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)
Triplosensitivity:
No Evidence for Triplosensitivity
(0)
Last Evaluated:
12/04/2019
Haploinsufficiency (HI) Score Details
HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency
(Disclaimer)
HI Disease:
- Marfan syndrome Monarch
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)