FLNB

Chr 3

filamin B

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

NCBI Gene: 2317ENSG00000136068UniProt: O75369

This gene encodes a member of the filamin family. The encoded protein interacts with glycoprotein Ib alpha as part of the process to repair vascular injuries. The platelet glycoprotein Ib complex includes glycoprotein Ib alpha, and it binds the actin cytoskeleton. Mutations in this gene have been found in several conditions: atelosteogenesis type 1 and type 3; boomerang dysplasia; autosomal dominant Larsen syndrome; and spondylocarpotarsal synostosis syndrome. Multiple alternatively spliced transcript variants that encode different protein isoforms have been described for this gene. [provided by RefSeq, Nov 2009]

Primary Disease Associations & Inheritance

UniProtAtelosteogenesis 1
UniProtAtelosteogenesis 3
UniProtBoomerang dysplasia
UniProtLarsen syndrome
550
ClinVar variants
38
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— FLNB
🧬
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.
📋
ClinVar Variants
38 Pathogenic / Likely Pathogenic· 324 VUS of 550 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.44LOEUF
pLI 0.000
Z-score 6.50
OE 0.34 (0.26–0.44)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.14Z-score
OE missense 0.85 (0.81–0.89)
1326 obs / 1564.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.34 (0.26–0.44)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.85 (0.81–0.89)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.01
0≤1.21.6
LoF obs/exp: 38 / 112.4Missense obs/exp: 1326 / 1564.2Syn Z: -0.13

ClinVar Variant Classifications

550 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic18
Likely Pathogenic20
VUS324
Likely Benign181
Benign2
Conflicting5
18
Pathogenic
20
Likely Pathogenic
324
VUS
181
Likely Benign
2
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
11
2
5
0
18
Likely Pathogenic
12
4
4
0
20
VUS
2
302
18
2
324
Likely Benign
0
10
84
87
181
Benign
0
1
0
1
2
Conflicting
—5
Total2531911190550

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View 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.

Gene2Phenotype Curations

FLNB-related atelosteogenesis, type 1

definitive
ADGain Of FunctionAltered Gene Product Structure
Dev. DisordersSkeletal
G2P ↗

FLNB-related atelosteogenesis, type 3

definitive
ADGain Of FunctionAltered Gene Product Structure
Dev. DisordersSkeletal
G2P ↗

FLNB-related Larsen syndrome

definitive
ADUndeterminedAltered Gene Product Structure, Uncertain
Dev. DisordersEyeSkeletal
G2P ↗
missense variantinframe deletioninframe insertion

FLNB-related spondylocarpotarsal synostosis syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersEyeSkeletal
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

📖
GeneReview available — FLNB
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Fine-tuning levels of filamins a and b as a specific mechanism sustaining Th2 lymphocyte functions.
Maire K et al.·Nat Commun
2024Functional
A Stop-gain Variant c.220C>T (p.(Gln74*)) in FLNB Segregates with Spondylocarpotarsal Synostosis Syndrome in a Consanguineous Family.
Shahid H et al.·Yale J Biol Med
2023Review
CircFLNB upregulated by chemotherapy via alternative splicing suppresses the progression of colorectal cancer.
Han Y et al.·Cancer Lett
2025
Filamin B: The next hotspot in skeletal research?
Xu Q et al.·J Genet Genomics
2017Review
The Genetic Landscape of Children Born Small for Gestational Age with Persistent Short Stature.
Toni L et al.·Horm Res Paediatr
2024
A molecular and clinical study of Larsen syndrome caused by mutations in FLNB.
Bicknell LS et al.·J Med Genet
2007
Cell-Dependent Pathogenic Roles of Filamin B in Different Skeletal Malformations.
Wu H et al.·Oxid Med Cell Longev
2022
GLI2 and FLNB Define Periocular Morphoeic Basal Cell Carcinoma.
Bladen JC et al.·Int J Mol Sci
2025
Prenatal diagnosis and pregnancy outcomes in fetuses with vertebral abnormalities.
Hu J et al.·J Matern Fetal Neonatal Med
2025
Oligogenic analysis across broad phenotypes of 46,XY differences in sex development associated with NR5A1/SF-1 variants: findings from the international SF1next study.
Kouri C et al.·EBioMedicine
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools