Herpes simplex encephalitis

Summary

Herpes simplex encephalitis (MONDO:0012521) is a disease with 1 cohort gene and 4 clinical trials. Top therapeutic interventions include dexamethasone.

At a glance

• Prevalence: 1-9 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• Phenotypes (HPO): 30
• Clinical trials: 4

Clinical features

Epidemiology

Prevalence records

3 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Annual incidence	1-9 / 1 000 000	0.3	Worldwide	Validated
Annual incidence	1-9 / 1 000 000	0.3	United Kingdom	Validated
Annual incidence	1-9 / 1 000 000	0.3	United States	Validated

Signs & symptoms

Clinical features (HPO)

30 HPO clinical features (Orphanet curated; top 30 by frequency):

HPO ID	Term	Frequency
HP:0002353	EEG abnormality	Very frequent (80-99%)
HP:0004372	Reduced consciousness/confusion	Very frequent (80-99%)
HP:0012443	Abnormality of brain morphology	Very frequent (80-99%)
HP:0200149	CSF lymphocytic pleiocytosis	Very frequent (80-99%)
HP:0001250	Seizure	Frequent (30-79%)
HP:0001945	Fever	Frequent (30-79%)
HP:0001974	Leukocytosis	Frequent (30-79%)
HP:0002017	Nausea and vomiting	Frequent (30-79%)
HP:0002167	Abnormality of speech or vocalization	Frequent (30-79%)
HP:0002315	Headache	Frequent (30-79%)
HP:0002902	Hyponatremia	Frequent (30-79%)
HP:0002922	Increased CSF protein concentration	Frequent (30-79%)
HP:0004887	Respiratory failure requiring assisted ventilation	Frequent (30-79%)
HP:0007185	Loss of consciousness	Frequent (30-79%)
HP:0011897	Neutrophilia	Frequent (30-79%)
HP:0012378	Fatigue	Frequent (30-79%)
HP:0031179	Nuchal rigidity	Frequent (30-79%)
HP:0001259	Coma	Occasional (5-29%)
HP:0001262	Excessive daytime somnolence	Occasional (5-29%)
HP:0001347	Hyperreflexia	Occasional (5-29%)
HP:0002133	Status epilepticus	Occasional (5-29%)
HP:0002181	Cerebral edema	Occasional (5-29%)
HP:0002349	Focal aware seizure	Occasional (5-29%)
HP:0002384	Focal impaired awareness seizure	Occasional (5-29%)
HP:0002721	Immunodeficiency	Occasional (5-29%)
HP:0004302	Functional motor deficit	Occasional (5-29%)
HP:0011227	Elevated circulating C-reactive protein concentration	Occasional (5-29%)
HP:0011972	Hypoglycorrhachia	Occasional (5-29%)
HP:0025143	Chills	Occasional (5-29%)
HP:0030955	Alcoholism	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	herpes simplex encephalitis
Mondo ID	MONDO:0012521
MeSH	D020803
Orphanet	1930
ICD-11	320069644
NCIT	C84762
UMLS	C0276226
MedGen	75794
GARD	0006649
NORD	1087
Is cancer (heuristic)	no

Also known as: Encephalitis, Herpes Simplex · Herpes simplex meningo-encephalitis · Herpes simplex neuroinvasion · herpetic encephalitis · HSE · HSV encephalitis · HSVE · Simplexvirus caused infectious encephalitis · Simplexvirus infectious encephalitis

Data availability: 1 GenCC gene-disease record · 1 cell line.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of primarily extrinsic mechanism › infectious disease › viral infectious disease › primary viral infectious disease › Herpesviridae infectious disease › herpes simplex infectious disease › herpes simplex encephalitis

Related subtypes (9): herpetic whitlow, herpes simplex dermatitis, genital herpes, herpes simplex virus gingivostomatitis, herpes simplex virus keratitis, congenital herpes simplex virus infection, herpes labialis, herpes simplex type 1 infectious disease, herpes simplex type 2 infectious disease

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: 1 · Orphanet: 0 · 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
GTF3A	Limited	Autosomal recessive	herpes simplex encephalitis

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
GTF3A	HGNC:4662	ENSG00000122034	Q92664	Transcription factor IIIA	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GTF3A	Transcription factor IIIA	Involved in ribosomal large subunit biogenesis.

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)
GTF3A	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_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
gluteal muscle	1
heart right ventricle	1
parotid gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GTF3A	294	ubiquitous	marker	parotid gland, gluteal muscle, heart right ventricle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GTF3A	1,278

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
GTF3A	Q92664	70.42

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. 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
RNA Polymerase III Transcription Initiation From Type 1 Promoter	1	407.9×	0.004	GTF3A
RNA Polymerase III Transcription Initiation	1	335.9×	0.004	GTF3A
RNA Polymerase III Transcription	1	326.3×	0.004	GTF3A
RNA Polymerase III Abortive And Retractive Initiation	1	278.5×	0.004	GTF3A
Gene expression (Transcription)	1	17.8×	0.056	GTF3A

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
rRNA transcription	1	991.3×	0.002	GTF3A
transcription by RNA polymerase III	1	766.0×	0.002	GTF3A
ribosomal large subunit biogenesis	1	443.5×	0.002	GTF3A

Therapeutics

Drugs indicated for this disease

0 approved, 1 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Dexamethasone	Phase 3 (in late-stage trials)

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GTF3A	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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	GTF3A

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)
GTF3A	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 4.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	3
PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03084783	PHASE3	UNKNOWN	Dexamethasone in Herpes Simplex Virus Encephalitis
NCT04339127	Not specified	UNKNOWN	Autoimmune Encephalitis With Anti-NMDA Receptor Antibodies Following Herpetic Encephalitis
NCT05127395	Not specified	COMPLETED	Impact of Obesity on Clinical Outcomes in Patients Receiving Acyclovir for HSV Encephalitis
NCT06627010	Not specified	UNKNOWN	Herpes Simplex Meningo Encephalitis Recurrence

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
DEXAMETHASONE	4	1