FCN1

Summary

FCN1 (ficolin 1, HGNC:3623) is a protein-coding gene on chromosome 9q34.3, encoding Ficolin-1 (O00602). Extracellular lectin, which acts as a pattern recognition receptor that initiates the lectin pathway of the complement system, a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive immune system.

The ficolin family of proteins are characterized by the presence of a leader peptide, a short N-terminal segment, followed by a collagen-like region, and a C-terminal fibrinogen-like domain. The collagen-like and the fibrinogen-like domains are also found separately in other proteins such as complement protein C1q, C-type lectins known as collectins, and tenascins. However, all these proteins recognize different targets, and are functionally distinct. Ficolin 1 encoded by FCN1 is predominantly expressed in the peripheral blood leukocytes, and has been postulated to function as a plasma protein with elastin-binding activity.

Source: NCBI Gene 2219 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 72 total
• MANE Select transcript: NM_002003

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3623
Approved symbol	FCN1
Name	ficolin 1
Location	9q34.3
Locus type	gene with protein product
Status	Approved
Aliases	FCNM
Ensembl gene	ENSG00000085265
Ensembl biotype	protein_coding
OMIM	601252
Entrez	2219

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000371806, ENST00000867921, ENST00000867922, ENST00000867923, ENST00000867924, ENST00000954365, ENST00000954366

RefSeq mRNA: 1 — MANE Select: NM_002003 NM_002003

CCDS: CCDS6985

Canonical transcript exons

ENST00000371806 — 9 exons

Exon	Start	End
ENSE00000418292	134914385	134914420
ENSE00000828380	134916348	134916461
ENSE00000828382	134914756	134914809
ENSE00000828385	134913581	134913613
ENSE00001096640	134917769	134917912
ENSE00001740230	134903232	134910045
ENSE00002355674	134913016	134913143
ENSE00002385104	134911133	134911267
ENSE00002720023	134912486	134912615

Expression profiles

Bgee: expression breadth ubiquitous, 175 present calls, max score 99.53.

FANTOM5 (CAGE): breadth broad, TPM avg 48.6158 / max 5388.7919, expressed in 362 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
103076	48.6158	362

Top tissues by expression

283 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	99.53	gold quality
mononuclear cell	CL:0000842	99.53	gold quality
leukocyte	CL:0000738	99.51	gold quality
granulocyte	CL:0000094	99.37	gold quality
trabecular bone tissue	UBERON:0002483	98.45	gold quality
bone marrow	UBERON:0002371	98.37	gold quality
blood	UBERON:0000178	97.94	gold quality
bone marrow cell	CL:0002092	97.10	gold quality
buccal mucosa cell	CL:0002336	88.89	silver quality
vermiform appendix	UBERON:0001154	87.13	gold quality
spleen	UBERON:0002106	83.95	gold quality
periodontal ligament	UBERON:0008266	83.14	gold quality
right lung	UBERON:0002167	82.15	gold quality
caecum	UBERON:0001153	79.82	gold quality
upper lobe of left lung	UBERON:0008952	77.61	gold quality
upper lobe of lung	UBERON:0008948	76.63	gold quality
germinal epithelium of ovary	UBERON:0001304	74.84	gold quality
parietal pleura	UBERON:0002400	74.77	gold quality
decidua	UBERON:0002450	73.11	silver quality
lung	UBERON:0002048	72.98	gold quality
gall bladder	UBERON:0002110	71.81	gold quality
pleura	UBERON:0000977	71.56	gold quality
smooth muscle tissue	UBERON:0001135	70.22	gold quality
lower lobe of lung	UBERON:0008949	70.22	gold quality
right coronary artery	UBERON:0001625	68.46	gold quality
adipose tissue of abdominal region	UBERON:0007808	68.28	gold quality
omental fat pad	UBERON:0010414	67.95	gold quality
peritoneum	UBERON:0002358	67.91	gold quality
lymph node	UBERON:0000029	67.81	gold quality
mucosa of urinary bladder	UBERON:0001259	67.23	gold quality

Single-cell (SCXA)

Detected in 31 experiment(s), a significant marker in 30.

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	5164.89
E-GEOD-150728	yes	4238.85
E-GEOD-149689	yes	2947.74
E-MTAB-8207	yes	2876.93
E-MTAB-9221	yes	2451.91
E-HCAD-15	yes	2390.18
E-HCAD-4	yes	2382.90
E-CURD-112	yes	2279.07
E-MTAB-8322	yes	2265.05
E-MTAB-9067	yes	2203.51
E-MTAB-8498	yes	2136.49
E-HCAD-1	yes	2101.68
E-MTAB-6701	yes	2056.24
E-HCAD-10	yes	2004.66
E-CURD-122	yes	1925.07

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

21 targeting FCN1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-377-5P	99.70	65.28	712
HSA-MIR-6086	99.70	65.38	699
HSA-MIR-4743-3P	99.62	68.12	2095
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-4710	98.61	65.96	1048
HSA-MIR-6867-3P	98.12	66.07	1305
HSA-MIR-4469	97.93	65.81	1319
HSA-MIR-4286	97.20	64.37	1587
HSA-MIR-4296	96.35	63.55	1233
HSA-MIR-2276-5P	96.27	65.85	937
HSA-MIR-4265	96.18	64.68	557
HSA-MIR-4322	96.18	64.85	539
HSA-MIR-4433B-5P	95.91	66.56	727
HSA-MIR-6796-5P	95.37	66.08	1120

Literature-anchored findings (GeneRIF, showing 40)

• Results describe the x-ray structure of human mannan-binding lectin-associated protein 19 (MAp19), and identify the residues involved in the interaction of MAp19 with mannan-binding lectin and L-ficolin. (PMID:15117939)
• M-ficolin is present on the surface of peripheral blood monocytes and binds to acetylated compounds. (PMID:16305643)
• The crystal structure and ligand binding study of human M-ficolin reveal how the three fibrinogen domains form a trimer and provide a structural basis for understanding how ficolins discriminate between self and non-self. (PMID:17148457)
• M-Ficolin expression is silenced in macrophages but can be re-activated after prolonged activation via TLR2 and TLR4 (PMID:17928056)
• This study was conducted to determine mannose-binding lectin (MBL)/MBL-associated serine protease (MASP) complexes and L-ficolin/MASP complexes bind to different strains of group B streptococci to activate the lectin pathway. (PMID:17938215)
• FCN1 GENE POLYMORPHISM IS ASSOCIATED WITH THE DEVELOPMENT OF RHEUMATOID ARTHITIS. (PMID:18032536)
• Ficolin-1 exists in human plasma and serum under normal conditions, hereby revising the general assumption that Ficolin-1 is solely a cellular associated protein. (PMID:18343499)
• Data show that low cord blood M-ficolin was associated with higher NEC-associated fatality and with increased need for mechanical ventilation, and future studies need to assess whether M-ficolin is involved in multiorgan failure and pulmonary disease. (PMID:19539995)
• Ficolin-1 is present in a highly mobilizable subset of human neutrophil granules and associates with the cell surface after stimulation with fMLP. (PMID:19741154)
• CRP binding is enhanced by conformational bending at the neck region of M-ficolin, to avoid steric hindrance by the COL domain. (PMID:19853918)
• sialic acid binding specificity of M-ficolin, emphasizing the essential role of Tyr(271) in this respect (PMID:20032467)
• We suggest that M-ficolin should also be considered as a humoral pattern recognition molecule. (PMID:20375634)
• a novel self-recognition mechanism of leukocytes mediated by the fibrinogen-like domain of Ficolin-1. (PMID:20400674)
• M-ficolin collaborates with its interacting partners (G protein-coupled receptor 43 and C-reactive protein) to initiate, mediate, and regulate the immune response during bacterial infection. (PMID:21037097)
• serum levels associate with neutrophil and monocyte counts in blood and bone marrow from children with cancer (PMID:21112665)
• data indicate interaction of M-ficolin with PTX3 arises from its ability to bind sialylated ligands; M-ficolin-PTX3 interaction described represents a novel case of cross-talk between soluble pattern-recognition molecules (PMID:21490156)
• Data identified the binding interface between CRP and FBG, locating it to the pH- and calcium-sensitive C-terminal region of FBG (PMID:21689722)
• It is postulated that the elevation of concentration of the two components of the leptin pathway, L-ficolin and MASP-2, may compensate for the insufficient activity of the LP in mannose-binding lectin deficiency (PMID:21974696)
• In patients with haematological malignancy undergoing chemotherapy, those with high MASP-2 were less likely to develop severe infections. (PMID:22236007)
• M-ficolin concentrations in cord blood are related to circulating phagocytes and to early-onset sepsis (PMID:22391637)
• Two polymorphisms in the promoter region of FCN1 is associated with the expression and synthesis of ficolin-1 as well as associated with decreased survival in a cohort of patient with systemic inflammatory response syndrome and sepsis. (PMID:22673311)
• A genotype study of common promoter FCN1 single nucleotide polymorphisms (SNPs) finds evidence for opposite associations between different FCN1 haplotypes and clinical leprosy in Euro-Brazilians and Afro-Brazilians. (PMID:22941510)
• Data show that a photodynamic therapy (PDT) dose-dependent upregulation of CRP gene, as well as of PTX3 and ficolin 1 genes in lung tumor A549 cells, and indicate critical role played by PI3K/Akt/AP-1 pathway. (PMID:23182717)
• M-ficolin bound strongly to serotype 19B and 19C polysaccharides. (PMID:23184524)
• Study interlinks the genotype and phenotype relationship concerning polymorphisms in FCN1 and corresponding concentrations and biological functions of M-ficolin. (PMID:23209787)
• These results demonstrate that ficolin-1 and PTX3 heterocomplex formation acts as a noninflammatory “find me and eat me” signal to sequester altered-host cells. (PMID:23817411)
• In patients with early rheumatoid arthritis, elevated plasma M-ficolin levels correlated with a high disease activity score at baseline and 1 year. A low M-ficolin level was the strongest predictor of remission and low disease activity. (PMID:24022747)
• the differential binding of ficolin-1 to lymphocyte subsets suggests ficolin-1 as a novel link between innate and adaptive immunity. (PMID:24161415)
• This study aims to investigate whether an association exists between the ficolins that are part of the lectin complement pathway and systemic lupus erythematosus. (PMID:25069872)
• Data indicate differences in the plasma concentrations of collectin liver 1 and collectin kidney 1, M-ficolin and H-ficol in systemic lupus erythematosus (SLE) patients compared to a group of healthy controls. (PMID:26154564)
• Ficolin-1 was decreased in patients compared with controls measured at 6 h (median 0.13 vs 0.33 mug/ml, respectively, p < 0.0001). At 48 h, ficolin-1 was significantly higher (PMID:26792363)
• Ficolin-1 could provide an alternative receptor-mediated mechanism for enhancing Ebola Virus infection, thereby contributing to viral subversion of the host innate immune system. (PMID:26984723)
• higher ficolin-1 levels were associated with brain ischemic lesions and vasospasm following subarachnoid hemorrhage. (PMID:27734336)
• systemic lupus erythematosus patients with high ficolin-1 plasma levels had an increased risk of end-stage renal disease; there was no significant association between ficolin-1 and ficolin-3 with lupus nephritis (PMID:27981461)
• in northeastern Brazilian children and adolescents, FCN1 rs1071583 SNP was correlated with earlier age of type 1 diabetes mellitus (T1D) diagnosis; the SNP combination rs2989727 and rs1071583 was involved with T1D protection (PMID:27994205)
• M-ficolin interacts with A. fumigatus through interaction with chitin and beta-1,3 glucan and thereby mediates complement activation and potentiates IL-8 secretion of A549 cells. (PMID:28060571)
• There is a strong association between serum levels of PTX3, M-ficolin, and SPA with the severity of ischemic stroke. Clinically, such association may be considered to evaluate the severity of the ischemic stroke. (PMID:28601054)
• These results suggest that FCN1 is a molecular target of intravenous IVIG in KD patients. We propose that these peptides and a humanized monoclonal antibody against FCN1 could be useful in combination therapy with IVIG. (PMID:28900133)
• Study of FCN1 promoter polymorphisms in rheumatic fever (RF) and rheumatic heart disease (RHD) patient revealed that minor FCN1 promoter variants may play a protective role against RF, by encouraging bacteria elimination as well as increasing gene expression and protein levels. On the other hand, they may also predispose the patients to RHD symptoms thus emphasizing the dual importance of ficolin-1 in both conditions. (PMID:30619357)
• Ficolin-1 gene (FCN1) -144 C/A polymorphism is associated with adverse outcome of severe pneumonia in the under-five Egyptian children: A multicenter study. (PMID:32142211)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Fcnb	ENSMUSG00000026835
rattus_norvegicus	Fcnb	ENSRNOG00000009342

Paralogs (25): TNC (ENSG00000041982), ANGPT2 (ENSG00000091879), ANGPT4 (ENSG00000101280), FGL1 (ENSG00000104760), FN1 (ENSG00000115414), TNR (ENSG00000116147), ANGPTL1 (ENSG00000116194), TNN (ENSG00000120332), FGL2 (ENSG00000127951), FIBCD1 (ENSG00000130720), ANGPTL6 (ENSG00000130812), ANGPTL3 (ENSG00000132855), ANGPTL2 (ENSG00000136859), FCN3 (ENSG00000142748), FNDC7 (ENSG00000143107), ANGPT1 (ENSG00000154188), FCN2 (ENSG00000160339), MFAP4 (ENSG00000166482), ANGPTL4 (ENSG00000167772), TNXB (ENSG00000168477), FGG (ENSG00000171557), FGA (ENSG00000171560), FGB (ENSG00000171564), ANGPTL7 (ENSG00000171819), ANGPTL5 (ENSG00000187151)

Protein

Protein identifiers

Ficolin-1 — O00602 (reviewed: O00602)

Alternative names: Collagen/fibrinogen domain-containing protein 1, Ficolin-A, Ficolin-alpha, M-ficolin

All UniProt accessions (1): O00602

UniProt curated annotations — full annotation on UniProt →

Function. Extracellular lectin, which acts as a pattern recognition receptor that initiates the lectin pathway of the complement system, a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive immune system. Specifically recognizes and binds carbohydrates on the pathogen surface, activating the MASP1 serine protease and initiating the proteolytic cascade of the lectin complement pathway. 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. May also activate monocytes through a G protein-coupled receptor, FFAR2, inducing the secretion of interleukin-8/IL-8.

Subunit / interactions. Homotrimer. Interacts with elastin/ELN. Interacts (via Fibrinogen C-terminal domain) with FFAR2. Interacts with CRP; may regulate monocyte activation by FCN1.

Subcellular location. Secreted. Cell surface.

Tissue specificity. Peripheral blood leukocytes, monocytes and granulocytes. Also detected in spleen, lung, and thymus, may be due to the presence of tissue macrophages or trapped blood in these tissues. Not detected on lymphocytes.

Domain organisation. The fibrinogen C-terminal domain mediates calcium-dependent binding to carbohydrates and tethering to the cell surface in monocytes and granulocytes. The domain undergoes a conformational switch at pH under 6.2, and looses its carbohydrate-binding ability.

Similarity. Belongs to the ficolin lectin family.

RefSeq proteins (1): NP_001994* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002181	Fibrinogen_a/b/g_C_dom	Domain
IPR008160	Collagen	Repeat
IPR014716	Fibrinogen_a/b/g_C_1	Homologous_superfamily
IPR020837	Fibrinogen_CS	Conserved_site
IPR036056	Fibrinogen-like_C	Homologous_superfamily
IPR050373	Fibrinogen_C-term_domain	Family

Pfam: PF00147, PF01391

UniProt features (54 total): strand 16, helix 7, binding site 5, region of interest 4, disulfide bond 3, sequence variant 3, mutagenesis site 3, site 2, domain 2, sequence conflict 2, turn 2, compositionally biased region 2, signal peptide 1, chain 1, glycosylation site 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
2WNP	X-RAY DIFFRACTION	1.21
2JHM	X-RAY DIFFRACTION	1.52
2JHH	X-RAY DIFFRACTION	1.7
2JHK	X-RAY DIFFRACTION	1.75
2JHL	X-RAY DIFFRACTION	1.75
2JHI	X-RAY DIFFRACTION	1.8
2D39	X-RAY DIFFRACTION	1.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00602-F1	85.95	0.69

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (2): 300 (mediates specificity for sialic acids); 312 (mediates specificity for sialic acids)

Ligand- & substrate-binding residues (5): 262; 264; 266; 268; 282–284

Disulfide bonds (3): 111–139, 118–146, 270–283

Glycosylation sites (1): 305

Mutagenesis-validated functional residues (3):

Position	Phenotype
250	inhibits binding to the 9-o-acetylated sialic acid derivatives.
285	inhibits binding to the 9-o-acetylated sialic acid derivatives.
300	abolishes interaction with all sialic acid-containing glycans.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-166662	Lectin pathway of complement activation
R-HSA-166663	Initial triggering of complement
R-HSA-2855086	Ficolins bind to repetitive carbohydrate structures on the target cell surface
R-HSA-6798695	Neutrophil degranulation

MSigDB gene sets: 263 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, MCLACHLAN_DENTAL_CARIES_UP, GOBP_POSITIVE_REGULATION_OF_INTERLEUKIN_8_PRODUCTION, GOCC_SECRETORY_GRANULE, GOCC_COLLAGEN_TRIMER, REACTOME_CREATION_OF_C4_AND_C2_ACTIVATORS, MODULE_45, GOCC_CELL_SURFACE, GOBP_APOPTOTIC_CELL_CLEARANCE, GOBP_MODULATION_OF_PROCESS_OF_ANOTHER_ORGANISM, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS

GO Biological Process (17): complement activation, lectin pathway (GO:0001867), cell surface pattern recognition receptor signaling pathway (GO:0002752), proteolysis (GO:0006508), G protein-coupled receptor signaling pathway (GO:0007186), positive regulation of interleukin-8 production (GO:0032757), protein localization to cell surface (GO:0034394), recognition of apoptotic cell (GO:0043654), host-mediated suppression of symbiont invasion (GO:0046597), positive regulation of opsonization (GO:1903028), activation of membrane attack complex (GO:0001905), immune system process (GO:0002376), complement activation (GO:0006956), opsonization (GO:0008228), zymogen activation (GO:0031638), killing of cells of another organism (GO:0031640), innate immune response (GO:0045087), protein maturation (GO:0051604)

GO Molecular Function (9): G protein-coupled receptor binding (GO:0001664), antigen binding (GO:0003823), signaling receptor binding (GO:0005102), carbohydrate binding (GO:0030246), sialic acid binding (GO:0033691), pattern recognition receptor activity (GO:0038187), metal ion binding (GO:0046872), carbohydrate derivative binding (GO:0097367), protein binding (GO:0005515)

GO Cellular Component (11): extracellular region (GO:0005576), collagen trimer (GO:0005581), obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), extracellular matrix (GO:0031012), secretory granule lumen (GO:0034774), symbiont cell surface (GO:0106139), ficolin-1-rich granule lumen (GO:1904813), serine-type endopeptidase complex (GO:1905370), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Creation of C4 and C2 activators	1
Complement cascade	1
Lectin pathway of complement activation	1
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	4
complement activation	2
innate immune response	2
protein metabolic process	2
phagocytosis, recognition	2
immune effector process	2
cellular anatomical structure	2
innate immune response activating cell surface receptor signaling pathway	1
pattern recognition receptor signaling pathway	1
G protein-coupled receptor activity	1
signal transduction	1
positive regulation of cytokine production	1
interleukin-8 production	1
regulation of interleukin-8 production	1
intracellular protein localization	1
apoptotic cell clearance	1
host-mediated perturbation of symbiont process	1
positive regulation of immune effector process	1
opsonization	1
positive regulation of phagocytosis	1
regulation of opsonization	1
biological_process	1
activation of immune response	1
humoral immune response	1
protein activation cascade	1
protein processing	1
cell killing	1
disruption of cell in another organism	1
immune response	1
defense response to symbiont	1
gene expression	1
signaling receptor binding	1
protein binding	1
carboxylic acid binding	1
carbohydrate derivative binding	1
signaling receptor activity	1
cation binding	1
protein-containing complex	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1616 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FCN1	F8W876	F8W876	997
FCN1	MASP2	O00187	965
FCN1	PTX3	P26022	938
FCN1	MBL2	P11226	863
FCN1	CRP	P02741	816
FCN1	KIR3DL1	P43629	801
FCN1	COLEC11	Q9BWP8	738
FCN1	C1S	P09871	712
FCN1	C1R	P00736	695
FCN1	ELN	P15502	665
FCN1	FCN3	O75636	659
FCN1	C3	P01024	645
FCN1	SERPING1	P05155	639
FCN1	CR1	P17927	634
FCN1	PRSS2	P07478	612

IntAct

34 interactions, top by confidence:

A	B	Type	Score
CRIPTO	AIP	psi-mi:“MI:0914”(association)	0.640
	FCN1	psi-mi:“MI:0407”(direct interaction)	0.600
FCN1	CRP	psi-mi:“MI:0407”(direct interaction)	0.600
FCN1	CRP	psi-mi:“MI:2364”(proximity)	0.600
FCN1	CRP-1	psi-mi:“MI:0407”(direct interaction)	0.560
CRP-1	FCN1	psi-mi:“MI:0407”(direct interaction)	0.560
FCN1	POTEF	psi-mi:“MI:0914”(association)	0.530
TRABD	FCN1	psi-mi:“MI:0914”(association)	0.530
PTX3	FCN1	psi-mi:“MI:0407”(direct interaction)	0.440
FCN1	TLR4	psi-mi:“MI:0407”(direct interaction)	0.440
	FCN1	psi-mi:“MI:0407”(direct interaction)	0.440
FCN1	UMOD	psi-mi:“MI:0407”(direct interaction)	0.440
DMBT1	FCN1	psi-mi:“MI:0407”(direct interaction)	0.440
FCN1	MASP1	psi-mi:“MI:0915”(physical association)	0.400
FCN1	MASP2	psi-mi:“MI:0915”(physical association)	0.400
C8orf58	FCN1	psi-mi:“MI:0915”(physical association)	0.400
FCN1	FCN1	psi-mi:“MI:0915”(physical association)	0.370
TRABD	NME2	psi-mi:“MI:0914”(association)	0.350
	MASP2	psi-mi:“MI:0914”(association)	0.350
FCN1	PLOD2	psi-mi:“MI:0914”(association)	0.350
COPS5	FCN1	psi-mi:“MI:0914”(association)	0.350

BioGRID (53): KIAA0319L (Affinity Capture-MS), DNAJC13 (Affinity Capture-MS), PTPRA (Affinity Capture-MS), POTEF (Affinity Capture-MS), COLGALT2 (Affinity Capture-MS), PTPRG (Affinity Capture-MS), PODXL (Affinity Capture-MS), FCN2 (Affinity Capture-MS), SUSD5 (Affinity Capture-MS), FBLN1 (Affinity Capture-MS), SEZ6L2 (Affinity Capture-MS), KIAA1549 (Affinity Capture-MS), FCN1 (Affinity Capture-MS), FCN2 (Affinity Capture-MS), SUSD5 (Affinity Capture-MS)

ESM2 similar proteins: D8VNS7, D8VNS8, D8VNS9, D8VNT0, E2IYB3, O00602, O43827, O70165, O70497, O95841, P02675, P02679, P02680, P04115, P12799, P12804, P14480, P17634, P19477, P55083, P55918, P57756, P85031, P86239, Q08830, Q0P4P2, Q14314, Q15485, Q1RMR1, Q29041, Q29042, Q29RY7, Q3SZZ7, Q5EA66, Q5I2E5, Q5M8C6, Q5XK91, Q640P2, Q6AX44, Q71KU9

Diamond homologs: A0A8J8, A2AV25, D8VNS7, D8VNS8, D8VNS9, D8VNT0, E2IYB3, E9PV24, O00602, O08538, O15123, O18920, O35460, O35462, O35608, O43827, O70165, O70497, O75636, O77802, O93526, O95841, P02671, P02675, P02676, P02678, P02679, P02680, P04115, P06399, P10039, P12799, P12804, P14448, P14480, P17634, P19477, P21520, P22105, P24821

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
FCN1	“form complex”	“Ficolin lectin-protease complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 20 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
inflammatory response	5	10.5×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

72 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	57
Likely benign	7
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1267 predictions. Top by Δscore:

Variant	Effect	Δscore
9:134911132:CCCG:C	donor_gain	1.0000
9:134911175:T:TA	donor_gain	1.0000
9:134911266:TCC:T	acceptor_loss	1.0000
9:134911269:T:C	acceptor_loss	1.0000
9:134912480:CCCTA:C	donor_loss	1.0000
9:134912481:CCTAC:C	donor_loss	1.0000
9:134912482:CTA:C	donor_loss	1.0000
9:134912483:TACC:T	donor_loss	1.0000
9:134912484:A:AC	donor_gain	1.0000
9:134912484:AC:A	donor_gain	1.0000
9:134912485:C:A	donor_gain	1.0000
9:134912485:C:CA	donor_loss	1.0000
9:134912485:C:CC	donor_gain	1.0000
9:134912531:C:CA	donor_gain	1.0000
9:134912532:C:A	donor_gain	1.0000
9:134912612:AAAC:A	acceptor_gain	1.0000
9:134912614:AC:A	acceptor_gain	1.0000
9:134912615:CC:C	acceptor_gain	1.0000
9:134912616:C:CC	acceptor_gain	1.0000
9:134912616:CT:C	acceptor_loss	1.0000
9:134912617:T:G	acceptor_loss	1.0000
9:134913014:A:AC	donor_gain	1.0000
9:134913014:ACGGT:A	donor_gain	1.0000
9:134913015:C:CC	donor_gain	1.0000
9:134913015:CGGTC:C	donor_gain	1.0000
9:134917765:TCA:T	donor_loss	1.0000
9:134917766:CA:C	donor_loss	1.0000
9:134917767:ACCTG:A	donor_loss	1.0000
9:134911127:ACTC:A	donor_loss	0.9900
9:134911128:CTCA:C	donor_loss	0.9900

AlphaMissense

2116 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:134912580:G:C	F168L	0.990
9:134912580:G:T	F168L	0.990
9:134912582:A:G	F168L	0.990
9:134912547:G:C	F179L	0.989
9:134912547:G:T	F179L	0.989
9:134912549:A:G	F179L	0.989
9:134909944:A:G	W279R	0.986
9:134909944:A:T	W279R	0.986
9:134913021:A:G	W155R	0.984
9:134913021:A:T	W155R	0.984
9:134909834:G:C	S315R	0.983
9:134909834:G:T	S315R	0.983
9:134909836:T:G	S315R	0.983
9:134909942:C:A	W279C	0.983
9:134909942:C:G	W279C	0.983
9:134913019:C:A	W155C	0.982
9:134913019:C:G	W155C	0.982
9:134909861:C:A	W306C	0.981
9:134909861:C:G	W306C	0.981
9:134912525:A:G	W187R	0.980
9:134912525:A:T	W187R	0.980
9:134913047:C:G	C146S	0.980
9:134913048:A:T	C146S	0.980
9:134912601:C:A	R161S	0.979
9:134912601:C:G	R161S	0.979
9:134912568:C:A	W172C	0.978
9:134912568:C:G	W172C	0.978
9:134909947:A:G	W278R	0.977
9:134909947:A:T	W278R	0.977
9:134912526:G:C	F186L	0.977

dbSNP variants (sampled 300 via entrez): RS1000471152 (9:134916222 G>A,C), RS1000665862 (9:134908829 A>C), RS1000732066 (9:134906809 G>A,T), RS1000792867 (9:134910373 C>T), RS1001076887 (9:134910195 G>A), RS1001351829 (9:134905576 T>A,C), RS1001587529 (9:134914699 T>A,G), RS1001656854 (9:134908057 T>C), RS1001960321 (9:134908394 C>T), RS1002676083 (9:134903494 G>A,C,T), RS1002705474 (9:134911097 C>A), RS1003087470 (9:134908134 G>C), RS1003135068 (9:134910896 G>A), RS1003349700 (9:134911808 A>G), RS1003367100 (9:134903234 G>A)

Disease associations

OMIM: gene MIM:601252 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003940_1	Trans-epidermal water loss	8.000000e-10
GCST006585_1617	Blood protein levels	4.000000e-66

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression, increases expression	2
Nickel	increases expression	2
2,4,6-tribromophenol	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
decabromobiphenyl ether	increases expression	1
sodium bichromate	decreases expression	1
butyraldehyde	increases expression	1
tetrabromobisphenol A	increases expression	1
pentabrominated diphenyl ether 100	increases expression	1
hexabrominated diphenyl ether 153	increases expression	1
Acetylglucosamine	affects binding	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Endosulfan	decreases expression	1
Methotrexate	decreases expression	1
Dronabinol	decreases expression	1
Antirheumatic Agents	decreases expression	1
Copper Sulfate	decreases expression	1
Particulate Matter	increases abundance, decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.