Geleophysic dysplasia
diseaseOn this page
Also known as geleophysic dwarfismgeleophysic dwarfism syndrome
Summary
Geleophysic dysplasia (MONDO:0000127) is a disease with 4 cohort genes. The dominant Reactome pathway is Elastic fibre formation (3 cohort genes).
At a glance
- Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
- Cohort genes: 4
- ClinVar variants: 120
- Phenotypes (HPO): 47
Clinical features
Epidemiology
Prevalence records
2 prevalence record(s), Orphanet:
| Type | Class | Value | Geography | Validation |
|---|---|---|---|---|
| Cases/families | 27 | Worldwide | Validated | |
| Point prevalence | <1 / 1 000 000 | Worldwide | Validated |
Signs & symptoms
Clinical features (HPO)
47 HPO clinical features (Orphanet curated; top 47 by frequency):
| HPO ID | Term | Frequency |
|---|---|---|
| HP:0004322 | Short stature | Very frequent (80-99%) |
| HP:0000219 | Thin upper lip vermilion | Frequent (30-79%) |
| HP:0000311 | Round face | Frequent (30-79%) |
| HP:0000343 | Long philtrum | Frequent (30-79%) |
| HP:0000405 | Conductive hearing impairment | Frequent (30-79%) |
| HP:0000463 | Anteverted nares | Frequent (30-79%) |
| HP:0001072 | Thickened skin | Frequent (30-79%) |
| HP:0001156 | Brachydactyly | Frequent (30-79%) |
| HP:0001376 | Limitation of joint mobility | Frequent (30-79%) |
| HP:0001511 | Intrauterine growth retardation | Frequent (30-79%) |
| HP:0001561 | Polyhydramnios | Frequent (30-79%) |
| HP:0001773 | Short foot | Frequent (30-79%) |
| HP:0002099 | Asthma | Frequent (30-79%) |
| HP:0002750 | Delayed skeletal maturation | Frequent (30-79%) |
| HP:0003026 | Short long bone | Frequent (30-79%) |
| HP:0003196 | Short nose | Frequent (30-79%) |
| HP:0004279 | Short palm | Frequent (30-79%) |
| HP:0004890 | Elevated pulmonary artery pressure | Frequent (30-79%) |
| HP:0006536 | Airway obstruction | Frequent (30-79%) |
| HP:0011428 | Short fetal femur length | Frequent (30-79%) |
| HP:0034281 | Phalangeal cone-shaped epiphyses | Frequent (30-79%) |
| HP:0034350 | Valvular pulmonary stenosis | Frequent (30-79%) |
| HP:0034392 | Joint contracture | Frequent (30-79%) |
| HP:0040261 | Increased size of nasopharyngeal adenoids | Frequent (30-79%) |
| HP:0410018 | Recurrent ear infections | Frequent (30-79%) |
| HP:0000316 | Hypertelorism | Occasional (5-29%) |
| HP:0000483 | Astigmatism | Occasional (5-29%) |
| HP:0000540 | Hypermetropia | Occasional (5-29%) |
| HP:0000545 | Myopia | Occasional (5-29%) |
| HP:0001385 | Hip dysplasia | Occasional (5-29%) |
| HP:0001601 | Laryngomalacia | Occasional (5-29%) |
| HP:0001602 | Laryngeal stenosis | Occasional (5-29%) |
| HP:0001650 | Aortic valve stenosis | Occasional (5-29%) |
| HP:0001653 | Mitral regurgitation | Occasional (5-29%) |
| HP:0001718 | Mitral stenosis | Occasional (5-29%) |
| HP:0002091 | Restrictive ventilatory defect | Occasional (5-29%) |
| HP:0002093 | Respiratory insufficiency | Occasional (5-29%) |
| HP:0002240 | Hepatomegaly | Occasional (5-29%) |
| HP:0002777 | Tracheal stenosis | Occasional (5-29%) |
| HP:0002779 | Tracheomalacia | Occasional (5-29%) |
| HP:0002870 | Obstructive sleep apnea | Occasional (5-29%) |
| HP:0006530 | Abnormal pulmonary interstitial morphology | Occasional (5-29%) |
| HP:0006695 | Atrioventricular canal defect | Occasional (5-29%) |
| HP:0012185 | Constrictive median neuropathy | Occasional (5-29%) |
| HP:0030051 | Tip-toe gait | Occasional (5-29%) |
| HP:0000501 | Glaucoma | Very rare (<1-4%) |
| HP:0000821 | Hypothyroidism | Very rare (<1-4%) |
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | geleophysic dysplasia |
| Mondo ID | MONDO:0000127 |
| OMIM | 231050 |
| Orphanet | 2623 |
| DOID | DOID:0111724 |
| ICD-11 | 518828851 |
| SNOMED CT | 28557005 |
| UMLS | C3489726 |
| MedGen | 483679 |
| GARD | 0002449 |
| MedDRA | 10063361 |
| Is cancer (heuristic) | no |
Also known as: geleophysic dwarfism · geleophysic dwarfism syndrome
Data availability: 120 ClinVar variants · 2 GenCC gene-disease records · 1 cell line.
Disease family
An umbrella term covering 3 Mondo subtypes.
Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › skeletal dysplasia › acromelic dysplasia › geleophysic dysplasia
Related subtypes (17): Acromicric dysplasia, pseudohypoparathyroidism type 1A, Angel-shaped phalango-epiphyseal dysplasia, Myhre syndrome, Leri pleonosteosis, peripheral dysostosis, short-rib thoracic dysplasia 9 with or without polydactyly, terminal osseous dysplasia-pigmentary defects syndrome, intellectual disability-balding-patella luxation-acromicria syndrome, acrocapitofemoral dysplasia, pseudohypoparathyroidism type 1C, pseudopseudohypoparathyroidism, short stature-brachydactyly-obesity-global developmental delay syndrome, trichorhinophalangeal syndrome, Weill-Marchesani syndrome, craniofacial conodysplasia, acrodysostosis
Subtypes (3): geleophysic dysplasia 1, geleophysic dysplasia 2, geleophysic dysplasia 3
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
120 retrieved; paginated sample, class counts are floors:
59 conflicting classifications of pathogenicity, 35 benign/likely benign, 22 benign, 2 uncertain significance, 1 likely benign, 1 pathogenic/likely pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 430150 | NM_000138.5(FBN1):c.5183C>T (p.Ala1728Val) | FBN1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 695 | NM_014694.4(ADAMTSL2):c.340G>A (p.Glu114Lys) | ADAMTSL2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 137300 | NM_000138.5(FBN1):c.-176A>T | FBN1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 137306 | NM_000138.5(FBN1):c.3590-8T>C | FBN1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 161237 | NM_000138.5(FBN1):c.7846A>G (p.Ile2616Val) | FBN1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 161244 | NM_000138.5(FBN1):c.1027G>A (p.Gly343Arg) | FBN1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 16445 | NM_000138.5(FBN1):c.8176C>T (p.Arg2726Trp) | FBN1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 178035 | NM_000138.5(FBN1):c.247+10T>C | FBN1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 199954 | NM_000138.5(FBN1):c.8185A>C (p.Lys2729Gln) | FBN1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 199960 | NM_000138.5(FBN1):c.902G>T (p.Gly301Val) | FBN1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 228686 | NM_000138.5(FBN1):c.6314-15G>A | FBN1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 237081 | NM_000138.5(FBN1):c.1884C>T (p.Cys628=) | FBN1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 237089 | NM_000138.5(FBN1):c.3936C>T (p.Ser1312=) | FBN1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 237105 | NM_000138.5(FBN1):c.783T>C (p.Asn261=) | FBN1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 237106 | NM_000138.5(FBN1):c.8149G>A (p.Glu2717Lys) | FBN1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 263431 | NM_000138.5(FBN1):c.7056C>T (p.Ser2352=) | FBN1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 263632 | NM_000138.5(FBN1):c.3089A>G (p.Asn1030Ser) | FBN1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 264529 | NM_000138.5(FBN1):c.2094G>T (p.Pro698=) | FBN1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 281682 | NM_000138.5(FBN1):c.4998C>T (p.Thr1666=) | FBN1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 316306 | NM_000138.5(FBN1):c.*2395G>A | FBN1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 316328 | NM_000138.5(FBN1):c.*1580G>A | FBN1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 316331 | NM_000138.5(FBN1):c.*1484C>T | FBN1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 316337 | NM_000138.5(FBN1):c.*1325T>C | FBN1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 316338 | NM_000138.5(FBN1):c.*1298C>G | FBN1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 316340 | NM_000138.5(FBN1):c.*1245C>T | FBN1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 316345 | NM_000138.5(FBN1):c.*967C>T | FBN1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 316350 | NM_000138.5(FBN1):c.*764G>A | FBN1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 316360 | NM_000138.5(FBN1):c.8310C>T (p.His2770=) | FBN1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 316362 | NM_000138.5(FBN1):c.8202C>T (p.Asn2734=) | FBN1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 316364 | NM_000138.5(FBN1):c.7661G>A (p.Arg2554Gln) | FBN1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 64 · Orphanet: 19 · 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 |
|---|---|---|---|---|
| FBN1 | Strong | Autosomal dominant | Acromicric dysplasia | 24 |
| LTBP2 | Strong | Autosomal dominant | geleophysic dysplasia 3 | 20 |
| LTBP3 | Strong | Autosomal dominant | geleophysic dysplasia 3 | 20 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| 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 |
| LTBP2 | Orphanet:238763 | Glaucoma secondary to spherophakia/ectopia lentis and megalocornea |
| LTBP2 | Orphanet:3449 | Weill-Marchesani syndrome |
| LTBP2 | Orphanet:98976 | Congenital glaucoma |
| LTBP3 | Orphanet:2623 | Geleophysic dysplasia |
| LTBP3 | Orphanet:2899 | Brachyolmia-amelogenesis imperfecta syndrome |
| LTBP3 | Orphanet:969 | Acromicric dysplasia |
| ADAMTSL2 | Orphanet:1901 | Dermatosparaxis Ehlers-Danlos syndrome |
| ADAMTSL2 | Orphanet:2623 | Geleophysic dysplasia |
Cohort genes → proteins
4 cohort genes, 4 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 4 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| FBN1 | HGNC:3603 | ENSG00000166147 | P35555 | Fibrillin-1 | gencc,clinvar |
| LTBP2 | HGNC:6715 | ENSG00000119681 | Q14767 | Latent-transforming growth factor beta-binding protein 2 | gencc,clinvar |
| LTBP3 | HGNC:6716 | ENSG00000168056 | Q9NS15 | Latent-transforming growth factor beta-binding protein 3 | gencc,clinvar |
| ADAMTSL2 | HGNC:14631 | ENSG00000197859 | Q86TH1 | ADAMTS-like protein 2 | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| 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. |
| LTBP2 | Latent-transforming growth factor beta-binding protein 2 | May play an integral structural role in elastic-fiber architectural organization and/or assembly. |
| LTBP3 | Latent-transforming growth factor beta-binding protein 3 | Key regulator of transforming growth factor beta (TGFB1, TGFB2 and TGFB3) that controls TGF-beta activation by maintaining it in a latent state during storage in extracellular space. |
Protein-family classification
Druggable: 0 · Difficult: 0 · Unknown: 4 · 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 | 4 | 1.8× | 0.097 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| FBN1 | Other/Unknown | no | EGF-type_Asp/Asn_hydroxyl_site, EGF, EGF-like_Ca-bd_dom | |
| LTBP2 | Other/Unknown | no | EGF-type_Asp/Asn_hydroxyl_site, EGF, EGF-like_Ca-bd_dom | |
| LTBP3 | Other/Unknown | no | EGF-type_Asp/Asn_hydroxyl_site, EGF, EGF-like_Ca-bd_dom | |
| ADAMTSL2 | Other/Unknown | no | TSP1_rpt, ADAMTS_spacer1, PLAC |
Expression context
Cohort genes with no expression data: 0.
4 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) | 4 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| ascending aorta | 2 |
| descending thoracic aorta | 2 |
| thoracic aorta | 2 |
| decidua | 1 |
| skin of hip | 1 |
| synovial joint | 1 |
| cardiac atrium | 1 |
| metanephros cortex | 1 |
| right atrium auricular region | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| FBN1 | 275 | ubiquitous | marker | synovial joint, skin of hip, decidua |
| LTBP2 | 276 | ubiquitous | marker | descending thoracic aorta, thoracic aorta, ascending aorta |
| LTBP3 | 279 | broad | marker | descending thoracic aorta, thoracic aorta, ascending aorta |
| ADAMTSL2 | 159 | broad | marker | right atrium auricular region, metanephros cortex, cardiac atrium |
Protein interactions among cohort
Intra-cohort edges: 4.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| FBN1 | 3,640 |
| LTBP2 | 2,658 |
| LTBP3 | 2,339 |
| ADAMTSL2 | 600 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| ADAMTSL2 | FBN1 | string_interaction |
| ADAMTSL2 | LTBP3 | string_interaction |
| FBN1 | LTBP2 | string_interaction |
| FBN1 | LTBP3 | string_interaction |
Structural data
PDB: 1 · AlphaFold-only: 3 · 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 |
|---|---|---|
| ADAMTSL2 | Q86TH1 | 67.10 |
| LTBP3 | Q9NS15 | 64.21 |
| LTBP2 | Q14767 | 58.33 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 20. Enrichment computed across 4 evidence-associated genes (4 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 4 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 | 3 | 251.9× | 8e-07 | FBN1, LTBP2, LTBP3 |
| TGF-beta receptor signaling activates SMADs | 3 | 244.7× | 8e-07 | FBN1, LTBP2, LTBP3 |
| Molecules associated with elastic fibres | 3 | 231.5× | 8e-07 | FBN1, LTBP2, LTBP3 |
| Signaling by TGF-beta Receptor Complex | 2 | 100.2× | 7e-04 | LTBP2, LTBP3 |
| Signaling by TGFB family members | 2 | 57.7× | 0.002 | LTBP2, LTBP3 |
| Extracellular matrix organization | 2 | 31.6× | 0.005 | LTBP2, LTBP3 |
| Defective B3GALTL causes PpS | 1 | 77.2× | 0.033 | ADAMTSL2 |
| O-glycosylation of TSR domain-containing proteins | 1 | 75.1× | 0.033 | ADAMTSL2 |
| Diseases associated with O-glycosylation of proteins | 1 | 53.9× | 0.041 | ADAMTSL2 |
| O-linked glycosylation | 1 | 36.1× | 0.050 | ADAMTSL2 |
| Integrin cell surface interactions | 1 | 33.6× | 0.050 | FBN1 |
| Diseases of glycosylation | 1 | 32.8× | 0.050 | ADAMTSL2 |
| Degradation of the extracellular matrix | 1 | 29.4× | 0.052 | FBN1 |
| Post-translational protein phosphorylation | 1 | 25.0× | 0.056 | FBN1 |
| Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) | 1 | 21.6× | 0.060 | FBN1 |
| Diseases of metabolism | 1 | 20.1× | 0.060 | ADAMTSL2 |
| Signal Transduction | 2 | 5.1× | 0.060 | LTBP2, LTBP3 |
| Post-translational protein modification | 1 | 4.8× | 0.214 | ADAMTSL2 |
| Disease | 1 | 3.3× | 0.286 | ADAMTSL2 |
| Metabolism of proteins | 1 | 3.1× | 0.286 | ADAMTSL2 |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| lobar bronchus epithelium development | 1 | 4213.0× | 0.004 | ADAMTSL2 |
| transforming growth factor beta receptor signaling pathway | 2 | 79.5× | 0.004 | LTBP2, LTBP3 |
| post-embryonic eye morphogenesis | 1 | 1404.3× | 0.006 | FBN1 |
| obsolete sequestering of BMP in extracellular matrix | 1 | 1053.2× | 0.006 | FBN1 |
| obsolete sequestering of TGFbeta in extracellular matrix | 1 | 1053.2× | 0.006 | FBN1 |
| negative regulation of osteoclast development | 1 | 842.6× | 0.007 | FBN1 |
| positive regulation of mesenchymal stem cell differentiation | 1 | 601.9× | 0.007 | LTBP3 |
| lung saccule development | 1 | 526.6× | 0.007 | LTBP3 |
| positive regulation of mesenchymal stem cell proliferation | 1 | 526.6× | 0.007 | LTBP3 |
| embryonic eye morphogenesis | 1 | 383.0× | 0.009 | FBN1 |
| cellular response to insulin-like growth factor stimulus | 1 | 324.1× | 0.010 | FBN1 |
| supramolecular fiber organization | 1 | 263.3× | 0.010 | LTBP2 |
| positive regulation of bone resorption | 1 | 247.8× | 0.010 | LTBP3 |
| negative regulation of bone mineralization | 1 | 234.1× | 0.010 | LTBP3 |
| bone remodeling | 1 | 234.1× | 0.010 | LTBP3 |
| negative regulation of chondrocyte differentiation | 1 | 168.5× | 0.012 | LTBP3 |
| cell adhesion mediated by integrin | 1 | 168.5× | 0.012 | FBN1 |
| bone morphogenesis | 1 | 150.5× | 0.013 | LTBP3 |
| negative regulation of osteoclast differentiation | 1 | 135.9× | 0.013 | FBN1 |
| metanephros development | 1 | 127.7× | 0.013 | FBN1 |
| protein targeting | 1 | 91.6× | 0.017 | LTBP2 |
| camera-type eye development | 1 | 89.6× | 0.017 | FBN1 |
| lung alveolus development | 1 | 87.8× | 0.017 | FBN1 |
| chondrocyte differentiation | 1 | 75.2× | 0.019 | LTBP3 |
| cellular response to transforming growth factor beta stimulus | 1 | 69.1× | 0.019 | FBN1 |
| bone mineralization | 1 | 68.0× | 0.019 | LTBP3 |
| protein secretion | 1 | 65.8× | 0.019 | LTBP2 |
| glucose metabolic process | 1 | 63.8× | 0.019 | FBN1 |
| negative regulation of transforming growth factor beta receptor signaling pathway | 1 | 43.4× | 0.027 | ADAMTSL2 |
| glucose homeostasis | 1 | 32.7× | 0.034 | FBN1 |
Therapeutics
Drug target analysis
Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 4
Druggability breadth: 0 of 4 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 |
|---|---|---|
| FBN1 | 0 | 0 |
| LTBP2 | 0 | 0 |
| LTBP3 | 0 | 0 |
| ADAMTSL2 | 0 | 0 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 0.
Pharmacogenomics
Cohort genes with a PharmGKB record: 4; 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 | 4 | FBN1, LTBP2, LTBP3, ADAMTSL2 |
Undrugged target profiles
4 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| FBN1 | 0 | — |
| LTBP2 | 0 | — |
| LTBP3 | 0 | — |
| ADAMTSL2 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.