FLNA

Chr X

filamin A

Also known as: ABP-280, ABPX, CSBS, CVD1, FGS2, FLN, FLN-A, FLN1

NCBI Gene: 2316 ENSG00000196924 UniProt: P21333

The encoded protein is an actin-binding protein that crosslinks actin filaments and links them to membrane glycoproteins, functioning in cytoskeletal remodeling to control cell shape and migration. Loss-of-function mutations cause X-linked periventricular nodular heterotopia, otopalatodigital syndromes, frontometaphyseal dysplasia, Melnick-Needles syndrome, and congenital intestinal pseudoobstruction, with inheritance patterns varying from X-linked recessive (typically for periventricular heterotopia in females) to X-linked dominant (for the skeletal dysplasias). The protein interacts with integrins and transmembrane complexes, and its disruption leads to abnormal neuronal migration and skeletal development.

ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

The protein encoded by this gene is an actin-binding protein that crosslinks actin filaments and links actin filaments to membrane glycoproteins. The encoded protein is involved in remodeling the cytoskeleton to effect changes in cell shape and migration. This protein interacts with integrins, transmembrane receptor complexes, and second messengers. Defects in this gene are a cause of several syndromes, including periventricular nodular heterotopias (PVNH1, PVNH4), otopalatodigital syndromes (OPD1, OPD2), frontometaphyseal dysplasia (FMD), Melnick-Needles syndrome (MNS), and X-linked congenital idiopathic intestinal pseudoobstruction (CIIPX). Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2009]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtPeriventricular nodular heterotopia 1

UniProtOtopalatodigital syndrome 1

UniProtOtopalatodigital syndrome 2

UniProtFrontometaphyseal dysplasia 1

Clinical highlights

Gene-disease validity (ClinGen)

periventricular nodular heterotopia · XLDefinitivesufficient evidence for diagnostic panels2 gene-disease associations curated in total

Interpreting a novel variant

Curated mechanisms (Gene2Phenotype) include both loss of function and gain of function. Which applies is variant-dependent — do not assume a null variant is, or isn’t, the pathogenic class without checking the specific variant.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

164

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.08

LOEUF· LoF intol.

Multiple*

Mechanism· G2P

Some data sources returned errors (1)