CFD
protein-codingcomplement factor D, the group of Granule associated serine proteases of immune defence|Complement system activation components
Gene summary
This gene encodes a member of the S1, or chymotrypsin, family of serine peptidases. This protease catalyzes the cleavage of factor B, the rate-limiting step of the alternative pathway of complement activation. This protein also functions as an adipokine, a cell signaling protein secreted by adipocytes, which regulates insulin secretion in mice. Mutations in this gene underlie complement factor D deficiency, which is associated with recurrent bacterial meningitis infections in human patients. Alternative splicing of this gene results in multiple transcript variants. At least one of these variants encodes a preproprotein that is proteolytically processed to generate the mature protease. [provided by RefSeq, Nov 2015]
- DF
- PFD
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~8.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0013487
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0013487
Submitter: Ambry Genetics
Clinical Genomic Database (CGD)
Manifestation: Allergy/Immunology/Infectious
Intervention: Allergy/Immunology/Infectious
Rationale: Individuals may manifest with increased susceptibility to bacterial infections (especially Neisseria), and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CFD variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001928.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 88 | 1 | 90 | ||
| missense | 157 | 6 | 1 | 164 | ||
| nonsense | 5 | 5 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 3 | 3 | 7 | ||
| splice donor/acceptor (+/-2bp) | 7 | 1 | 8 | |||
| Total | 6 | 10 | 162 | 94 | 2 | 274 |
Highest pathogenic variant AF is 0.0000505139
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001919.2 | 5 | MANE Select | |
| Ensembl | ENSP00000332139.4 | 5 | MANE Select | |
| RefSeq | NP_001304264.1 | 5 | Standard | |
| Ensembl | ENSP00000468253.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Complement and coagulation cascades - Homo sapiens (human)
- Staphylococcus aureus infection - Homo sapiens (human)
- Adipogenesis
- Human Complement System
- Dengue-2 Interactions with Complement and Coagulation Cascades
Biological Process
- platelet degranulation
- proteolysis
- complement activation
- complement activation, alternative pathway
- neutrophil degranulation
Molecular Function
- serine-type endopeptidase activity
- serine-type peptidase activity
Cellular Component
- extracellular region
- platelet alpha granule lumen
- secretory granule lumen
- extracellular exosome
- ficolin-1-rich granule lumen
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000327726
- Coding exons
- 5
- Length
- 4001
- Individuals with no LoFs
- 119325
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 9
- Defined
- 119334
- p
- 0.0000377
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.625 | 193 | 170 | 1.13 | 0.0000103 | 1544 |
| Missense (PolyPhen) | 71 | 65.495 | 1.0841 | 651 | ||
| Synonymous | -0.560 | 84 | 77.7 | 1.08 | 0.00000465 | 547 |
| Loss of Function | 0.0892 | 8 | 8.28 | 0.967 | 3.55e-7 | 89 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000090 | 0.000085 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Factor D cleaves factor B when the latter is complexed with factor C3b, activating the C3bbb complex, which then becomes the C3 convertase of the alternate pathway. Its function is homologous to that of C1s in the classical pathway.;
- Disease
- DISEASE: Complement factor D deficiency (CFDD) [MIM:613912]: An immunologic disorder characterized by increased susceptibility to bacterial infections, particularly Neisseria infections, due to a defect in the alternative complement pathway. {ECO:0000269|PubMed:16527897}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.500
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- H
- Indispensability pred.
- E
- Indispensability score
- 0.782
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |