FLNA
Chr XX-linkedXLRXLDfilamin A
Also known as: ABP-280, ABPX, CSBS, CVD1, FGS2, FLN, FLN-A, FLN1
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.
Definitive — sufficient evidence for diagnostic panels
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Highly missense-constrained (top ~0.1%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
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
405 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 17 | 0 | 3 | 0 | 20 |
Likely Pathogenic | 4 | 1 | 0 | 0 | 5 |
VUS | 2 | 127 | 10 | 4 | 143 |
Likely Benign | 0 | 10 | 53 | 52 | 115 |
Benign | 0 | 5 | 1 | 3 | 9 |
Conflicting | — | 1 | |||
| Total | 23 | 143 | 67 | 59 | 293 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View 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.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools