Congenital contractural arachnodactyly

Summary

Congenital contractural arachnodactyly (MONDO:0007363) is a disease caused by FBN2 (GenCC Definitive), with 2 cohort genes and 1 clinical trial.

At a glance

• Prevalence: Unknown (Worldwide)
• Causal gene: FBN2 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 3,043
• Phenotypes (HPO): 21
• Clinical trials: 1

Clinical features

Signs & symptoms

Clinical features (HPO)

21 HPO clinical features (Orphanet curated; top 21 by frequency):

HPO ID	Term	Frequency
HP:0000218	High palate	Very frequent (80-99%)
HP:0001166	Arachnodactyly	Very frequent (80-99%)
HP:0001371	Flexion contracture	Very frequent (80-99%)
HP:0001387	Joint stiffness	Very frequent (80-99%)
HP:0001533	Slender build	Very frequent (80-99%)
HP:0002650	Scoliosis	Very frequent (80-99%)
HP:0002803	Congenital contracture	Very frequent (80-99%)
HP:0002804	Arthrogryposis multiplex congenita	Very frequent (80-99%)
HP:0003011	Abnormality of the musculature	Very frequent (80-99%)
HP:0008453	Congenital kyphoscoliosis	Very frequent (80-99%)
HP:0008544	Abnormally folded helix	Very frequent (80-99%)
HP:0009901	Crumpled ear	Very frequent (80-99%)
HP:0100490	Camptodactyly of finger	Very frequent (80-99%)
HP:0001519	Disproportionate tall stature	Frequent (30-79%)
HP:0001083	Ectopia lentis	Occasional (5-29%)
HP:0001634	Mitral valve prolapse	Occasional (5-29%)
HP:0002247	Duodenal atresia	Occasional (5-29%)
HP:0002566	Intestinal malrotation	Occasional (5-29%)
HP:0002575	Tracheoesophageal fistula	Occasional (5-29%)
HP:0004942	Aortic aneurysm	Occasional (5-29%)
HP:0030680	Abnormal cardiovascular system morphology	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital contractural arachnodactyly
Mondo ID	MONDO:0007363
MeSH	C536211
OMIM	121050
Orphanet	115
DOID	DOID:0111595
ICD-11	1376425921
NCIT	C129865
SNOMED CT	205821003
UMLS	C0220668
MedGen	67391
GARD	0005899
NORD	844
Is cancer (heuristic)	no

Also known as: arachnodactyly, contractural Beals type · arthrogryposis, distal, type 9 · Beals syndrome · Beals-Hecht syndrome · CCA · CCA syndrome · contractures, multiple with arachnodactyly · DA9 · distal arthrogryposis type 9 · Ear anomalies-contractures-dysplasia of bone with kyphoscoliosis

Data availability: 3,043 ClinVar variants · 6 GenCC gene-disease records · 4 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › congenital contractural arachnodactyly

Related subtypes (216): polymicrogyria, congenital myasthenic syndrome with tubular aggregates, prenatal-onset spinal muscular atrophy with congenital bone fractures, anencephaly, cerebral cavernous malformation, meningocele, progressive external ophthalmoplegia, congenital nystagmus, congenital toxoplasmosis, congenital trigeminal anesthesia, familial congenital palsy of trochlear nerve, Myhre syndrome, Aase-Smith syndrome, KBG syndrome, autosomal dominant primary microcephaly, Mobius syndrome, MYH7-related skeletal myopathy, congenital stationary night blindness autosomal dominant 2, Prader-Willi syndrome, congenital myopathy 7A, myosin storage, autosomal dominant, Smith-Magenis syndrome, spina bifida, Freeman-Sheldon syndrome, isolated cerebellar hypoplasia/agenesis, Chediak-Higashi syndrome, Cohen syndrome, multiple pterygium-malignant hyperthermia syndrome, corpus callosum, agenesis of, congenital lactic acidosis, Saguenay-Lac-Saint-Jean type, facial dysmorphism-macrocephaly-myopia-Dandy-Walker malformation syndrome, diastematomyelia, EEM syndrome, Mowat-Wilson syndrome, Johanson-Blizzard syndrome, intellectual disability, Buenos-Aires type, myasthenia, congenital, refractory to acetylcholinesterase inhibitors, congenital myasthenic syndrome 6, Bailey-Bloch congenital myopathy, congenital stationary night blindness 1B, radioulnar synostosis-developmental delay-hypotonia syndrome, Schinzel-Giedion syndrome, schizencephaly, intellectual disability, Wolff type, X-linked intellectual disability-plagiocephaly syndrome, X-linked adrenal hypoplasia congenita, syndromic X-linked intellectual disability 7, syndromic X-linked intellectual disability Shashi type, syndromic X-linked intellectual disability Lubs type, syndromic X-linked intellectual disability Abidi type, syndromic X-linked intellectual disability Siderius type, X-linked intellectual disability, Cabezas type, X-linked intellectual disability-cubitus valgus-dysmorphism syndrome, syndromic X-linked intellectual disability Claes-Jensen type, moyamoya angiopathy-short stature-facial dysmorphism-hypergonadotropic hypogonadism syndrome, multiple congenital anomalies-hypotonia-seizures syndrome 2, developmental and epileptic encephalopathy, 36, blepharophimosis - intellectual disability syndrome, MKB type, X-linked intellectual disability-short stature-overweight syndrome, intellectual disability, X-linked, syndromic 33, syndromic X-linked intellectual disability 34, infantile-onset X-linked spinal muscular atrophy, syndromic X-linked intellectual disability 5, holoprosencephaly-hypokinesia-congenital contractures syndrome, X-linked intellectual disability with marfanoid habitus, Wieacker-Wolff syndrome, MERRF syndrome, macrocephaly-spastic paraplegia-dysmorphism syndrome, intellectual disability-sparse hair-brachydactyly syndrome, myofibrillar myopathy 1, isolated hereditary congenital facial paralysis, fibrosis of extraocular muscles, congenital, 2, Pierpont syndrome, congenital cataracts-facial dysmorphism-neuropathy syndrome, Bohring-Opitz syndrome, PHACE syndrome, B4GALT1-congenital disorder of glycosylation, developmental malformations-deafness-dystonia syndrome, sensory ataxic neuropathy, dysarthria, and ophthalmoparesis, AICA-ribosiduria, myofibrillar myopathy 3, fibrosis of extraocular muscles, congenital, 3c, myofibrillar myopathy 4, myofibrillar myopathy 5, cone-rod synaptic disorder, congenital nonprogressive, congenital stationary night blindness autosomal dominant 3, congenital stationary night blindness autosomal dominant 1, intellectual disability, autosomal recessive 12, progressive myoclonic epilepsy type 3, chromosome 15q13.3 microdeletion syndrome, combined pituitary hormone deficiencies, genetic form, congenital stationary night blindness 1D, DYRK1A-related intellectual disability syndrome, Pitt-Hopkins-like syndrome 2, developmental and epileptic encephalopathy, 15, Schuurs-Hoeijmakers syndrome, severe intellectual disability-poor language-strabismus-grimacing face-long fingers syndrome, severe intellectual disability-progressive spastic diplegia syndrome, hypotonia, infantile, with psychomotor retardation and characteristic facies, developmental and epileptic encephalopathy, 18, CTCF-related neurodevelopmental disorder, autism spectrum disorder due to AUTS2 deficiency, developmental and epileptic encephalopathy, 23, ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder, Bardet-Biedl syndrome 11, cerebellar-facial-dental syndrome, fibrosis of extraocular muscles, congenital, 5, congenital myasthenic syndrome 15, lethal fetal cerebrorenogenitourinary agenesis/hypoplasia syndrome, autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome, congenital myasthenic syndrome 18, autosomal recessive spinocerebellar ataxia 20, Houge-Janssens syndrome 1, intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome, congenital stationary night blindness 1G, hypomyelinating leukodystrophy 10, developmental and epileptic encephalopathy, 50, congenital insensitivity to pain-hypohidrosis syndrome, macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome, SLC39A8-CDG, spastic paraplegia-severe developmental delay-epilepsy syndrome, cardiac anomalies - developmental delay - facial dysmorphism syndrome, severe intellectual disability-corpus callosum agenesis-facial dysmorphism-cerebellar ataxia syndrome, intellectual disability, autosomal recessive 53, TELO2-related intellectual disability-neurodevelopmental disorder, micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome, autosomal recessive limb-girdle muscular dystrophy type 2Y, myofibrillar myopathy 7, short stature-brachydactyly-obesity-global developmental delay syndrome, autosomal recessive limb-girdle muscular dystrophy type 2R1, severe microbrachycephaly-intellectual disability-athetoid cerebral palsy syndrome, congenital laryngeal palsy, congenital or early infantile CACH syndrome, congenital epulis, severe congenital nemaline myopathy, intermediate nemaline myopathy, typical nemaline myopathy, childhood-onset nemaline myopathy, adult-onset nemaline myopathy, qualitative or quantitative defects of protein involved in O-glycosylation of alpha-dystroglycan, holoprosencephaly, congenital insensitivity to pain with hyperhidrosis, congenital hydrocephalus, familial congenital mirror movements, macrocephaly-short stature-paraplegia syndrome, cephalocele, mitochondrial neurogastrointestinal encephalomyopathy, X-linked intellectual disability-hypogonadism-ichthyosis-obesity-short stature syndrome, 7p22.1 microduplication syndrome, congenital achiasma, congenital retinal arteriovenous communication, 3q27.3 microdeletion syndrome, Prader-Willi-like syndrome, 9q31.1q31.3 microdeletion syndrome, congenital oculomotor nerve palsy, congenital abducens nerve palsy, neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-hip dysplasia syndrome, congenital insensitivity to pain with severe intellectual disability, X-linked intellectual disability-cerebellar hypoplasia-spondylo-epiphyseal dysplasia syndrome, global developmental delay-visual anomalies-progressive cerebellar atrophy-truncal hypotonia syndrome, lissencephaly spectrum disorders, hyaline body myopathy, 22q11.2 deletion syndrome, craniorachischisis, Leber congenital amaurosis, Ritscher-Schinzel syndrome, Rubinstein-Taybi syndrome, X-linked intellectual disability-hypogammaglobulinemia-progressive neurological deterioration syndrome, X-linked intellectual disability-epilepsy-progressive joint contractures-dysmorphism syndrome, X-linked intellectual disability, Pai type, X-linked intellectual disability, Stevenson type, X-linked intellectual disability, Stoll type, congenital muscular dystrophy, congenital vitreoretinal dysplasia, periventricular nodular heterotopia, postsynaptic congenital myasthenic syndrome, subcortical band heterotopia, congenital fibrosis of extraocular muscles type 1, Al Gazali Khidr Prem Chandran syndrome, distal arthrogryposis Moore weaver type, congenital myotonic dystrophy, myasthenic syndrome, congenital, 7B, presynaptic, autosomal recessive, intellectual disability, autosomal dominant 47, intellectual disability, autosomal dominant 48, spondyloepiphyseal dysplasia, sensorineural hearing loss, impaired intellectual development, and leber congenital amaurosis, myasthenic syndrome, congenital, 23, presynaptic, myasthenic syndrome, congenital, 24, presynaptic, myasthenic syndrome, congenital, 25, presynaptic, developmental and epileptic encephalopathy, 77, night blindness, congenital stationary, type1i, neuropathy, congenital hypomelinating, congenital axonal neuropathy with encephalopathy, developmental and epileptic encephalopathy, 73, PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome, isolated exencephaly, myasthenic syndrome, congenital, 22, intellectual developmental disorder with gastrointestinal difficulties and high pain threshold, intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies, 9q33.3q34.11 microdeletion syndrome, congenital labioscrotal agenesis-cerebellar malformation-corneal dystrophy-facial dysmorphism syndrome, early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome, SIN3A-related intellectual disability syndrome, childhood-onset motor and cognitive regression syndrome with extrapyramidal movement disorder, X-linked congenital stationary night blindness, neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies, FOXG1 disorder, alpha-actinopathy, TPM3-related myopathy, X-linked recessive mitochondrial myopathy, RYR1-related myopathy, TTN-related myopathy, TPM2-related myopathy, myopathy caused by variation in POMGNT1, central hypoventilation syndrome, congenital, 1, with or without Hirschsprung disease, segmental spinal dysgenesis, myopathy, myofibrillar, 13, with rimmed vacuoles, congenital neuronal ceroid lipofuscinosis 10

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

600 retrieved; paginated sample, class counts are floors:

209 uncertain significance, 203 likely benign, 89 conflicting classifications of pathogenicity, 45 benign/likely benign, 36 benign, 11 likely pathogenic, 4 pathogenic/likely pathogenic, 3 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1003634	NM_001999.4(FBN2):c.3803G>C (p.Cys1268Ser)	FBN2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1030504	NM_001999.4(FBN2):c.3437A>G (p.Tyr1146Cys)	FBN2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1333458	NM_001999.4(FBN2):c.4296C>A (p.Tyr1432Ter)	FBN2	Pathogenic	criteria provided, single submitter
1420674	NM_001999.4(FBN2):c.4592_4594+3del	FBN2	Pathogenic	criteria provided, single submitter
1454127	NM_001999.4(FBN2):c.3472+2T>C	FBN2	Pathogenic	criteria provided, multiple submitters, no conflicts
1459134	NM_001999.4(FBN2):c.3736T>G (p.Cys1246Gly)	FBN2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1675083	NM_001999.4(FBN2):c.3424T>G (p.Cys1142Gly)	FBN2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1003175	NM_001999.4(FBN2):c.3803G>T (p.Cys1268Phe)	FBN2	Likely pathogenic	criteria provided, single submitter
1067400	NM_001999.4(FBN2):c.6122G>A (p.Cys2041Tyr)	FBN2	Likely pathogenic	criteria provided, single submitter
1346549	NM_001999.4(FBN2):c.3521G>A (p.Cys1174Tyr)	FBN2	Likely pathogenic	criteria provided, single submitter
1349684	NC_000005.9:g.(?127666245)(127668746_?)del	FBN2	Likely pathogenic	criteria provided, single submitter
1493488	NM_001999.4(FBN2):c.3298T>A (p.Cys1100Ser)	FBN2	Likely pathogenic	criteria provided, single submitter
1509864	NM_001999.4(FBN2):c.4184G>A (p.Cys1395Tyr)	FBN2	Likely pathogenic	criteria provided, single submitter
1524703	NM_001999.4(FBN2):c.4340G>A (p.Cys1447Tyr)	FBN2	Likely pathogenic	criteria provided, single submitter
1708150	NM_001999.4(FBN2):c.3778T>C (p.Ser1260Pro)	FBN2	Likely pathogenic	criteria provided, single submitter
1709548	NM_001999.4(FBN2):c.91C>T (p.Gln31Ter)	FBN2	Likely pathogenic	criteria provided, single submitter
1709725	NM_001999.4(FBN2):c.5917+1del	FBN2	Likely pathogenic	criteria provided, single submitter
1739861	NM_001999.4(FBN2):c.4340G>T (p.Cys1447Phe)	FBN2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1004936	NM_001999.4(FBN2):c.968G>A (p.Ser323Asn)	FBN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1006685	NM_001999.4(FBN2):c.86A>C (p.Gln29Pro)	FBN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1017420	NM_001999.4(FBN2):c.8413A>G (p.Met2805Val)	FBN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1020508	NM_001999.4(FBN2):c.220G>A (p.Val74Ile)	FBN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1025668	NM_001999.4(FBN2):c.3680G>A (p.Cys1227Tyr)	FBN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1035043	NM_001999.4(FBN2):c.6205T>C (p.Phe2069Leu)	FBN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1035926	NM_001999.4(FBN2):c.6433A>G (p.Lys2145Glu)	FBN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1039471	NM_001999.4(FBN2):c.251G>A (p.Arg84Gln)	FBN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1042687	NM_001999.4(FBN2):c.704C>T (p.Thr235Met)	FBN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1044078	NM_001999.4(FBN2):c.3957C>G (p.Asp1319Glu)	FBN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1055239	NM_001999.4(FBN2):c.4052A>G (p.His1351Arg)	FBN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1056342	NM_001999.4(FBN2):c.3862G>A (p.Glu1288Lys)	FBN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 12 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
FBN2	Definitive	Autosomal dominant	congenital contractural arachnodactyly	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FBN2	Orphanet:115	Congenital contractural arachnodactyly
FBN1	Orphanet:1885	Isolated ectopia lentis
FBN1	Orphanet:2084	Glaucoma-ectopia lentis-microspherophakia-stiff joints-short stature syndrome
FBN1	Orphanet:2462	Shprintzen-Goldberg syndrome
FBN1	Orphanet:2623	Geleophysic dysplasia
FBN1	Orphanet:2833	Stiff skin syndrome
FBN1	Orphanet:284963	Marfan syndrome type 1
FBN1	Orphanet:284979	Neonatal Marfan syndrome
FBN1	Orphanet:300382	Progeroid and marfanoid aspect-lipodystrophy syndrome
FBN1	Orphanet:3449	Weill-Marchesani syndrome
FBN1	Orphanet:91387	Familial thoracic aortic aneurysm and aortic dissection
FBN1	Orphanet:969	Acromicric dysplasia

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
FBN2	HGNC:3604	ENSG00000138829	P35556	Fibrillin-2	gencc,clinvar
FBN1	HGNC:3603	ENSG00000166147	P35555	Fibrillin-1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FBN2	Fibrillin-2	Fibrillins are structural components of 10-12 nm extracellular calcium-binding microfibrils, which occur either in association with elastin or in elastin-free bundles.
FBN1	Fibrillin-1	Structural component of the 10-12 nm diameter microfibrils of the extracellular matrix, which conveys both structural and regulatory properties to load-bearing connective tissues.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FBN2	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, EGF-like_Ca-bd_dom
FBN1	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, EGF-like_Ca-bd_dom

Expression context

Cohort genes with no expression data: 0.

2 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
adrenal tissue	1
cartilage tissue	1
placenta	1
decidua	1
skin of hip	1
synovial joint	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FBN2	194	ubiquitous	marker	cartilage tissue, placenta, adrenal tissue
FBN1	275	ubiquitous	marker	synovial joint, skin of hip, decidua

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FBN1	3,640
FBN2	2,570

Intra-cohort edges

A	B	Sources
FBN1	FBN2	intact, string_interaction

Structural data

PDB: 1 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FBN1	P35555	11

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FBN2	P35556

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. Enrichment computed across 2 evidence-associated genes (2 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Elastic fibre formation	2	335.9×	4e-05	FBN2, FBN1
Molecules associated with elastic fibres	2	308.6×	4e-05	FBN2, FBN1
Degradation of the extracellular matrix	2	117.7×	2e-04	FBN2, FBN1
TGF-beta receptor signaling activates SMADs	1	163.1×	0.011	FBN1
Integrin cell surface interactions	1	67.2×	0.021	FBN1
Post-translational protein phosphorylation	1	50.1×	0.023	FBN1
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	1	43.3×	0.023	FBN1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
obsolete sequestering of TGFbeta in extracellular matrix	2	4213.0×	9e-07	FBN2, FBN1
embryonic eye morphogenesis	2	1532.0×	4e-06	FBN2, FBN1
camera-type eye development	2	358.6×	5e-05	FBN2, FBN1
glucose metabolic process	2	255.3×	8e-05	FBN2, FBN1
glucose homeostasis	2	130.6×	2e-04	FBN2, FBN1
post-embryonic eye morphogenesis	1	2808.7×	0.001	FBN1
obsolete sequestering of BMP in extracellular matrix	1	2106.5×	0.001	FBN1
negative regulation of osteoclast development	1	1685.2×	0.002	FBN1
bone trabecula formation	1	1053.2×	0.002	FBN2
cellular response to insulin-like growth factor stimulus	1	648.1×	0.003	FBN1
cell adhesion mediated by integrin	1	337.0×	0.006	FBN1
negative regulation of osteoclast differentiation	1	271.8×	0.006	FBN1
metanephros development	1	255.3×	0.006	FBN1
embryonic limb morphogenesis	1	200.6×	0.007	FBN2
positive regulation of bone mineralization	1	195.9×	0.007	FBN2
lung alveolus development	1	175.5×	0.007	FBN1
cellular response to transforming growth factor beta stimulus	1	138.1×	0.009	FBN1
positive regulation of osteoblast differentiation	1	112.3×	0.010	FBN2
skeletal system development	1	62.9×	0.018	FBN1
gene expression	1	39.9×	0.025	FBN1
heart development	1	39.4×	0.025	FBN1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FBN2	0	0
FBN1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	FBN2, FBN1

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
FBN2	0	—
FBN1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03440697	Not specified	ACTIVE_NOT_RECRUITING	Pathogenetic Basis of Aortopathy and Aortic Valve Disease