FLNA

Chr XX-linkedXLRXLD

filamin A

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

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]

OMIMResearchGenerating clinical summary…
MultiplemechanismX-linked/XLR/XLDLOEUF 0.0810 OMIM phenotypes
Clinical SummaryFLNA
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Gene-Disease Validity (ClinGen)
periventricular nodular heterotopia · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint?
0.08LOEUF
pLI 1.000
Z-score 7.89
OE 0.03 (0.010.08)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?
3.78Z-score
OE missense 0.70 (0.660.74)
867 obs / 1241.9 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?
LoF OE?0.03 (0.010.08)
00.351.4
Missense OE?0.70 (0.660.74)
00.61.4
Synonymous OE?1.16
01.21.6
LoF obs/exp: 2 / 76.5Missense obs/exp: 867 / 1241.9Syn Z: -2.98
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveFLNA-related epileptic encephalopathyOTHERmonoallelic_X_heterozygous
definitiveFLNA-related otopalatodigital syndromeOTHERXLR
definitiveFLNA-related frontometaphyseal dysplasiaGOFXLR
definitiveFLNA-related Melnick-Needles syndromeOTHERmonoallelic_X_heterozygous
definitiveFLNA-related terminal osseous dysplasiaLOFXLR
definitiveFLNA-related periventricular nodular heterotopiaLOFmonoallelic_X_heterozygous
definitiveFLNA-related congenital idiopathic intestinal pseudoobstructionOTHERXLR

This gene — mechanism propensity

DN
0.3296th %ile
GOF
0.5856th %ile
LOF
0.73top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.08 · ClinGen HI: Sufficient evidence for dosage pathogenicity

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

FLNA · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.