FCN3

ficolin 3, the group of Complement system activation components|Fibrinogen C domain containing

Basic information

Region (hg38): 1:27369109-27374824

Links

ENSG00000142748 ∙ NCBI:8547 ∙ OMIM:604973 ∙ HGNC:3625 ∙ Uniprot:O75636 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• immunodeficiency due to ficolin3 deficiency (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ficolin 3 deficiency	AR	Allergy/Immunology/Infectious	Sequelae have been described as including frequent and severe infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial	Allergy/Immunology/Infectious	19535802

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FCN3 gene.

• Inborn genetic diseases (15 variants)
• Immunodeficiency due to ficolin3 deficiency (8 variants)
• not provided (4 variants)
• not specified (2 variants)
• Microcephaly (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FCN3 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				1		1
missense			18	2		20
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region						0
non coding						0
Total	0	0	20	3	0

Variants in FCN3

This is a list of pathogenic ClinVar variants found in the FCN3 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-27369253-G-A		not specified	Uncertain significance (Jul 06, 2021)
1-27369282-C-T		not specified	Uncertain significance (Jun 07, 2023)
1-27369339-C-G		not specified	Uncertain significance (Nov 29, 2023)
1-27369339-C-T		Immunodeficiency due to ficolin3 deficiency	Uncertain significance (Jul 20, 2022)
1-27369357-C-G		not specified	Uncertain significance (Jul 13, 2022)
1-27369357-C-T		not specified	Likely benign (Aug 08, 2023)
1-27369372-T-C			Uncertain significance (-)
1-27369386-G-A		Immunodeficiency due to ficolin3 deficiency	Benign/Likely benign (Oct 01, 2022)
1-27369477-C-G		not specified	Uncertain significance (May 10, 2023)
1-27370346-G-T		Rheumatic heart disease	risk factor (Jan 09, 2019)
1-27370605-C-G		not specified	Uncertain significance (Jan 04, 2024)
1-27370634-T-C		Immunodeficiency due to ficolin3 deficiency	Uncertain significance (Aug 13, 2019)
1-27370658-C-T			Uncertain significance (Apr 18, 2019)
1-27370659-G-A		not specified	Uncertain significance (Jul 08, 2022)
1-27370689-T-C		not specified	Uncertain significance (Mar 02, 2023)
1-27370715-C-T		not specified	Uncertain significance (Oct 13, 2023)
1-27370854-A-G		not specified	Uncertain significance (Jul 08, 2022)
1-27370868-C-G		not specified • Immunodeficiency due to ficolin3 deficiency	Likely benign (Apr 18, 2022)
1-27370908-C-T		not specified	Uncertain significance (Sep 29, 2022)
1-27370926-C-A		Immunodeficiency due to ficolin3 deficiency	Uncertain significance (Oct 16, 2019)
1-27370933-G-A		FCN3-related disorder	Uncertain significance (Nov 08, 2023)
1-27370950-C-T		not specified	Uncertain significance (Aug 30, 2021)
1-27372958-A-T		Rheumatic heart disease	Uncertain significance (Jan 09, 2019)
1-27373135-C-T		FCN3-related disorder	Uncertain significance (Nov 08, 2023)
1-27373143-C-T		Microcephaly • not specified	Uncertain significance (Jun 10, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FCN3	protein_coding	protein_coding	ENST00000270879	8	5713

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00380	0.961	125306	2	426	125734	0.00170

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.422	162	178	0.911	0.0000106	1922
Missense in Polyphen		55	55.073	0.99867		653
Synonymous	1.67	50	67.4	0.742	0.00000383	598
Loss of Function	1.84	6	13.2	0.454	5.64e-7	149

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00508	0.00501
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.000695	0.000693
European (Non-Finnish)	0.00250	0.00248
Middle Eastern	0.0000544	0.0000544
South Asian	0.000392	0.000392
Other	0.00229	0.00228

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May function in innate immunity through activation of the lectin complement pathway. Calcium-dependent and GlcNAc- binding lectin. Has affinity with GalNAc, GlcNAc, D-fucose, as mono/oligosaccharide and lipopolysaccharides from S.typhimurium and S.minnesota. {ECO:0000269|PubMed:11907111, ECO:0000269|PubMed:17215869}.
• Disease: DISEASE: Ficolin 3 deficiency (FCN3D) [MIM:613860]: A disorder characterized by immunodeficiency, recurrent infections, brain abscesses and recurrent warts on the fingers. Affected individuals have normal levels of lymphocytes, normal T-cell responses, and normal antibodies, but a selective deficient antibody response to pneumococcal polysaccharide vaccine. {ECO:0000269|PubMed:19535802}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Innate Immune System;Immune System;Initial triggering of complement;Ficolins bind to repetitive carbohydrate structures on the target cell surface;Lectin pathway of complement activation;Creation of C4 and C2 activators;Complement cascade (Consensus)

Recessive Scores

• pRec: 0.113

Intolerance Scores

• loftool: 0.600
• rvis_EVS: 0.31
• rvis_percentile_EVS: 72.6

Haploinsufficiency Scores

• pHI: 0.0966
• hipred: N
• hipred_score: 0.198
• ghis: 0.439

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.139

Gene Damage Prediction

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

Gene ontology

• Biological process: complement activation, lectin pathway;proteolysis;complement activation;recognition of apoptotic cell;negative regulation of viral entry into host cell;defense response to virus;negative regulation of RNA biosynthetic process
• Cellular component: extracellular region;collagen trimer;blood microparticle
• Molecular function: antigen binding;serine-type endopeptidase activity;protein binding;carbohydrate binding;metal ion binding