Varicella zoster infection

Summary

Varicella zoster infection (MONDO:0005608) is a disease with 2 cohort genes and 12 clinical trials. Top therapeutic interventions include valacyclovir, varicella zoster virus envelope glycoprotein e, and varicella zoster virus, live attenuated.

At a glance

• Cohort genes: 2
• Clinical trials: 12

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	varicella zoster infection
Mondo ID	MONDO:0005608
EFO	EFO:0006509
NCIT	C96407
SNOMED CT	309465005
UMLS	C0586989
MedGen	668886
Is cancer (heuristic)	no

Also known as: varicella zoster infection · Varicella-zoster Virus infection

Data availability: 2 GenCC gene-disease records.

Disease family

An umbrella term covering 4 Mondo subtypes.

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 › varicella zoster infection

Related subtypes (7): herpetic gastritis, herpes simplex infectious disease, Epstein-Barr virus infection, cytomegalovirus infection, human herpesvirus 8 infection, roseolovirus infectious disease, congenital herpes virus infection

Subtypes (4): herpes zoster, chickenpox, herpes zoster dermatitis, herpetic vulvovaginitis

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: 13 · Orphanet: 6 · 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
POLR3A	Moderate	Autosomal dominant	varicella zoster infection	12
POLR3C	Moderate	Autosomal dominant	varicella zoster infection

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
POLR3A	Orphanet:137639	Hypomyelinating leukodystrophy-ataxia-hypodontia-hypomyelination syndrome
POLR3A	Orphanet:3455	Wiedemann-Rautenstrauch syndrome
POLR3A	Orphanet:447893	Hypomyelination-cerebellar atrophy-hypoplasia of the corpus callosum syndrome
POLR3A	Orphanet:447896	Tremor-ataxia-central hypomyelination syndrome
POLR3A	Orphanet:77295	Odontoleukodystrophy
POLR3A	Orphanet:88637	Hypomyelination-hypogonadotropic hypogonadism-hypodontia syndrome

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
POLR3A	HGNC:30074	ENSG00000148606	O14802	DNA-directed RNA polymerase III subunit RPC1	gencc
POLR3C	HGNC:30076	ENSG00000186141	Q9BUI4	DNA-directed RNA polymerase III subunit RPC3	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
POLR3A	DNA-directed RNA polymerase III subunit RPC1	Catalytic core component of RNA polymerase III (Pol III), a DNA-dependent RNA polymerase which synthesizes small non-coding RNAs using the four ribonucleoside triphosphates as substrates.
POLR3C	DNA-directed RNA polymerase III subunit RPC3	DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
POLR3A	Other/Unknown	no		RNA_pol_asu, RNA_pol_N, RNA_pol_Rpb1_3
POLR3C	Other/Unknown	no		RNA_pol_III_Rpc82_C, RNA_pol_III_RPC82-rel_HTH, WH-like_DNA-bd_sf

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
buccal mucosa cell	1
middle temporal gyrus	1
secondary oocyte	1
calcaneal tendon	1
primordial germ cell in gonad	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
POLR3A	242	ubiquitous	marker	buccal mucosa cell, middle temporal gyrus, secondary oocyte
POLR3C	260	ubiquitous	marker	primordial germ cell in gonad, calcaneal tendon, stromal cell of endometrium

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
POLR3A	4,915
POLR3C	2,985

Intra-cohort edges

A	B	Sources
POLR3A	POLR3C	string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
POLR3C	Q9BUI4	32
POLR3A	O14802	29

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 12. 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
RNA Polymerase III Chain Elongation	2	634.4×	1e-05	POLR3A, POLR3C
RNA Polymerase III Transcription Termination	2	496.5×	1e-05	POLR3A, POLR3C
RNA Polymerase III Transcription Initiation From Type 2 Promoter	2	423.0×	1e-05	POLR3A, POLR3C
RNA Polymerase III Transcription Initiation From Type 1 Promoter	2	407.9×	1e-05	POLR3A, POLR3C
RNA Polymerase III Transcription Initiation From Type 3 Promoter	2	407.9×	1e-05	POLR3A, POLR3C
RNA Polymerase III Transcription Initiation	2	335.9×	2e-05	POLR3A, POLR3C
RNA Polymerase III Transcription	2	326.3×	2e-05	POLR3A, POLR3C
Cytosolic sensors of pathogen-associated DNA	2	285.5×	2e-05	POLR3A, POLR3C
RNA Polymerase III Abortive And Retractive Initiation	2	278.5×	2e-05	POLR3A, POLR3C
Innate Immune System	2	25.5×	0.002	POLR3A, POLR3C
Gene expression (Transcription)	2	17.8×	0.003	POLR3A, POLR3C
Immune System	2	13.0×	0.006	POLR3A, POLR3C

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
positive regulation of interferon-beta production	2	391.9×	4e-05	POLR3A, POLR3C
DNA-templated transcription	2	224.7×	7e-05	POLR3A, POLR3C
defense response to virus	2	69.3×	5e-04	POLR3A, POLR3C
regulation of transcription by RNA polymerase III	1	842.6×	0.002	POLR3C
tRNA transcription by RNA polymerase III	1	766.0×	0.002	POLR3A
innate immune response	2	33.6×	0.002	POLR3A, POLR3C
positive regulation of innate immune response	1	263.3×	0.004	POLR3C

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
POLR3A	0	0
POLR3C	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	POLR3A, POLR3C

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)
POLR3A	0	—
POLR3C	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 12.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	7
PHASE4	2
PHASE1	2
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04403139	PHASE4	ACTIVE_NOT_RECRUITING	VZV-specific Tissue Resident Memory T-cells After Shingrix Vaccination
NCT01682109	PHASE4	COMPLETED	Palatability Testing of a New Paediatric Formulation of Valacyclovir
NCT02329457	PHASE2/PHASE3	COMPLETED	VZV Vaccine for Hematopoietic Stem Cell Transplantation
NCT06409494	PHASE1	ACTIVE_NOT_RECRUITING	Clinical Trial to Evaluate EuHZV in Healthy Adults Aged 50 to 69 Years
NCT01689285	PHASE1	COMPLETED	Bioequivalence Study in Healthy Volunteers of a New Paediatric Formulation of Valacyclovir
NCT05198570	Not specified	RECRUITING	Pharmacokinetics of Intravenous Acyclovir in Oncologic Paediatric Patients
NCT05532540	Not specified	ACTIVE_NOT_RECRUITING	Herpesvirus Immunology in Solid Organ Transplant Recipients - Liver Transplant Study
NCT05604911	Not specified	ACTIVE_NOT_RECRUITING	Herpes Virus Infections in Kidney Transplant Patients
NCT02715752	Not specified	COMPLETED	A Retrospective Chart Review Study of Gene-Eden-VIR/Novirin
NCT03509701	Not specified	UNKNOWN	Reversible Cerebral Vasoconstriction Syndrome and Varicella Zoster Virus
NCT04081480	Not specified	TERMINATED	Pharmacokinetics of Valacyclovir Oral Solution in Children
NCT05664152	Not specified	UNKNOWN	An Open-label, Bridging Study of BARYCELA Inj. in Healthy Vietnamese Children Aged Between 12 Months to 12 Years

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
VALACYCLOVIR	4	3
VARICELLA ZOSTER VIRUS ENVELOPE GLYCOPROTEIN E	4	2
VARICELLA ZOSTER VIRUS, LIVE ATTENUATED	4	1