Primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection

Summary

Primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection (MONDO:0014715) is a disease caused by STAT2 (GenCC Strong), with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: STAT2 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 523

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

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

Identifiers

Disease identifiers

Field	Value
Canonical name	primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection
Mondo ID	MONDO:0014715
OMIM	616636
Orphanet	431166
DOID	DOID:0111975
UMLS	C4225260
MedGen	904009
GARD	0017711
Is cancer (heuristic)	no

Also known as: IMD44 · immunodeficiency 44 · immunodeficiency type 44 · primary immunodeficiency with post-MMR vaccine viral infection

Data availability: 523 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › immune system disorder › inborn error of immunity › primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection

Related subtypes (40): B cell deficiency, complement deficiency, phagocyte bactericidal dysfunction, trichohepatoenteric syndrome, hepatic veno-occlusive disease-immunodeficiency syndrome, immunodeficiency with defective T-cell response to interleukin 1, Say-Barber-Miller syndrome, familial isolated congenital asplenia, X-linked immunoneurologic disorder, ectodermal dysplasia and immune deficiency, immunodeficiency 33, immunodeficiency 47, combined immunodeficiency due to moesin deficiency, immunodeficiency, X-linked, with deficiency of 115,000 Dalton surface glycoprotein, properdin deficiency, X-linked, combined immunodeficiency with faciooculoskeletal anomalies, recurrent infections associated with rare immunoglobulin isotypes deficiency, immunodeficiency 28, autosomal recessive primary immunodeficiency with defective spontaneous natural killer cell cytotoxicity, immunodeficiency 37, immunodeficiency 39, BENTA disease, immunodeficiency 49, chronic mucocutaneous candidiasis, hereditary hemophagocytic lymphohistiocytosis, immunoglobulin heavy chain deficiency, immuno-osseous dysplasia, lymphoproliferative syndrome, IL10-related early-onset inflammatory bowel disease, T-cell immunodeficiency with epidermodysplasia verruciformis, Aicardi-Goutieres syndrome, immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections-lymphopenia syndrome, inflammatory bowel disease-recurrent sinopulmonary infections syndrome, A20 haploinsufficiency, NK cell deficiency, T cell and NK cell immunodeficiency, dendritic cell deficiency, immunodysregulation with variable immunodeficiency and autoimmunity, immune dysregulation with immunodeficiency due to AIOLOS haploinsufficiency, STAT5 haploinsufficiency

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

523 retrieved; paginated sample, class counts are floors:

262 likely benign, 207 uncertain significance, 29 pathogenic, 9 benign, 7 conflicting classifications of pathogenicity, 5 benign/likely benign, 3 likely pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
976791	NM_207585.3(IFNAR2):c.555_559del (p.Ile185fs)	IFNAR2	Pathogenic	criteria provided, multiple submitters, no conflicts
977219	NM_207585.3(IFNAR2):c.236del (p.Asp78_Leu79insTer)	IFNAR2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1028887	NM_005419.4(STAT2):c.820C>T (p.Gln274Ter)	STAT2	Pathogenic	criteria provided, multiple submitters, no conflicts
1360363	NM_005419.4(STAT2):c.676dup (p.Thr226fs)	STAT2	Pathogenic	criteria provided, single submitter
1451222	NM_005419.4(STAT2):c.667C>T (p.Arg223Ter)	STAT2	Pathogenic	criteria provided, single submitter
1451841	NM_005419.4(STAT2):c.124C>T (p.Gln42Ter)	STAT2	Pathogenic	criteria provided, single submitter
1452515	NM_005419.4(STAT2):c.1580del (p.Gln527fs)	STAT2	Pathogenic	criteria provided, single submitter
1453231	NM_005419.4(STAT2):c.1528C>T (p.Arg510Ter)	STAT2	Pathogenic	criteria provided, single submitter
1453440	NM_005419.4(STAT2):c.1826del (p.Gly609fs)	STAT2	Pathogenic	criteria provided, single submitter
1455233	NM_005419.4(STAT2):c.1852C>T (p.Gln618Ter)	STAT2	Pathogenic	criteria provided, single submitter
1457429	NM_005419.4(STAT2):c.1467dup (p.Lys490fs)	STAT2	Pathogenic	criteria provided, single submitter
2137378	NM_005419.4(STAT2):c.1576G>A (p.Gly526Arg)	STAT2	Pathogenic	criteria provided, single submitter
218140	NM_005419.4(STAT2):c.381+5G>C	STAT2	Pathogenic	no assertion criteria provided
218141	NM_005419.4(STAT2):c.1836C>A (p.Cys612Ter)	STAT2	Pathogenic	no assertion criteria provided
2190527	NM_005419.4(STAT2):c.403G>T (p.Glu135Ter)	STAT2	Pathogenic	criteria provided, single submitter
2728515	NM_005419.4(STAT2):c.1728_1734dup (p.Gly579fs)	STAT2	Pathogenic	criteria provided, single submitter
2753872	NM_005419.4(STAT2):c.1658del (p.Phe553fs)	STAT2	Pathogenic	criteria provided, single submitter
2787614	NM_005419.4(STAT2):c.1630C>T (p.Arg544Ter)	STAT2	Pathogenic	criteria provided, single submitter
2791440	NM_005419.4(STAT2):c.2266del (p.Glu756fs)	STAT2	Pathogenic	criteria provided, single submitter
2798041	NM_005419.4(STAT2):c.778del (p.Thr260fs)	STAT2	Pathogenic	criteria provided, single submitter
2831685	NM_005419.4(STAT2):c.1180C>T (p.Gln394Ter)	STAT2	Pathogenic	criteria provided, single submitter
2832802	NM_005419.4(STAT2):c.2197del (p.Leu733fs)	STAT2	Pathogenic	criteria provided, single submitter
3605839	NM_005419.4(STAT2):c.94C>T (p.Arg32Ter)	STAT2	Pathogenic	criteria provided, single submitter
4386842	NM_005419.4(STAT2):c.633+2T>C	STAT2	Pathogenic	criteria provided, single submitter
4722763	NM_005419.4(STAT2):c.171_172insT (p.Met58fs)	STAT2	Pathogenic	criteria provided, single submitter
4748275	NM_005419.4(STAT2):c.1467del (p.Lys490fs)	STAT2	Pathogenic	criteria provided, single submitter
4765527	NM_005419.4(STAT2):c.1027C>T (p.Arg343Ter)	STAT2	Pathogenic	criteria provided, single submitter
578415	NM_005419.4(STAT2):c.1999C>T (p.Arg667Ter)	STAT2	Pathogenic	criteria provided, single submitter
663294	NM_005419.4(STAT2):c.1209+1del	STAT2	Pathogenic	criteria provided, single submitter
966700	NM_005419.4(STAT2):c.1791del (p.Leu599fs)	STAT2	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 2 · 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
STAT2	Strong	Autosomal recessive	primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
STAT2	Orphanet:431166	Primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection
IFNAR2	Orphanet:431166	Primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
STAT2	HGNC:11363	ENSG00000170581	P52630	Signal transducer and activator of transcription 2	gencc,clinvar
IFNAR2	HGNC:5433	ENSG00000159110	P48551	Interferon alpha/beta receptor 2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
STAT2	Signal transducer and activator of transcription 2	Signal transducer and activator of transcription that mediates signaling by type I interferons (IFN-alpha and IFN-beta).
IFNAR2	Interferon alpha/beta receptor 2	Together with IFNAR1, forms the heterodimeric receptor for type I interferons (including interferons alpha, beta, epsilon, omega and kappa).

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.5

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	14.6×	0.135
Transcription factor	1	4.1×	0.228

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
STAT2	Transcription factor	no		SH2, STAT, p53-like_TF_DNA-bd_sf
IFNAR2	Antibody/Immunoglobulin	yes		FN3_dom, Ig-like_fold, Interferon/interleukin_rcp_dom

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
monocyte	2
granulocyte	1
stromal cell of endometrium	1
blood	1
leukocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
STAT2	277	ubiquitous	marker	granulocyte, stromal cell of endometrium, monocyte
IFNAR2	275	ubiquitous	marker	blood, monocyte, leukocyte

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
STAT2	2,770
IFNAR2	2,159

Intra-cohort edges

A	B	Sources
IFNAR2	STAT2	biogrid_interaction, intact, string_interaction

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
IFNAR2	P48551	9
STAT2	P52630	6

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 19. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Regulation of IFNA/IFNB signaling	2	439.2×	9e-05	STAT2, IFNAR2
Evasion by RSV of host interferon responses	2	326.3×	9e-05	STAT2, IFNAR2
Interferon alpha/beta signaling	2	152.3×	3e-04	STAT2, IFNAR2
Potential therapeutics for SARS	2	114.2×	4e-04	STAT2, IFNAR2
SARS-CoV-2 activates/modulates innate and adaptive immune responses	2	89.2×	5e-04	STAT2, IFNAR2
Interleukin-20 family signaling	1	211.5×	0.015	STAT2
Dengue virus activates/modulates innate and adaptive immune responses	1	167.9×	0.016	STAT2
Respiratory Syncytial Virus Infection Pathway	1	98.5×	0.024	STAT2
RSV-host interactions	1	78.2×	0.027	STAT2
Interferon Signaling	1	60.1×	0.029	STAT2
SARS-CoV-2-host interactions	1	59.5×	0.029	STAT2
SARS-CoV-2 Infection	1	40.2×	0.039	STAT2
Signaling by Interleukins	1	32.1×	0.045	STAT2
SARS-CoV Infections	1	27.7×	0.049	STAT2
Cytokine Signaling in Immune system	1	20.4×	0.061	STAT2
Viral Infection Pathways	1	15.4×	0.076	STAT2
Infectious disease	1	12.4×	0.088	STAT2
Disease	1	6.5×	0.148	STAT2
Immune System	1	6.5×	0.148	STAT2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
type I interferon-mediated signaling pathway	2	343.9×	1e-04	STAT2, IFNAR2
cell surface receptor signaling pathway via JAK-STAT	2	290.6×	1e-04	STAT2, IFNAR2
defense response to virus	2	69.3×	0.001	STAT2, IFNAR2
regulation of mitochondrial fission	1	1053.2×	0.004	STAT2
response to interferon-alpha	1	842.6×	0.004	IFNAR2
response to interferon-beta	1	766.0×	0.004	IFNAR2
regulation of protein phosphorylation	1	561.7×	0.004	STAT2
negative regulation of type I interferon-mediated signaling pathway	1	383.0×	0.006	STAT2
cellular response to interferon-beta	1	263.3×	0.007	IFNAR2
response to peptide hormone	1	195.9×	0.009	STAT2
defense response	1	108.0×	0.014	STAT2
cellular response to virus	1	100.3×	0.014	IFNAR2
response to virus	1	72.0×	0.018	IFNAR2
regulation of cell population proliferation	1	57.7×	0.021	STAT2
cell surface receptor signaling pathway	1	32.0×	0.035	IFNAR2
positive regulation of transcription by RNA polymerase II	1	7.4×	0.138	STAT2
regulation of transcription by RNA polymerase II	1	5.8×	0.164	STAT2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 2 of 2 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
STAT2	0	0
IFNAR2	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
STAT2	24	Binding:24

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	IFNAR2
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	STAT2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
STAT2	24	—
IFNAR2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.