CFD

complement factor D, the group of Granule associated serine proteases of immune defence|Complement system activation components

Basic information

Region (hg38): 19:859453-867884

Previous symbols: [ "DF", "PFD" ]

Links

ENSG00000197766 ∙ NCBI:1675 ∙ OMIM:134350 ∙ HGNC:2771 ∙ Uniprot:P00746 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• recurrent Neisseria infections due to factor D deficiency (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Complement factor D deficiency	AR	Allergy/Immunology/Infectious	Individuals may manifest with increased susceptibility to bacterial infections (especially Neisseria), and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial	Allergy/Immunology/Infectious	11457876; 16527897

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CFD gene.

• not provided (4 variants)
• Recurrent Neisseria infections due to factor D deficiency (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CFD gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				60	4	64
missense			109	6	3	118
nonsense	3					3
start loss						0
frameshift	1		1			2
inframe indel			2			2
splice donor/acceptor (+/-2bp)		4	1			5
splice region			7	9	2	18
non coding				22	5	27
Total	4	4	113	88	12

Highest pathogenic variant AF is 0.0000197

Variants in CFD

This is a list of pathogenic ClinVar variants found in the CFD region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
19-859682-G-A		CFD-related disorder	Likely benign (Sep 18, 2019)
19-859693-C-T			Uncertain significance (Jun 27, 2022)
19-859697-GC-TT			Uncertain significance (Jun 29, 2022)
19-859704-G-A			Likely benign (Dec 05, 2023)
19-859706-G-A			Uncertain significance (Jun 13, 2022)
19-859722-C-A			Likely benign (Jan 31, 2024)
19-859728-A-G			Likely benign (Jun 14, 2023)
19-859729-G-T			Pathogenic (Oct 13, 2023)
19-859734-G-A			Likely benign (May 20, 2023)
19-859735-G-A			Uncertain significance (Jun 12, 2021)
19-859743-C-G		not specified	Uncertain significance (May 22, 2023)
19-859751-A-C			Likely benign (Jul 10, 2023)
19-859756-T-C			Likely benign (Sep 09, 2023)
19-859759-G-C			Likely benign (Jan 25, 2024)
19-859760-C-A			Likely benign (Apr 01, 2022)
19-860602-C-T			Likely benign (Dec 06, 2023)
19-860604-C-T			Benign (Dec 11, 2023)
19-860605-G-T			Likely benign (Aug 09, 2021)
19-860608-C-A			Likely benign (Oct 13, 2023)
19-860610-C-T			Likely benign (Nov 27, 2023)
19-860611-C-G			Uncertain significance (May 16, 2021)
19-860612-C-T			Likely benign (Sep 26, 2023)
19-860616-G-C		Recurrent Neisseria infections due to factor D deficiency	Likely pathogenic (Apr 04, 2024)
19-860619-G-A		not specified	Uncertain significance (Jun 16, 2024)
19-860620-C-T			Uncertain significance (Jan 29, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CFD	protein_coding	protein_coding	ENST00000327726	5	4001

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000670	0.291	119325	0	9	119334	0.0000377

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.625	193	170	1.13	0.0000103	1544
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000901	0.0000847
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• 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.
• Pathway: 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;Complement Activation;Complement and Coagulation Cascades;Neutrophil degranulation;alternative complement pathway;Innate Immune System;Immune System;Platelet degranulation ;Response to elevated platelet cytosolic Ca2+;Platelet activation, signaling and aggregation;Initial triggering of complement;Hemostasis;Complement cascade;Alternative complement activation (Consensus)

Recessive Scores

• pRec: 0.500

Haploinsufficiency Scores

• pHI: 0.157
• hipred: N
• hipred_score: 0.213
• ghis: 0.500

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.782

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Cfd
• Phenotype: immune system phenotype

Gene ontology

• Biological process: platelet degranulation;proteolysis;complement activation;complement activation, alternative pathway;neutrophil degranulation
• Cellular component: extracellular region;platelet alpha granule lumen;secretory granule lumen;extracellular exosome;ficolin-1-rich granule lumen
• Molecular function: serine-type endopeptidase activity;serine-type peptidase activity