Pierson syndrome

Summary

Pierson syndrome (MONDO:0012184) is a disease caused by LAMB2 (GenCC Definitive), with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: LAMB2 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 1,145
• Phenotypes (HPO): 17

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		98	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

17 HPO clinical features (Orphanet curated; top 17 by frequency):

HPO ID	Term	Frequency
HP:0001967	Diffuse mesangial sclerosis	Very frequent (80-99%)
HP:0008677	Congenital nephrotic syndrome	Very frequent (80-99%)
HP:0000083	Renal insufficiency	Frequent (30-79%)
HP:0000518	Cataract	Frequent (30-79%)
HP:0000639	Nystagmus	Frequent (30-79%)
HP:0001104	Macular hypoplasia	Frequent (30-79%)
HP:0001252	Hypotonia	Frequent (30-79%)
HP:0001263	Global developmental delay	Frequent (30-79%)
HP:0001270	Motor delay	Frequent (30-79%)
HP:0001562	Oligohydramnios	Frequent (30-79%)
HP:0008872	Feeding difficulties in infancy	Frequent (30-79%)
HP:0025492	Microcoria	Frequent (30-79%)
HP:0000505	Visual impairment	Occasional (5-29%)
HP:0001265	Hyporeflexia	Occasional (5-29%)
HP:0007676	Hypoplasia of the iris	Occasional (5-29%)
HP:0007968	Remnants of the hyaloid vascular system	Occasional (5-29%)
HP:0034375	Spherophakia	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Pierson syndrome
Mondo ID	MONDO:0012184
MeSH	C537185
OMIM	609049
Orphanet	2670
DOID	DOID:0060852
ICD-11	555082533
NCIT	C128145
SNOMED CT	723449004
UMLS	C1836876
MedGen	373199
GARD	0009420
Is cancer (heuristic)	no

Also known as: microcoria - congenital nephrosis · microcoria - congenital nephrotic syndrome · microcoria-congenital nephrosis syndrome · Pierson syndrome

Data availability: 1,145 ClinVar variants · 3 GenCC gene-disease records.

Disease family

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

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:

283 uncertain significance, 223 likely benign, 31 pathogenic, 28 conflicting classifications of pathogenicity, 9 likely pathogenic, 9 benign/likely benign, 9 benign, 8 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1032809	NM_002292.4(LAMB2):c.2344+1G>A	LAMB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1179056	NM_002292.4(LAMB2):c.1564del (p.Cys522fs)	LAMB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1179149	NM_002292.4(LAMB2):c.1276del (p.His426fs)	LAMB2	Pathogenic	criteria provided, multiple submitters, no conflicts
1323180	NM_002292.3(LAMB2):c.1037_1038del	LAMB2	Pathogenic	criteria provided, multiple submitters, no conflicts
1323182	NM_002292.4(LAMB2):c.3595C>T (p.Arg1199Ter)	LAMB2	Pathogenic	criteria provided, multiple submitters, no conflicts
1344739	NM_002292.4(LAMB2):c.4573C>T (p.Gln1525Ter)	LAMB2	Pathogenic	criteria provided, multiple submitters, no conflicts
1366297	NM_002292.4(LAMB2):c.4201del (p.Ser1401fs)	LAMB2	Pathogenic	criteria provided, single submitter
1377324	NM_002292.4(LAMB2):c.3882_3892del (p.Asn1294fs)	LAMB2	Pathogenic	criteria provided, single submitter
1446226	NM_002292.4(LAMB2):c.3477_3483del (p.Gly1160fs)	LAMB2	Pathogenic	criteria provided, single submitter
14529	NM_002292.4(LAMB2):c.3015del (p.Gln1006fs)	LAMB2	Pathogenic	no assertion criteria provided
14530	NM_002292.4(LAMB2):c.736C>T (p.Arg246Trp)	LAMB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
14531	NM_002292.4(LAMB2):c.5258dup (p.Glu1754fs)	LAMB2	Pathogenic	no assertion criteria provided
14532	NM_002292.4(LAMB2):c.2067C>G (p.Tyr689Ter)	LAMB2	Pathogenic	criteria provided, single submitter
14533	NM_002292.4(LAMB2):c.1122T>A (p.Cys374Ter)	LAMB2	Pathogenic	no assertion criteria provided
1453552	NM_002292.4(LAMB2):c.1390_1391insA (p.Arg464fs)	LAMB2	Pathogenic	criteria provided, single submitter
14538	NM_002292.4(LAMB2):c.4804del (p.Gln1602fs)	LAMB2	Pathogenic	criteria provided, single submitter
1455722	NM_002292.4(LAMB2):c.1934dup (p.Gly646fs)	LAMB2	Pathogenic	criteria provided, single submitter
1456187	NM_002292.4(LAMB2):c.1241_1242dup (p.Met415fs)	LAMB2	Pathogenic	criteria provided, single submitter
1686687	NM_002292.4(LAMB2):c.4822C>T (p.Gln1608Ter)	LAMB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1712424	NM_002292.4(LAMB2):c.2369C>G (p.Ser790Ter)	LAMB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
180395	NM_002292.4(LAMB2):c.2890C>T (p.Arg964Ter)	LAMB2	Pathogenic	no assertion criteria provided
1976270	NM_002292.4(LAMB2):c.3251G>A (p.Trp1084Ter)	LAMB2	Pathogenic	criteria provided, single submitter
1998213	NM_002292.4(LAMB2):c.752_756dup (p.His253fs)	LAMB2	Pathogenic	criteria provided, single submitter
2002665	NM_002292.4(LAMB2):c.2249dup (p.His750fs)	LAMB2	Pathogenic	criteria provided, single submitter
2021063	NM_002292.4(LAMB2):c.3690_3697del (p.Ser1230fs)	LAMB2	Pathogenic	criteria provided, single submitter
2115550	NM_002292.4(LAMB2):c.3328-1G>C	LAMB2	Pathogenic	criteria provided, single submitter
2115551	NM_002292.4(LAMB2):c.2018+2T>C	LAMB2	Pathogenic	criteria provided, single submitter
2116167	NM_002292.4(LAMB2):c.4806_4807del (p.Lys1603fs)	LAMB2	Pathogenic	criteria provided, single submitter
2116168	NM_002292.4(LAMB2):c.2884+1del	LAMB2	Pathogenic	criteria provided, single submitter
2203392	NM_002292.4(LAMB2):c.4198_4199del (p.Leu1400fs)	LAMB2	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 6 · 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
LAMB2	Definitive	Autosomal recessive	Pierson syndrome	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
LAMB2	Orphanet:2670	Pierson syndrome
LAMB2	Orphanet:98915	Synaptic congenital myasthenic syndrome
DAG1	Orphanet:206599	Isolated asymptomatic elevation of creatine phosphokinase
DAG1	Orphanet:280333	Alpha-dystroglycan-related limb-girdle muscular dystrophy R16
DAG1	Orphanet:370997	Muscle-eye-brain disease with bilateral multicystic leucodystrophy
DAG1	Orphanet:899	Walker-Warburg syndrome

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
LAMB2	HGNC:6487	ENSG00000172037	P55268	Laminin subunit beta-2	gencc,clinvar
DAG1	HGNC:2666	ENSG00000173402	Q14118	Dystroglycan 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
LAMB2	Laminin subunit beta-2	Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components.
DAG1	Dystroglycan 1	The dystroglycan complex is involved in a number of signaling events and processes including laminin deposition and extracellular matrix assembly, acetylcholine receptor clustering, sarcolemmal stability, cell survival, peripheral nerve my…

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Antibody/Immunoglobulin	1	14.6×	0.135
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
LAMB2	Other/Unknown	no		EGF, LE_dom, Laminin_N
DAG1	Antibody/Immunoglobulin	yes		Cadg, DAG1_C, Ig-like_fold

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
apex of heart	1
right lobe of thyroid gland	1
stromal cell of endometrium	1
dorsal root ganglion	1
olfactory bulb	1
trigeminal ganglion	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LAMB2	268	ubiquitous	marker	apex of heart, right lobe of thyroid gland, stromal cell of endometrium
DAG1	299	ubiquitous	marker	olfactory bulb, trigeminal ganglion, dorsal root ganglion

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DAG1	2,301
LAMB2	1,548

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DAG1	Q14118	8

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
LAMB2	P55268	75.94

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 25. 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
Formation of the dystrophin-glycoprotein complex (DGC)	2	308.6×	3e-04	LAMB2, DAG1
Non-integrin membrane-ECM interactions	2	154.3×	4e-04	LAMB2, DAG1
ECM proteoglycans	2	150.3×	4e-04	LAMB2, DAG1
Defective POMGNT1 causes MDDGA3, MDDGB3 and MDDGC3	1	2855.0×	0.002	DAG1
Defective POMT2 causes MDDGA2, MDDGB2 and MDDGC2	1	1903.3×	0.002	DAG1
Defective POMT1 causes MDDGA1, MDDGB1 and MDDGC1	1	1903.3×	0.002	DAG1
DAG1 core M1 glycosylations	1	1427.5×	0.003	DAG1
DAG1 core M2 glycosylations	1	1142.0×	0.003	DAG1
DAG1 core M3 glycosylations	1	951.7×	0.003	DAG1
Matriglycan biosynthesis on DAG1	1	407.9×	0.006	DAG1
MET promotes cell motility	1	300.5×	0.008	LAMB2
Attachment of bacteria to epithelial cells	1	248.3×	0.008	LAMB2
Laminin interactions	1	190.3×	0.009	LAMB2
MET activates PTK2 signaling	1	190.3×	0.009	LAMB2
EGR2 and SOX10-mediated initiation of Schwann cell myelination	1	184.2×	0.009	DAG1
Signaling by MET	1	158.6×	0.010	LAMB2
Developmental Lineage of Pancreatic Ductal Cells	1	114.2×	0.013	LAMB2
Post-translational protein phosphorylation	1	50.1×	0.028	LAMB2
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	1	43.3×	0.030	LAMB2
Regulation of expression of SLITs and ROBOs	1	34.6×	0.036	DAG1
Extracellular matrix organization	1	31.6×	0.037	LAMB2
Signaling by Receptor Tyrosine Kinases	1	25.8×	0.044	LAMB2
Post-translational protein modification	1	9.6×	0.110	LAMB2
Metabolism of proteins	1	6.2×	0.162	LAMB2
Signal Transduction	1	5.1×	0.187	LAMB2

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
muscle attachment	1	8426.0×	0.002	DAG1
nerve maturation	1	8426.0×	0.002	DAG1
metanephric glomerular basement membrane development	1	8426.0×	0.002	LAMB2
axon guidance	2	90.6×	0.002	LAMB2, DAG1
calcium-dependent cell-matrix adhesion	1	4213.0×	0.002	DAG1
metanephric podocyte development	1	4213.0×	0.002	LAMB2
axon extension involved in regeneration	1	2808.7×	0.002	LAMB2
retrograde trans-synaptic signaling by trans-synaptic protein complex	1	2808.7×	0.002	DAG1
regulation of basement membrane organization	1	1404.3×	0.004	LAMB2
response to denervation involved in regulation of muscle adaptation	1	1203.7×	0.004	DAG1
morphogenesis of an epithelial sheet	1	842.6×	0.004	DAG1
angiogenesis involved in wound healing	1	842.6×	0.004	DAG1
radial glial cell differentiation	1	766.0×	0.004	LAMB2
branching involved in salivary gland morphogenesis	1	702.2×	0.004	DAG1
microtubule anchoring	1	648.1×	0.004	DAG1
positive regulation of integrin-mediated signaling pathway	1	648.1×	0.004	LAMB2
astrocyte development	1	561.7×	0.004	LAMB2
axon regeneration	1	561.7×	0.004	DAG1
positive regulation of muscle cell differentiation	1	561.7×	0.004	LAMB2
Schwann cell development	1	526.6×	0.004	LAMB2
commissural neuron axon guidance	1	495.6×	0.004	DAG1
nerve development	1	468.1×	0.004	DAG1
myelination in peripheral nervous system	1	443.5×	0.004	DAG1
skeletal muscle tissue regeneration	1	443.5×	0.004	DAG1
regulation of neurotransmitter receptor localization to postsynaptic specialization membrane	1	443.5×	0.004	DAG1
epithelial tube branching involved in lung morphogenesis	1	421.3×	0.004	DAG1
cellular response to cholesterol	1	421.3×	0.004	DAG1
positive regulation of myelination	1	383.0×	0.005	DAG1
positive regulation of cell-matrix adhesion	1	337.0×	0.005	DAG1
positive regulation of oligodendrocyte differentiation	1	337.0×	0.005	DAG1

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 2 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
LAMB2	0	0
DAG1	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
DAG1	4	Binding:4

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	1	DAG1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	LAMB2

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)
LAMB2	0	—
DAG1	4	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.