Immunodeficiency 96

Summary

Immunodeficiency 96 (MONDO:0030693) is a disease caused by LIG1 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: LIG1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 17

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	immunodeficiency 96
Mondo ID	MONDO:0030693
OMIM	619774
DOID	DOID:0061066
UMLS	C5676930
MedGen	1810465
Is cancer (heuristic)	no

Also known as: IMD96 · immunodeficiency 96 · immunodeficiency, autosomal recessive due to LIG1 deficiency

Data availability: 17 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › immunodeficiency disease › immunodeficiency 96

Related subtypes (94): B cell deficiency, T-cell immunodeficiency, complement deficiency, myalgic encephalomeyelitis/chronic fatigue syndrome, hypoproteinemia, hypercatabolic, X-linked lymphoproliferative syndrome, Wiskott-Aldrich syndrome, autosomal dominant form, immunodeficiency due to CD25 deficiency, immunodeficiency 67, primary immunodeficiency with natural-killer cell deficiency and adrenal insufficiency, immunodeficiency 35, pyogenic bacterial infections due to MyD88 deficiency, lymphoproliferative syndrome 1, FADD-related immunodeficiency, immunodeficiency 31B, Wiskott-Aldrich syndrome 2, cryptosporidiosis-chronic cholangitis-liver disease syndrome, idiopathic CD4 lymphocytopenia, immunodeficiency 23, DOCK2 deficiency, immunodeficiency 45, TFRC-related combined immunodeficiency, combined immunodeficiency, autoimmune hemolytic anemia-autoimmune thrombocytopenia-primary immunodeficiency syndrome, immunodeficiency due to selective anti-polysaccharide antibody deficiency, immunodeficiency 57, immunodeficiency 14b, autosomal recessive, immunodeficiency 98 with autoinflammation, X-linked, immunodeficiency 102, immunodeficiency 74, COVID-19-related, X-linked, immunodeficiency 66, immunodeficiency 80 with or without congenital cardiomyopathy, immunodeficiency 81, immunodeficiency 82 with systemic inflammation, immunodeficiency 84, immunodeficiency 85 and autoimmunity, immunodeficiency 86, immunodeficiency 87 and autoimmunity, immunodeficiency 88, immunodeficiency 89 and autoimmunity, immunodeficiency 91 and hyperinflammation, immunodeficiency 92, immunodeficiency 93 and hypertrophic cardiomyopathy, immunodeficiency 95, immunodeficiency 97 with autoinflammation, immunodeficiency 99 with hypogammaglobulinemia and autoimmune cytopenias, immunodeficiency 101 (varicella zoster virus-specific), immunodeficiency 75, immunodeficiency 76, immunodeficiency 106, susceptibility to viral infections, immunodeficiency 78 with autoimmunity and developmental delay, immunodeficiency 77, immunodeficiency 107, susceptibility to invasive staphylococcus aureus infection, immunodeficiency 15a, immunodeficiency 60, immunodeficiency 62, immunodeficiency 63 with lymphoproliferation and autoimmunity, immunodeficiency 64, immunodeficiency 65, susceptibility to viral infections, immunodeficiency 69, immunodeficiency 70, immunodeficiency 72 with autoinflammation, GATA2 deficiency with susceptibility to MDS/AML, Shwachman-Diamond syndrome 1, immunodeficiency 53, immunodeficiency 11b with atopic dermatitis, IKBKG-related immunodeficiency with or without ectodermal dysplasia, FNIP1-associated syndrome, FASLG-related immunodeficiency, TNFRSF9-related immunodeficiency, DNAJC21-related Shwachman Diamond syndrome, IRF4-related immune disorder, PTEN harmartoma tumor syndrome with immune disorder, primary immunodeficiency due to calcium channel deficiency, chronic mucocutaneous candidiasis and connective tissue disease due to JNK1 haploinsufficiency, immune deficiency due to impaired neutrophil phagocytosis and migration, hatipoglu immunodeficiency syndrome, immunodeficiency 112, immunodeficiency 113 with autoimmunity and autoinflammation, immunodeficiency 114, folate-responsive, immunodeficiency 115 with autoinflammation, immunodeficiency 117, immunodeficiency 118, immunodeficiency 119, immunodeficiency 121 with autoinflammation, immunodeficiency 122, immunodeficiency 123 with HPV-related verrucosis, immunodeficiency 125, immunodeficiency 126, susceptibility to, immunodeficiency 127, immunodeficiency 128, immunodeficiency 132b, immunodeficiency 133 with ectodermal dysplasia with or without peripheral neuropathy, immunodeficiency 134 (Epstein-Barr virus-specific)

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

17 retrieved; paginated sample, class counts are floors:

11 uncertain significance, 2 conflicting classifications of pathogenicity, 2 pathogenic, 1 likely pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1343095	NM_000234.3(LIG1):c.1244del (p.Thr415fs)	LIG1	Pathogenic	criteria provided, single submitter
16775	NM_000234.3(LIG1):c.1696G>A (p.Glu566Lys)	LIG1	Pathogenic	no assertion criteria provided
2504596	NM_000234.3(LIG1):c.2444del (p.Leu815fs)	LIG1	Likely pathogenic	criteria provided, single submitter
1145405	NM_000234.3(LIG1):c.776+5G>T	LIG1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
16776	NM_000234.3(LIG1):c.2311C>T (p.Arg771Trp)	LIG1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1343096	NM_000234.3(LIG1):c.1922G>T (p.Arg641Leu)	LIG1	Uncertain significance	criteria provided, single submitter
1409787	NM_000234.3(LIG1):c.778C>T (p.Pro260Ser)	LIG1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1412834	NM_000234.3(LIG1):c.1331+6C>T	LIG1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1521453	NM_000234.3(LIG1):c.2014C>T (p.Arg672Cys)	LIG1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2150646	NM_000234.3(LIG1):c.2326G>A (p.Gly776Arg)	LIG1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2433433	NM_000234.3(LIG1):c.1306del (p.His436fs)	LIG1	Uncertain significance	criteria provided, single submitter
3234860	NM_000234.3(LIG1):c.97C>A (p.Pro33Thr)	LIG1	Uncertain significance	criteria provided, single submitter
3242588	NM_000234.3(LIG1):c.848C>T (p.Pro283Leu)	LIG1	Uncertain significance	criteria provided, single submitter
3254808	NM_000234.3(LIG1):c.191T>C (p.Leu64Pro)	LIG1	Uncertain significance	criteria provided, single submitter
3290644	NM_000234.3(LIG1):c.598G>A (p.Val200Ile)	LIG1	Uncertain significance	criteria provided, multiple submitters, no conflicts
4279630	NM_000234.3(LIG1):c.1657G>A (p.Glu553Lys)	LIG1	Uncertain significance	criteria provided, single submitter
734140	NM_000234.3(LIG1):c.140C>T (p.Ser47Phe)	LIG1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 0 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
LIG1	Definitive	Autosomal recessive	immunodeficiency 96	3

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
LIG1	HGNC:6598	ENSG00000105486	P18858	DNA ligase 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
LIG1	DNA ligase 1	DNA ligase that seals nicks in double-stranded during DNA repair.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
LIG1	Enzyme (other)	yes	6.5.1.1	DNA_ligase_ATP-dep, DNA_ligase_ATP-dep_N, DNA_ligase_ATP-dep_C

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ganglionic eminence	1
right uterine tube	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LIG1	198	ubiquitous	marker	right uterine tube, ventricular zone, ganglionic eminence

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LIG1	2,305

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
LIG1	P18858	35

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Early Phase of HIV Life Cycle	1	1631.4×	0.002	LIG1
Regulation of MITF-M-dependent genes involved in DNA replication, damage repair and senescence	1	1631.4×	0.002	LIG1
POLB-Dependent Long Patch Base Excision Repair	1	1268.9×	0.002	LIG1
Processive synthesis on the lagging strand	1	1142.0×	0.002	LIG1
Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha)	1	815.7×	0.002	LIG1
Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta)	1	815.7×	0.002	LIG1
Processive synthesis on the C-strand of the telomere	1	761.3×	0.002	LIG1
PCNA-Dependent Long Patch Base Excision Repair	1	519.1×	0.003	LIG1
Gap-filling DNA repair synthesis and ligation in GG-NER	1	439.2×	0.003	LIG1
HDR through Single Strand Annealing (SSA)	1	292.8×	0.004	LIG1
Gap-filling DNA repair synthesis and ligation in TC-NER	1	178.4×	0.006	LIG1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
Okazaki fragment processing involved in mitotic DNA replication	1	16852.0×	7e-04	LIG1
lagging strand elongation	1	5617.3×	1e-03	LIG1
telomere maintenance via semi-conservative replication	1	2808.7×	0.001	LIG1
base-excision repair, gap-filling	1	1123.5×	0.002	LIG1
DNA biosynthetic process	1	802.5×	0.003	LIG1
mismatch repair	1	648.1×	0.003	LIG1
base-excision repair	1	468.1×	0.003	LIG1
DNA recombination	1	337.0×	0.004	LIG1
anatomical structure morphogenesis	1	139.3×	0.009	LIG1
DNA repair	1	63.8×	0.017	LIG1
cell division	1	46.2×	0.022	LIG1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
LIG1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
LIG1	32	Binding:32

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
LIG1	6.5.1.1	DNA ligase (ATP)

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	LIG1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
LIG1	32	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.