FN1

fibronectin 1, the group of Fibronectin type III domain containing|Receptor ligands

Basic information

Region (hg38): 2:215360440-215436073

Links

ENSG00000115414 ∙ NCBI:2335 ∙ OMIM:135600 ∙ HGNC:3778 ∙ Uniprot:P02751 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• spondylometaphyseal dysplasia, 'corner fracture' type (Strong), mode of inheritance: AD
• spondylometaphyseal dysplasia, 'corner fracture' type (Strong), mode of inheritance: AD
• fibronectin glomerulopathy (Supportive), mode of inheritance: AD
• spondylometaphyseal dysplasia, 'corner fracture' type (Supportive), mode of inheritance: AD
• glomerulopathy with fibronectin deposits 2 (Moderate), mode of inheritance: AD
• glomerulopathy with fibronectin deposits 2 (Strong), mode of inheritance: AD
• spondylometaphyseal dysplasia, 'corner fracture' type (Strong), mode of inheritance: AD
• spondylometaphyseal dysplasia, 'corner fracture' type (Definitive), mode of inheritance: AD
• glomerulopathy with fibronectin deposits 2 (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Glomerulopathy with fibronectin deposits 2; Spondylometaphyseal dysplasia, corner fracture type	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Musculoskeletal; Renal	2869211; 1544672; 7747733; 7564073; 12042895; 18268355; 29100092

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FN1 gene.

• not provided (3 variants)
• Spondylometaphyseal dysplasia - Sutcliffe type (2 variants)
• Spondylometaphyseal dysplasia - Sutcliffe type;Glomerulopathy with fibronectin deposits 2 (1 variants)
• Spondylometaphyseal dysplasia (1 variants)
• Glomerulopathy with fibronectin deposits 2 (1 variants)
• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FN1 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			6	236	26	268
missense	5	7	475	63	14	564
nonsense			8			8
start loss						0
frameshift		2	7			9
inframe indel			7			7
splice donor/acceptor (+/-2bp)	1		9			10
splice region		1	25	40	6	72
non coding			5	180	183	368
Total	6	9	517	479	223

Variants in FN1

This is a list of pathogenic ClinVar variants found in the FN1 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-215361425-G-A			Likely benign (Mar 31, 2020)
2-215361562-C-T		Inborn genetic diseases	Conflicting classifications of pathogenicity (Feb 13, 2024)
2-215361563-G-A			Uncertain significance (Oct 13, 2022)
2-215361581-C-G		Chronic kidney disease	Uncertain significance (Sep 23, 2022)
2-215361587-C-T		Glomerulopathy with fibronectin deposits 2;Spondylometaphyseal dysplasia - Sutcliffe type	Uncertain significance (Jul 17, 2023)
2-215361588-A-T			Uncertain significance (Oct 01, 2022)
2-215361596-G-C		Inborn genetic diseases	Uncertain significance (Dec 03, 2021)
2-215361610-A-G		Nephrotic syndrome	Likely pathogenic (Nov 10, 2017)
2-215361621-A-C			Benign (Aug 19, 2023)
2-215361623-C-T			Uncertain significance (Nov 22, 2022)
2-215361645-G-A			Benign (Nov 28, 2023)
2-215361645-GA-G		Spondylometaphyseal dysplasia - Sutcliffe type;Glomerulopathy with fibronectin deposits 2	Benign/Likely benign (Nov 28, 2023)
2-215361656-T-C			Likely benign (Jan 16, 2020)
2-215361670-G-A			Likely benign (Jul 26, 2020)
2-215361694-C-CG			Likely benign (Jan 16, 2020)
2-215361861-GT-G			Likely benign (Dec 18, 2019)
2-215361861-G-GTT			Likely benign (May 01, 2020)
2-215361907-G-C			Benign/Likely benign (Sep 01, 2022)
2-215361919-A-C			Benign (Nov 11, 2018)
2-215361949-T-C			Likely benign (Aug 10, 2023)
2-215361961-G-C			Likely benign (Dec 06, 2022)
2-215361965-T-G			Uncertain significance (Jun 03, 2023)
2-215361966-T-TA			Uncertain significance (Mar 02, 2023)
2-215361976-G-A			Uncertain significance (Nov 20, 2023)
2-215361985-T-C			Likely benign (Nov 28, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FN1	protein_coding	protein_coding	ENST00000354785	46	75733

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00140	0.999	125669	0	79	125748	0.000314

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.65	1196	1.37e+3	0.875	0.0000790	16072
Missense in Polyphen		519	699.87	0.74157		8402
Synonymous	-0.582	541	524	1.03	0.0000328	4969
Loss of Function	8.00	34	134	0.254	0.00000770	1457

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000770	0.000770
Ashkenazi Jewish	0.000298	0.000298
East Asian	0.000218	0.000217
Finnish	0.000277	0.000277
European (Non-Finnish)	0.000335	0.000325
Middle Eastern	0.000218	0.000217
South Asian	0.000392	0.000359
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin. Fibronectins are involved in cell adhesion, cell motility, opsonization, wound healing, and maintenance of cell shape. Involved in osteoblast compaction through the fibronectin fibrillogenesis cell-mediated matrix assembly process, essential for osteoblast mineralization. Participates in the regulation of type I collagen deposition by osteoblasts.
• Disease: DISEASE: Glomerulopathy with fibronectin deposits 2 (GFND2) [MIM:601894]: Genetically heterogeneous autosomal dominant disorder characterized clinically by proteinuria, microscopic hematuria, and hypertension that leads to end-stage renal failure in the second to fifth decade of life. {ECO:0000269|PubMed:18268355}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Spondylometaphyseal dysplasia, corner fracture type (SMDCF) [MIM:184255]: An autosomal dominant form of spondylometaphyseal dysplasia, a group of short stature disorders distinguished by abnormalities in the vertebrae and the metaphyses of the tubular bones. SMDCF is characterized by flake-like, triangular, or curvilinear ossification centers at the edges of irregular metaphyses that simulate fractures. These corner fractures involve the distal tibia, the ulnar aspect of the distal radius, the proximal humerus, and the proximal femur. They represent irregular ossification at the growth plates and secondary ossification centers. {ECO:0000269|PubMed:29100092}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);ECM-receptor interaction - Homo sapiens (human);Focal adhesion - Homo sapiens (human);AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human);Small cell lung cancer - Homo sapiens (human);Amoebiasis - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);Bacterial invasion of epithelial cells - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);miRNA targets in ECM and membrane receptors;Focal Adhesion;Overview of nanoparticle effects;Rac1-Pak1-p38-MMP-2 pathway;TGF-beta Signaling Pathway;Simplified Interaction Map Between LOXL4 and Oxidative Stress Pathway;Association Between Physico-Chemical Features and Toxicity Associated Pathways;TGF-B Signaling in Thyroid Cells for Epithelial-Mesenchymal Transition;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;miR-509-3p alteration of YAP1-ECM axis;Interleukin-4 and 13 signaling;PI3K-Akt Signaling Pathway;EMT transition in Colorectal Cancer;Inflammatory Response Pathway;Regulation of Actin Cytoskeleton;Senescence and Autophagy in Cancer;MAP2K and MAPK activation;Disease;Signal Transduction;Post-translational protein phosphorylation;Integrin cell surface interactions;Post-translational protein modification;Metabolism of proteins;Extracellular matrix organization;GRB2:SOS provides linkage to MAPK signaling for Integrins ;p130Cas linkage to MAPK signaling for integrins;Integrin alphaIIb beta3 signaling;Fibronectin matrix formation;Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs);Platelet Aggregation (Plug Formation);Platelet degranulation ;Response to elevated platelet cytosolic Ca2+;Platelet activation, signaling and aggregation;Beta3 integrin cell surface interactions;Integrin;Integrin signaling;Cell surface interactions at the vascular wall;Hemostasis;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;VEGFR3 signaling in lymphatic endothelium;Angiopoietin receptor Tie2-mediated signaling;Signaling by RAS mutants;Signaling by high-kinase activity BRAF mutants;Signaling by moderate kinase activity BRAF mutants;Paradoxical activation of RAF signaling by kinase inactive BRAF;Alpha9 beta1 integrin signaling events;Signaling by BRAF and RAF fusions;Oncogenic MAPK signaling;Diseases of signal transduction;Beta5 beta6 beta7 and beta8 integrin cell surface interactions;Beta1 integrin cell surface interactions;Urokinase-type plasminogen activator (uPA) and uPAR-mediated signaling;Alpha4 beta1 integrin signaling events;Syndecan-4-mediated signaling events;Integrins in angiogenesis;Syndecan-2-mediated signaling events (Consensus)

Recessive Scores

• pRec: 0.992

Intolerance Scores

• loftool: 0.719
• rvis_EVS: -2.32
• rvis_percentile_EVS: 1.19

Haploinsufficiency Scores

• pHI: 0.922
• hipred: Y
• hipred_score: 0.725
• ghis: 0.567

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.698

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Fn1
• Phenotype: hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); normal 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); neoplasm; embryo phenotype; liver/biliary system phenotype; limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype

Zebrafish Information Network

• Gene name: fn1b
• Affected structure: atrioventricular valve
• Phenotype tag: abnormal
• Phenotype quality: morphology

Gene ontology

• Biological process: angiogenesis;regulation of protein phosphorylation;platelet degranulation;acute-phase response;cell-substrate junction assembly;cell adhesion;calcium-independent cell-matrix adhesion;positive regulation of cell population proliferation;regulation of cell shape;response to wounding;positive regulation of gene expression;positive regulation of peptidase activity;peptide cross-linking;cytokine-mediated signaling pathway;extracellular matrix organization;integrin activation;substrate adhesion-dependent cell spreading;endodermal cell differentiation;wound healing;post-translational protein modification;cellular protein metabolic process;positive regulation of axon extension;positive regulation of fibroblast proliferation;leukocyte migration;interaction with symbiont;interaction with other organism via secreted substance involved in symbiotic interaction;regulation of ERK1 and ERK2 cascade;neural crest cell migration involved in autonomic nervous system development;positive regulation of substrate-dependent cell migration, cell attachment to substrate;negative regulation of transforming growth factor-beta secretion
• Cellular component: extracellular region;fibrinogen complex;basement membrane;extracellular space;endoplasmic reticulum lumen;endoplasmic reticulum-Golgi intermediate compartment;apical plasma membrane;extracellular matrix;platelet alpha granule lumen;collagen-containing extracellular matrix;extracellular exosome;blood microparticle
• Molecular function: protease binding;signaling receptor binding;integrin binding;extracellular matrix structural constituent;protein binding;collagen binding;protein C-terminus binding;heparin binding;peptidase activator activity;enzyme binding;identical protein binding;proteoglycan binding;chaperone binding;disordered domain specific binding