FBN1
  • 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
FBN1 (HGNC:3603) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
fibrillin 1
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
FBN, MFS1, WMS
Alias symbols
MASS, OCTD, SGS
%HI
2.53(Read more about the DECIPHER Haploinsufficiency Index)
pLI
1(Read more about gnomAD pLI score)
LOEUF
0.11(Read more about gnomAD LOEUF score)
Cytoband
15q21.1
Genomic Coordinates
GRCh37/hg19: chr15:48700510-48937906 NCBI Ensembl UCSC
GRCh38/hg38: chr15:48408313-48645709 NCBI Ensembl UCSC
MANE Select Transcript
NM_000138.5 ENST00000316623.10 (Read more about MANE Select)
Function
[Fibrillin-1]: Structural component of the 10-12 nm diameter microfibrils of the extracellular matrix, which conveys both structural and regulatory properties to load-bearing connective tissues (PubMed:1860873, PubMed:15062093). Fibrillin-1-containing microfibrils provide long-term force bearing structural support (PubMed:27026396). In tissues such as the lung, blood vessels and skin, microfibrils form the periphery of the elastic fiber, acting as a scaffold for the deposition of elastin (PubMed... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-30689
ClinGen Curation ID:
CCID:007127
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Read full report...
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Read full report...
Last Evaluated:
12/04/2019

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
HI Evidence:
  • PUBMED: 17701892
    Faivre et al. (2007) report on 1,013 patients with Marfan Syndrome or another fibrillinopathy and a pathogenic FBN1 mutation as part of the Universal Mutation Database for FBN1. There are 170 frameshift mutations and 137 nonsense mutations in this group.
  • PUBMED: 30286810
    Yang et al. (2018) performed MLPA on 115 unrelated patients with suspected Marfan or early onset aortic aneurysm/dissection were evaluated for deletions and duplications of FBN1 and TGFBR2. The authors identified 5 patients with single or multi exon deletions within the FBN1 gene. All 5 patients had multisystem deformities. Three patients were diagnosed with Classic Marfan syndrome. The additional 2 patients were eventually diagnosed with Marfan based on added criteria. No gross deleteions or duplication were identified in patients with only aortic aneurysm dissection without systemic involvement . The author suggests that gross deletions of FBN1 leads to Classic Marfan.
  • PUBMED: 21063442
    Hilhorst-Hofstee et al. (2011) report 5 patients from 1 family with a deletion that included the entire FBN1 gene. All deletion carriers had a diagnosis of Marfans based on the Ghent criteria for Marfan syndrome. The grandmother in this family was found to be mosaic based on the intensity of signals in both the MLPA and SNP analysis and was asymptomatic . The grandmother's results suggest a mosaic deletion.
HI Evidence Comments:
In summary, Loss of function variants (exonic deletions and whole gene deletions) of the FBN1 gene have been described in individuals with Marfan phenotype. Additional PMIDs: 21936929, 30479897, 17492313, 28842177 GeneReviews: Dietz H. Marfan Syndrome. 2001 Apr 18 [Updated 2017 Oct 12]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1335/

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)

Genomic View

Select assembly: (NC_000015.9) (NC_000015.10)