Meningococcal infection

Summary

Meningococcal infection (MONDO:0005373) is a disease with 2 cohort genes (1 GWAS associations across 1 studies) and 132 clinical trials. Top therapeutic interventions include sodium chloride, hepatitis b virus hbsag surface protein antigen, and neisseria meningitidis oligosaccharide conjugated to corynebacterium diphtheriae crm197.

At a glance

• Cohort genes: 2
• GWAS associations: 1
• Clinical trials: 132

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	meningococcal infection
Mondo ID	MONDO:0005373
EFO	EFO:0004249
MeSH	D008589
ICD-10-CM	A39
SNOMED CT	23511006
UMLS	C0025303
MedGen	7537
GARD	0009547
Is cancer (heuristic)	no

Also known as: infections, Neisseria meningitidis · meningococcal disease · Neisseria meningitidis infection

Data availability: 1 GWAS association (1 study).

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of primarily extrinsic mechanism › infectious disease › bacterial infectious disease › meningococcal infection

Related subtypes (51): primary bacterial infectious disease, commensal bacterial infectious disease, opportunistic bacterial infectious disease, chorioamnionitis, Clostridium difficile colitis, bacterial gastritis, bacterial arthritis, bacterial pneumonia, Whipple disease, Aeromonas hydrophila infectious disease, Pectobacterium carotovorum infection, Pseudomonas infection, septic peritonitis, bacterial infectious disease with sepsis, empyema, bacterial urinary tract infection, bacterial sexually transmitted disease, pasteurellosis, peritonsillar abscess, pneumonic pasteurellosis, tracheitis, Actinobacillus infectious disease, bacterial conjunctivitis, bacterial endocarditis, bacterial meningitis, Bifidobacteriales infectious disease, haemophilus infectious disease, Proteus infectious disease, pulpitis, rat-bite fever, Rickettsiosis, vibrio infectious disease, Yersinia infectious disease, bacterial myositis, noma, idiopathic severe pneumococcemia, necrotizing soft tissue infection, mycobacterial infectious disease, escherichia coli infection, gram-negative bacterial infections, gram-positive bacterial infections, spirochaetales infections, skin disease caused by bacterial infection, staphylococcal infection, anaerobic bacteria infectious disease, Klebsiella infectious disease, fournier gangrene, botryomycosis, bacterial hemorrhagic fever, Mycoplasmoides infection, Enterococcus infectious disease

Subtypes (2): meningococcal meningitis, meningococcemia

Genetics & variants

GWAS landscape

1 GWAS associations across 1 studies. Top hits map to 1 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs426736	5e-13	CFHR3	?	1.59

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST000762	Davila S	2010	475	4,703	Genome-wide association study identifies variants in the CFH region associated with host susceptibility to meningococcal disease.

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	1

MAF distribution

Bucket	Variants
common (>=0.05)	1
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	0

Functional consequences

Consequence	Count
intron_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs426736	1	196791287	A>G,T	0.16	intron_variant	CFHR3	5e-13	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 8 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CFHR3	Orphanet:329931	C3 glomerulonephritis
CFH	Orphanet:200421	Immunodeficiency with factor H anomaly
CFH	Orphanet:244242	HELLP syndrome
CFH	Orphanet:244275	De novo thrombotic microangiopathy after kidney transplantation
CFH	Orphanet:329903	Immunoglobulin-mediated membranoproliferative glomerulonephritis
CFH	Orphanet:544472	Atypical hemolytic uremic syndrome with complement gene abnormality
CFH	Orphanet:75376	Familial drusen
CFH	Orphanet:93571	Dense deposit disease

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CFHR3	HGNC:16980	ENSG00000116785	Q02985	Complement factor H-related protein 3	gwas
CFH	HGNC:4883	ENSG00000000971	P08603	Complement factor H	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CFHR3	Complement factor H-related protein 3	Might be involved in complement regulation.
CFH	Complement factor H	Glycoprotein that plays an essential role in maintaining a well-balanced immune response by modulating complement activation.

Protein-family classification

Druggable: 2 · 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
Complement	2	268.0×	1e-05

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CFHR3	Complement	yes		Sushi_SCR_CCP_dom, Sushi/SCR/CCP_sf, ComplSys_Reg/VirEntry_Med
CFH	Complement	yes		Sushi_SCR_CCP_dom, Sushi/SCR/CCP_sf, ComplSys_Reg/VirEntry_Med

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
liver	1
male germ line stem cell (sensu Vertebrata) in testis	1
right lobe of liver	1
calcaneal tendon	1
right coronary artery	1
urethra	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CFHR3	127	tissue_specific	marker	right lobe of liver, liver, male germ line stem cell (sensu Vertebrata) in testis
CFH	267	ubiquitous	marker	urethra, calcaneal tendon, right coronary artery

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CFH	1,844
CFHR3	373

Intra-cohort edges

A	B	Sources
CFH	CFHR3	biogrid_interaction, intact

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CFH	P08603	51

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CFHR3	Q02985	91.93

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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 Complement cascade	2	233.1×	2e-05	CFHR3, CFH

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
complement activation	2	624.1×	2e-05	CFHR3, CFH
regulation of complement activation, alternative pathway	1	4213.0×	9e-04	CFH
regulation of complement-dependent cytotoxicity	1	1685.2×	0.002	CFH
regulation of complement activation	1	1053.2×	0.002	CFH
complement activation, alternative pathway	1	495.6×	0.003	CFH
central nervous system myelination	1	495.6×	0.003	CFH
inflammatory response	1	18.9×	0.058	CFH
proteolysis	1	17.1×	0.058	CFH

Therapeutics

Drugs indicated for this disease

0 approved, 10 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Diphtheria Toxoid	Phase 3 (in late-stage trials)
HAEMOPHILUS INFLUENZAE TYPE B STRAIN 20752 CAPSULAR POLYSACCHARIDE TETANUS TOXOID CONJUGATE ANTIGEN	Phase 3 (in late-stage trials)
Hepatitis B Virus Hbsag Surface Protein Antigen	Phase 3 (in late-stage trials)
Measles Virus Vaccine Live	Phase 3 (in late-stage trials)
Meningococcal Polysaccharide Vaccine Group A	Phase 3 (in late-stage trials)
Meningococcal Polysaccharide Vaccine Group C	Phase 3 (in late-stage trials)
Mumps Virus Vaccine Live	Phase 3 (in late-stage trials)
Poliovirus Vaccine Inactivated	Phase 3 (in late-stage trials)
Rubella Virus Vaccine Live	Phase 3 (in late-stage trials)
Tetanus Toxoid	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Sodium Chloride.

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
CFHR3	0	0
CFH	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
CFH	1	Binding:1

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	CFH
D	Druggable family + AlphaFold only, no drug	1	CFHR3
E	Difficult family or no structure, no drug	0

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)
CFHR3	0	—
CFH	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 132.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE3	42
PHASE2	33
Not specified	28
PHASE4	19
PHASE2/PHASE3	4
PHASE1/PHASE2	3
PHASE1	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04875819	PHASE4	RECRUITING	Safety and Immunogenicity Following Meningococcal and Pneumococcal Immunization Among Adult People Living With HIV
NCT00197808	PHASE4	COMPLETED	Response of United Kingdom (UK) Infants to a Reduced Primary Schedule With Meningococcal C and Pneumococcal Conjugate Vaccines
NCT00310635	PHASE4	COMPLETED	Safety, Tolerability and Immunogenicity of Meningococcal C Conjugate Vaccine to Children 32 to 40 Months of Age
NCT00392808	PHASE4	COMPLETED	Immunogenicity of the Booster Dose of Two MenC Vaccines
NCT00625677	PHASE4	COMPLETED	Study to Evaluate the Immune Response of United Kingdom (UK) Infants Receiving DTaP/Hib/IPV, Meningococcal C Conjugate and Pneumococcal Conjugate Vaccines, Antibody Persistence and Responses to Booster Doses in the Second Year of Life
NCT00850603	PHASE4	COMPLETED	Safety and Immunogenicity of Intradermal Versus Subcutaneous Doses of Menomune®
NCT01270503	PHASE4	COMPLETED	Post-Marketing Safety Study of Menactra® in Healthy Children, Adolescents, and Adults in the Philippines
NCT01430611	PHASE4	COMPLETED	Study of Sanofi Pasteur and Lanzhou Institute’s Meningococcal (Group A and C) Polysaccharide Vaccine in Children
NCT01593514	PHASE4	COMPLETED	Understanding the Immune Response to Two Different Meningitis Vaccines
NCT01659996	PHASE4	COMPLETED	Study of Menactra® in Healthy Subjects at 9 Months and Concomitantly With Pentacel® at 15 to 18 Months of Age
NCT01766206	PHASE4	COMPLETED	Safety of One Dose of Meningococcal ACWY Conjugate Vaccine in Subjects From 2 Months to 55 Years of Age in the Republic of South Korea
NCT01823536	PHASE4	COMPLETED	Persistence of Immunogenicity of MenACWY Conjugate Vaccine 5 Years After Childhood Vaccination, and Immune Response to a Booster Dose
NCT01896596	PHASE4	COMPLETED	Hepatitis B Vaccination in Infants
NCT02569632	PHASE4	COMPLETED	Investigating the Immunogenicity of a U.S.-Licensed Meningococcal Serogroup B Vaccine (Trumenba)
NCT02591290	PHASE4	COMPLETED	Immunogenicity and Safety of Two-Dose Series of Menactra® in Japanese Healthy Adult Subjects
NCT02633787	PHASE4	COMPLETED	Persistence of Bactericidal Antibodies in Adults Who Received a Booster Dose of Menactra® Approximately 4 Years Earlier
NCT02864927	PHASE4	COMPLETED	Postmarketing Surveillance Study for Use of Menactra® in the Republic of Korea
NCT03089086	PHASE4	COMPLETED	South Australian Meningococcal B Vaccine Herd Immunity Study
NCT03125616	PHASE4	COMPLETED	Babies Born Early Antibody Response to Men B Vaccination: BEAR Men B
NCT07135986	PHASE3	ACTIVE_NOT_RECRUITING	Immunogenicity and Safety Study of an Investigational Quadrivalent Meningococcal Conjugate Vaccine Administered in Healthy Children and Adolescents in China
NCT07204457	PHASE2/PHASE3	RECRUITING	Immunogenicity and Safety of Meningococcal Conjugate Vaccine (EG-MCV4) in Healthy Adults Aged 19 to 55 Years Old
NCT00329849	PHASE3	COMPLETED	Safety and Immunogenicity of Meningococcal ACWY Conjugate Versus Polysaccharide Vaccine in Children 2 to 10 Years of Age
NCT00329901	PHASE3	COMPLETED	Immunogenicity and Safety of the Concomitant Administration of a Tdap Vaccine and Meningococcal ACWY Conjugate Vaccine in Healthy Subjects Aged 11-25 Years
NCT00444951	PHASE3	COMPLETED	Immunogenicity and Safety of Menactra® Vaccine in Adolescents in Saudi Arabia
NCT00450437	PHASE3	COMPLETED	A Study to Evaluate Safety and Immune Response of Novartis Meningococcal ACWY Conjugate Vaccine In US Adolescents and Adults
NCT00474487	PHASE3	COMPLETED	A Study to Evaluate Safety and Immune Response of Novartis Meningococcal ACWY Vaccine In Healthy Adults
NCT00616421	PHASE3	COMPLETED	Safety and Immune Response of Novartis of MenACWY Conjugate Vaccine When Given to Healthy Children
NCT00626327	PHASE3	COMPLETED	Safety and Immune Response of Novartis MenACWY-CRM Conjugate Vaccine When Given to Healthy Toddlers
NCT00661713	PHASE2/PHASE3	COMPLETED	Safety, Tolerability and Immunogenicity of Novartis Meningococcal B Recombinant Vaccine Administered to Healthy Adolescents According to Different Vaccination Schedules
NCT00806195	PHASE3	COMPLETED	Study to Evaluate the Safety of Novartis MenACWY Conjugate Vaccine When Administered With Routine Infant Vaccinations to Healthy Infants
NCT00847145	PHASE3	COMPLETED	Extension Study of V72P13 to Evaluate the Safety, Tolerability and Immunogenicity of Novartis Meningococcal B Recombinant Vaccine When Administered as a Booster or as a Two-dose Catch-up to Healthy Toddlers
NCT00944034	PHASE2/PHASE3	COMPLETED	Safety, Tolerability and Immunogenicity of Meningococcal B Recombinant Vaccine Administered as Booster Dose at 12, 18 or 24 Months of Age in Toddlers (12-24 Months) Primed With a Three-Dose Immunization Series as Infants in Study V72P12
NCT01000311	PHASE3	COMPLETED	A Study to Evaluate the Safety and Immunogenicity of 4 Doses of MenACWY Conjugate Vaccine, Administered Concomitantly With Routine Vaccines, Among Infants Aged 2 Months
NCT01086969	PHASE3	COMPLETED	A Study of Meningococcal Vaccine, Menactra® in Healthy Subjects in India
NCT01139021	PHASE3	COMPLETED	One Year Antibody Persistence After a Fourth Dose Boost or Two Catch-Up Doses of Novartis Meningococcal B Recombinant Vaccine Administered Starting From 12 Months of Age and Response to a Third Dose Boost or Two Catch-Up Doses Starting at 24 Months of Age
NCT01148524	PHASE2/PHASE3	COMPLETED	Assessment of Antibody Persistence at Eighteen Months After the Completion of the Vaccination Course in Study V72P10
NCT01214837	PHASE3	COMPLETED	Safety and Immunogenicity of 2 or 3 Doses of MenACWY Conjugate Vaccine in Healthy Infants and the Effects of a Booster Dose of MenACWY Administered in the Second Year of Life
NCT01274897	PHASE3	COMPLETED	A Multi-center, Observer-blind, Placebo-controlled, Randomized Study to Evaluate the Immunogenicity and Safety of MenACWY in Adolescents and Adults in Korea
NCT01339923	PHASE3	COMPLETED	A Phase 3B, Open Label, Multi-Center Study to Evaluate the Safety, Tolerability and Immunogenicity of Novartis Meningococcal B Recombinant Vaccine When Administered Alone to Healthy Infants According to Different Immunization Schedules and to Healthy Children Aged 2 to 10 Years
NCT01340898	PHASE3	COMPLETED	Immunogenicity and Safety Study of GSK Biologicals’ Meningococcal Conjugate Vaccine When Co-administered With Routine Vaccines in Healthy Infants and Toddlers

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
SODIUM CHLORIDE	4	3
HEPATITIS B VIRUS HBSAG SURFACE PROTEIN ANTIGEN	4	1
NEISSERIA MENINGITIDIS OLIGOSACCHARIDE CONJUGATED TO CORYNEBACTERIUM DIPHTHERIAE CRM197	4	1
RABIES VACCINE	3	1
RUBELLA VIRUS VACCINE LIVE	3	1
SALMONELLA TYPHI TY2 VI POLYSACCHARIDE ANTIGEN	3	1
TYPHOID VI POLYSACCHARIDE VACCINE	3	1
YELLOW FEVER VACCINE	3	1