de Barsy syndrome

Summary

de Barsy syndrome (MONDO:0017569) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 623
• Phenotypes (HPO): 66

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		40	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

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

HPO ID	Term	Frequency
HP:0001611	Hypernasal speech	Very frequent (80-99%)
HP:0001762	Talipes equinovarus	Very frequent (80-99%)
HP:0001788	Premature rupture of membranes	Very frequent (80-99%)
HP:0001884	Talipes calcaneovalgus	Very frequent (80-99%)
HP:0002305	Athetosis	Very frequent (80-99%)
HP:0002645	Wormian bones	Very frequent (80-99%)
HP:0002750	Delayed skeletal maturation	Very frequent (80-99%)
HP:0002751	Kyphoscoliosis	Very frequent (80-99%)
HP:0002761	Generalized joint laxity	Very frequent (80-99%)
HP:0002812	Coxa vara	Very frequent (80-99%)
HP:0003199	Decreased muscle mass	Very frequent (80-99%)
HP:0004322	Short stature	Very frequent (80-99%)
HP:0005272	Prominent nasolabial fold	Very frequent (80-99%)
HP:0005328	Progeroid facial appearance	Very frequent (80-99%)
HP:0005425	Recurrent sinopulmonary infections	Very frequent (80-99%)
HP:0007457	Prominent veins on trunk	Very frequent (80-99%)
HP:0007957	Corneal opacity	Very frequent (80-99%)
HP:0008070	Sparse hair	Very frequent (80-99%)
HP:0008897	Postnatal growth retardation	Very frequent (80-99%)
HP:0008947	Floppy infant	Very frequent (80-99%)
HP:0009125	Lipodystrophy	Very frequent (80-99%)
HP:0009748	Large earlobe	Very frequent (80-99%)
HP:0010648	Dermal translucency	Very frequent (80-99%)
HP:0011003	High myopia	Very frequent (80-99%)
HP:0011220	Prominent forehead	Very frequent (80-99%)
HP:0025167	Fragmented elastic fibers in the dermis	Very frequent (80-99%)
HP:0200141	Small, conical teeth	Very frequent (80-99%)
HP:0000023	Inguinal hernia	Very frequent (80-99%)
HP:0000160	Narrow mouth	Very frequent (80-99%)
HP:0000218	High palate	Very frequent (80-99%)
HP:0000248	Brachycephaly	Very frequent (80-99%)
HP:0000253	Progressive microcephaly	Very frequent (80-99%)
HP:0000286	Epicanthus	Very frequent (80-99%)
HP:0000316	Hypertelorism	Very frequent (80-99%)
HP:0000369	Low-set ears	Very frequent (80-99%)
HP:0000490	Deeply set eye	Very frequent (80-99%)
HP:0000494	Downslanted palpebral fissures	Very frequent (80-99%)
HP:0000684	Delayed eruption of teeth	Very frequent (80-99%)
HP:0000750	Delayed speech and language development	Very frequent (80-99%)
HP:0000767	Pectus excavatum	Very frequent (80-99%)
HP:0000938	Osteopenia	Very frequent (80-99%)
HP:0000963	Thin skin	Very frequent (80-99%)
HP:0000973	Cutis laxa	Very frequent (80-99%)
HP:0001181	Adducted thumb	Very frequent (80-99%)
HP:0001263	Global developmental delay	Very frequent (80-99%)
HP:0001347	Hyperreflexia	Very frequent (80-99%)
HP:0001374	Congenital hip dislocation	Very frequent (80-99%)
HP:0001476	Delayed closure of the anterior fontanelle	Very frequent (80-99%)
HP:0001508	Failure to thrive	Very frequent (80-99%)
HP:0001511	Intrauterine growth retardation	Very frequent (80-99%)

Identifiers

Disease identifiers

Field	Value
Canonical name	de Barsy syndrome
Mondo ID	MONDO:0017569
MeSH	C535990
Orphanet	2962
DOID	DOID:0070143
SNOMED CT	238826008
UMLS	C0268354
MedGen	82794
GARD	0000049
NORD	1034
Is cancer (heuristic)	no

Also known as: corneal clouding, cutis laxa and intellectual disability · corneal clouding, cutis laxa and mental retardation · cutis laxa growth deficiency syndrome · cutis laxa-corneal clouding-intellectual disability syndrome · De Barsy syndrome · progeroid syndrome of de Barsy · progeroid syndrome, De Barsy type · progeroid syndrome, de Barsy type

Data availability: 623 ClinVar variants.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal recessive disease › de Barsy syndrome

Related subtypes (218): immunodeficiency-centromeric instability-facial anomalies syndrome, hypercalcemia, infantile, Ochoa syndrome, autosomal recessive Ehlers-Danlos syndrome, vascular type, hydrolethalus syndrome, 3-M syndrome, isolated hyperchlorhidrosis, dacryocystitis-osteopoikilosis syndrome, Hutchinson-Gilford progeria syndrome, achalasia microcephaly syndrome, acrorenal syndrome, autosomal recessive, beta-ketothiolase deficiency, autosomal recessive Alport syndrome, Alstrom syndrome, microphthalmia with limb anomalies, camptodactyly-arthropathy-coxa vara-pericarditis syndrome, Behr syndrome, bifid nose, autosomal recessive, Bloom syndrome, Bowen-Conradi syndrome, camptodactyly with fibrous tissue hyperplasia and skeletal dysplasia, heart defects-limb shortening syndrome, autosomal recessive palmoplantar keratoderma and congenital alopecia, COFS syndrome, craniometaphyseal dysplasia, autosomal recessive, Fraser syndrome, cystic fibrosis, polycystic lipomembranous osteodysplasia with sclerosing leukoencephaly, persistent hyperplastic primary vitreous, autosomal recessive, Donnai-Barrow syndrome, Schöpf-Schulz-Passarge syndrome, cleft lip/palate-ectodermal dysplasia syndrome, Ellis-van Creveld syndrome, Wolcott-Rallison syndrome, autosomal recessive faciodigitogenital syndrome, acromesomelic dysplasia 2B, brittle cornea syndrome, triple-A syndrome, autosomal recessive humeroradial synostosis, multinucleated neurons-anhydramnios-renal dysplasia-cerebellar hypoplasia-hydranencephaly syndrome, hydrocephalus, nonsyndromic, autosomal recessive 1, autosomal recessive hydrocephalus due to congenital stenosis of aqueduct of Sylvius, hypertelorism, microtia, facial clefting syndrome, hypoparathyroidism-retardation-dysmorphism syndrome, Vici syndrome, Johanson-Blizzard syndrome, autosomal recessive Kenny-Caffey syndrome, Papillon-Lefevre disease, Haim-Munk syndrome, Laurence-Moon syndrome, Donohue syndrome, lipase deficiency, combined, autosomal recessive familial Mediterranean fever, thiamine-responsive megaloblastic anemia syndrome, cartilage-hair hypoplasia, Nijmegen breakage syndrome, pseudo-TORCH syndrome, Galloway-Mowat syndrome, mulibrey nanism, myotonia congenita, autosomal recessive, Schwartz-Jampel syndrome, proteosome-associated autoinflammatory syndrome, Netherton syndrome, Niemann-Pick disease type A, oculodentodigital dysplasia, autosomal recessive, odonto-onycho-dermal dysplasia, autosomal recessive omodysplasia, osteoporosis-pseudoglioma syndrome, Shwachman-Diamond syndrome, phenylketonuria, Bjornstad syndrome, Laron syndrome, autosomal recessive polycystic kidney disease, autosomal recessive inherited pseudoxanthoma elasticum, autosomal recessive multiple pterygium syndrome, rapadilino syndrome, short-rib thoracic dysplasia 9 with or without polydactyly, autosomal recessive Robinow syndrome, Sjogren-Larsson syndrome, scapuloperoneal spinal muscular atrophy, autosomal recessive, spondyloepiphyseal dysplasia tarda, autosomal recessive, inherited threoninemia, Pendred syndrome, autosomal recessive spondylocostal dysostosis, Werner syndrome, ABCD syndrome, Naxos disease, autosomal recessive amelia, human HOXA1 syndromes, sickle cell disease, autosomal recessive proximal renal tubular acidosis, hyper-IgM syndrome type 2, temtamy preaxial brachydactyly syndrome, TH-deficient dopa-responsive dystonia, craniosynostosis syndrome, autosomal recessive, Niemann-Pick disease type B, skin fragility-woolly hair-palmoplantar keratoderma syndrome, CoQ-responsive OXPHOS deficiency, familial adenomatous polyposis 2, Pierson syndrome, palmoplantar keratoderma-XX sex reversal-predisposition to squamous cell carcinoma syndrome, cardiomyopathy-hypotonia-lactic acidosis syndrome, PHARC syndrome, Kahrizi syndrome, cutis laxa with severe pulmonary, gastrointestinal and urinary anomalies, congenital prothrombin deficiency, immunodeficiency 31B, dyskeratosis congenita, autosomal recessive 2, dyskeratosis congenita, autosomal recessive 3, Nestor-Guillermo progeria syndrome, leukoencephalopathy with calcifications and cysts, mitochondrial pyruvate carrier deficiency, branched-chain keto acid dehydrogenase kinase deficiency, dyskeratosis congenita, autosomal recessive 5, hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome, alacrima, achalasia, and intellectual disability syndrome, hyperlipoproteinemia, type 1D, microcephaly and chorioretinopathy 2, congenital stationary night blindness 1G, combined oxidative phosphorylation deficiency 29, hypermanganesemia with dystonia 2, growth retardation, intellectual developmental disorder, hypotonia, and hepatopathy, gnb5-related intellectual disability-cardiac arrhythmia syndrome, autosomal recessive spastic paraplegia type 78, autosomal recessive limb-girdle muscular dystrophy, Bardet-Biedl syndrome, autosomal recessive cerebellar ataxia, neuronopathy, distal hereditary motor, autosomal recessive, UV-sensitive syndrome, Ehlers-Danlos syndrome, kyphoscoliotic type 1, Cockayne syndrome, hyperphenylalaninemia due to tetrahydrobiopterin deficiency, leukoencephalopathy-palmoplantar keratoderma syndrome, autosomal recessive hypohidrotic ectodermal dysplasia, Warburg micro syndrome, autosomal recessive primary microcephaly, autosomal recessive progressive external ophthalmoplegia, Meier-Gorlin syndrome, autosomal recessive sideroblastic anemia, autosomal recessive intermediate Charcot-Marie-Tooth disease, Perrault syndrome, autosomal recessive hypophosphatemic rickets, leukocyte adhesion deficiency, Senior-Loken syndrome, autosomal recessive spastic ataxia, childhood-onset autosomal recessive myopathy with external ophthalmoplegia, autosomal recessive cerebral atrophy, GM3 synthase deficiency, autosomal recessive distal renal tubular acidosis, pigmentation defects-palmoplantar keratoderma-skin carcinoma syndrome, autosomal recessive brachyolmia, Aicardi-Goutieres syndrome, homocystinuria without methylmalonic aciduria, Niemann-Pick disease type C, nephronophthisis, autosomal recessive osteopetrosis, peroxisome biogenesis disorder, congenital non-bullous ichthyosiform erythroderma, Seckel syndrome, Usher syndrome, autosomal recessive cutis laxa type 1, autosomal recessive cutis laxa type 2, hearing loss, autosomal recessive, microcephaly, growth restriction, and increased sister chromatid exchange 2, encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1, congenital vertebral-cardiac-renal anomalies syndrome, hair defect with photosensitivity and intellectual disability syndrome, autosomal recessive severe congenital neutropenia, severe combined immunodeficiency due to CARMIL2 deficiency, extraoral halitosis due to methanethiol oxidase deficiency, neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities, mitochondrial complex 2 deficiency, nuclear type 3, mitochondrial complex 2 deficiency, nuclear type 4, mismatch repair cancer syndrome, spondyloepimetaphyseal dysplasia with joint laxity, type 3, Kilquist syndrome, Duane anomaly-myopathy-scoliosis syndrome, autosomal recessive axonal charcot-marie-tooth disease due to copper metabolism defect, immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections-lymphopenia syndrome, optic atrophy-ataxia-peripheral neuropathy-global developmental delay syndrome, congenital myopathy with reduced type 2 muscle fibers, NAD(P)HX dehydratase deficiency, autosomal recessive ocular albinism, ichthyosis linearis circumflexa, eosinophil peroxidase deficiency, hyperphenylalaninemia due to DNAJC12 deficiency, autosomal recessive epidermolytic ichthyosis, Ehlers-Danlos syndrome, classic-like, 2, joint laxity, short stature, and myopia, HELIX syndrome, auditory neuropathy-optic atrophy syndrome, glycosylphosphatidylinositol biosynthesis defect 15, neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures, SCN4A-related myopathy, autosomal recessive, Uner Tan Syndrome, nephropathic cystinosis, Imerslund-Grasbeck syndrome type 1, Imerslund-Grasbeck syndrome type 2, permanent neonatal diabetes mellitus 1, growth hormone insensitivity with immune dysregulation 1, autosomal recessive, Rajab interstitial lung disease with brain calcifications 1, Roberts-SC phocomelia syndrome, neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities, RPE65-related recessive retinopathy, GUCY2D-related recessive retinopathy, autosomal recessive titinopathy, intellectual disability, autosomal recessive, ALPL-related autosomal recessive hypophosphatasia, spastic paraplegia 18b, autosomal recessive, CEP164-related ciliopathy, RP1-related recessive retinopathy, pseudohypoaldosteronism, type IB2, autosomal recessive, pseudohypoaldosteronism, type IB3, autosomal recessive, spastic paraplegia 30B, autosomal recessive, cerebral arteriopathy, autosomal recessive, with subcortical infarcts and leukoencephalopathy 1, brain small vessel disease 2B, autosomal recessive, IMPG1-related recessive retinopathy, PROM1-related recessive retinopathy

Subtypes (2): ALDH18A1-related de Barsy syndrome, PYCR1-related de Barsy syndrome

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:

318 uncertain significance, 196 likely benign, 42 conflicting classifications of pathogenicity, 20 pathogenic, 10 likely pathogenic, 8 benign, 3 pathogenic/likely pathogenic, 3 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1333373	NM_002860.4(ALDH18A1):c.1596_1600del (p.Val533fs)	ALDH18A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2003911	NM_002860.4(ALDH18A1):c.545del (p.Ile182fs)	ALDH18A1	Pathogenic	criteria provided, single submitter
2035292	NM_002860.4(ALDH18A1):c.2117_2118del (p.Thr706fs)	ALDH18A1	Pathogenic	criteria provided, single submitter
2058971	NM_002860.4(ALDH18A1):c.1993C>T (p.Arg665Ter)	ALDH18A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
217117	NM_002860.4(ALDH18A1):c.755G>A (p.Arg252Gln)	ALDH18A1	Pathogenic	criteria provided, multiple submitters, no conflicts
217118	NM_002860.4(ALDH18A1):c.359T>C (p.Val120Ala)	ALDH18A1	Pathogenic	criteria provided, single submitter
217260	NM_002860.4(ALDH18A1):c.413G>A (p.Arg138Gln)	ALDH18A1	Pathogenic	criteria provided, multiple submitters, no conflicts
2253522	NM_002860.4(ALDH18A1):c.250C>T (p.Arg84Ter)	ALDH18A1	Pathogenic	criteria provided, multiple submitters, no conflicts
2424550	NC_000010.10:g.(?97376214)(97376391_?)del	ALDH18A1	Pathogenic	criteria provided, single submitter
2924294	NM_002860.4(ALDH18A1):c.1321C>T (p.Arg441Ter)	ALDH18A1	Pathogenic	criteria provided, multiple submitters, no conflicts
2930570	NM_002860.4(ALDH18A1):c.1795del (p.Arg599fs)	ALDH18A1	Pathogenic	criteria provided, single submitter
2939892	NM_002860.4(ALDH18A1):c.1227dup (p.Asp410fs)	ALDH18A1	Pathogenic	criteria provided, single submitter
2940959	NM_002860.4(ALDH18A1):c.339del (p.Met113fs)	ALDH18A1	Pathogenic	criteria provided, single submitter
2949341	NM_002860.4(ALDH18A1):c.1804del (p.Arg602fs)	ALDH18A1	Pathogenic	criteria provided, single submitter
2950800	NM_002860.4(ALDH18A1):c.1713dup (p.Lys572Ter)	ALDH18A1	Pathogenic	criteria provided, single submitter
3244833	NC_000010.10:g.(?97366519)(97626140_?)del	ALDH18A1	Pathogenic	criteria provided, single submitter
3756046	NM_002860.4(ALDH18A1):c.467T>G (p.Leu156Ter)	ALDH18A1	Pathogenic	criteria provided, single submitter
3760154	NM_002860.4(ALDH18A1):c.684dup (p.Ala229fs)	ALDH18A1	Pathogenic	criteria provided, single submitter
3767627	NM_002860.4(ALDH18A1):c.475C>T (p.Arg159Ter)	ALDH18A1	Pathogenic	criteria provided, multiple submitters, no conflicts
392664	NM_002860.4(ALDH18A1):c.754C>T (p.Arg252Ter)	ALDH18A1	Pathogenic	criteria provided, multiple submitters, no conflicts
459841	NM_002860.4(ALDH18A1):c.741del (p.Asp247fs)	ALDH18A1	Pathogenic	criteria provided, single submitter
4794356	NM_002860.4(ALDH18A1):c.1702C>T (p.Gln568Ter)	ALDH18A1	Pathogenic	criteria provided, single submitter
807367	NM_002860.4(ALDH18A1):c.2246G>A (p.Arg749Gln)	ALDH18A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1209475	NM_002860.4(ALDH18A1):c.809-1G>A	ALDH18A1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1487261	NM_002860.4(ALDH18A1):c.933+1G>A	ALDH18A1	Likely pathogenic	criteria provided, single submitter
1720743	NM_002860.4(ALDH18A1):c.408C>A (p.Ser136Arg)	ALDH18A1	Likely pathogenic	criteria provided, single submitter
1995401	NM_002860.4(ALDH18A1):c.1152+1G>A	ALDH18A1	Likely pathogenic	criteria provided, single submitter
217115	NM_002860.4(ALDH18A1):c.2143G>C (p.Asp715His)	ALDH18A1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2940641	NM_002860.4(ALDH18A1):c.1468-2A>C	ALDH18A1	Likely pathogenic	criteria provided, single submitter
3755775	NM_002860.4(ALDH18A1):c.191G>A (p.Arg64His)	ALDH18A1	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 5 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ALDH18A1	HGNC:9722	ENSG00000059573	P54886	Delta-1-pyrroline-5-carboxylate synthase	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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: 0 · Druggable fraction: 1.0

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
Kinase	1	27.7×	0.036

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ALDH18A1	Kinase	yes		GPR_dom, Asp/Glu/Uridylate_kinase, Glu/AcGlu_kinase

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ileal mucosa	1
jejunal mucosa	1
parotid gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ALDH18A1	263	ubiquitous	marker	parotid gland, jejunal mucosa, ileal mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ALDH18A1	7,351

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ALDH18A1	P54886	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Glutamate and glutamine metabolism	1	815.7×	0.002	ALDH18A1
Mitochondrial protein degradation	1	114.2×	0.009	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 1 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	16852.0×	3e-04	ALDH18A1
L-citrulline biosynthetic process	1	4213.0×	6e-04	ALDH18A1
L-proline biosynthetic process	1	2808.7×	6e-04	ALDH18A1
response to temperature stimulus	1	1532.0×	8e-04	ALDH18A1
glutamate metabolic process	1	1123.5×	9e-04	ALDH18A1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
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: 1; 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	0

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ALDH18A1	3	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.