FLNA |
- 3
Haplo
Score - 0
Triplo
Score
Gene Facts External Data Attribution
- HGNC Symbol
- FLNA (HGNC:3754) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
- HGNC Name
- filamin A
- Gene type
- protein-coding gene
- Locus type
- gene with protein product
- Previous symbols
- FLN1, FLN, OPD2, OPD1
- Alias symbols
- ABP-280
- %HI
- 8.01(Read more about the DECIPHER Haploinsufficiency Index)
- pLI
- 1(Read more about gnomAD pLI score)
- LOEUF
- 0.08(Read more about gnomAD LOEUF score)
- Cytoband
- Xq28
- Genomic Coordinates
-
GRCh37/hg19: chrX:153576899-153603002 NCBI Ensembl UCSC GRCh38/hg38: chrX:154348531-154374634 NCBI Ensembl UCSC - MANE Select Transcript
- NM_001110556.2 ENST00000369850.10 (Read more about MANE Select)
- Function
- Promotes orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins. Anchors various transmembrane proteins to the actin cytoskeleton and serves as a scaffold for a wide range of cytoplasmic signaling proteins. Interaction with FLNB may allow neuroblast migration from the ventricular zone into the cortical plate. Tethers cell surface- localized furin, modulates its rate of internalization and directs its intracellular trafficking (By similarity). Involved in cili... (Source: Uniprot)
Dosage Sensitivity Summary (Gene)
Haploinsufficiency (HI) Score Details
- X-linked periventricular heterotopia (PVNH1) Monarch
-
PUBMED:
16684786
Parrini et al., (2013) identified 25 loss of function sequence variants (frameshift, splice site, nonsense) in 40 patients with periventricular nodular heterotopia (PNH). FLNA variants were found in 100% of familial cases with X-linked PNH (10 families) and in 26% of sporadic cases with classical bilateral PNH (affected females: 93% and affected males 7%).
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PUBMED:
23032111
Reinstein et al., (2013) reported FLNA variants in 11 males and females with a wide spectrum of connective tissue and vascular anomalies. The variants included frameshift, splice site, nonsense, and a deletion of exons 2-13 detected by MLPA. The authors identified 4 de novo loss of function variants, including the exonic deletion. The authors suggested that the variants leading to disease in males were likely to be hypomorphic to permit survival in hemizygotes. The diagnosis of X-linked periventricular heterotopia (PH) was established by neuroimaging in individuals with variable clinical manifestations including seizures, developmental delay, muscle weakness, and family history of PH.
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PUBMED:
26471271
Lange et al., (2015) described 39 FLNA variants, mainly truncating, in 47 patients with periventricular nodular heterotopia (PVNH). Missense variants were only identified in 2 patients. The authors reported 10 de novo variants (1 missense, 2 nonsense, 4 frameshift, 1 splice site, 1 exonic deletion: exons 40 to 3’UTR, and 1 complex genomic rearrangement: deletion of exon 46 and duplications exons 4-22).
The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.
Triplosensitivity (TS) Score Details
-
PUBMED: 24098143
Sajan et al., (2013) reported a male patient with cerebellar hypoplasia with an 0.49 Mb duplication of Xq28 involving entire FLNA .
The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.