autosomal recessive Mendelian susceptibility to mycobacterial diseases due to complete IFNgammaR2 deficiency

Summary

autosomal recessive Mendelian susceptibility to mycobacterial diseases due to complete IFNgammaR2 deficiency (MONDO:0017900) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		13	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal recessive Mendelian susceptibility to mycobacterial diseases due to complete IFNgammaR2 deficiency
Mondo ID	MONDO:0017900
Orphanet	319547
UMLS	C4303071
MedGen	928740
GARD	0017457
Is cancer (heuristic)	no

Also known as: autosomal recessive mendelian susceptibility to mycobacterial diseases due to a complete deficiency caused by mutation in IFNGR2 · IFNGR2 autosomal recessive mendelian susceptibility to mycobacterial diseases due to a complete deficiency · Mendelian susceptibility to mycobacterial diseases due to complete interferon gamma receptor 2 deficiency · MSMD due to complete IFNgammaR2 deficiency · MSMD due to complete interferon gamma receptor 2 deficiency

Data availability: 1 GenCC gene-disease record.

Disease family

Classification path: disease susceptibility › inherited disease susceptibility › inherited susceptibility to mycobacterial diseases › autosomal recessive Mendelian susceptibility to mycobacterial diseases due to complete IFNgammaR2 deficiency

Related subtypes (13): immunodeficiency 27A, Mendelian susceptibility to mycobacterial diseases due to complete IL12B deficiency, Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 deficiency, Mendelian susceptibility to mycobacterial diseases due to partial STAT1 deficiency, Mendelian susceptibility to mycobacterial diseases due to partial IRF8 deficiency, autosomal dominant mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiency, Mendelian susceptibility to mycobacterial diseases due to complete ISG15 deficiency, autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency, autosomal dominant mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR2 deficiency, X-linked Mendelian susceptibility to mycobacterial diseases, Mendelian susceptibility to mycobacterial diseases due to complete IFNgammaR1 deficiency, Mendelian susceptibility to mycobacterial diseases due to a complete deficiency, Mendelian susceptibility to mycobacterial diseases due to a partial deficiency

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
IFNGR2	Supportive	Autosomal recessive	autosomal recessive Mendelian susceptibility to mycobacterial diseases due to complete IFNgammaR2 deficiency	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
IFNGR2	Orphanet:319547	Mendelian susceptibility to mycobacterial diseases due to complete IFNgammaR2 deficiency
IFNGR2	Orphanet:319574	Autosomal recessive mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR2 deficiency
IFNGR2	Orphanet:319589	Autosomal dominant mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR2 deficiency

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
IFNGR2	HGNC:5440	ENSG00000159128	P38484	Interferon gamma receptor 2	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
IFNGR2	Interferon gamma receptor 2	Associates with IFNGR1 to form a receptor for the cytokine interferon gamma (IFNG).

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
Antibody/Immunoglobulin	1	29.2×	0.034

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
IFNGR2	Antibody/Immunoglobulin	yes		FN3_dom, Ig-like_fold, Interferon/interleukin_rcp_dom

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
blood	1
leukocyte	1
monocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
IFNGR2	144	ubiquitous	marker	monocyte, leukocyte, blood

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
IFNGR2	1,794

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
IFNGR2	P38484	3

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
IFNG signaling activates MAPKs	1	1427.5×	0.007	IFNGR2
Regulation of IFNG signaling	1	815.7×	0.007	IFNGR2
Interferon gamma signaling	1	125.5×	0.019	IFNGR2
Interferon Signaling	1	120.2×	0.019	IFNGR2
Potential therapeutics for SARS	1	114.2×	0.019	IFNGR2
SARS-CoV Infections	1	55.4×	0.033	IFNGR2
Cytokine Signaling in Immune system	1	40.8×	0.039	IFNGR2
Viral Infection Pathways	1	30.8×	0.045	IFNGR2
Infectious disease	1	24.8×	0.049	IFNGR2
Disease	1	13.1×	0.077	IFNGR2
Immune System	1	13.0×	0.077	IFNGR2

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
type III interferon-mediated signaling pathway	1	1532.0×	0.002	IFNGR2
positive regulation of glutamate receptor signaling pathway	1	1532.0×	0.002	IFNGR2
type II interferon-mediated signaling pathway	1	1203.7×	0.002	IFNGR2
microglial cell activation	1	624.1×	0.004	IFNGR2
cellular response to virus	1	200.6×	0.009	IFNGR2
response to virus	1	144.0×	0.010	IFNGR2
cytokine-mediated signaling pathway	1	130.6×	0.010	IFNGR2
defense response to virus	1	69.3×	0.016	IFNGR2
cell surface receptor signaling pathway	1	64.1×	0.016	IFNGR2

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
IFNGR2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	IFNGR2
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)
IFNGR2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.