FLNB

filamin B

Ensembl:
ENSG00000136068
UniProt:
O75369
OMIM:
603381
Synonyms:
ABP-278, FH1, FLN1L, LRS1, TABP

Cilia effects upon perturbation of FLNB

Ciliogenesis screen results (3 screens)

  • Wheway et al. 2015 (siRNA) [siRNA]: Ciliogenesis Defect (z=-3.09) PMID:26167766
  • Breslow et al. 2018 (CRISPR) [CRISPR]: No Significant Effect PMID:29459680
  • Roosing et al. 2015 (siRNA) [siRNA]: No effect PMID:26595381

Phenotypes

Mouse phenotype:
decreased bone mineral density; decreased neutrophil cell number; decreased bone mineral content; increased circulating serum albumin level; decreased lean body mass; decreased red blood cell distribution width; increased total body fat amount; preweaning lethality; complete penetrance

Ciliopathy associations

  • Visceral Heterotaxy / Situs Inversus

Subcellular localization

actin filaments, basal body, cilia, cytoskeleton, cytosol, golgi apparatus, plasma membrane

Functional category

  • Metabolism; Cilia???cytoskeleton/adhesion links

Function

Cytoskeletal protein. Listed as novel Congenital Heart Disease (CHD) gene with Ciliopathy-like phenotypes, likely involved in structural stability of the cilium or centrosome anchoring(41279393). We identified 5 probands with CHD and HTX, 3 with recessive and 2 with damaging heterozygous variants in FLNB. Disrupting flnb in Xenopus reproduced key features of the human HTX phenotype, including defects in cardiac development and impaired motile cilia function. Rescue experiments confirmed the functional conservation of human FLNB, directly implicating actin cytoskeletal disruption in ciliogenesis and left-right patterning defects. Our results provide crucial evidence linking human FLNB dysfunction to ciliopathies and CHD and HTX(PMID: 41674076).

Model organism evidence

Xenopus (2 references)

Patient-informed CRISPR screen identifies FLNB as a congenital heart disease and ciliopathy gene.

Patient-informed CRISPR Screen Identifies FLNB as a Novel Congenital Heart Disease and Ciliopathy Gene.

PMIDs: 41674076, 41279393