and can ligate across gaps. (PMID:17290226)
• Results describe the activity requirements for DNA ligases III and IV in the pathways of non-homologous DNA end joining. (PMID:17492771)
• DNA ligase IV gene polymorphisms might have a role in acute lymphoblastic leukemia in children (PMID:17541392)
• DNA Ligase IV/XRCC4 recruitment by DNA-PK to DNA double-strand breaks prevents the formation of long ssDNA ends at double-strand breaks during the S phase. (PMID:17963495)
• Haplotype analysis revealed an association of glioma risk with genetic variants in LIG4 block 1 (global P=0.011), and XRCC4 blocks 2 and 4 (both global P<0.0001). (PMID:18165945)
• DNA ligase IV is not required in microhomology-mediated end joining but facilitates Ku-dependent DNA nonhomologous end-joining. (PMID:18440984)
• DNA damage left unrepaired by DNA-ligase IV or DNA-PK might be the initiator for caspase activation by doxorubicin in cancer cells (PMID:18508926)
• Omenn syndrome is associated with mutations in DNA ligase IV. (PMID:18845326)
• In cells infected with E1B 55k-deficient adenovirus, ligase IV could not be found in XRCC4-containing complexes and was observed in a novel ligase IV/E4 34k/Cul5/Elongin BC complex. (PMID:18952251)
• DNA-PK regulates the dysbindin-1 isoforms A and B by phosphorylation in nucleus (PMID:19142223)
• The high-resolution crystal structure of human XRCC4 bound to the carboxy-terminal tandem BRCT repeat of DNA ligase IV, is reported. (PMID:19332554)
• study reports 2 siblings with LIG4 syndrome; mutational analysis of the family revealed a novel sequence variant; homozygous trinucleotide deletion, 1762delAAG, was detected in the brother, resulting in deletion of a lysine at amino acid position 588 (PMID:19418549)
• role of NHEJ enzyme Ligase IV in the pathogenesis of MDS (PMID:19727724)
• provide a first sight of the structural organization of the Lig4-Xrcc4 complex, which suggests that the BRCT domains could provide the link of the ligase to Xrcc4 while permitting some movements of the catalytic domains of Lig4. (PMID:19837014)
• Polymorphisms in the LIG4, BTBD2, HMGA2, and RTEL1 genes, which are involved in the double-strand break repair pathway, are associated with glioblastoma multiforme survival. (PMID:20368557)
• in the Chinese population, LIG4 Ile658Val has only a slight impact on the risk of developing cervical carcinoma (PMID:20400235)
• these results suggest that some variants in XRCC4, LIG4 and Ku80 genes can contribute to thyroid cancer susceptibility (PMID:20811692)
• The current results indicated that NHEJ genetic polymorphisms, particularly LIG4 rs1805388, may modulate the risk of RP in patients with NSCLC who receive definitive radio(chemo)therapy (PMID:21717429)
• polymorphisms in LIG4 do not contribute to cancer risk in a population of Lynch syndrome patients with colorectal cancer (PMID:21974800)
• XRCC4 modulates the dynamic interaction of the Ligase IV/XRCC4 complex with the NHEJ machinery at double-stranded DNA breaks (PMID:21982441)
• The alpha2 helix in the Lig4 BRCT-1 domain is required for adenovirus-mediated degradation of Lig4. (PMID:22534089)
• The flexibility of the DNA ligase IV catalytic region is limited in a manner that affects the formation of the LigIV/XRCC4/XLF-Cernunnos complex. (PMID:22658747)
• No association between LIG4 gene polymorphisms (rs1805386 T>C, rs1805389 C>T, rs1805388 C>T and rs2232641 A>G) and breast cancer risk. (PMID:22994770)
• Structural basis of DNA ligase IV-Artemis interaction in nonhomologous end-joining. (PMID:23219551)
• DNA Ligase IV is differentially required for certain chromosome fusion events induced by telomere dysfunction. (PMID:23275564)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	lig4	ENSDARG00000060620
mus_musculus	Lig4	ENSMUSG00000049717
rattus_norvegicus	Lig4	ENSRNOG00000014605
drosophila_melanogaster	DNAlig4	FBGN0030506
caenorhabditis_elegans		WBGENE00002986

Paralogs (2): LIG3 (ENSG00000005156), LIG1 (ENSG00000105486)

Protein

Protein identifiers

DNA ligase 4 — P49917 (reviewed: P49917)

Alternative names: DNA ligase IV, Polydeoxyribonucleotide synthase [ATP] 4

All UniProt accessions (2): A0A0C4DGV9, P49917

UniProt curated annotations — full annotation on UniProt →

Function. DNA ligase involved in DNA non-homologous end joining (NHEJ); required for double-strand break (DSB) repair and V(D)J recombination. Catalyzes the NHEJ ligation step of the broken DNA during DSB repair by resealing the DNA breaks after the gap filling is completed. Joins single-strand breaks in a double-stranded polydeoxynucleotide in an ATP-dependent reaction. LIG4 is mechanistically flexible: it can ligate nicks as well as compatible DNA overhangs alone, while in the presence of XRCC4, it can ligate ends with 2-nucleotides (nt) microhomology and 1-nt gaps. Forms a subcomplex with XRCC4; the LIG4-XRCC4 subcomplex is responsible for the NHEJ ligation step and XRCC4 enhances the joining activity of LIG4. Binding of the LIG4-XRCC4 complex to DNA ends is dependent on the assembly of the DNA-dependent protein kinase complex DNA-PK to these DNA ends. LIG4 regulates nuclear localization of XRCC4.

Subunit / interactions. Interacts with XRCC4; the LIG4-XRCC4 subcomplex has a 1:2 stoichiometry and XRCC4 is required for LIG4 stability. Component of the core long-range non-homologous end joining (NHEJ) complex (also named DNA-PK complex) composed of PRKDC, LIG4, XRCC4, XRCC6/Ku70, XRCC5/Ku86 and NHEJ1/XLF. Additional component of the NHEJ complex includes PAXX. Following autophosphorylation, PRKDC dissociates from DNA, leading to formation of the short-range NHEJ complex, composed of LIG4, XRCC4, XRCC6/Ku70, XRCC5/Ku86 and NHEJ1/XLF. Interacts with DCLRE1C; the interaction is direct. Interacts with APLF.

Subcellular location. Nucleus.

Tissue specificity. Testis, thymus, prostate and heart.

Disease relevance. LIG4 syndrome (LIG4S) [MIM:606593] Characterized by immunodeficiency and developmental and growth delay. Patients display unusual facial features, microcephaly, growth and/or developmental delay, pancytopenia, and various skin abnormalities. The disease is caused by variants affecting the gene represented in this entry. Severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-negative/NK-cell-positive with sensitivity to ionizing radiation (RSSCID) [MIM:602450] A form of severe combined immunodeficiency, a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients present in infancy with recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T-cell development. Individuals affected by RS-SCID show defects in the DNA repair machinery necessary for coding joint formation and the completion of V(D)J recombination. A subset of cells from such patients show increased radiosensitivity. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Can also use manganese, calcium, nickel and cobalt ions in the ligation reaction.

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

RefSeq proteins (12): NP_001091738, NP_001317524, NP_001339527, NP_001339528, NP_001339529, NP_001339530, NP_001339531, NP_001339532, NP_001339533, NP_001366024, NP_002303, NP_996820* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000977	DNA_ligase_ATP-dep	Family
IPR001357	BRCT_dom	Domain
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
IPR021536	DNA_ligase_IV_dom	Domain
IPR029710	LIG4	Family
IPR036420	BRCT_dom_sf	Homologous_superfamily
IPR036599	DNA_ligase_N_sf	Homologous_superfamily
IPR044125	Adenylation_DNA_ligase_IV	Domain

Pfam: PF00533, PF01068, PF04675, PF04679, PF11411

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 (124 total): helix 43, strand 37, binding site 14, sequence variant 14, turn 10, domain 2, chain 1, region of interest 1, sequence conflict 1, active site 1

Structure

Experimental structures (PDB)

31 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
4HTP	X-RAY DIFFRACTION	2.25
1IK9	X-RAY DIFFRACTION	2.3
3II6	X-RAY DIFFRACTION	2.4
3W1B	X-RAY DIFFRACTION	2.4
6BKG	X-RAY DIFFRACTION	2.4
3W1G	X-RAY DIFFRACTION	2.55
7D9Y	X-RAY DIFFRACTION	2.76
9CQ3	ELECTRON MICROSCOPY	2.8
9N81	ELECTRON MICROSCOPY	2.8
4HTO	X-RAY DIFFRACTION	2.81
3W5O	X-RAY DIFFRACTION	2.84
7D9K	X-RAY DIFFRACTION	2.9
3VNN	X-RAY DIFFRACTION	2.9
9CQ6	ELECTRON MICROSCOPY	3.1
9N83	ELECTRON MICROSCOPY	3.1
6BKF	X-RAY DIFFRACTION	3.25
9N82	ELECTRON MICROSCOPY	3.3
9CQC	ELECTRON MICROSCOPY	3.4
9IAX	ELECTRON MICROSCOPY	3.97
7NFC	ELECTRON MICROSCOPY	4.14
9GD7	ELECTRON MICROSCOPY	4.25
7NFE	ELECTRON MICROSCOPY	4.29
8EZA	ELECTRON MICROSCOPY	4.39
8BHV	ELECTRON MICROSCOPY	4.51
8BH3	ELECTRON MICROSCOPY	4.55
7LT3	ELECTRON MICROSCOPY	4.6
8BHY	ELECTRON MICROSCOPY	5.33
8BOT	ELECTRON MICROSCOPY	7.76
7LSY	ELECTRON MICROSCOPY	8.4
8EZB	ELECTRON MICROSCOPY	8.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P49917-F1	88.44	0.64

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 (1): 273 (n6-amp-lysine intermediate)

Ligand- & substrate-binding residues (14): 331; 331; 345; 367; 427; 427; 432; 449; 451; 271; 272; 273 …

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-164843	2-LTR circle formation
R-HSA-5693571	Nonhomologous End-Joining (NHEJ)

MSigDB gene sets: 610 (showing top): GOBP_CHROMOSOME_ORGANIZATION, GOBP_HEMATOPOIETIC_PROGENITOR_CELL_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_RESPONSE_TO_IONIZING_RADIATION, GOBP_SOMATIC_STEM_CELL_POPULATION_MAINTENANCE, REACTOME_INTEGRATION_OF_PROVIRUS, GOBP_B_CELL_ACTIVATION, ENK_UV_RESPONSE_KERATINOCYTE_UP, GOBP_POSITIVE_REGULATION_OF_FIBROBLAST_PROLIFERATION, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, KAUFFMANN_DNA_REPAIR_GENES

GO Biological Process (37): single strand break repair (GO:0000012), in utero embryonic development (GO:0001701), pro-B cell differentiation (GO:0002328), base-excision repair (GO:0006284), nucleotide-excision repair, DNA gap filling (GO:0006297), double-strand break repair (GO:0006302), double-strand break repair via nonhomologous end joining (GO:0006303), central nervous system development (GO:0007417), cell population proliferation (GO:0008283), response to X-ray (GO:0010165), response to gamma radiation (GO:0010332), neurogenesis (GO:0022008), T cell differentiation in thymus (GO:0033077), V(D)J recombination (GO:0033151), immunoglobulin V(D)J recombination (GO:0033152), T cell receptor V(D)J recombination (GO:0033153), somatic stem cell population maintenance (GO:0035019), negative regulation of neuron apoptotic process (GO:0043524), isotype switching (GO:0045190), fibroblast proliferation (GO:0048144), positive regulation of fibroblast proliferation (GO:0048146), positive regulation of neurogenesis (GO:0050769), chromosome organization (GO:0051276), cell division (GO:0051301), neuron apoptotic process (GO:0051402), cellular response to lithium ion (GO:0071285), cellular response to ionizing radiation (GO:0071479), DNA biosynthetic process (GO:0071897), stem cell proliferation (GO:0072089), establishment of integrated proviral latency (GO:0075713), double-strand break repair via classical nonhomologous end joining (GO:0097680), DN2 thymocyte differentiation (GO:1904155), positive regulation of chromosome organization (GO:2001252), DNA repair (GO:0006281), DNA recombination (GO:0006310), DNA damage response (GO:0006974), response to ionizing radiation (GO:0010212)

GO Molecular Function (10): magnesium ion binding (GO:0000287), DNA binding (GO:0003677), DNA ligase activity (GO:0003909), DNA ligase (ATP) activity (GO:0003910), ATP binding (GO:0005524), AMP binding (GO:0016208), ligase activity (GO:0016874), nucleotide binding (GO:0000166), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (7): chromosome, telomeric region (GO:0000781), condensed chromosome (GO:0000793), nucleus (GO:0005634), nucleoplasm (GO:0005654), DNA-dependent protein kinase-DNA ligase 4 complex (GO:0005958), DNA ligase IV complex (GO:0032807), nonhomologous end joining complex (GO:0070419)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Integration of provirus	1
DNA Double-Strand Break Repair	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA repair	3
nervous system development	2
response to ionizing radiation	2
V(D)J recombination	2
adenyl ribonucleotide binding	2
cation binding	2
nonhomologous end joining complex	2
nuclear protein-containing complex	2
chordate embryonic development	1
lymphoid progenitor cell differentiation	1
DNA metabolic process	1
nucleotide-excision repair	1
double-strand break repair	1
system development	1
cellular process	1
cell differentiation	1
T cell differentiation	1
somatic diversification of immune receptors via germline recombination within a single locus	1
somatic recombination of immunoglobulin gene segments	1
somatic recombination of T cell receptor gene segments	1
stem cell population maintenance	1
negative regulation of apoptotic process	1
regulation of neuron apoptotic process	1
neuron apoptotic process	1
somatic recombination of immunoglobulin genes involved in immune response	1
B cell activation involved in immune response	1
cell population proliferation	1
metal ion binding	1
nucleic acid binding	1
ligase activity, forming phosphoric ester bonds	1
catalytic activity, acting on DNA	1
DNA ligase activity	1
purine ribonucleoside triphosphate binding	1
anion binding	1
catalytic activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
chromosomal region	1
chromosome	1

Protein interactions and networks

STRING

2062 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LIG4	NHEJ1	Q9H9Q4	999
LIG4	XRCC4	Q13426	999
LIG4	PRKDC	P78527	989
LIG4	XRCC5	P13010	985
LIG4	XRCC6	P12956	982
LIG4	DCLRE1C	Q96SD1	929
LIG4	XRCC1	P18887	877
LIG4	TP53BP1	Q12888	869
LIG4	ATM	Q13315	868
LIG4	PAXX	Q9BUH6	847
LIG4	NBN	O60934	814
LIG4	XRCC3	O43542	807
LIG4	POLL	Q9UGP5	791
LIG4	RAD52	P43351	777
LIG4	RAD51	Q06609	774

IntAct

73 interactions, top by confidence:

A	B	Type	Score
LIG4	XRCC4	psi-mi:“MI:0915”(physical association)	0.970
XRCC4	LIG4	psi-mi:“MI:0407”(direct interaction)	0.970
XRCC4	LIG4	psi-mi:“MI:0915”(physical association)	0.970
LIG4	XRCC4	psi-mi:“MI:0914”(association)	0.970
XRCC4	LIG4	psi-mi:“MI:0914”(association)	0.970
CSNK1A1	FAM83G	psi-mi:“MI:0914”(association)	0.900
APLF	LIG4	psi-mi:“MI:0407”(direct interaction)	0.820
APLF	LIG4	psi-mi:“MI:0915”(physical association)	0.820
LIG4	DCLRE1C	psi-mi:“MI:0407”(direct interaction)	0.790
DCLRE1C	LIG4	psi-mi:“MI:0914”(association)	0.790
DCLRE1C	LIG4	psi-mi:“MI:0915”(physical association)	0.790
LIG4	DCLRE1C	psi-mi:“MI:0915”(physical association)	0.790
DCLRE1C	LIG4	psi-mi:“MI:0407”(direct interaction)	0.790

BioGRID (217): XRCC4 (Two-hybrid), LIG4 (Affinity Capture-MS), LIG4 (Affinity Capture-MS), LIG4 (Affinity Capture-MS), LIG4 (Affinity Capture-MS), XRCC4 (Two-hybrid), LIG4 (Affinity Capture-MS), LIG4 (Affinity Capture-MS), LIG4 (Two-hybrid), LIG4 (Affinity Capture-Western), LIG4 (Affinity Capture-Western), LIG4 (Affinity Capture-MS), LIG4 (Affinity Capture-MS), LIG4 (Protein-peptide), LIG4 (Protein-peptide)

ESM2 similar proteins: A0A0G2K344, A0A3Q1N1R0, E1BKH1, G3GTP0, G5EF51, O13728, O70481, P06814, P16259, P16885, P20807, P24135, P32871, P34529, P35875, P42336, P42337, P43368, P49917, P51186, P97393, Q09879, Q11208, Q13017, Q32TF8, Q32TG3, Q4V8Q1, Q5JST6, Q5JVL4, Q5R6L3, Q64691, Q6GL75, Q6GQ76, Q6J756, Q6NU25, Q758X6, Q803R5, Q8BTF7, Q8BTI9, Q8CIH5

Diamond homologs: A8N936, G3GTP0, O74833, P0CN08, P0CN09, P49917, P52496, Q0UCI9, Q1DKE7, Q2U6A1, Q4WVG8, Q54CR9, Q5BH83, Q5R6L3, Q6C8A3, Q6CSH0, Q6FVD8, Q75CA4, Q7SB49, Q7Z7W5, Q8BTF7, Q90YB1, Q9LL84, Q18GX5, Q46BA3, Q8TMT1, Q6L195, P04819, Q08387, A9A3K1, C3MJ14, C3MYD2, C3MZR1, C3N834, C3NF77, C4KIZ2, P12000, P51892, Q7X7E9, Q869E1

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
PRKDC	down-regulates	LIG4	phosphorylation
LIG4	“form complex”	“Lig4-Xrcc4 complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 24 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
Nonhomologous End-Joining (NHEJ)	6	67.2×	2e-08

GO biological processes:

GO term	Partners	Fold	FDR
double-strand break repair via nonhomologous end joining	9	172.3×	1e-16
telomere maintenance	5	60.8×	2e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	87
Likely pathogenic	16
Uncertain significance	368
Likely benign	263
Benign	20

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1020928	NM_206937.2(LIG4):c.2690C>G (p.Ser897Ter)	Pathogenic
1338655	NM_206937.2(LIG4):c.1512_1513dup (p.Arg505fs)	Pathogenic
1418233	NM_206937.2(LIG4):c.1246_1250dup (p.Leu418fs)	Pathogenic
1450499	NM_206937.2(LIG4):c.1475del (p.Pro492fs)	Pathogenic
1453558	NM_206937.2(LIG4):c.73C>T (p.Arg25Ter)	Pathogenic
1456881	NM_206937.2(LIG4):c.2175del (p.Trp725fs)	Pathogenic
1459476	NC_000013.10:g.(?108860881)(108863616_?)del	Pathogenic
1983356	NM_206937.2(LIG4):c.2317C>T (p.Gln773Ter)	Pathogenic
2088321	NM_206937.2(LIG4):c.1578G>A (p.Trp526Ter)	Pathogenic
2131256	NM_206937.2(LIG4):c.1037_1044del (p.Gly346fs)	Pathogenic
2134586	NM_206937.2(LIG4):c.2653_2654dup (p.Phe886fs)	Pathogenic
2693449	NM_206937.2(LIG4):c.22C>T (p.Gln8Ter)	Pathogenic
2697967	NM_206937.2(LIG4):c.250dup (p.Ile84fs)	Pathogenic
2699025	NM_206937.2(LIG4):c.807del (p.Phe268_Tyr269insTer)	Pathogenic
2701101	NM_206937.2(LIG4):c.1636G>T (p.Glu546Ter)	Pathogenic
2703202	NM_206937.2(LIG4):c.1621G>T (p.Gly541Ter)	Pathogenic
2703249	NM_206937.2(LIG4):c.2190del (p.Phe730fs)	Pathogenic
2720977	NM_206937.2(LIG4):c.1880dup (p.Arg628fs)	Pathogenic
2721503	NM_206937.2(LIG4):c.1383del (p.Glu461fs)	Pathogenic
2724097	NM_206937.2(LIG4):c.1210del (p.Gln404fs)	Pathogenic
2732222	NM_206937.2(LIG4):c.106dup (p.Ile36fs)	Pathogenic
2735102	NM_206937.2(LIG4):c.1870C>T (p.Gln624Ter)	Pathogenic
2736055	NM_206937.2(LIG4):c.839A>G (p.Gln280Arg)	Pathogenic
2736056	NM_206937.2(LIG4):c.833G>T (p.Arg278Leu)	Pathogenic
2736058	NM_206937.2(LIG4):c.482del (p.Ala161fs)	Pathogenic
2745502	NM_206937.2(LIG4):c.536C>G (p.Ser179Ter)	Pathogenic
2749009	NM_206937.2(LIG4):c.374_375del (p.Phe125fs)	Pathogenic
2763805	NM_206937.2(LIG4):c.575del (p.Lys192fs)	Pathogenic
2768964	NM_206937.2(LIG4):c.678del (p.Arg226fs)	Pathogenic
2771552	NM_206937.2(LIG4):c.1536_1537delinsTT (p.Met512_Lys513delinsIleTer)	Pathogenic

SpliceAI

462 predictions. Top by Δscore:

Variant	Effect	Δscore
13:108211294:TAA:T	acceptor_gain	0.9900
13:108211297:C:CC	acceptor_gain	0.9900
13:108211292:TTTAA:T	acceptor_gain	0.9800
13:108211293:TTAA:T	acceptor_gain	0.9800
13:108215479:CCCA:C	donor_loss	0.9800
13:108215480:CCA:C	donor_loss	0.9800
13:108215481:CAC:C	donor_loss	0.9800
13:108215483:C:CT	donor_loss	0.9800
13:108211296:ACTAG:A	acceptor_loss	0.9700
13:108211297:C:G	acceptor_loss	0.9700
13:108211298:T:A	acceptor_loss	0.9700
13:108214561:CCT:C	donor_gain	0.9700
13:108215479:C:A	donor_gain	0.9700
13:108215506:G:C	donor_gain	0.9700
13:108215505:AG:A	donor_gain	0.9600
13:108211295:AA:A	acceptor_gain	0.9500
13:108214719:C:CC	acceptor_gain	0.9500
13:108215484:C:G	donor_loss	0.9500
13:108215489:G:C	donor_gain	0.9500
13:108214623:C:CT	acceptor_gain	0.9300
13:108215492:AAG:A	donor_gain	0.9100
13:108215494:G:A	donor_gain	0.9100
13:108214556:CGTTA:C	donor_loss	0.9000
13:108214557:GTTAC:G	donor_loss	0.9000
13:108214558:TTACC:T	donor_loss	0.9000
13:108214559:T:TG	donor_loss	0.9000
13:108214560:A:C	donor_loss	0.9000
13:108214561:C:CA	donor_loss	0.9000
13:108214562:C:T	donor_loss	0.9000
13:108214624:A:C	acceptor_gain	0.9000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000618045 (13:108220061 C>T), RS1000701102 (13:108213000 A>G), RS1000737457 (13:108219067 C>T), RS1000801421 (13:108219646 C>G,T), RS1000810940 (13:108213312 G>A), RS1000843785 (13:108212081 A>G), RS1001511452 (13:108214674 G>A), RS1001607543 (13:108208154 C>G,T), RS1001852841 (13:108219713 C>G), RS1002018005 (13:108207210 A>G), RS1002246874 (13:108213485 C>T), RS1002438378 (13:108213791 T>C), RS1002822158 (13:108217444 G>A), RS1003302220 (13:108219785 A>C,G), RS1003328012 (13:108219967 C>A,T)

Disease associations

OMIM: gene MIM:601837 | disease phenotypes: MIM:606593, MIM:254500, MIM:602450

GenCC curated gene-disease

Disease	Classification	Inheritance
DNA ligase IV deficiency	Definitive	Autosomal recessive
Dubowitz syndrome	Supportive	Autosomal recessive
Omenn syndrome	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
DNA ligase IV deficiency	Definitive	AR

Mondo (7): DNA ligase IV deficiency (MONDO:0011686), plasma cell myeloma (MONDO:0009693), severe combined immunodeficiency due to DCLRE1C deficiency (MONDO:0011225), severe combined immunodeficiency (MONDO:0015974), thyroid gland papillary carcinoma (MONDO:0005075), Dubowitz syndrome (MONDO:0009124), Omenn syndrome (MONDO:0011338)

Orphanet (6): LIG4 syndrome (Orphanet:99812), Multiple myeloma (Orphanet:29073), AL amyloidosis (Orphanet:85443), Severe combined immunodeficiency due to DCLRE1C deficiency (Orphanet:275), Severe combined immunodeficiency (Orphanet:183660), Differentiated thyroid carcinoma (Orphanet:146)

HPO phenotypes

164 total (30 of 164 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000054	Micropenis
HP:0000055	Abnormal female external genitalia morphology
HP:0000100	Nephrotic syndrome
HP:0000126	Hydronephrosis
HP:0000141	Amenorrhea
HP:0000154	Wide mouth
HP:0000164	Abnormality of the dentition
HP:0000176	Submucous cleft hard palate
HP:0000218	High palate
HP:0000233	Thin vermilion border
HP:0000238	Hydrocephalus
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000260	Wide anterior fontanel
HP:0000270	Delayed cranial suture closure
HP:0000275	Narrow face
HP:0000286	Epicanthus
HP:0000294	Low anterior hairline
HP:0000316	Hypertelorism
HP:0000320	Bird-like facies
HP:0000340	Sloping forehead
HP:0000341	Narrow forehead
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000365	Hearing impairment
HP:0000403	Recurrent otitis media
HP:0000411	Protruding ear

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST000253_9	Attention deficit hyperactivity disorder and conduct disorder	1.000000e-06
GCST006304_13	Irritable bowel syndrome	5.000000e-06

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D009101	Multiple Myeloma	C04.557.595.500; C14.907.454.460; C15.378.147.780.650; C15.378.463.515.460; C20.683.515.845; C20.683.780.650
D016511	Severe Combined Immunodeficiency	C16.320.798.750; C16.614.815; C18.452.284.800; C20.673.795.750
C535718	Dubowitz syndrome (supp.)
C564694	LIG4 Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4296097 (PROTEIN COMPLEX), CHEMBL4523595 (SINGLE PROTEIN)

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
5.30	IC50	5000	nM	CHEMBL4458668

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
6-amino-5-(benzylideneamino)-2-sulfanylidene-1H-pyrimidin-4-one	1540614: Competitive inhibition of human DNA ligase 4 using nicked DNA as substrate by high-throughput fluorescence energy transfer-based DNA joining assay	ic50	5.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	4
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	2
Acrolein	affects cotreatment, decreases expression, increases abundance	2
Doxorubicin	increases activity, decreases expression, affects reaction	2
Ozone	affects cotreatment, decreases expression, increases abundance	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
GSK-J4	decreases expression	1
methylmercuric chloride	decreases expression	1
lasiocarpine	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	decreases expression, increases abundance, affects cotreatment	1
4-biphenylamine	decreases reaction, increases expression	1
bisphenol A	increases expression, increases reaction	1
selenocystine	decreases expression	1
terbufos	increases methylation	1
trichostatin A	increases expression	1
nickel chloride	decreases expression	1
zinc chromate	increases abundance, increases expression	1
1-nitropyrene	increases expression	1
chromium hexavalent ion	increases abundance, increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
cylindrospermopsin	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	decreases expression	1
riccardin D	increases expression	1
Bortezomib	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Air Pollutants	affects cotreatment, 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
CHEMBL4142330	Binding	Inhibition of human DNA Lig4/XRCCR at 10 uM using double strand nicked DNA as substrate after 30 mins in presence of ATP by acrylamide-based fluorescence-assay	Synthesis and bio-evaluation of indole-chalcone based benzopyrans as promising antiligase and antiproliferative agents. — Eur J Med Chem

Cellosaurus cell lines

18 cell lines: 10 cancer cell line, 5 finite cell line, 2 transformed cell line, 1 telomerase immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_1K21	GM17523	Finite cell line	Female
CVCL_1Q95	H414-LIG4(+/-)	Cancer cell line	Male
CVCL_1R04	HCT116-LIG4(+/-)	Cancer cell line	Male
CVCL_2278	180BR	Finite cell line	Male
CVCL_A1TX	411BR	Finite cell line	Sex unspecified
CVCL_A1TY	411BRneo	Finite cell line	Sex unspecified
CVCL_A1TZ	FB2303	Finite cell line	Sex unspecified
CVCL_A1UA	LB2304	Transformed cell line	Sex unspecified
CVCL_E2B3	HAP1 LIG4 (-) 3	Cancer cell line	Male
CVCL_E2B4	HAP1 LIG4 (-) 4	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00104104	PHASE4	COMPLETED	A Multiple Myeloma Trial in Patients With Bone Metastases
NCT00211211	PHASE4	COMPLETED	FREE Study - Fracture Reduction Evaluation
NCT00242528	PHASE4	WITHDRAWN	Open-label Study, to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Bone Lesions Secondary to Multiple Myeloma.
NCT00257114	PHASE4	COMPLETED	Evaluation of VELCADE Given as Retreatment to Multiple Myeloma Patients for Efficacy, Safety and Tolerability
NCT00352703	PHASE4	COMPLETED	PROMPT - Palifermin in Reduction of Oral Mucositis in PBSC Transplantation
NCT00361140	PHASE4	COMPLETED	Busulfan Safety/Efficacy as Conditioning Prior to Hematopoietic Cell Transplantation (HCT)
NCT00622505	PHASE4	COMPLETED	Zoledronic Acid Treatment (Every 4 or 12 Weeks) to Prevent Skeletal Complications in Advanced Multiple Myeloma Participants
NCT00652041	PHASE4	COMPLETED	Bortezomib/Adriamycine/Melfalan/Prednisone (VAMP)/Thalidomide/Cyclophosphamide/Dexamethasone (TaCyDex) or Bortezomib/Melfalan/Prednisone (V-MP)/TaCyDex) in Refractary or Relapsed Multiple Myeloma
NCT00733538	PHASE4	COMPLETED	Stage I Multiple Myeloma Treatment
NCT01087008	PHASE4	COMPLETED	Zoledronic Acid in Patients With Multiple Myeloma and Asymptomatic Biochemical Relapse
NCT01249690	PHASE4	UNKNOWN	Efficacy Study of PAD and TAD in Newly Diagnosed Multiple Myeloma
NCT01410929	PHASE4	WITHDRAWN	Evaluation of Vertebral Compression Fracture Fixation With RF Kyphoplasty in Patients With Multiple Myeloma
NCT01731886	PHASE4	COMPLETED	Lenalidomide and Dexamethasone With/Without Stem Cell Transplant in Patients With Multiple Myeloma
NCT01868828	PHASE4	UNKNOWN	A Study of PAD Versus Velcade, Cyclophosphamide and Dexamethasone (VCD) Treatment in Subjects With Multiple Myeloma
NCT02268890	PHASE4	COMPLETED	A Pharmacokinetic Study of Bortezomib in Taiwanese Participants With Multiple Myeloma
NCT02286830	PHASE4	COMPLETED	Prolonged Protection From Bone Disease in Multiple Myeloma
NCT02559154	PHASE4	UNKNOWN	Modified Bortezomib-based Combination Therapy for Multiple Myeloma
NCT02577783	PHASE4	UNKNOWN	PDD vs PAD to Treat Initially Diagnosed MM
NCT02773550	PHASE4	TERMINATED	Treatment With a Scheme With Low Doses of Bortezomib / Melphalan / Prednisone (MPV) in Patients With Multiple Myeloma
NCT02958969	PHASE4	COMPLETED	Apixaban for Primary Prevention of Venous Thromboembolism in Patients With Multiple Myeloma
NCT03173092	PHASE4	TERMINATED	A Study of Ixazomib (NINLARO®) in Combination With Lenalidomide and Dexamethasone (IRD) for the Treatment of Participants With Multiple Myeloma (MM)
NCT03619252	PHASE4	COMPLETED	Pneumococcal Vaccination of Multiple Myeloma Patients on Novel Agents
NCT03768960	PHASE4	COMPLETED	A Study of DARZALEX (Daratumumab) In Indian Participants With Relapsed and Refractory Multiple Myeloma, Whose Prior Therapy Included a Proteasome Inhibitor and an Immunomodulatory Agent
NCT03829371	PHASE4	ACTIVE_NOT_RECRUITING	STUDY COMPARING TWO STANDARD TREATMENTS IN AUTOLOGOUS STEM CELL TRANSPLANTATION INELIGIBLE POPULATION AFFECTED BY MULTIPLE MYELOMA
NCT03908138	PHASE4	UNKNOWN	RDD Versus VDD in Newly Diagnosed Patients With Multiple Myeloma
NCT04217967	PHASE4	COMPLETED	Ixazomib, Lenalidomide, and Combination for Maintenance in NDMM Patients
NCT04952766	PHASE4	COMPLETED	Study Evaluating SARS-CoV-2 (COVID-19) Humoral Response After BNT162b2 Vaccine in Immunocompromised Adults Compared to Healthy Adults
NCT04989140	PHASE4	UNKNOWN	Study of Pomalidomide, Oral Dexamethasone and Ixazomib in Patients With Relapsed MM Who Have Received Lenalidomide
NCT05183139	PHASE4	WITHDRAWN	A Multicenter In-class Transition Study of Ixazomib Combined With Pomalidomide and Dexamethasone or With Lenalidomide and Dexamethasone in Adults With Relapsed/Refractory Multiple Myeloma
NCT05201781	PHASE4	RECRUITING	A Long-term Study for Participants Previously Treated With Ciltacabtagene Autoleucel
NCT05429515	PHASE4	NOT_YET_RECRUITING	Effect of HFR-SUPRA in the Treatment of Multiple Myeloma-related Acute Kidney Injury
NCT05511428	PHASE4	COMPLETED	Home Based Daratumumab Administration for Patients With Multiple Myeloma
NCT05545202	PHASE4	UNKNOWN	A Randomized, Comparative, Double-blind Trial of Pentaisomaltose and Dimethyl Sulphoxide for Cryoprotection of Hematopoietic Stem Cells in Subjects With Multiple Myeloma or Malignant Lymphoma With a Need for Autologous Transplantation
NCT05555329	PHASE4	COMPLETED	Alternative Dosing Scheme of Pomalidomide 4 mg Every Other Day Versus Pomalidomide 2 mg and 4 mg Every Day; the POMAlternative Study
NCT05722405	PHASE4	RECRUITING	Ixazomib Plus Low-dose Lenalidomide Versus Ixazomib Alone for Maintenance Treatment of High Risk Multiple Myeloma
NCT05855122	PHASE4	UNKNOWN	Safety and ASCT-related Symptom Burden Optimization of Tocilizumab in ASCT Following HD Melphalan Conditioning for Multiple Myeloma Patients
NCT05944783	PHASE4	NOT_YET_RECRUITING	Bioequivalence Studies of Dasatinib 100 Mg
NCT06057402	PHASE4	RECRUITING	Elranatamab Post Trial Access Study for Participants With Multiple Myeloma (MM)
NCT06251076	PHASE4	RECRUITING	Plan Development for Giving Teclistamab in the Outpatient Setting