Infectious meningitis

Summary

Infectious meningitis (MONDO:0004796) is a disease (an umbrella term covering 5 Mondo subtypes) with 1 cohort gene (7 GWAS associations across 5 studies).

At a glance

• Umbrella term: 5 Mondo subtypes
• Cohort genes: 1
• GWAS associations: 7

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	infectious meningitis
Mondo ID	MONDO:0004796
EFO	EFO:0000584
DOID	DOID:9471
NCIT	C79598
SNOMED CT	312216007
UMLS	C0729584
MedGen	152668
GARD	0024106
Is cancer (heuristic)	no

Also known as: infectious meningitis · infective meningitis

Data availability: 7 GWAS associations (5 studies) · 1 GenCC gene-disease record · 1 HPO phenotype.

Disease family

An umbrella term covering 5 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › encephalomyelitis › meningitis › infectious meningitis

Related subtypes (3): chronic meningitis, aseptic meningitis, non-infectious meningitis

Subtypes (5): bacterial meningitis, fungal meningitis, viral meningitis, arachnoiditis, meningitis caused by poliovirus

Genetics & variants

GWAS landscape

7 GWAS associations across 5 studies. Top hits map to 2 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs182754811	1e-12	MARK2P13 - EEPD1	C	3.85
rs543029525	3e-12	NRP2	G	2.51
rs377608659	1e-11	RPL7AP27 - ICE2P1	C	2.11
rs1325047820	1e-11	LINC02620 - SORCS3	G	3.31
rs375194115	2e-11	RNU7-51P - RNU6ATAC28P	G	3.27
rs190161374	2e-11	RIN3	G	3.62
rs575896748	2e-11	PKMYT1 - GREP1	T	3.48

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90477476	Verma A	2024	872	449,485	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90435894	Zhou W	2018	441	407,888	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90479995	Verma A	2024	308	121,301	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90481852	Verma A	2024	308	121,301	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90473299	UK Biobank Whole-Genome Sequencing Consortium	2025	220	458,220	Whole-genome sequencing of 490,640 UK Biobank participants.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	0
Tier 3: regulatory	0
Tier 4: intronic/intergenic	7

MAF distribution

Bucket	Variants
common (>=0.05)	0
low_freq (0.01-0.05)	0
rare (<0.01)	7
unknown	0

Functional consequences

Consequence	Count
intron_variant	4
intergenic_variant	2
non_coding_transcript_exon_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs182754811	7	36147182	C>A	0	non_coding_transcript_exon_variant	MARK2P13 - EEPD1	1e-12	Tier 4: intronic/intergenic
rs543029525	2	205775091	G>A	0.001	intron_variant	NRP2	3e-12	Tier 4: intronic/intergenic
rs377608659	4	188382452	C>T	0.001	intron_variant	RPL7AP27 - ICE2P1	1e-11	Tier 4: intronic/intergenic
rs1325047820	10	104630955	G>A,C	0	intergenic_variant	LINC02620 - SORCS3	1e-11	Tier 4: intronic/intergenic
rs375194115	14	83436216	G>A,T	0	intergenic_variant	RNU7-51P - RNU6ATAC28P	2e-11	Tier 4: intronic/intergenic
rs190161374	14	92550005	G>A	0	intron_variant	RIN3	2e-11	Tier 4: intronic/intergenic
rs575896748	16	2982040	T>C,G	0	intron_variant	PKMYT1 - GREP1	2e-11	Tier 4: intronic/intergenic

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
ATG4A	Limited	X-linked	infectious meningitis

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
ATG4A	HGNC:16489	ENSG00000101844	Q8WYN0	Cysteine protease ATG4A	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ATG4A	Cysteine protease ATG4A	Cysteine protease that plays a key role in autophagy by mediating both proteolytic activation and delipidation of ATG8 family proteins.

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
Protease	1	36.6×	0.027

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ATG4A	Protease	yes		Peptidase_C54, Papain-like_cys_pep_sf, Peptidase_C54_cat

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
body of pancreas	1
gastrocnemius	1
hindlimb stylopod muscle	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ATG4A	272	ubiquitous	marker	body of pancreas, gastrocnemius, hindlimb stylopod muscle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ATG4A	1,161

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ATG4A	Q8WYN0	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
Autophagy	1	148.3×	0.009	ATG4A
Macroautophagy	1	115.3×	0.009	ATG4A

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
protein delipidation	1	3370.4×	0.003	ATG4A
aggrephagy	1	1685.2×	0.003	ATG4A
piecemeal microautophagy of the nucleus	1	936.2×	0.004	ATG4A
mitophagy	1	318.0×	0.008	ATG4A
autophagosome assembly	1	224.7×	0.009	ATG4A
protein processing	1	170.2×	0.010	ATG4A
autophagy	1	110.1×	0.013	ATG4A
lipid metabolic process	1	91.6×	0.014	ATG4A
protein transport	1	43.9×	0.025	ATG4A
proteolysis	1	34.2×	0.029	ATG4A

Therapeutics

Drugs indicated for this disease

5 approved. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Ampicillin	Approved (phase 4)
Flucytosine	Approved (phase 4)
Meropenem	Approved (phase 4)
Neisseria Meningitidis Factor H Binding Protein	Approved (phase 4)
Penicillin V	Approved (phase 4)

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
ATG4A	TIOCONAZOLE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ATG4A	1	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
TIOCONAZOLE	4	ATG4A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
ATG4A	1	Binding:1

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

1 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.

Compound	Max phase	Cohort target (bioactivity)
TIOCONAZOLE	4	ATG4A

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	ATG4A
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.