Alagille syndrome due to a JAG1 point mutation

Summary

Alagille syndrome due to a JAG1 point mutation (MONDO:0016862) is a disease caused by JAG1 (GenCC Definitive), with 6 cohort genes.

At a glance

• Causal gene: JAG1 (GenCC Definitive)
• Cohort genes: 6
• ClinVar variants: 1,582

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Alagille syndrome due to a JAG1 point mutation
Mondo ID	MONDO:0016862
OMIM	118450
Orphanet	261619
UMLS	C1956125
MedGen	365434
GARD	0017251
Is cancer (heuristic)	no

Also known as: Alagille syndrome 1 · Alagille syndrome due to a JAG1 point mutation · Alagille syndrome type 1 · Alagille syndrome-JAG1 · Alagille-Watson syndrome due to a JAG1 point mutation · ALGS1 · arteriohepatic dysplasia due to a JAG1 point mutation · syndromic bile duct paucity due to a JAG1 point mutation

Data availability: 1,582 ClinVar variants · 4 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 dominant disease › Alagille syndrome due to a JAG1 point mutation

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, 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 cutis laxa, 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

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:

234 likely benign, 181 uncertain significance, 69 pathogenic, 66 conflicting classifications of pathogenicity, 21 likely pathogenic, 16 benign/likely benign, 11 benign, 2 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1710295	t(4;20)(q22.1;p12.2)	FAM13A	Pathogenic	no assertion criteria provided
1028619	NM_000214.3(JAG1):c.2372+1G>T	JAG1	Pathogenic	criteria provided, single submitter
1032929	NM_000214.3(JAG1):c.3001_3002dup (p.Cys1002fs)	JAG1	Pathogenic	criteria provided, multiple submitters, no conflicts
1065116	NM_000214.3(JAG1):c.1485del (p.Cys496fs)	JAG1	Pathogenic	no assertion criteria provided
1069512	NM_000214.3(JAG1):c.3203del (p.Phe1068fs)	JAG1	Pathogenic	criteria provided, single submitter
1069646	NM_000214.3(JAG1):c.273del (p.Cys92fs)	JAG1	Pathogenic	criteria provided, multiple submitters, no conflicts
1070550	NM_000214.3(JAG1):c.734dup (p.Cys245fs)	JAG1	Pathogenic	criteria provided, single submitter
1070837	NM_000214.3(JAG1):c.1779T>A (p.Tyr593Ter)	JAG1	Pathogenic	criteria provided, single submitter
1070945	NM_000214.3(JAG1):c.3049-2A>G	JAG1	Pathogenic	criteria provided, single submitter
1071570	NC_000020.11:g.10641783dup	JAG1	Pathogenic	criteria provided, single submitter
1071992	NM_000214.3(JAG1):c.1312dup (p.Cys438fs)	JAG1	Pathogenic	criteria provided, single submitter
1072898	NM_000214.3(JAG1):c.2917-1G>T	JAG1	Pathogenic	criteria provided, single submitter
1073158	NM_000214.3(JAG1):c.655dup (p.Thr219fs)	JAG1	Pathogenic	criteria provided, single submitter
1073270	NM_000214.3(JAG1):c.1101dup (p.Gly368fs)	JAG1	Pathogenic	criteria provided, single submitter
1074174	NM_000214.3(JAG1):c.1829del (p.Gly610fs)	JAG1	Pathogenic	criteria provided, single submitter
1074592	NM_000214.3(JAG1):c.1308C>A (p.Cys436Ter)	JAG1	Pathogenic	criteria provided, multiple submitters, no conflicts
1074995	NM_000214.3(JAG1):c.682G>T (p.Glu228Ter)	JAG1	Pathogenic	criteria provided, single submitter
1075491	NM_000214.3(JAG1):c.2318del (p.Gly773fs)	JAG1	Pathogenic	criteria provided, single submitter
1210293	NM_000214.3(JAG1):c.2358C>A (p.Cys786Ter)	JAG1	Pathogenic	no assertion criteria provided
1251969	NM_000214.2:c.(755+1_756-1)_(1120+1_1121-1)del	JAG1	Pathogenic	no assertion criteria provided
1319943	NM_000214.3(JAG1):c.1007-2A>G	JAG1	Pathogenic	no assertion criteria provided
1333228	NM_000214.3(JAG1):c.2650C>T (p.Gln884Ter)	JAG1	Pathogenic	criteria provided, multiple submitters, no conflicts
1341895	NM_000214.3(JAG1):c.1653C>A (p.Cys551Ter)	JAG1	Pathogenic	criteria provided, single submitter
1353005	NM_000214.3(JAG1):c.622G>T (p.Gly208Ter)	JAG1	Pathogenic	criteria provided, multiple submitters, no conflicts
1353877	NM_000214.3(JAG1):c.1139del (p.Pro380fs)	JAG1	Pathogenic	criteria provided, single submitter
1354095	NM_000214.3(JAG1):c.1687del (p.His562_Leu563insTer)	JAG1	Pathogenic	criteria provided, single submitter
1358138	NM_000214.3(JAG1):c.936T>A (p.Cys312Ter)	JAG1	Pathogenic	criteria provided, single submitter
1360035	NM_000214.3(JAG1):c.2209G>T (p.Gly737Ter)	JAG1	Pathogenic	criteria provided, single submitter
1365424	NM_000214.3(JAG1):c.1878C>A (p.Cys626Ter)	JAG1	Pathogenic	criteria provided, single submitter
1371613	NM_000214.3(JAG1):c.1868dup (p.Thr624fs)	JAG1	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 5 · 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
JAG1	Definitive	Autosomal dominant	Alagille syndrome due to a JAG1 point mutation	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
JAG1	Orphanet:261600	Alagille syndrome due to 20p12 microdeletion
JAG1	Orphanet:261619	Alagille syndrome due to a JAG1 point mutation
JAG1	Orphanet:3303	Tetralogy of Fallot
FAM13A	Orphanet:2032	Idiopathic pulmonary fibrosis
PLCB4	Orphanet:137888	Auriculocondylar syndrome

Cohort genes → proteins

6 cohort genes, 6 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	6

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
JAG1	HGNC:6188	ENSG00000101384	P78504	Protein jagged-1	gencc,clinvar
ANKEF1	HGNC:15803	ENSG00000132623	Q9NU02	Ankyrin repeat and EF-hand domain-containing protein 1	clinvar
SLX4IP	HGNC:16225	ENSG00000149346	Q5VYV7	Protein SLX4IP	clinvar
FAM13A	HGNC:19367	ENSG00000138640	O94988	Protein FAM13A	clinvar
NCAPH2	HGNC:25071	ENSG00000025770	Q6IBW4	Condensin-2 complex subunit H2	clinvar
PLCB4	HGNC:9059	ENSG00000101333	Q15147	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
JAG1	Protein jagged-1	Ligand for multiple Notch receptors and involved in the mediation of Notch signaling.
NCAPH2	Condensin-2 complex subunit H2	Regulatory subunit of the condensin-2 complex, a complex that seems to provide chromosomes with an additional level of organization and rigidity and in establishing mitotic chromosome architecture.
PLCB4	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4	Activated phosphatidylinositol-specific phospholipase C enzymes catalyze the production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) involved in G-protein coupled receptor signaling pathways.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 4 · Druggable fraction: 0.17

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
Scaffold/PPI	1	2.9×	0.458
Enzyme (other)	1	2.0×	0.458
Other/Unknown	4	1.2×	0.458

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
JAG1	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, VWF_dom
ANKEF1	Scaffold/PPI	no		EF_hand_dom, Ankyrin_rpt, EF-hand-dom_pair
SLX4IP	Other/Unknown	no		SLX4IP
FAM13A	Other/Unknown	no		RhoGAP_dom, Rho_GTPase_activation_prot, FAM13
NCAPH2	Other/Unknown	no		H2_N, H2_M, CNDH2_C
PLCB4	Enzyme (other)	yes	3.1.4.11	C2_dom, PLipase_C_PInositol-sp_X_dom, PI-PLC_fam

Expression context

Cohort genes with no expression data: 0.

6 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)	6
unknown	0

Top tissues across cohort

Tissue	Cohort genes
blood vessel layer	1
skin of hip	1
upper leg skin	1
left testis	1
male germ cell	1
sperm	1
corpus epididymis	1
epithelial cell of pancreas	1
pancreatic ductal cell	1
jejunal mucosa	1
oocyte	1
secondary oocyte	1
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1
lateral nuclear group of thalamus	1
parotid gland	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
JAG1	297	ubiquitous	marker	upper leg skin, skin of hip, blood vessel layer
ANKEF1	209	ubiquitous	marker	sperm, male germ cell, left testis
SLX4IP	236	ubiquitous	marker	epithelial cell of pancreas, pancreatic ductal cell, corpus epididymis
FAM13A	293	ubiquitous	marker	secondary oocyte, oocyte, jejunal mucosa
NCAPH2	260	ubiquitous	marker	cerebellar hemisphere, right hemisphere of cerebellum, cerebellar cortex
PLCB4	273	ubiquitous	marker	parotid gland, lateral nuclear group of thalamus, sural nerve

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
JAG1	4,405
PLCB4	1,595
NCAPH2	1,561
ANKEF1	861
FAM13A	830
SLX4IP	695

Intra-cohort edges

A	B	Sources
ANKEF1	SLX4IP	string_interaction

Structural data

PDB: 3 · AlphaFold-only: 3 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
JAG1	P78504	7
SLX4IP	Q5VYV7	2
NCAPH2	Q6IBW4	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PLCB4	Q15147	86.03
ANKEF1	Q9NU02	80.95
FAM13A	O94988	61.00

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 39. Enrichment computed across 6 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
Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant	1	713.8×	0.021	JAG1
Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant	1	407.9×	0.021	JAG1
Signaling by NOTCH1 HD Domain Mutants in Cancer	1	317.2×	0.021	JAG1
NOTCH4 Activation and Transmission of Signal to the Nucleus	1	259.6×	0.021	JAG1
Nephron development	1	219.6×	0.021	JAG1
RUNX3 regulates NOTCH signaling	1	203.9×	0.021	JAG1
Kidney development	1	203.9×	0.021	JAG1
Constitutive Signaling by NOTCH1 HD Domain Mutants	1	190.3×	0.021	JAG1
Signaling by NOTCH2	1	178.4×	0.021	JAG1
Signaling by NOTCH3	1	129.8×	0.021	JAG1
Signaling by NOTCH4	1	124.1×	0.021	JAG1
NOTCH3 Activation and Transmission of Signal to the Nucleus	1	119.0×	0.021	JAG1
NOTCH2 Activation and Transmission of Signal to the Nucleus	1	109.8×	0.021	JAG1
Synthesis of IP3 and IP4 in the cytosol	1	105.7×	0.021	PLCB4
Signaling by NOTCH1 PEST Domain Mutants in Cancer	1	102.0×	0.021	JAG1
Signaling by NOTCH1 in Cancer	1	102.0×	0.021	JAG1
Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer	1	102.0×	0.021	JAG1
RAC1 GTPase cycle	2	30.5×	0.021	JAG1, FAM13A
Signaling by NOTCH1	1	89.2×	0.022	JAG1
Activated NOTCH1 Transmits Signal to the Nucleus	1	89.2×	0.022	JAG1
Transcriptional regulation by RUNX3	1	68.0×	0.027	JAG1
PLC beta mediated events	1	66.4×	0.027	PLCB4
Constitutive Signaling by NOTCH1 PEST Domain Mutants	1	49.2×	0.033	JAG1
Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants	1	49.2×	0.033	JAG1
Signaling by NOTCH	1	43.9×	0.035	JAG1
Condensation of Prophase Chromosomes	1	39.1×	0.038	NCAPH2
RAC3 GTPase cycle	1	29.7×	0.048	JAG1
RHOA GTPase cycle	1	18.7×	0.073	FAM13A
RHO GTPase cycle	1	15.0×	0.086	JAG1
G alpha (q) signalling events	1	14.3×	0.086	PLCB4

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
endocardial cushion cell development	1	4213.0×	0.006	JAG1
phospholipase C-activating endothelin receptor signaling pathway	1	4213.0×	0.006	PLCB4
female meiosis chromosome separation	1	2106.5×	0.006	NCAPH2
loop of Henle development	1	2106.5×	0.006	JAG1
cardiac neural crest cell development involved in outflow tract morphogenesis	1	1404.3×	0.006	JAG1
distal tubule development	1	1404.3×	0.006	JAG1
inhibition of neuroepithelial cell differentiation	1	1053.2×	0.006	JAG1
ciliary body morphogenesis	1	1053.2×	0.006	JAG1
positive regulation of cardiac epithelial to mesenchymal transition	1	1053.2×	0.006	JAG1
negative regulation of endothelial cell differentiation	1	842.6×	0.006	JAG1
positive regulation of myeloid cell differentiation	1	842.6×	0.006	JAG1
mitotic sister chromatid separation	1	842.6×	0.006	NCAPH2
meiotic chromosome condensation	1	702.2×	0.006	NCAPH2
pulmonary artery morphogenesis	1	702.2×	0.006	JAG1
neuroendocrine cell differentiation	1	601.9×	0.007	JAG1
positive regulation of chromosome condensation	1	526.6×	0.007	NCAPH2
nephron development	1	468.1×	0.007	JAG1
morphogenesis of an epithelial sheet	1	421.3×	0.007	JAG1
positive regulation of chromosome separation	1	421.3×	0.007	NCAPH2
podocyte development	1	383.0×	0.008	JAG1
cardiac right ventricle morphogenesis	1	351.1×	0.008	JAG1
response to muramyl dipeptide	1	351.1×	0.008	JAG1
positive regulation of chromosome segregation	1	324.1×	0.008	NCAPH2
inner ear auditory receptor cell differentiation	1	300.9×	0.008	JAG1
cardiac septum morphogenesis	1	300.9×	0.008	JAG1
endothelial cell differentiation	1	280.9×	0.008	JAG1
T cell mediated immunity	1	247.8×	0.008	JAG1
mitotic chromosome condensation	1	247.8×	0.008	NCAPH2
negative regulation of cell-cell adhesion	1	247.8×	0.008	JAG1
cell fate determination	1	234.1×	0.008	JAG1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 6

Druggability breadth: 1 of 6 evidence-associated genes (17%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
JAG1	0	0
ANKEF1	0	0
SLX4IP	0	0
FAM13A	0	0
NCAPH2	0	0
PLCB4	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
JAG1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PLCB4	3.1.4.11	phosphoinositide phospholipase C

Pharmacogenomics

Cohort genes with a PharmGKB record: 6; 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	1	PLCB4
E	Difficult family or no structure, no drug	5	JAG1, ANKEF1, SLX4IP, FAM13A, NCAPH2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
JAG1	1	—
ANKEF1	0	—
SLX4IP	0	—
FAM13A	0	—
NCAPH2	0	—
PLCB4	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.