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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
CFD
complement factor D
Chromosome 19 Β· 19p13.3
NCBI Gene: 1675Ensembl: ENSG00000197766.10HGNC: HGNC:2771UniProt: A6XNE2
72PubMed Papers
21Diseases
2Drugs
12Pathogenic Variants
FUNCTIONAL ROLE
Protease
CLINICAL
FDA Approved TargetOMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
serine-type endopeptidase activitycomplement activation, alternative pathwayzymogen activationGO:0005615recurrent Neisseria infections due to factor D deficiencyparoxysmal nocturnal hemoglobinuriahemolysiscomplement deficiency
✦AI Summary

CFD (complement factor D) is a serine protease that serves as the rate-limiting enzyme in the alternative complement pathway, a critical component of innate immunity 1. CFD cleaves factor B when complexed with complement C3b, thereby activating the C3 convertase and initiating complement cascade amplification that leads to pathogen elimination and immune signaling 1. Beyond its classical immune function, CFD exhibits diverse tissue-specific roles. In skeletal muscle, CFD expression in fibro/adipogenic progenitor cells promotes intramuscular adipogenesis through NAB2-mediated transcriptional regulation, with CFD levels serving as predictive biomarkers for intramuscular fat accumulation 2. In pulmonary hypertension, intracellular CFD drives metabolic reprogramming and proinflammatory responses in vascular fibroblasts, contributing to disease pathogenesis 3. CFD also plays roles in cancer progression, where CFD-positive inflammatory cancer-associated fibroblasts promote colorectal cancer liver metastasis via SFRP1-FGFR2-HIF1 signaling 4. Therapeutically, CFD represents a promising target, as demonstrated by long-acting anti-CFD antibodies that protected against COVID-19-associated endotheliopathy and complement-mediated vascular damage in both organoid and primate models 1. These findings highlight CFD's expanding roles beyond complement activation in metabolism, tissue remodeling, and disease pathogenesis.

Sources cited
1
CFD is a serine protease in alternative complement pathway and anti-CFD antibodies protect against COVID-19 endotheliopathy
PMID: 37802037
2
CFD expression in fibro/adipogenic progenitor cells promotes intramuscular adipogenesis and serves as predictive biomarker
PMID: 37439037
3
Intracellular CFD drives metabolic reprogramming and proinflammatory responses in pulmonary hypertension fibroblasts
PMID: 39946184
4
CFD-positive inflammatory cancer-associated fibroblasts promote colorectal cancer liver metastasis
PMID: 40225580
⚠Limited data available β€” This gene has 4 indexed publications. Summary and analysis may be incomplete.
Disease Associationsβ“˜21
recurrent Neisseria infections due to factor D deficiencyOpen Targets
0.77Strong
paroxysmal nocturnal hemoglobinuriaOpen Targets
0.49Moderate
complement deficiencyOpen Targets
0.46Moderate
hemolysisOpen Targets
0.46Moderate
atrophic macular degenerationOpen Targets
0.36Weak
neurodegenerative diseaseOpen Targets
0.32Weak
gastrointestinal diseaseOpen Targets
0.27Weak
macular degenerationOpen Targets
0.26Weak
type 2 diabetes mellitusOpen Targets
0.11Weak
neoplasmOpen Targets
0.10Weak
preeclampsiaOpen Targets
0.09Suggestive
non-alcoholic fatty liver diseaseOpen Targets
0.09Suggestive
rheumatoid arthritisOpen Targets
0.08Suggestive
coronary artery diseaseOpen Targets
0.08Suggestive
acute myeloid leukemiaOpen Targets
0.08Suggestive
myocardial infarctionOpen Targets
0.08Suggestive
breast cancerOpen Targets
0.08Suggestive
COVID-19Open Targets
0.08Suggestive
injuryOpen Targets
0.08Suggestive
malariaOpen Targets
0.08Suggestive
Complement factor D deficiencyUniProt
Pathogenic Variants12
NM_001928.4(CFD):c.212+2T>GLikely pathogenic
not provided|Recurrent Neisseria infections due to factor D deficiency
β˜…β˜…β˜†β˜†2025
NM_001928.4(CFD):c.56-1G>CLikely pathogenic
Recurrent Neisseria infections due to factor D deficiency|not provided
β˜…β˜…β˜†β˜†2024
NM_001928.4(CFD):c.285C>A (p.Tyr95Ter)Pathogenic
not provided|Recurrent Neisseria infections due to factor D deficiency
β˜…β˜…β˜†β˜†2024β†’ Residue 95
NM_001928.4(CFD):c.125C>A (p.Ser42Ter)Pathogenic
Recurrent Neisseria infections due to factor D deficiency|not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 42
NM_001928.4(CFD):c.153C>A (p.Cys51Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 51
NM_001928.4(CFD):c.444C>A (p.Cys148Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 148
NM_001928.4(CFD):c.132del (p.Gln44fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 44
NM_001928.4(CFD):c.40G>T (p.Gly14Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 14
NM_001928.4(CFD):c.278_279dup (p.Leu94fs)Likely pathogenic
Recurrent Neisseria infections due to factor D deficiency
β˜…β˜†β˜†β˜†2023β†’ Residue 94
NM_001928.4(CFD):c.213-1G>CLikely pathogenic
Recurrent Neisseria infections due to factor D deficiency
β˜…β˜†β˜†β˜†2022
NM_001928.4(CFD):c.213-2A>CLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2022
NM_001928.4(CFD):c.358-259_461delinsCATTGALikely pathogenic
not provided
β˜…β˜†β˜†β˜†2022
View on ClinVar β†—
Drug Targets2
DANICOPANApproved
Complement factor D inhibitor
LAMPALIZUMABPhase III
Complement factor D inhibitor
Related Genes
C3Protein interaction100%ADIPOQProtein interaction97%LEPProtein interaction93%RETNProtein interaction91%CFBProtein interaction81%RETNLBProtein interaction72%
Tissue Expression6 tissues
Lung
100%
Ovary
13%
Heart
11%
Bone Marrow
5%
Liver
2%
Brain
0%
Gene Interaction Network
Click a node to explore
CFDC3ADIPOQLEPRETNCFBRETNLB
PROTEIN STRUCTURE
Preparing viewer…
PDB5NAT Β· 1.17 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.95LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF1.65 [1.17–1.95]
RankingsWhere CFD stands among ~20K protein-coding genes
  • #6,535of 20,598
    Most Researched72
  • #975of 1,025
    FDA-Approved Drug Targets1
  • #2,679of 5,498
    Most Pathogenic Variants12
  • #17,657of 17,882
    Most Constrained (LOEUF)1.95
Genes detectedCFD
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
FOS-driven inflammatory CAFs promote colorectal cancer liver metastasis via the SFRP1-FGFR2-HIF1 axis.
PMID: 40225580
Theranostics Β· 2025
1.00
2
A single-cell atlas of bovine skeletal muscle reveals mechanisms regulating intramuscular adipogenesis and fibrogenesis.
PMID: 37439037
J Cachexia Sarcopenia Muscle Β· 2023
0.90
3
An intracellular complement system drives metabolic and proinflammatory reprogramming of vascular fibroblasts in pulmonary hypertension.
PMID: 39946184
JCI Insight Β· 2025
0.80
4
Transcriptome-wide analysis reveals potential roles of CFD and ANGPTL4 in fibroblasts regulating B cell lineage for extracellular matrix-driven clustering and novel avenues for immunotherapy in breast cancer.
PMID: 40340806
Mol Med Β· 2025
0.70
5
Complement factor D targeting protects endotheliopathy in organoid and monkey models of COVID-19.
PMID: 37802037
Cell Stem Cell Β· 2023
0.60