FBLN1

Chr 22

fibulin 1

Also known as: FBLN, FIBL1

NCBI Gene: 2192ENSG00000077942UniProt: P23142

Fibulin 1 is a secreted glycoprotein that becomes incorporated into a fibrillar extracellular matrix. Calcium-binding is apparently required to mediate its binding to laminin and nidogen. It mediates platelet adhesion via binding fibrinogen. Four splice variants which differ in the 3' end have been identified. Each variant encodes a different isoform, but no functional distinctions have been identified among the four variants. [provided by RefSeq, Jul 2008]

420
ClinVar variants
74
Pathogenic / LP
0.92
pLI score· haploinsufficient
0
Active trials
Clinical Summary— FBLN1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.92). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
74 Pathogenic / Likely Pathogenic· 142 VUS of 420 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.34LOEUF
pLI 0.919
Z-score 4.74
OE 0.18 (0.10–0.34)
Highly constrained

Highly LoF-intolerant (top ~10% 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.
1.43Z-score
OE missense 0.81 (0.74–0.88)
350 obs / 433.6 exp
Tolerant

Mild missense constraint

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.0.18 (0.10–0.34)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.81 (0.74–0.88)
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.1.06
0≤1.21.6
LoF obs/exp: 7 / 38.9Missense obs/exp: 350 / 433.6Syn Z: -0.65

ClinVar Variant Classifications

420 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic73
Likely Pathogenic1
VUS142
Likely Benign88
Benign90
Conflicting5
73
Pathogenic
1
Likely Pathogenic
142
VUS
88
Likely Benign
90
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
73
0
73
Likely Pathogenic
0
0
1
0
1
VUS
1
131
7
3
142
Likely Benign
0
16
25
47
88
Benign
0
3
78
9
90
Conflicting
—5
Total115018459399

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

View in ClinVar →

Protein Context — Lollipop Plot

FBLN1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

FBLN1-related synpolydactyly, 3/3-prime/4, associated with metacarpal and metatarsal synostoses

limited
ARUndeterminedAltered Gene Product Structure
Dev. DisordersSkeletal
G2P ↗
missense variantinframe deletioninframe insertion

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
FIBULIN 1; FBLN1
MIM #135820 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
State of the Science for Kidney Disorders in Phelan-McDermid Syndrome: UPK3A, FBLN1, WNT7B, and CELSR1 as Candidate Genes.
McCoy MD et al.·Genes (Basel)
2022Review
Abnormal hypermethylation and clinicopathological significance of FBLN1 gene in cutaneous melanoma.
Wu BJ et al.·Tumour Biol
2014
The fibulin-1 gene (FBLN1) is disrupted in a t(12;22) associated with a complex type of synpolydactyly.
Debeer P et al.·J Med Genet
2002
Analysis of ferroptosis-related key genes and regulatory networks in diabetic foot ulcers.
Qiao J et al.·Gene
2025
Fibulin1 as a Novel Target for Promoting the Biological Function of Bone Marrow Mesenchymal Stem Cells and Implant Osseointegration in Diabetic Patients.
Zhang Y et al.·Int Dent J
2025Cohort
Fibulin-1: a novel biomarker for predicting disease activity of the thyroid-associated ophthalmopathy.
Hu H et al.·Eye (Lond)
2023
Fibulin-1 is downregulated through promoter hypermethylation in colorectal cancer: a CONSORT study.
Xu Z et al.·Medicine (Baltimore)
2015
Transcriptional landscape of oncogene-induced senescence: a machine learning-based meta-analytic approach.
Han Y et al.·Ageing Res Rev
2023Review
The genomic and clinical landscape of fetal akinesia.
Pergande M et al.·Genet Med
2020
Construction of store-operated calcium entry-related gene signature for predicting prognosis and indicates immune microenvironment infiltration in stomach adenocarcinomas.
Zhang Z et al.·Sci Rep
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
FBLN1 regulates ferroptosis in acute respiratory distress syndrome by reducing free ferrous iron by inhibiting the TGF-β/Smad pathway.
Yuan Y et al.·PLoS One
2024🔓 Open Access
A Bioinformatics-Based Study on Methylation Alterations of the FBLN1 Gene in Hippocampal Tissue of Alzheimer's Disease Model DKO and DTG Mice.
Tang R et al.·Int J Mol Sci
2024🔓 Open AccessFunctional
miR615-3p inhibited FBLN1 and osteogenic differentiation of umbilical cord mesenchymal stem cells by associated with YTHDF2 in a m6A-miRNA interaction manner.
Yang H et al.·Cell Prolif
2024🔓 Open Access
The Osteoblast Transcriptome in Developing Zebrafish Reveals Key Roles for Extracellular Matrix Proteins Col10a1a and Fbln1 in Skeletal Development and Homeostasis.
Raman R et al.·Biomolecules
2024🔓 Open AccessFunctional
Synergistic effects of rare variants of ARHGAP31 and FBLN1 in vitro in terminal transverse limb defects.
Tian H et al.·Front Genet
2022🔓 Open Access
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