FLNB

Chr 3ADAR

filamin B

Also known as: ABP-278, ABP-280, FH1, FLN-B, FLN1L, LRS1, TABP, TAP

Filamin B connects cell membrane constituents to the actin cytoskeleton, promotes orthogonal branching of actin filaments, and anchors transmembrane proteins to the cytoskeleton. Mutations cause skeletal dysplasias including atelosteogenesis types I and III, boomerang dysplasia, Larsen syndrome, and spondylocarpotarsal synostosis syndrome. The gene shows both autosomal dominant and autosomal recessive inheritance patterns and is highly constrained against loss-of-function variants.

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismAD/ARLOEUF 0.445 OMIM phenotypes
Clinical SummaryFLNB
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Gene-Disease Validity (ClinGen)
FLNB-associated autosomal dominant filamin related bone disorder · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.34) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.44LOEUF
pLI 0.000
Z-score 6.50
OE 0.34 (0.260.44)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.14Z-score
OE missense 0.85 (0.810.89)
1326 obs / 1564.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.34 (0.260.44)
00.351.4
Missense OE0.85 (0.810.89)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 38 / 112.4Missense obs/exp: 1326 / 1564.2Syn Z: -0.13
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveFLNB-related atelosteogenesis, type 1GOFAD
definitiveFLNB-related atelosteogenesis, type 3GOFAD
definitiveFLNB-related Larsen syndromeOTHERAD
definitiveFLNB-related spondylocarpotarsal synostosis syndromeLOFAR
DN
0.7326th %ile
GOF
0.75top 25%
LOF
0.3068th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median · 1 literature citation
DNprediction above median

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.

Literature Evidence

GOFThese mutations cluster in particular FLNB protein domains and act in a presumptive gain-of-function mechanism.PMID:19505475

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

FLNB · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC