LIG3

DNA ligase 3, the group of DNA ligases|Zinc fingers PARP-type

Basic information

Region (hg38): 17:34980512-35009743

Previous symbols: [ "LIG2" ]

Links

ENSG00000005156 ∙ NCBI:3980 ∙ OMIM:600940 ∙ HGNC:6600 ∙ Uniprot:P49916 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mitochondrial DNA depletion syndrome 20 (mngie type) (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mitochondrial DNA depletion syndrome 20 (MNGIE type)	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Gastrointestinal; Neurologic; Ophthalmologic	33855352; 34165507

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LIG3 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LIG3 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				8	9	17
missense			46	10	1	57
nonsense						0
start loss						0
frameshift		1	1			2
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region			1	1	1	3
non coding			3		3	6
Total	0	1	51	18	13

Variants in LIG3

This is a list of pathogenic ClinVar variants found in the LIG3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-34983072-C-T			Benign (Aug 10, 2017)
17-34983075-T-G		Inborn genetic diseases	Uncertain significance (Aug 13, 2021)
17-34983079-G-A		not specified	Likely benign (Jul 03, 2023)
17-34983091-G-A		Mitochondrial DNA depletion syndrome 20 (mngie type)	Pathogenic (Mar 15, 2022)
17-34983128-A-G		not specified	Likely benign (Apr 10, 2023)
17-34983280-G-A		Inborn genetic diseases	Uncertain significance (Aug 17, 2022)
17-34983288-G-A		Inborn genetic diseases	Uncertain significance (Mar 04, 2024)
17-34983307-G-A		Inborn genetic diseases	Uncertain significance (Jan 24, 2023)
17-34983358-G-A		Inborn genetic diseases	Uncertain significance (Nov 18, 2022)
17-34983387-T-G		not specified	Uncertain significance (Jul 27, 2021)
17-34983451-G-A		not specified	Uncertain significance (Aug 23, 2021)
17-34983457-G-A		not specified	Likely benign (Jun 16, 2020)
17-34983476-C-A		not specified	Benign/Likely benign (Mar 12, 2018)
17-34985987-G-C		Inborn genetic diseases	Uncertain significance (Nov 03, 2021)
17-34986083-G-A		Inborn genetic diseases	Likely benign (Nov 09, 2021)
17-34986110-C-T		not specified	Benign/Likely benign (Oct 30, 2021)
17-34986111-G-T		Inborn genetic diseases	Uncertain significance (Sep 16, 2021)
17-34986117-T-C		Inborn genetic diseases	Uncertain significance (Mar 30, 2024)
17-34989472-C-G		Inborn genetic diseases	Uncertain significance (Nov 08, 2022)
17-34989487-A-T		Inborn genetic diseases	Uncertain significance (May 26, 2024)
17-34989496-C-T		not specified	Likely benign (Nov 02, 2020)
17-34989518-T-A		not specified	Uncertain significance (Apr 10, 2023)
17-34989564-C-T		Inborn genetic diseases	Uncertain significance (Jan 18, 2022)
17-34989573-C-T		Mitochondrial DNA depletion syndrome 20 (mngie type)	Likely pathogenic (Apr 26, 2024)
17-34989616-C-G		Inborn genetic diseases	Uncertain significance (Apr 07, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LIG3	protein_coding	protein_coding	ENST00000378526	19	24571

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.44e-10	1.00	125660	0	88	125748	0.000350

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.63	478	589	0.811	0.0000341	6638
Missense in Polyphen		128	197.58	0.64783		2160
Synonymous	0.426	215	223	0.964	0.0000126	1961
Loss of Function	3.39	25	51.2	0.488	0.00000304	579

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000601	0.000601
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000218	0.000217
Finnish	0.00	0.00
European (Non-Finnish)	0.000620	0.000563
Middle Eastern	0.000218	0.000217
South Asian	0.000196	0.000196
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Isoform 3 functions as heterodimer with DNA-repair protein XRCC1 in the nucleus and can correct defective DNA strand- break repair and sister chromatid exchange following treatment with ionizing radiation and alkylating agents. Isoform 1 is targeted to mitochondria, where it functions as DNA ligase in mitochondrial base-excision DNA repair (PubMed:10207110, PubMed:24674627). {ECO:0000269|PubMed:10207110, ECO:0000269|PubMed:24674627}.
• Pathway: Base excision repair - Homo sapiens (human);HDR through MMEJ (alt-NHEJ);DNA Repair;DNA Double-Strand Break Repair;Homology Directed Repair;Resolution of Abasic Sites (AP sites);Base Excision Repair;Resolution of AP sites via the single-nucleotide replacement pathway;Gap-filling DNA repair synthesis and ligation in GG-NER;Global Genome Nucleotide Excision Repair (GG-NER);APEX1-Independent Resolution of AP Sites via the Single Nucleotide Replacement Pathway;Gap-filling DNA repair synthesis and ligation in TC-NER;Transcription-Coupled Nucleotide Excision Repair (TC-NER);Nucleotide Excision Repair (Consensus)

Recessive Scores

• pRec: 0.222

Intolerance Scores

• loftool: 0.853
• rvis_EVS: -1.39
• rvis_percentile_EVS: 4.25

Haploinsufficiency Scores

• pHI: 0.326
• hipred: Y
• hipred_score: 0.715
• ghis: 0.627

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.649

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Lig3
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype; growth/size/body region phenotype; embryo phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: lig3
• Affected structure: double-strand break repair via alternative nonhomologous end joining
• Phenotype tag: abnormal
• Phenotype quality: decreased process quality

Gene ontology

• Biological process: double-strand break repair via homologous recombination;lagging strand elongation;transcription-coupled nucleotide-excision repair;base-excision repair, DNA ligation;nucleotide-excision repair, DNA gap filling;double-strand break repair;cell cycle;V(D)J recombination;mitochondrial DNA repair;cell division;DNA biosynthetic process;negative regulation of mitochondrial DNA replication;double-strand break repair via alternative nonhomologous end joining
• Cellular component: nucleus;nucleoplasm;cytoplasm;mitochondrion
• Molecular function: DNA binding;DNA ligase activity;DNA ligase (ATP) activity;protein binding;ATP binding;zinc ion binding