FBLN1

fibulin 1, the group of Fibulins

Basic information

Region (hg38): 22:45502238-45601135

Links

ENSG00000077942 ∙ NCBI:2192 ∙ OMIM:135820 ∙ HGNC:3600 ∙ Uniprot:P23142 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• synpolydactyly type 2 (Limited), mode of inheritance: AR
• FBLN1-related developmental delay-central nervous system anomaly-syndactyly syndrome (Supportive), mode of inheritance: AR
• synpolydactyly type 2 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Synpolydactyly 2	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; In Cutis laxa, individuals can have cardiac manifestations such as supravalvular aortic stenosis, but the condition should be recognizable	Musculoskeletal	8831136; 11836357

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FBLN1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FBLN1 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			4	33	9	46
missense			61	13	3	77
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			2	6	5	13
non coding				10	67	77
Total	0	0	66	56	79

Variants in FBLN1

This is a list of pathogenic ClinVar variants found in the FBLN1 region.

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

Position	Type	Phenotype	Significance	ClinVar
22-45502712-G-C			Benign (Nov 11, 2018)
22-45502794-G-C			Benign (May 12, 2021)
22-45503015-C-A			Likely benign (Jul 06, 2018)
22-45503017-C-A		Synpolydactyly type 2	Uncertain significance (Jun 03, 2020)
22-45503043-C-T			Uncertain significance (Jun 23, 2023)
22-45503047-C-T			Uncertain significance (Jun 26, 2023)
22-45503057-G-A		not specified	Benign/Likely benign (Oct 05, 2023)
22-45503059-C-A			Uncertain significance (Jul 17, 2023)
22-45503059-C-T			Uncertain significance (Jan 25, 2024)
22-45503070-G-A		FBLN1-related disorder	Likely benign (Feb 22, 2021)
22-45503077-C-G			Likely benign (May 31, 2023)
22-45503078-G-C			Likely benign (Aug 17, 2023)
22-45503083-C-T			Likely benign (Aug 30, 2022)
22-45518581-G-A			Benign (May 11, 2021)
22-45518661-C-T			Benign (May 15, 2021)
22-45518688-C-T		not specified	Uncertain significance (Apr 28, 2022)
22-45518689-G-A			Likely benign (Mar 05, 2018)
22-45518691-A-G			Uncertain significance (Aug 01, 2023)
22-45518715-C-T		not specified	Uncertain significance (Mar 21, 2023)
22-45518754-C-T		not specified	Uncertain significance (Dec 22, 2023)
22-45518772-A-C		not specified	Uncertain significance (Dec 20, 2023)
22-45518791-C-T			Benign (Jun 26, 2023)
22-45518795-T-C			Benign (Jan 29, 2024)
22-45518804-C-T			Likely benign (Dec 06, 2022)
22-45518812-T-G			Benign (May 15, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FBLN1	protein_coding	protein_coding	ENST00000327858	17	98898

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.919	0.0812	125729	0	19	125748	0.0000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.43	350	434	0.807	0.0000321	4633
Missense in Polyphen		128	158.76	0.80624		1532
Synonymous	-0.645	191	180	1.06	0.0000148	1325
Loss of Function	4.74	7	38.9	0.180	0.00000216	426

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000362	0.000362
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000578	0.0000544
Finnish	0.000142	0.000139
European (Non-Finnish)	0.0000440	0.0000439
Middle Eastern	0.0000578	0.0000544
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Incorporated into fibronectin-containing matrix fibers. May play a role in cell adhesion and migration along protein fibers within the extracellular matrix (ECM). Could be important for certain developmental processes and contribute to the supramolecular organization of ECM architecture, in particular to those of basement membranes. Has been implicated in a role in cellular transformation and tumor invasion, it appears to be a tumor suppressor. May play a role in haemostasis and thrombosis owing to its ability to bind fibrinogen and incorporate into clots. Could play a significant role in modulating the neurotrophic activities of APP, particularly soluble APP. {ECO:0000269|PubMed:11792823, ECO:0000269|PubMed:9393974, ECO:0000269|PubMed:9466671}.
• Disease: DISEASE: Note=A chromosomal aberration involving FBLN1 is found in a complex type of synpolydactyly referred to as 3/3-prime/4 synpolydactyly associated with metacarpal and metatarsal synostoses. Reciprocal translocation t(12;22)(p11.2;q13.3) with RASSF8. Fibroblasts derived from a patient with synpolydactyly displayed alterations in the level of isoform D splice variant incorporated into the ECM and secreted into the conditioned culture medium. By contrast, the expression of isoform C was not perturbed in the patients fibroblasts. Furthermore, no aberrant polypeptides were detected in extracts of cultured patients fibroblasts. The translocation t(12;22) may result in haploinsufficiency of the isoform D splice variant, which could lead to the observed limb malformation. {ECO:0000269|PubMed:11836357}.; DISEASE: Note=Elevated expression and altered processing of FBLN1 protein is associated with human breast cancer. {ECO:0000269|PubMed:12644824}.
• Pathway: Extracellular matrix organization;Molecules associated with elastic fibres;Elastic fibre formation (Consensus)

Recessive Scores

• pRec: 0.235

Intolerance Scores

• loftool: 0.0203
• rvis_EVS: -0.35
• rvis_percentile_EVS: 29.61

Haploinsufficiency Scores

• pHI: 0.673
• hipred: Y
• hipred_score: 0.793
• ghis: 0.553

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.740

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Fbln1
• Phenotype: embryo phenotype; respiratory system 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); 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); hematopoietic 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); hearing/vestibular/ear phenotype; vision/eye phenotype; immune system phenotype; renal/urinary system phenotype; skeleton 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); growth/size/body region phenotype; endocrine/exocrine gland phenotype; muscle phenotype; craniofacial phenotype; cellular phenotype

Gene ontology

• Biological process: negative regulation of protein phosphorylation;negative regulation of cell adhesion;integrin-mediated signaling pathway;embryo implantation;positive regulation of peptidase activity;viral process;extracellular matrix organization;negative regulation of ERK1 and ERK2 cascade;blood coagulation, fibrin clot formation;negative regulation of substrate adhesion-dependent cell spreading;negative regulation of cell motility;negative regulation of stem cell proliferation
• Cellular component: extracellular region;basement membrane;extracellular space;extracellular matrix;collagen-containing extracellular matrix;extracellular exosome;elastic fiber
• Molecular function: fibronectin binding;extracellular matrix structural constituent;calcium ion binding;protein C-terminus binding;peptidase activator activity;identical protein binding;protein-containing complex binding;fibrinogen binding