recurrent Neisseria infections due to factor D deficiency

Summary

recurrent Neisseria infections due to factor D deficiency (MONDO:0013487) is a disease caused by CFD (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: CFD (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 10

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	recurrent Neisseria infections due to factor D deficiency
Mondo ID	MONDO:0013487
MeSH	C565027
OMIM	613912
Orphanet	169467
ICD-11	528757185
SNOMED CT	234607008
UMLS	C0398764
MedGen	97989
GARD	0017055
Is cancer (heuristic)	no

Also known as: CFDD · complement factor D deficiency · recurrent Neisseria infections due to factor D deficiency

Data availability: 10 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › immune system disorder › inborn error of immunity › complement deficiency › recurrent Neisseria infections due to factor D deficiency

Related subtypes (7): classic complement early component deficiency, complement factor I deficiency, immunodeficiency due to a classical component pathway complement deficiency, immunodeficiency due to a late component of complement deficiency, atypical hemolytic-uremic syndrome, complement receptor deficiency, disorder of lectin complement activation pathway

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

10 retrieved; paginated sample, class counts are floors:

4 likely pathogenic, 3 pathogenic, 3 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
16565	NM_001928.2(CFD):c.[638T>G;640T>C]		Pathogenic	no assertion criteria provided
1454250	NM_001928.4(CFD):c.285C>A (p.Tyr95Ter)	CFD	Pathogenic	criteria provided, multiple submitters, no conflicts
16564	NM_001928.4(CFD):c.125C>A (p.Ser42Ter)	CFD	Pathogenic	criteria provided, single submitter
2417863	NM_001928.4(CFD):c.212+2T>G	CFD	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3779511	NM_001928.4(CFD):c.213-1G>C	CFD	Likely pathogenic	criteria provided, single submitter
3779512	NM_001928.4(CFD):c.278_279dup (p.Leu94fs)	CFD	Likely pathogenic	criteria provided, single submitter
636704	NM_001928.4(CFD):c.56-1G>C	CFD	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3362284	NM_001928.4(CFD):c.155G>A (p.Gly52Asp)	CFD	Uncertain significance	criteria provided, single submitter
3898024	NM_001928.4(CFD):c.646G>A (p.Gly216Ser)	CFD	Uncertain significance	criteria provided, single submitter
625914	NM_001928.4(CFD):c.463A>G (p.Ile155Val)	CFD	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · 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
CFD	Strong	Autosomal recessive	recurrent Neisseria infections due to factor D deficiency	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CFD	Orphanet:169467	Recurrent Neisseria infections due to factor D deficiency

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
CFD	HGNC:2771	ENSG00000197766	P00746	Complement factor D	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CFD	Complement factor D	Serine protease that initiates the alternative pathway of the complement system, a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive immune system.

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)
CFD	Protease	yes	3.4.21.46	Trypsin_dom, Peptidase_S1A, Peptidase_S1_PA

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
adipose tissue	1
mucosa of stomach	1
subcutaneous adipose tissue	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CFD	133	broad	marker	subcutaneous adipose tissue, adipose tissue, mucosa of stomach

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CFD	1,604

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CFD	P00746	40

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
Alternative complement activation	1	2284.0×	0.001	CFD
Platelet degranulation	1	87.8×	0.017	CFD
Neutrophil degranulation	1	23.1×	0.043	CFD

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
complement activation, alternative pathway	1	991.3×	0.003	CFD
zymogen activation	1	674.1×	0.003	CFD
complement activation	1	624.1×	0.003	CFD
response to bacterium	1	193.7×	0.007	CFD
protein maturation	1	163.6×	0.007	CFD
proteolysis	1	34.2×	0.029	CFD

Therapeutics

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
CFD	DANICOPAN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CFD	1	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
DANICOPAN	4	CFD

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
CFD	82	Binding:81, ADMET:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CFD	3.4.21.46	complement factor D

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)
DANICOPAN	4	CFD

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	CFD
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.