LIG1

DNA ligase 1, the group of Nucleotide excision repair|DNA ligases

Basic information

Region (hg38): 19:48115445-48170603

Links

ENSG00000105486 ∙ NCBI:3978 ∙ OMIM:126391 ∙ HGNC:6598 ∙ Uniprot:P18858 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• immunodeficiency 96 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency 96	AR	Allergy/Immunology/Infectious; Hematologic	Antiinfectious prophylaxis and early and aggressive treatment of infections and hematologic anomalies may be beneficial; Individuals have been described as affected by hematolgic disturbances, such as anemia requiring RBC transfusions, and awareness may allow early diagnosis and medical management; HSCT has been described	Allergy/Immunology/Infectious; Hematologic	1351188; 1581963; 30395541

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LIG1 gene.

• not provided (1 variants)
• Immunodeficiency 96 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LIG1 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			4	174	13	191
missense			221	9	9	239
nonsense			5			5
start loss						0
frameshift	1	1	5			7
inframe indel			3			3
splice donor/acceptor (+/-2bp)			3			3
splice region			15	39	3	57
non coding			4	122	35	161
Total	1	1	245	305	57

Highest pathogenic variant AF is 0.0000131

Variants in LIG1

This is a list of pathogenic ClinVar variants found in the LIG1 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-48115666-G-A		not specified	Uncertain significance (Dec 26, 2023)
19-48115679-G-C			Uncertain significance (Dec 07, 2021)
19-48115684-C-T			Uncertain significance (Mar 29, 2023)
19-48115685-G-A			Uncertain significance (Mar 20, 2023)
19-48115688-T-G			Uncertain significance (Apr 25, 2022)
19-48115691-T-C			Likely benign (Oct 22, 2023)
19-48115709-T-C			Benign (Jan 25, 2024)
19-48115716-C-T			Uncertain significance (Jul 25, 2022)
19-48115717-G-A			Uncertain significance (Jun 08, 2022)
19-48115728-G-C		not specified	Uncertain significance (Mar 11, 2022)
19-48115734-TGC-T			Likely benign (Sep 08, 2023)
19-48115736-C-G			Likely benign (Jun 23, 2023)
19-48115736-C-T			Likely benign (Jul 17, 2023)
19-48115747-T-C			Likely benign (Feb 21, 2022)
19-48115752-C-T			Likely benign (Jul 31, 2023)
19-48115862-C-G			Likely benign (Dec 20, 2022)
19-48115878-C-T			Uncertain significance (Jun 22, 2022)
19-48115884-T-C		not specified	Uncertain significance (Feb 22, 2023)
19-48115896-C-T			Uncertain significance (May 31, 2021)
19-48115897-C-T			Benign (Aug 01, 2024)
19-48115898-G-A		not specified	Uncertain significance (Aug 10, 2021)
19-48115899-G-A		not specified	Uncertain significance (May 28, 2024)
19-48115904-T-C			Uncertain significance (Feb 22, 2021)
19-48115906-G-A			Likely benign (Mar 26, 2023)
19-48115919-C-T		not specified	Uncertain significance (Jun 07, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LIG1	protein_coding	protein_coding	ENST00000263274	27	55159

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00421	0.996	125709	0	39	125748	0.000155

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.820	512	567	0.903	0.0000388	5914
Missense in Polyphen		167	205.95	0.81088		2016
Synonymous	-0.696	253	239	1.06	0.0000175	1847
Loss of Function	4.61	14	48.7	0.288	0.00000222	594

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000271	0.000271
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.000240	0.000231
European (Non-Finnish)	0.000213	0.000211
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000654	0.0000653
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: DNA ligase that seals nicks in double-stranded DNA during DNA replication, DNA recombination and DNA repair.
• Pathway: Nucleotide excision repair - Homo sapiens (human);Base excision repair - Homo sapiens (human);Mismatch repair - Homo sapiens (human);DNA replication - Homo sapiens (human);Nucleotide Excision Repair ;Mismatch repair;Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta);Mismatch Repair;DNA Repair;Disease;HIV Life Cycle;HIV Infection;Infectious disease;DNA Replication;Processive synthesis on the lagging strand;Lagging Strand Synthesis;DNA strand elongation;Synthesis of DNA;POLB-Dependent Long Patch Base Excision Repair;S Phase;PCNA-Dependent Long Patch Base Excision Repair;Resolution of AP sites via the multiple-nucleotide patch replacement pathway;Resolution of Abasic Sites (AP sites);Base Excision Repair;Processive synthesis on the C-strand of the telomere;Telomere C-strand (Lagging Strand) Synthesis;Extension of Telomeres;Telomere Maintenance;Chromosome Maintenance;Cell Cycle;Gap-filling DNA repair synthesis and ligation in GG-NER;Global Genome Nucleotide Excision Repair (GG-NER);Cell Cycle, Mitotic;Early Phase of HIV Life Cycle;Gap-filling DNA repair synthesis and ligation in TC-NER;Transcription-Coupled Nucleotide Excision Repair (TC-NER);Nucleotide Excision Repair;Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha) (Consensus)

Recessive Scores

• pRec: 0.388

Intolerance Scores

• loftool: 0.547
• rvis_EVS: 0.37
• rvis_percentile_EVS: 74.73

Haploinsufficiency Scores

• pHI: 0.980
• hipred: Y
• hipred_score: 0.715
• ghis: 0.554

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.982

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Lig1
• Phenotype: immune system phenotype; hematopoietic system phenotype; 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); neoplasm; embryo phenotype; liver/biliary system phenotype; homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); endocrine/exocrine gland phenotype

Gene ontology

• Biological process: DNA ligation;lagging strand elongation;DNA repair;transcription-coupled nucleotide-excision repair;base-excision repair;nucleotide-excision repair, DNA gap filling;mismatch repair;anatomical structure morphogenesis;V(D)J recombination;DNA ligation involved in DNA repair;cell division;DNA biosynthetic process;Okazaki fragment processing involved in mitotic DNA replication
• Cellular component: nucleus;nucleoplasm;cytoplasm;mitochondrion;intracellular membrane-bounded organelle
• Molecular function: DNA binding;DNA ligase activity;DNA ligase (ATP) activity;ATP binding;metal ion binding