Autosomal dominant cutis laxa

Summary

Autosomal dominant cutis laxa (MONDO:0019571) is a disease with 3 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 3
• ClinVar variants: 8
• Phenotypes (HPO): 59

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		50	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

59 HPO clinical features (Orphanet curated; top 50 by frequency):

HPO ID	Term	Frequency
HP:0000973	Cutis laxa	Very frequent (80-99%)
HP:0000974	Hyperextensible skin	Very frequent (80-99%)
HP:0001582	Redundant skin	Very frequent (80-99%)
HP:0007522	Increased number of skin folds	Very frequent (80-99%)
HP:0025167	Fragmented elastic fibers in the dermis	Very frequent (80-99%)
HP:0100678	Premature skin wrinkling	Very frequent (80-99%)
HP:0001382	Joint hypermobility	Frequent (30-79%)
HP:0000023	Inguinal hernia	Frequent (30-79%)
HP:0001653	Mitral regurgitation	Frequent (30-79%)
HP:0001659	Aortic regurgitation	Frequent (30-79%)
HP:0001999	Abnormal facial shape	Frequent (30-79%)
HP:0004942	Aortic aneurysm	Frequent (30-79%)
HP:0007495	Prematurely aged appearance	Frequent (30-79%)
HP:0010674	Abnormality of the curvature of the vertebral column	Frequent (30-79%)
HP:0100790	Hernia	Frequent (30-79%)
HP:0000015	Bladder diverticulum	Occasional (5-29%)
HP:0000252	Microcephaly	Occasional (5-29%)
HP:0000270	Delayed cranial suture closure	Occasional (5-29%)
HP:0000325	Triangular face	Occasional (5-29%)
HP:0000337	Broad forehead	Occasional (5-29%)
HP:0000369	Low-set ears	Occasional (5-29%)
HP:0000411	Protruding ear	Occasional (5-29%)
HP:0000486	Strabismus	Occasional (5-29%)
HP:0000508	Ptosis	Occasional (5-29%)
HP:0000519	Developmental cataract	Occasional (5-29%)
HP:0001181	Adducted thumb	Occasional (5-29%)
HP:0001252	Hypotonia	Occasional (5-29%)
HP:0001263	Global developmental delay	Occasional (5-29%)
HP:0001270	Motor delay	Occasional (5-29%)
HP:0001348	Brisk reflexes	Occasional (5-29%)
HP:0001511	Intrauterine growth retardation	Occasional (5-29%)
HP:0001635	Congestive heart failure	Occasional (5-29%)
HP:0001680	Coarctation of aorta	Occasional (5-29%)
HP:0002097	Emphysema	Occasional (5-29%)
HP:0002110	Bronchiectasis	Occasional (5-29%)
HP:0002256	Small bowel diverticula	Occasional (5-29%)
HP:0002650	Scoliosis	Occasional (5-29%)
HP:0002827	Hip dislocation	Occasional (5-29%)
HP:0004969	Peripheral pulmonary artery stenosis	Occasional (5-29%)
HP:0005989	Redundant neck skin	Occasional (5-29%)
HP:0006698	Dilatation of the ventricular cavity	Occasional (5-29%)
HP:0007957	Corneal opacity	Occasional (5-29%)
HP:0008897	Postnatal growth retardation	Occasional (5-29%)
HP:0010648	Dermal translucency	Occasional (5-29%)
HP:0011220	Prominent forehead	Occasional (5-29%)
HP:0011950	Bronchiolitis	Occasional (5-29%)
HP:0011968	Feeding difficulties	Occasional (5-29%)
HP:0012330	Pyelonephritis	Occasional (5-29%)
HP:0100512	Low levels of vitamin D	Occasional (5-29%)
HP:0000122	Unilateral renal agenesis	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal dominant cutis laxa
Mondo ID	MONDO:0019571
MeSH	C562627
Orphanet	90348
DOID	DOID:0070142
ICD-11	720393698
SNOMED CT	111388003
UMLS	C0268350
MedGen	120630
GARD	0001639
Is cancer (heuristic)	no

Also known as: ADCL · cutis laxa, autosomal dominant

Data availability: 8 ClinVar variants · 3 GenCC gene-disease records.

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 › autosomal genetic disease › autosomal dominant disease › autosomal dominant cutis laxa

Related subtypes (191): autosomal dominant polycystic liver disease, cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1, tuberous sclerosis, Treacher-Collins syndrome, hereditary breast ovarian cancer syndrome, autosomal dominant polycystic kidney disease, Lynch syndrome, branchio-oto-renal syndrome, autosomal dominant Aarskog syndrome, acroosteolysis dominant type, ADULT syndrome, autosomal dominant Alport syndrome, amelogenesis imperfecta type 1B, Townes-Brocks syndrome, nevoid basal cell carcinoma syndrome, blepharophimosis, ptosis, and epicanthus inversus syndrome, autosomal dominant brachyolmia, branchiooculofacial syndrome, pheochromocytoma/paraganglioma syndrome 4, cataract-aberrant oral frenula-growth delay syndrome, cherubism, autosomal dominant chondrodysplasia punctata, autosomal dominant popliteal pterygium syndrome, blepharocheilodontic syndrome, cochleosaccular degeneration-cataract syndrome, renal coloboma syndrome, Beare-Stevenson cutis gyrata syndrome, autosomal dominant vibratory urticaria, neurohypophyseal diabetes insipidus, autosomal dominant Kenny-Caffey syndrome, Rapp-Hodgkin syndrome, Ehlers-Danlos syndrome, classic type, autosomal dominant Ehlers-Danlos syndrome, vascular type, multiple endocrine neoplasia type 1, Coffin-Siris syndrome 1, isolated congenital adermatoglyphia, Flynn-Aird syndrome, Frasier syndrome, hand-foot-genital syndrome, Holt-Oram syndrome, hyperkeratosis-hyperpigmentation syndrome, autosomal dominant ichthyosis vulgaris, hyper-IgE recurrent infection syndrome 1, autosomal dominant, autosomal dominant keratitis, autosomal dominant keratitis-ichthyosis-hearing loss syndrome, LADD syndrome, trichorhinophalangeal syndrome type II, Noonan syndrome with multiple lentigines, microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability, Marfan syndrome, melanoma, cutaneous malignant, susceptibility to, 2, autosomal dominant primary microcephaly, autosomal dominant progressive external ophthalmoplegia, monilethrix, Muir-Torre syndrome, autosomal dominant myoglobinuria, autosomal dominant centronuclear myopathy, nail-patella syndrome, multiple endocrine neoplasia type 2B, autosomal dominant omodysplasia, pheochromocytoma/paraganglioma syndrome 1, Pelger-Huet anomaly, multiple endocrine neoplasia type 2A, piebaldism, autosomal dominant medullary cystic kidney disease with or without hyperuricemia, generalized juvenile polyposis/juvenile polyposis coli, juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, Peutz-Jeghers syndrome, contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A, autosomal dominant distal renal tubular acidosis, retinoschisis, autosomal dominant, autosomal dominant Robinow syndrome, scapuloperoneal spinal muscular atrophy, autosomal dominant, autosomal dominant sideroblastic anemia, spondyloepiphyseal dysplasia tarda, autosomal dominant, proximal symphalangism, calcaneonavicular coalition, thanatophoric dysplasia type 1, trichorhinophalangeal syndrome type I, Muckle-Wells syndrome, autosomal dominant hypophosphatemic rickets, von Hippel-Lindau disease, Denys-Drash syndrome, autosomal dominant severe congenital neutropenia, Costello syndrome, EEC syndrome, multiple cutaneous and mucosal venous malformations, diffuse nonepidermolytic palmoplantar keratoderma, Timothy syndrome, pheochromocytoma/paraganglioma syndrome 2, spondyloepimetaphyseal dysplasia with multiple dislocations, Brooke-Spiegler syndrome, macrocephaly-autism syndrome, pheochromocytoma/paraganglioma syndrome 3, Duane-radial ray syndrome, PCWH syndrome, heart-hand syndrome, Slovenian type, congenital stationary night blindness autosomal dominant 3, mandibulofacial dysostosis-microcephaly syndrome, multiple endocrine neoplasia type 4, juvenile cataract-microcornea-renal glucosuria syndrome, Crouzon syndrome-acanthosis nigricans syndrome, Birk-Barel syndrome, thrombophilia due to protein S deficiency, autosomal dominant, dyskeratosis congenita, autosomal dominant 2, dyskeratosis congenita, autosomal dominant 3, colorectal cancer, hereditary nonpolyposis, type 6, colorectal cancer, hereditary nonpolyposis, type 7, brain small vessel disease 2A, autosomal dominant, intellectual disability, autosomal dominant 14, intellectual disability, autosomal dominant 15, intellectual disability, autosomal dominant 16, hypopigmentation-punctate palmoplantar keratoderma syndrome, intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency, postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome, intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism, intellectual disability, autosomal dominant 29, intellectual disability, autosomal dominant 30, Houge-Janssens syndrome 2, severe achondroplasia-developmental delay-acanthosis nigricans syndrome, dyskeratosis congenita, autosomal dominant 6, epidermolysis bullosa simplex 6, generalized, with scarring and hair loss, autosomal dominant complex spastic paraplegia, early-onset autosomal dominant Alzheimer disease, muscular dystrophy, limb-girdle, autosomal dominant, Feingold syndrome, Carney complex, neuronopathy, distal hereditary motor, autosomal dominant, autosomal dominant coarctation of aorta, autosomal dominant spondylocostal dysostosis, autosomal dominant hypohidrotic ectodermal dysplasia, Cowden disease, autosomal dominant distal myopathy, autosomal dominant rhegmatogenous retinal detachment, palmoplantar keratoderma-spastic paralysis syndrome, Alagille syndrome due to a JAG1 point mutation, PTEN hamartoma tumor syndrome, gastric adenocarcinoma and proximal polyposis of the stomach, autosomal dominant proximal renal tubular acidosis, autosomal dominant spastic ataxia, Waardenburg syndrome, hereditary retinoblastoma, autosomal dominant hypocalcemia, Li-Fraumeni syndrome, Loeys-Dietz syndrome, hereditary hemorrhagic telangiectasia, hereditary inclusion body myopathy-joint contractures-ophthalmoplegia syndrome, microcephalic osteodysplastic dysplasia, Saul-Wilson type, autosomal dominant intermediate Charcot-Marie-Tooth disease, autosomal dominant nonsyndromic hearing loss, autosomal dominant optic atrophy, autosomal dominant Emery-Dreifuss muscular dystrophy, autosomal dominant cerebellar ataxia, autosomal dominant osteopetrosis, autosomal dominant epidermolytic ichthyosis, ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome, distal arthrogryposis type 2B1, neurofibromatosis, autosomal dominant cataract, arthrogryposis, distal, type 2B2, arthrogryposis, distal, type 2B3, Charcot-Marie-Tooth disease, demyelinating, type 1G, Delpire-McNeill syndrome, LAMA5-related multisystemic syndrome, autosomal dominant oculocutaneous albinism, Charcot-Marie-tooth disease, axonal, type 2DD, Pilarowski-Bjornsson syndrome, intellectual disability, autosomal dominant, fatty acyl-CoA reductase 1 upregulation, GUCY2D-related dominant retinopathy, RPE65-related dominant retinopathy, autosomal dominant titinopathy, NOG-related symphalangism spectrum disorder, ALPL-related autosomal dominant hypophosphatasia, MYH10-related neurodevelopmental disorder with congenital anomalies, spastic paraplegia 30A, autosomal dominant, TMEM127-related tumor predisposition, MAX-related tumor predisposition, BMPR1A-related juvenile polyposis syndrome, RP1-related dominant retinopathy, Birt-Hogg-Dube syndrome, inclusion body myopathy and brain white matter abnormalities, KINSSHIP syndrome, autosomal dominant nebulin-related myopathy, IMPG1-related dominant retinopathy, PROM1-related dominant retinopathy, PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome, ALG8-related autosomal dominant polycystic kidney and/or liver disease, NOTCH1-related AOS spectrum disorder, FLNB-associated autosomal dominant filamin related bone disorder, familial antiphospholipid syndrome

Subtypes (3): cutis laxa, autosomal dominant 1, cutis laxa, autosomal dominant 2, cutis laxa, autosomal dominant 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

8 retrieved; paginated sample, class counts are floors:

5 conflicting classifications of pathogenicity, 2 uncertain significance, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1163081	NM_006329.4(FBLN5):c.850C>T (p.Arg284Ter)	FBLN5	Likely pathogenic	criteria provided, single submitter
502265	NM_000501.4(ELN):c.1178_1201del (p.Gly393_Gly400del)	ELN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
21451	NM_006329.4(FBLN5):c.1171G>T (p.Glu391Ter)	FBLN5	Conflicting classifications of pathogenicity	no assertion criteria provided
21453	NM_006329.4(FBLN5):c.604G>A (p.Gly202Arg)	FBLN5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
21454	NM_006329.4(FBLN5):c.649T>C (p.Cys217Arg)	FBLN5	Conflicting classifications of pathogenicity	no assertion criteria provided
5475	NM_006329.4(FBLN5):c.679T>C (p.Ser227Pro)	FBLN5	Conflicting classifications of pathogenicity	no assertion criteria provided
1804877	NM_006329.4(FBLN5):c.432C>G (p.Cys144Trp)	FBLN5	Uncertain significance	no assertion criteria provided
888450	NM_006329.4(FBLN5):c.901C>A (p.Leu301Met)	FBLN5	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 50 · 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
ALDH18A1	Definitive	Autosomal dominant	cutis laxa, autosomal dominant 3	25
ELN	Definitive	Autosomal dominant	cutis laxa, autosomal dominant 1	11
FBLN5	Definitive	Autosomal recessive	cutis laxa, autosomal recessive, type 1A	14

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ELN	Orphanet:3193	Supravalvular aortic stenosis
ELN	Orphanet:90348	Autosomal dominant cutis laxa
ELN	Orphanet:904	Williams syndrome
ELN	Orphanet:91387	Familial thoracic aortic aneurysm and aortic dissection
FBLN5	Orphanet:280598	Hereditary sensorimotor neuropathy with hyperelastic skin
FBLN5	Orphanet:90348	Autosomal dominant cutis laxa
FBLN5	Orphanet:90349	Autosomal recessive cutis laxa type 1
ALDH18A1	Orphanet:35664	ALDH18A1-related De Barsy syndrome
ALDH18A1	Orphanet:447753	Autosomal dominant spastic paraplegia type 9A
ALDH18A1	Orphanet:447757	Autosomal dominant spastic paraplegia type 9B
ALDH18A1	Orphanet:447760	Autosomal recessive spastic paraplegia type 9B
ALDH18A1	Orphanet:90348	Autosomal dominant cutis laxa

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ELN	HGNC:3327	ENSG00000049540	P15502	Elastin	gencc,clinvar
FBLN5	HGNC:3602	ENSG00000140092	Q9UBX5	Fibulin-5	gencc,clinvar
ALDH18A1	HGNC:9722	ENSG00000059573	P54886	Delta-1-pyrroline-5-carboxylate synthase	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ELN	Elastin	Major structural protein of tissues such as aorta and nuchal ligament, which must expand rapidly and recover completely.
FBLN5	Fibulin-5	Essential for elastic fiber formation, is involved in the assembly of continuous elastin (ELN) polymer and promotes the interaction of microfibrils and ELN.
ALDH18A1	Delta-1-pyrroline-5-carboxylate synthase	Bifunctional enzyme that converts glutamate to glutamate 5-semialdehyde, an intermediate in the biosynthesis of proline, ornithine and arginine.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.33

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
Kinase	1	9.2×	0.209
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ELN	Other/Unknown	no		Tropoelastin
FBLN5	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, EGF-like_Ca-bd_dom
ALDH18A1	Kinase	yes		GPR_dom, Asp/Glu/Uridylate_kinase, Glu/AcGlu_kinase

Expression context

Cohort genes with no expression data: 0.

3 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ascending aorta	2
descending thoracic aorta	2
thoracic aorta	2
ileal mucosa	1
jejunal mucosa	1
parotid gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ELN	227	broad	marker	descending thoracic aorta, ascending aorta, thoracic aorta
FBLN5	261	ubiquitous	marker	thoracic aorta, ascending aorta, descending thoracic aorta
ALDH18A1	263	ubiquitous	marker	parotid gland, jejunal mucosa, ileal mucosa

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ALDH18A1	7,351
ELN	2,692
FBLN5	2,301

Intra-cohort edges

A	B	Sources
ELN	FBLN5	intact, string_interaction

Structural data

PDB: 1 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ALDH18A1	P54886	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FBLN5	Q9UBX5	83.69
ELN	P15502	36.20

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. Enrichment computed across 3 evidence-associated genes (3 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 3 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	223.9×	8e-05	ELN, FBLN5
Molecules associated with elastic fibres	2	205.8×	8e-05	ELN, FBLN5
Glutamate and glutamine metabolism	1	271.9×	0.006	ALDH18A1
Degradation of the extracellular matrix	1	39.2×	0.026	ELN
Mitochondrial protein degradation	1	38.1×	0.026	ALDH18A1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
L-ornithine biosynthetic process	1	5617.3×	0.002	ALDH18A1
intramembranous bone growth	1	5617.3×	0.002	FBLN5
L-citrulline biosynthetic process	1	1404.3×	0.005	ALDH18A1
L-proline biosynthetic process	1	936.2×	0.005	ALDH18A1
regulation of removal of superoxide radicals	1	936.2×	0.005	FBLN5
secretion	1	702.2×	0.006	FBLN5
response to temperature stimulus	1	510.7×	0.006	ALDH18A1
elastic fiber assembly	1	510.7×	0.006	FBLN5
regulation of smooth muscle cell proliferation	1	432.1×	0.006	ELN
positive regulation of osteoblast proliferation	1	401.2×	0.006	FBLN5
glutamate metabolic process	1	374.5×	0.006	ALDH18A1
extracellular matrix assembly	1	312.1×	0.007	ELN
stress fiber assembly	1	255.3×	0.008	ELN
respiratory gaseous exchange by respiratory system	1	208.1×	0.009	ELN
regulation of actin filament polymerization	1	193.7×	0.009	ELN
blood circulation	1	170.2×	0.009	ELN
protein localization to cell surface	1	165.2×	0.009	FBLN5
aortic valve morphogenesis	1	144.0×	0.010	ELN
outflow tract morphogenesis	1	102.1×	0.013	ELN
skeletal muscle tissue development	1	96.8×	0.013	ELN
animal organ morphogenesis	1	63.8×	0.019	ELN
negative regulation of angiogenesis	1	56.2×	0.020	FBLN5
cell-matrix adhesion	1	54.5×	0.020	FBLN5
negative regulation of transcription by RNA polymerase II	1	5.9×	0.167	FBLN5
positive regulation of transcription by RNA polymerase II	1	5.0×	0.188	FBLN5

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 3 evidence-associated genes (67%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ELN	0	0
FBLN5	0	0
ALDH18A1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
ALDH18A1	3	Binding:3

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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	1	ALDH18A1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	ELN, FBLN5

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ELN	0	—
FBLN5	0	—
ALDH18A1	3	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.