Immunodeficiency 69

Summary

Immunodeficiency 69 (MONDO:0033541) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	immunodeficiency 69
Mondo ID	MONDO:0033541
OMIM	618963
Orphanet	699618
DOID	DOID:0112006
UMLS	C5436498
MedGen	1735911
Is cancer (heuristic)	no

Also known as: IMD69 · immunodeficiency 69, mycobacteriosis

Data availability: 4 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 69

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 96, 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 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

4 retrieved; paginated sample, class counts are floors:

1 uncertain significance, 1 benign, 1 likely benign, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
974678	NM_000619.3(IFNG):c.354_357del (p.Thr119fs)	IFNG	Pathogenic	no assertion criteria provided
3891373	NM_000619.3(IFNG):c.117T>G (p.Asn39Lys)	IFNG	Uncertain significance	criteria provided, single submitter
402962	NM_000619.3(IFNG):c.115-3del	IFNG	Benign	criteria provided, multiple submitters, no conflicts
4814058	NM_000619.3(IFNG):c.460del (p.Arg154fs)	IFNG	Likely benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 3 · 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
IFNG	Moderate	Autosomal recessive	immunodeficiency 69	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
IFNG	Orphanet:699618	Severe mendelian susceptibility to mycobacterial diseases due to complete IFNG deficiency
IFNG	Orphanet:805	Tuberous sclerosis complex
IFNG	Orphanet:88	Idiopathic aplastic anemia

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
IFNG	HGNC:5438	ENSG00000111537	P01579	Interferon gamma	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
IFNG	Interferon gamma	Type II interferon produced by immune cells such as T-cells and NK cells that plays crucial roles in antimicrobial, antiviral, and antitumor responses by activating effector immune cells and enhancing antigen presentation.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
IFNG	Other/Unknown	no		Interferon_gamma, 4_helix_cytokine-like_core

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
granulocyte	1
lymph node	1
male germ line stem cell (sensu Vertebrata) in testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
IFNG	119	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, granulocyte, lymph node

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
IFNG	7,383

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
IFNG	P01579	8

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. 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
IFNG signaling activates MAPKs	1	1427.5×	0.002	IFNG
RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs)	1	1142.0×	0.002	IFNG
Differentiation of naive CD4+ T cells to T helper 1 cells (Th1 cells)	1	878.5×	0.002	IFNG
Regulation of IFNG signaling	1	815.7×	0.002	IFNG
Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation	1	300.5×	0.004	IFNG
Interferon gamma signaling	1	125.5×	0.008	IFNG

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
positive regulation of fructose 1,6-bisphosphate metabolic process	1	16852.0×	0.001	IFNG
obsolete positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation involved in immune response	1	8426.0×	0.001	IFNG
positive regulation of peptidyl-serine phosphorylation of STAT protein	1	8426.0×	0.001	IFNG
positive regulation of vitamin D biosynthetic process	1	8426.0×	0.001	IFNG
positive regulation of iron ion import across plasma membrane	1	8426.0×	0.001	IFNG
positive regulation of tumor necrosis factor (ligand) superfamily member 11 production	1	8426.0×	0.001	IFNG
positive regulation of interleukin-23 production	1	2407.4×	0.003	IFNG
positive regulation of smooth muscle cell apoptotic process	1	2407.4×	0.003	IFNG
positive regulation of cellular respiration	1	1872.4×	0.003	IFNG
negative regulation of amyloid-beta clearance	1	1685.2×	0.003	IFNG
type III interferon-mediated signaling pathway	1	1532.0×	0.003	IFNG
neuroinflammatory response	1	1532.0×	0.003	IFNG
positive regulation of glutamate receptor signaling pathway	1	1532.0×	0.003	IFNG
negative regulation of epithelial cell differentiation	1	1203.7×	0.003	IFNG
positive regulation of MHC class II biosynthetic process	1	1203.7×	0.003	IFNG
type II interferon-mediated signaling pathway	1	1203.7×	0.003	IFNG
macrophage activation involved in immune response	1	1123.5×	0.003	IFNG
positive regulation of exosomal secretion	1	1123.5×	0.003	IFNG
negative regulation of interleukin-17 production	1	1053.2×	0.003	IFNG
astrocyte activation	1	991.3×	0.003	IFNG
positive regulation of membrane protein ectodomain proteolysis	1	936.2×	0.003	IFNG
positive regulation of amyloid-beta formation	1	887.0×	0.003	IFNG
positive regulation of tyrosine phosphorylation of STAT protein	1	732.7×	0.004	IFNG
Fc-gamma receptor signaling pathway involved in phagocytosis	1	702.2×	0.004	IFNG
positive regulation of glycolytic process	1	674.1×	0.004	IFNG
microglial cell activation	1	624.1×	0.004	IFNG
negative regulation of smooth muscle cell proliferation	1	624.1×	0.004	IFNG
positive regulation of osteoclast differentiation	1	581.1×	0.004	IFNG
positive regulation of neurogenesis	1	581.1×	0.004	IFNG
cell surface receptor signaling pathway via STAT	1	561.7×	0.004	IFNG

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
IFNG	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
IFNG	1	Binding:1

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	IFNG

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)
IFNG	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.