FBN2

Chr 5

fibrillin 2

Also known as: CCA, DA9, EOMD

NCBI Gene: 2201ENSG00000138829UniProt: P35556

The protein encoded by this gene is a component of connective tissue microfibrils and may be involved in elastic fiber assembly. Mutations in this gene cause congenital contractural arachnodactyly. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

UniProtContractural arachnodactyly, congenital
UniProtMacular degeneration, early-onset
575
ClinVar variants
19
Pathogenic / LP
1.00
pLI score· haploinsufficient
1
Active trials
Clinical Summary— FBN2
🧬
Gene-Disease Validity (ClinGen)
congenital contractural arachnodactyly · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
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.
📋
ClinVar Variants
19 Pathogenic / Likely Pathogenic· 313 VUS of 575 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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.
0.20LOEUF
pLI 1.000
Z-score 9.83
OE 0.14 (0.10–0.20)
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.
1.55Z-score
OE missense 0.89 (0.85–0.93)
1456 obs / 1632.1 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.0.14 (0.10–0.20)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.89 (0.85–0.93)
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: 22 / 153.4Missense obs/exp: 1456 / 1632.1Syn Z: -1.07

ClinVar Variant Classifications

575 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1
Likely Pathogenic18
VUS313
Likely Benign225
Benign12
Conflicting6
1
Pathogenic
18
Likely Pathogenic
313
VUS
225
Likely Benign
12
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
0
0
1
Likely Pathogenic
2
13
3
0
18
VUS
23
258
31
1
313
Likely Benign
0
20
87
118
225
Benign
0
3
0
9
12
Conflicting
—6
Total25295121128575

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

View in ClinVar →

Protein Context — Lollipop Plot

FBN2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

FBN2-related congenital contractural arachnodactyly

definitive
ADDominant NegativeAltered Gene Product Structure
Dev. DisordersEyeSkeletal
G2P ↗

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

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

📖
GeneReview available — FBN2
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
De novo variants underlying monogenic syndromes with intellectual disability in a neurodevelopmental cohort from India.
Pande S et al.·Eur J Hum Genet
2024Cohort
The fibrillinopathies: New insights with focus on the paradigm of opposing phenotypes for both FBN1 and FBN2.
Peeters S et al.·Hum Mutat
2022Review
Genetic models of fibrillinopathies.
Summers KM·Genetics
2024Review
Short stature, brachydactyly and joint contractures associated with novel FBN2 variants in two families.
Loid P et al.·J Med Genet
2025
Carrying both COL1A2 and FBN2 gene heterozygous mutations results in a severe skeletal clinical phenotype: an affected family.
Chen J et al.·BMC Med Genomics
2022
Genetic Overlap of Thoracic Aortic Aneurysms and Intracranial Aneurysms.
Changez MIK et al.·Genes (Basel)
2025Review
A comprehensive analysis of FBN2 in bladder cancer: A risk factor and the tumour microenvironment influencer.
Lu Z et al.·IET Syst Biol
2023
Thoracic Aortic Disease in Patients With Heterozygous Variants Outside the Central Region of FBN2.
Demal TJ et al.·Circ Genom Precis Med
2025Cohort
[Fibrillin-2 gene mutations associated with hereditary connective tissue diseases].
Xu FR et al.·Yi Chuan
2019Review
Delineation of a new fibrillin-2-opathy with evidence for a role of FBN2 in the pathogenesis of carpal tunnel syndrome.
Peeters S et al.·J Med Genet
2021
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
AortopathiesThoracic Aortic AneurysmAortic Valve Disease

Pathogenetic Basis of Aortopathy and Aortic Valve Disease

ACTIVE NOT RECRUITING
NCT03440697Yale UniversityStarted 2015-12-10

External Resources

Links to major genomics databases and tools