autosomal dominant mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiency

disease

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Also known as autosomal dominant mendelian susceptibility to mycobacterial diseases due to a partial deficiency caused by mutation in IFNGR1autosomal dominant mendelian susceptibility to mycobacterial diseases due to partial interferon gamma receptor 1 deficiencyautosomal dominant MSMD due to partial IFNgammaR1 deficiencyautosomal dominant MSMD due to partial interferon gamma receptor 1 deficiencyIFNGR1 autosomal dominant mendelian susceptibility to mycobacterial diseases due to a partial deficiencyIFNGR1 deficiency, autosomal dominantIMD27Bimmunodeficiency 27Bimmunodeficiency 27B, mycobacteriosis, ADimmunodeficiency 27B, Mycobacteriosis, autosomal dominantimmunodeficiency type 27B

Summary

autosomal dominant mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiency (MONDO:0014429) is a disease caused by IFNGR1 (GenCC Definitive), with 1 cohort gene.

At a glance

Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
Causal gene: IFNGR1 (GenCC Definitive)
Cohort genes: 1
ClinVar variants: 12

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		68	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal dominant mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiency
Mondo ID	MONDO:0014429
OMIM	615978
Orphanet	319581
DOID	DOID:0111956
UMLS	C4014863
MedGen	863300
GARD	0017461
Is cancer (heuristic)	no

Also known as: autosomal dominant mendelian susceptibility to mycobacterial diseases due to a partial deficiency caused by mutation in IFNGR1 · autosomal dominant mendelian susceptibility to mycobacterial diseases due to partial interferon gamma receptor 1 deficiency · autosomal dominant MSMD due to partial IFNgammaR1 deficiency · autosomal dominant MSMD due to partial interferon gamma receptor 1 deficiency · IFNGR1 autosomal dominant mendelian susceptibility to mycobacterial diseases due to a partial deficiency · IFNGR1 deficiency, autosomal dominant · IMD27B · immunodeficiency 27B · immunodeficiency 27B, mycobacteriosis, AD · immunodeficiency 27B, Mycobacteriosis, autosomal dominant · immunodeficiency type 27B

Data availability: 12 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease susceptibility › inherited disease susceptibility › inherited susceptibility to mycobacterial diseases › autosomal dominant mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 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

ClinVar germline variants

12 retrieved; paginated sample, class counts are floors:

5 uncertain significance, 4 pathogenic, 1 likely benign, 1 benign, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
17947	NM_000416.3(IFNGR1):c.819_822del (p.Asn274fs)	IFNGR1	Pathogenic	criteria provided, multiple submitters, no conflicts
17952	NM_000416.3(IFNGR1):c.819del (p.Asn274fs)	IFNGR1	Pathogenic	no assertion criteria provided
17954	NM_000416.3(IFNGR1):c.794del (p.Phe265fs)	IFNGR1	Pathogenic	no assertion criteria provided
3893292	NM_000416.3(IFNGR1):c.817del (p.Ile273fs)	IFNGR1	Pathogenic	no assertion criteria provided
355560	NM_000416.3(IFNGR1):c.490G>A (p.Glu164Lys)	IFNGR1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3895496	NM_000416.3(IFNGR1):c.1334T>C (p.Leu445Pro)	IFNGR1	Uncertain significance	criteria provided, single submitter
625961	NM_000416.3(IFNGR1):c.665A>G (p.His222Arg)	IFNGR1	Uncertain significance	criteria provided, multiple submitters, no conflicts
644527	NM_000416.3(IFNGR1):c.566C>A (p.Thr189Lys)	IFNGR1	Uncertain significance	criteria provided, multiple submitters, no conflicts
992563	NM_000416.3(IFNGR1):c.974C>T (p.Pro325Leu)	IFNGR1	Uncertain significance	criteria provided, multiple submitters, no conflicts
111209	NM_000416.3(IFNGR1):c.1204_1230dup (p.Cys402_Asn410dup)	IFNGR1	Likely benign	criteria provided, multiple submitters, no conflicts
355562	NM_000416.3(IFNGR1):c.85+10T>C	IFNGR1	Benign	criteria provided, multiple submitters, no conflicts
36371	NM_000416.3(IFNGR1):c.1004A>C (p.His335Pro)	IFNGR1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · Orphanet: 4 · 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
IFNGR1	Definitive	Autosomal dominant	autosomal dominant mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiency	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
IFNGR1	Orphanet:117	Behçet disease
IFNGR1	Orphanet:319569	Autosomal recessive mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiency
IFNGR1	Orphanet:319581	Autosomal dominant mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiency
IFNGR1	Orphanet:99898	Mendelian susceptibility to mycobacterial diseases due to complete IFNgammaR1 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
IFNGR1	HGNC:5439	ENSG00000027697	P15260	Interferon gamma receptor 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
IFNGR1	Interferon gamma receptor 1	Receptor subunit for interferon gamma/INFG that plays crucial roles in antimicrobial, antiviral, and antitumor responses by activating effector immune cells and enhancing antigen presentation.

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)
IFNGR1	Antibody/Immunoglobulin	yes		FN3_dom, Interferon_gamma_rcpt_asu, Ig-like_fold

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
epithelium of nasopharynx	1
lower lobe of lung	1
right lung	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
IFNGR1	295	ubiquitous	marker	lower lobe of lung, epithelium of nasopharynx, right lung

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
IFNGR1	2,353

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
IFNGR1	P15260	5

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	IFNGR1
Regulation of IFNG signaling	1	815.7×	0.007	IFNGR1
Interferon gamma signaling	1	125.5×	0.019	IFNGR1
Interferon Signaling	1	120.2×	0.019	IFNGR1
Potential therapeutics for SARS	1	114.2×	0.019	IFNGR1
SARS-CoV Infections	1	55.4×	0.033	IFNGR1
Cytokine Signaling in Immune system	1	40.8×	0.039	IFNGR1
Viral Infection Pathways	1	30.8×	0.045	IFNGR1
Infectious disease	1	24.8×	0.049	IFNGR1
Disease	1	13.1×	0.077	IFNGR1
Immune System	1	13.0×	0.077	IFNGR1

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of amyloid-beta clearance	1	1685.2×	0.003	IFNGR1
type III interferon-mediated signaling pathway	1	1532.0×	0.003	IFNGR1
type II interferon-mediated signaling pathway	1	1203.7×	0.003	IFNGR1
astrocyte activation	1	991.3×	0.003	IFNGR1
positive regulation of amyloid-beta formation	1	887.0×	0.003	IFNGR1
microglial cell activation	1	624.1×	0.003	IFNGR1
cellular response to virus	1	200.6×	0.009	IFNGR1
positive regulation of tumor necrosis factor production	1	153.2×	0.010	IFNGR1
response to virus	1	144.0×	0.010	IFNGR1
cytokine-mediated signaling pathway	1	130.6×	0.010	IFNGR1
defense response to virus	1	69.3×	0.017	IFNGR1
positive regulation of gene expression	1	38.7×	0.028	IFNGR1
signal transduction	1	16.1×	0.062	IFNGR1

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
IFNGR1	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	IFNGR1
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)
IFNGR1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: IFNGR1