Filamiini B (3p14.3) , thyroid autoantigen

 https://www.ncbi.nlm.nih.gov/gene/2317

 

Also known as

AOI; FH1; SCT; TAP; LRS1; TABP; FLN-B; FLN1L; ABP-278; ABP-280

Summary

This gene encodes a member of the filamin family. The encoded protein interacts with glycoprotein Ib alpha as part of the process to repair vascular injuries. The platelet glycoprotein Ib complex includes glycoprotein Ib alpha, and it binds the actin cytoskeleton. Mutations in this gene have been found in several conditions:

 atelosteogenesis type 1 and type 3; 

boomerang dysplasia; 

autosomal dominant Larsen syndrome; and 

spondylocarpotarsal synostosis syndrome.

 Multiple alternatively spliced transcript variants that encode different protein isoforms have been described for this gene. [provided by RefSeq, Nov 2009]

Expression

Ubiquitous expression in colon (RPKM 41.4), prostate (RPKM 35.6) and 25 other tissues

Preferred Names

filamin-B

Names

ABP-280 homolog

Larsen syndrome 1 (autosomal dominant)

actin binding protein 278

actin-binding-like protein

beta-filamin

filamin B, beta

filamin homolog 1

filamin-3

thyroid autoantigen

 

Conserved Domains (4) summary

smart00557
Location:1328 → 1417

IG_FLMN; Filamin-type immunoglobulin domains

cd00014
Location:17 → 121

CH; Calponin homology domain; actin-binding domain which may be present as a single copy or in tandem repeats (which increases binding affinity). The CH domain is found in cytoskeletal and signal transduction proteins, including actin-binding proteins like ...

pfam00630
Location:1037 → 1124

Filamin; Filamin/ABP280 repeat

cl23780
Location:1749 → 1804

PepSY_TM; PepSY-associated TM region

Related articles in PubMed

1. Quantification of transmission risk in a male patient with a FLNB mosaic mutation causing Larsen syndrome: Implications for genetic counseling in postzygotic mosaicism cases. Bernkopf M, et al. Hum Mutat, 2017 Oct. PMID 28639312, Free PMC Article
2. Filamin B Loss-of-Function Mutation in Dimerization Domain Causes Autosomal-Recessive Spondylocarpotarsal Synostosis Syndrome with Rib Anomalies. Yang CF, et al. Hum Mutat, 2017 May. PMID 28145000
3. Differential expression of filamin B splice variants in giant cell tumor cells. Tsui JC, et al. Oncol Rep, 2016 Dec. PMID 27779699, Free PMC Article
4. F-actin clustering and cell dysmotility induced by the pathological W148R missense mutation of filamin B at the actin-binding domain. Zhao Y, et al. Am J Physiol Cell Physiol, 2016 Jan 1. PMID 26491051, Free PMC Article
5. Conditional testing of multiple variants associated with bone mineral density in the FLNB gene region suggests that they represent a single association signal. Mullin BH, et al. BMC Genet, 2013 Oct 31. PMID 24176111, Free PMC Article

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

1. In conclusion, the authors identify filamin B as a novel host factor that can interact with core protein to promote hepatitis B virus replication in hepatocytes.
2. We report the case of a male patient with Larsen syndrome found to be mosaic for a novel point mutation in FLNB in whom it was possible to provide evidence-based personalized counseling on transmission risk to future offspring. Using dideoxy sequencing, a low-level FLNB c.698A>G, encoding p.(Tyr233Cys) mutation was detected in buccal mucosa and fibroblast DNA.
3. This is the first identified mutation in the dimerization domain of FLNB. This loss-of-function frameshift mutation in FLNB causes autosomal-recessive SCT with rarely reported rib anomalies. This report demonstrates the involvement of rib anomaly in SCT and its causative mutation in the dimerization domain of FLNB.
4. Our results provide evidence for the involvement of FLNB in the pathogenesis of isolated Congenital talipes equinovarusand have expanded the clinical spectrum of FLNB mutations.
5. FlnA more strongly binds RhoA, although both filamins overlap with RhoA expression in the cell cytoplasm. FlnA promotes RhoA activation whereas FlnB indirectly inhibits this pathway. Moreover, FlnA loss leads to diminished expression of b1-integrin, whereas FlnB loss promotes integrin expression
6. splicing variants of FLNB are differentially expressed in giant cell tumor cells and may play a role in the proliferation and differentiation of tumor cells.
7. F-actin clustering through the interaction with the mutant FLNB actin-binding domain may limit the cytoskeletal reorganization, preventing normal skeletal development.
8. FLNb enhances invasion of cancer cells through phosphorylation of MRLC and FAK.
9. Polymorphism at rs11720285, rs11130605 and rs9809315, all of which are located either 5' of the transcription start site or in intron 1 of the FLNB gene has been identified as significantly associated with BMD in Caucasian women.
10. study presents two patients with Atelosteogenesis Type I caused by two novel Filamin B (FLNB) mutations affecting the same FLNB residue: c.542G > A, predicting p.Gly181Asp and c.542G > C, predicting p.Gly181Arg