FCN1

ficolin 1, the group of Complement system activation components|Fibrinogen C domain containing

Basic information

Region (hg38): 9:134903231-134917912

Links

ENSG00000085265 ∙ NCBI:2219 ∙ OMIM:601252 ∙ HGNC:3623 ∙ Uniprot:O00602 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FCN1 gene.

• Inborn genetic diseases (17 variants)
• FCN1-related condition (2 variants)
• not provided (2 variants)
• not specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FCN1 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				2		2
missense			20			20
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	20	2	0

Variants in FCN1

This is a list of pathogenic ClinVar variants found in the FCN1 region.

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

Position	Type	Phenotype	Significance	ClinVar
9-134909808-C-T		not specified	Uncertain significance (May 25, 2023)
9-134909895-C-T		not specified	Uncertain significance (Feb 22, 2023)
9-134909977-A-G		not specified	Uncertain significance (Mar 28, 2016)
9-134910006-G-A		not specified	Uncertain significance (Oct 25, 2023)
9-134910008-G-A			Likely benign (Apr 01, 2022)
9-134910015-A-G		not specified	Uncertain significance (Mar 06, 2023)
9-134911154-C-G		not specified	Uncertain significance (May 05, 2023)
9-134911252-C-T		not specified	Uncertain significance (Feb 28, 2024)
9-134911253-G-A		not specified	Uncertain significance (Jan 23, 2023)
9-134911259-C-T		not specified	Uncertain significance (May 26, 2023)
9-134911267-C-T		not specified	Uncertain significance (Aug 12, 2021)
9-134912512-T-C		not specified	Uncertain significance (Nov 07, 2022)
9-134912529-C-G		not specified	Uncertain significance (Mar 11, 2024)
9-134912564-C-A		not specified	Uncertain significance (Sep 27, 2021)
9-134912570-A-G		not specified	Uncertain significance (Feb 27, 2023)
9-134912575-C-T		not specified	Uncertain significance (Jun 21, 2023)
9-134912606-G-T		FCN1-related disorder	Likely benign (Feb 06, 2024)
9-134913030-C-T		Monoclonal B-Cell Lymphocytosis	Uncertain significance (Dec 15, 2015)
9-134913102-G-A			Likely benign (Jul 01, 2022)
9-134913115-G-A		FCN1-related disorder	Likely benign (Sep 29, 2023)
9-134913115-G-T		not specified	Uncertain significance (Jan 04, 2024)
9-134913138-G-A		not specified	Uncertain significance (Aug 12, 2021)
9-134913608-C-T		not specified	Uncertain significance (Dec 06, 2022)
9-134914788-G-C		not specified	Uncertain significance (Feb 02, 2022)
9-134914801-C-T		FCN1-related disorder	Uncertain significance (Dec 20, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FCN1	protein_coding	protein_coding	ENST00000371806	9	8379

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.97e-17	0.000784	125424	0	324	125748	0.00129

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.292	214	202	1.06	0.0000126	2108
Missense in Polyphen		71	70.613	1.0055		791
Synonymous	-0.829	94	84.3	1.11	0.00000574	641
Loss of Function	-1.20	22	16.7	1.32	9.81e-7	171

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00124	0.00124
Ashkenazi Jewish	0.00716	0.00717
East Asian	0.00473	0.00474
Finnish	0.000390	0.000370
European (Non-Finnish)	0.000794	0.000783
Middle Eastern	0.00473	0.00474
South Asian	0.000394	0.000392
Other	0.00312	0.00310

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Extracellular lectin functioning as a pattern- recognition receptor in innate immunity. Binds the sugar moieties of pathogen-associated molecular patterns (PAMPs) displayed on microbes and activates the lectin pathway of the complement system. May also activate monocytes through a G protein-coupled receptor, FFAR2, inducing the secretion of interleukin-8/IL-8 (PubMed:21037097). Binds preferentially to 9-O-acetylated 2-6- linked sialic acid derivatives and to various glycans containing sialic acid engaged in a 2-3 linkage. {ECO:0000269|PubMed:20032467, ECO:0000269|PubMed:21037097}.
• Pathway: Human Complement System;Neutrophil degranulation;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)

Intolerance Scores

• loftool: 0.434
• rvis_EVS: -0.26
• rvis_percentile_EVS: 34.88

Haploinsufficiency Scores

• pHI: 0.265
• hipred: N
• hipred_score: 0.112
• ghis: 0.523

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.260

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Fcnb
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); immune system phenotype

Gene ontology

• Biological process: complement activation, lectin pathway;cell surface pattern recognition receptor signaling pathway;proteolysis;complement activation;G protein-coupled receptor signaling pathway;protein localization to cell surface;neutrophil degranulation;recognition of apoptotic cell;negative regulation of viral entry into host cell;positive regulation of interleukin-8 secretion
• Cellular component: extracellular region;collagen trimer;extrinsic component of external side of plasma membrane;secretory granule lumen;collagen-containing extracellular matrix;ficolin-1-rich granule lumen
• Molecular function: G protein-coupled receptor binding;serine-type endopeptidase activity;protein binding;signaling pattern recognition receptor activity;carbohydrate binding;sialic acid binding;metal ion binding