pseudo-TORCH syndrome 3

Summary

pseudo-TORCH syndrome 3 (MONDO:0030044) is a disease caused by STAT2 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: STAT2 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 6

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	pseudo-TORCH syndrome 3
Mondo ID	MONDO:0030044
OMIM	618886
UMLS	C5394391
MedGen	1708513
GARD	0025516
Is cancer (heuristic)	no

Also known as: PSEUDO-TORCH SYNDROME 3 · pseudo-torch syndrome 3 · PTORCH3

Data availability: 6 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal recessive disease › pseudo-TORCH syndrome › pseudo-TORCH syndrome 3

Related subtypes (2): pseudo-TORCH syndrome 2, pseudo-TORCH syndrome 1

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

6 retrieved; paginated sample, class counts are floors:

4 uncertain significance, 1 conflicting classifications of pathogenicity, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
973175	NM_005419.4(STAT2):c.442C>T (p.Arg148Trp)	STAT2	Pathogenic	no assertion criteria provided
907069	NM_005419.4(STAT2):c.443G>A (p.Arg148Gln)	STAT2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2671942	NM_005419.4(STAT2):c.1034G>A (p.Arg345Lys)	STAT2	Uncertain significance	criteria provided, single submitter
3575001	NM_005419.4(STAT2):c.1121G>A (p.Arg374Gln)	STAT2	Uncertain significance	criteria provided, single submitter
626024	NM_005419.4(STAT2):c.34A>G (p.Ser12Gly)	STAT2	Uncertain significance	criteria provided, multiple submitters, no conflicts
860056	NM_005419.4(STAT2):c.2000G>A (p.Arg667Gln)	STAT2	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 1 · 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	pseudo-TORCH syndrome 3	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

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
STAT2	HGNC:11363	ENSG00000170581	P52630	Signal transducer and activator of transcription 2	gencc,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).

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
STAT2	Transcription factor	no		SH2, STAT, p53-like_TF_DNA-bd_sf

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
monocyte	1
stromal cell of endometrium	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

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
STAT2	2,770

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
STAT2	P52630	6

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 19. 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
Regulation of IFNA/IFNB signaling	1	439.2×	0.015	STAT2
Interleukin-20 family signaling	1	423.0×	0.015	STAT2
Dengue virus activates/modulates innate and adaptive immune responses	1	335.9×	0.015	STAT2
Evasion by RSV of host interferon responses	1	326.3×	0.015	STAT2
Respiratory Syncytial Virus Infection Pathway	1	196.9×	0.017	STAT2
RSV-host interactions	1	156.4×	0.017	STAT2
Interferon alpha/beta signaling	1	152.3×	0.017	STAT2
Interferon Signaling	1	120.2×	0.017	STAT2
SARS-CoV-2-host interactions	1	119.0×	0.017	STAT2
Potential therapeutics for SARS	1	114.2×	0.017	STAT2
SARS-CoV-2 activates/modulates innate and adaptive immune responses	1	89.2×	0.019	STAT2
SARS-CoV-2 Infection	1	80.4×	0.020	STAT2
Signaling by Interleukins	1	64.2×	0.023	STAT2
SARS-CoV Infections	1	55.4×	0.024	STAT2
Cytokine Signaling in Immune system	1	40.8×	0.031	STAT2
Viral Infection Pathways	1	30.8×	0.039	STAT2
Infectious disease	1	24.8×	0.045	STAT2
Disease	1	13.1×	0.077	STAT2
Immune System	1	13.0×	0.077	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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of mitochondrial fission	1	2106.5×	0.005	STAT2
regulation of protein phosphorylation	1	1123.5×	0.005	STAT2
negative regulation of type I interferon-mediated signaling pathway	1	766.0×	0.005	STAT2
response to peptide hormone	1	391.9×	0.006	STAT2
type I interferon-mediated signaling pathway	1	343.9×	0.006	STAT2
cell surface receptor signaling pathway via JAK-STAT	1	290.6×	0.006	STAT2
defense response	1	216.1×	0.007	STAT2
regulation of cell population proliferation	1	115.4×	0.012	STAT2
defense response to virus	1	69.3×	0.018	STAT2
positive regulation of transcription by RNA polymerase II	1	14.9×	0.074	STAT2
regulation of transcription by RNA polymerase II	1	11.7×	0.086	STAT2

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
STAT2	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: 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	STAT2

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)
STAT2	24	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.