JAG1

Summary

JAG1 (jagged canonical Notch ligand 1, HGNC:6188) is a protein-coding gene on chromosome 20p12.2, encoding Protein jagged-1 (P78504). Ligand for multiple Notch receptors and involved in the mediation of Notch signaling. It is haploinsufficient (ClinGen: sufficient evidence).

The jagged 1 protein encoded by JAG1 is the human homolog of the Drosophilia jagged protein. Human jagged 1 is the ligand for the receptor notch 1, the latter is involved in signaling processes. Mutations that alter the jagged 1 protein cause Alagille syndrome. Jagged 1 signalling through notch 1 has also been shown to play a role in hematopoiesis.

Source: NCBI Gene 182 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Alagille syndrome due to a JAG1 point mutation (Definitive, GenCC) — +2 more curated relationships
• GWAS associations: 59
• Clinical variants (ClinVar): 2,698 total — 344 pathogenic, 110 likely-pathogenic
• Phenotypes (HPO): 103
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_000214

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6188
Approved symbol	JAG1
Name	jagged canonical Notch ligand 1
Location	20p12.2
Locus type	gene with protein product
Status	Approved
Aliases	AHD, AWS, HJ1, CD339
Ensembl gene	ENSG00000101384
Ensembl biotype	protein_coding
OMIM	601920
Entrez	182

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 7 protein_coding, 5 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000254958, ENST00000423891, ENST00000488480, ENST00000612857, ENST00000613518, ENST00000617357, ENST00000617965, ENST00000620743, ENST00000622545, ENST00000901230, ENST00000913736, ENST00000913737, ENST00000913738, ENST00000946613

RefSeq mRNA: 1 — MANE Select: NM_000214 NM_000214

CCDS: CCDS13112

Canonical transcript exons

ENST00000254958 — 26 exons

Exon	Start	End
ENSE00000859115	10637684	10639955
ENSE00001607073	10672701	10673006
ENSE00001678466	10663963	10664014
ENSE00001800294	10645143	10645256
ENSE00001871530	10673450	10673999
ENSE00003468001	10645356	10645469
ENSE00003654366	10658468	10658722
ENSE00003716574	10652131	10652250
ENSE00003716776	10651581	10651694
ENSE00003718897	10643778	10643863
ENSE00003723778	10644357	10644384
ENSE00003723870	10640783	10640933
ENSE00003725851	10641460	10641693
ENSE00003726125	10644863	10644979
ENSE00003726426	10646939	10647103
ENSE00003730021	10656398	10656458
ENSE00003730345	10648549	10648722
ENSE00003730865	10641783	10641892
ENSE00003732500	10650247	10650360
ENSE00003739154	10642488	10642601
ENSE00003740814	10649061	10649107
ENSE00003743785	10649522	10649635
ENSE00003751289	10647960	10648110
ENSE00003752659	10652468	10652598
ENSE00003752831	10645971	10646084
ENSE00003753136	10641113	10641244

Expression profiles

Bgee: expression breadth ubiquitous, 297 present calls, max score 99.26.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 38.1225 / max 804.6649, expressed in 1654 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
186450	32.9046	1643
186449	2.3992	914
186444	1.6900	215
186448	0.5278	310
186446	0.2638	130
186447	0.1542	69
186445	0.1102	58
186443	0.0728	20

Top tissues by expression

301 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
upper leg skin	UBERON:0004262	99.26	gold quality
skin of hip	UBERON:0001554	99.02	gold quality
blood vessel layer	UBERON:0004797	98.97	gold quality
gingival epithelium	UBERON:0001949	98.89	gold quality
gingiva	UBERON:0001828	98.87	gold quality
right coronary artery	UBERON:0001625	98.71	gold quality
penis	UBERON:0000989	98.70	gold quality
palpebral conjunctiva	UBERON:0001812	98.55	gold quality
urethra	UBERON:0000057	98.41	gold quality
oral cavity	UBERON:0000167	98.26	gold quality
mammalian vulva	UBERON:0000997	98.25	gold quality
hair follicle	UBERON:0002073	98.23	gold quality
mucosa of paranasal sinus	UBERON:0005030	98.19	gold quality
popliteal artery	UBERON:0002250	98.14	gold quality
tibial artery	UBERON:0007610	98.14	gold quality
artery	UBERON:0001637	98.08	gold quality
cervix squamous epithelium	UBERON:0006922	97.99	gold quality
saphenous vein	UBERON:0007318	97.98	gold quality
squamous epithelium	UBERON:0006914	97.89	gold quality
descending thoracic aorta	UBERON:0002345	97.88	gold quality
vagina	UBERON:0000996	97.84	gold quality
seminal vesicle	UBERON:0000998	97.71	gold quality
coronary artery	UBERON:0001621	97.69	gold quality
renal medulla	UBERON:0000362	97.65	gold quality
eye	UBERON:0000970	97.63	gold quality
pharyngeal mucosa	UBERON:0000355	97.62	gold quality
tongue squamous epithelium	UBERON:0006919	97.61	gold quality
esophagus squamous epithelium	UBERON:0006920	97.61	gold quality
left coronary artery	UBERON:0001626	97.59	gold quality
aorta	UBERON:0000947	97.58	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-GEOD-98556	yes	451.34
E-MTAB-10287	yes	51.11
E-HCAD-10	yes	29.77
E-GEOD-135922	yes	26.97
E-MTAB-8410	yes	15.87
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

5 targets.

Target	Regulation
ACTA2	Activation
HEY2	Activation
HEYL	Activation
SNAI1	Activation
SNAI2	Activation

Upstream regulators (CollecTRI, top): CD46, GATA5, GLI2, KDM4C, NFKB, NFKBIA, PPARG, REL, RELA, RUNX3, SMAD3, SNAI2, SOX10, SOX2, TP63, TP73

miRNA regulators (miRDB)

179 targeting JAG1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5692A	100.00	74.40	6850
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-MIR-98-3P	100.00	74.08	3907
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• a cell surface protein that functions in an ambryologically important signaling pathway (PMID:11745040)
• interaction with Notch1 on tumor cells dramatically induces proliferation and inhibition of apoptosis in vitro (PMID:11964309)
• inhibits proliferation of cd34+ macrophage progenitors (PMID:11999354)
• Familial deafness, congenital heart defects, and posterior embryotoxon caused by cysteine substitution in the first epidermal-growth-factor-like domain of jagged 1. (PMID:12022040)
• JAG1 gene abnormality may be an aggravating factor in extrahepatic biliary atresia (PMID:12297837)
• experiments in vitro showed that Jagged1 signaling inhibited process outgrowth from primary human oligodendrocytes (PMID:12357247)
• Activation of Notch-1 signaling by Jagged-1 induces monocyte-derived dendritic cell maturation in vitro. (PMID:12370358)
• Results of this study are consistent with the proposal that either haploinsufficiency for wild-type JAG1 and/or dominant negative effects produced by mutated JAG1 are responsible for the AGS phenotype. (PMID:12442286)
• identification of C-terminal PDZ-ligand is essential for cellular transformation (PMID:12496248)
• Identification of novel Jagged1 mutations in patients with Alagille syndrome. (PMID:12497640)
• Conditional mutation of this protein shows the developing heart is more sensitive than developing liver to JAG1 dosage. (PMID:12649809)
• suppresses the self-renewal capacity and long-term growth of two myeloblastic leukemia cell lines (PMID:12684674)
• Delta and Jagged undergo ADAM-mediated ectodomain processing followed by PS-mediated intramembrane proteolysis to release signaling fragments (PMID:12826675)
• Notch activation by JAG1 in the presence of alloantigen-presenting cells may therefore be a means of inducing specific regulatory T cells while preserving other T-cell functionality (PMID:12842995)
• Notch receptors 1&2 and their ligand Jagged1 are highly expressed in cultured and primary MM cells, suggesting Notch signaling is involved in the tight interactions between neoplastic plasma cells and their bone marrow microenvironment (PMID:14726396)
• induced an attenuation of cell motility which is accompanied by a decrease in actin stress fibers and an increase in adherence junctions and induces a NIH 3T3 cell tranformed phenotype mediated by FGF signaling. (PMID:14769803)
• Delta-1 and Jagged-1 have roles in growth suppression in two myeloid leukemia cell lines (PMID:15254769)
• soluble form of Jagged1, when present in the cell culture medium, was sufficient to induce keratinocyte differentiation (PMID:15258909)
• upregulated in Papillomavirus-mediated cervical neoplasia and required for notch activation. (PMID:15280477)
• structured in solution, as suggested by circular dichroism and NMR spectroscopy, and displays an EGF-like disulfide bond topology, as determined by disulfide mapping (PMID:15358557)
• Dysregulation of JAGGED1 protein levels plays a role in prostate cancer progression and metastasis and suggest that JAGGED1 may be a useful marker in distinguishing indolent and aggressive prostate cancers. (PMID:15466172)
• 12 new mutations are described: 5 frameshifts, 3 nonsense, 2 missense, and 2 splice site. (PMID:15712272)
• Down-regulation of Notch-1, Delta-like-1, or Jagged-1 by RNA interference induces apoptosis and inhibits proliferation in multiple glioma cell lines. (PMID:15781650)
• Jagged1 and GDNF/Ret/GFRalpha1 interact and have a role in regulating ureteric budding and branching (PMID:15905075)
• observed that Jagged1 is preferentially upregulated in human cervical tumors and sustains tumor progression by HPV 16 oncogenes (PMID:15919944)
• Identification of novel Jagged1 mutations in patients with Alagille syndrome. (PMID:16013021)
• Data describe the immunohistochemical staining pattern of four Notch receptors (Notch1-4) and their ligands (Delta1 and Jagged1) in synovial tissues obtained from rheumatoid arthritis patients. (PMID:16307184)
• Wild-type JAG1 is inhibitory for hepatocyte growth factor gene expression; mutant JAG1 reverses the inhibition (PMID:16403414)
• 83 novel mutations within the JAG1 gene are associated with Alagille syndrome. (PMID:16575836)
• data indicate a role for JAGGED/Notch signaling in the process of thymic involution (PMID:16791277)
• Increased expression of Notch3, Jagged1, Hes1, and Hes6 gene transcripts were observed during differentiation of cultured human skeletal muscle cells. (PMID:17301032)
• results reveal that Jagged1, which is regulated by hepatitis B virus X protein, may contribute to the development of hepatocellular carcinoma (PMID:17359939)
• absence of correlation between mutations in specific JAG1 gene exons and clinical features in patients with leukoencephalopathy CADASIL-like phenotype (PMID:17368936)
• patients with tumors expressing high levels of JAG1 protein had a worse outcome than those with tumors expressing low levels (PMID:17507991)
• Mutations in JAGGED1 is associated with Notch signaling inhibition and Alagille syndrome (PMID:17720887)
• Overexpression of jagged1 is associated with breast cancer (PMID:17822320)
• Aberrant expression of Jagged1 and Notch1 are associated with poor outcome in breast cancer (PMID:17984306)
• JAG1 expression is associated with a basal phenotype and recurrence in lymph node-negative breast cancer. (PMID:17990101)
• IL-6 treatment triggered Notch-3-dependent upregulation of the Notch ligand Jagged-1 and promotion of MS and MCF-7-derived spheroid growth (PMID:18060036)
• Notch-1 and the Notch ligand Jagged-1 were expressed at significantly higher levels in CCRCC tumors than in normal human renal tissue, and the growth of primary CCRCC cells was attenuated upon inhibition of Notch signaling. (PMID:18079963)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
mus_musculus	Jag1	ENSMUSG00000027276
rattus_norvegicus	Jag1	ENSRNOG00000007443
drosophila_melanogaster	Delta	FBGN0000463
drosophila_melanogaster	Ser	FBGN0004197
caenorhabditis_elegans	paml-2	WBGENE00009114
caenorhabditis_elegans	F55H12.3	WBGENE00010134
caenorhabditis_elegans		WBGENE00013498

Paralogs (5): DLL4 (ENSG00000128917), JAG2 (ENSG00000184916), DNER (ENSG00000187957), DLL1 (ENSG00000198719), NOTCH4 (ENSG00000204301)

Protein

Protein identifiers

Protein jagged-1 — P78504 (reviewed: P78504)

All UniProt accessions (3): P78504, A0A087WXH5, A0A087X1E8

UniProt curated annotations — full annotation on UniProt →

Function. Ligand for multiple Notch receptors and involved in the mediation of Notch signaling. May be involved in cell-fate decisions during hematopoiesis. Seems to be involved in early and late stages of mammalian cardiovascular development. Inhibits myoblast differentiation. Enhances fibroblast growth factor-induced angiogenesis (in vitro).

Subunit / interactions. Interacts with NOTCH2 and NOTCH3. Interacts with NOTCH1 (in the presence of calcium ions).

Subcellular location. Membrane. Cell membrane.

Tissue specificity. Widely expressed in adult and fetal tissues. In cervix epithelium expressed in undifferentiated subcolumnar reserve cells and squamous metaplasia. Expression is up-regulated in cervical squamous cell carcinoma. Expressed in bone marrow cell line HS-27a which supports the long-term maintenance of immature progenitor cells.

Disease relevance. Alagille syndrome 1 (ALGS1) [MIM:118450] A form of Alagille syndrome, an autosomal dominant multisystem disorder. It is clinically defined by hepatic bile duct paucity and cholestasis in association with cardiac, skeletal, and ophthalmologic manifestations. There are characteristic facial features and less frequent clinical involvement of the renal and vascular systems. The disease is caused by variants affecting the gene represented in this entry. Tetralogy of Fallot (TOF) [MIM:187500] A congenital heart anomaly which consists of pulmonary stenosis, ventricular septal defect, dextroposition of the aorta (aorta is on the right side instead of the left) and hypertrophy of the right ventricle. In this condition, blood from both ventricles (oxygen-rich and oxygen-poor) is pumped into the body often causing cyanosis. The disease is caused by variants affecting the gene represented in this entry. Deafness, congenital heart defects, and posterior embryotoxon (DCHE) [MIM:617992] An autosomal dominant disease characterized by mild to severe combined hearing loss, congenital heart defects, and posterior embryotoxon, a corneal abnormality consisting of a central collagen core surrounded by a thin layer of Descemets membrane and separated from the anterior chamber by a layer of endothelium. Congenital heart defects include tetralogy of Fallot, ventricular septal defect, or isolated peripheral pulmonic stenosis. The disease is caused by variants affecting the gene represented in this entry. Charcot-Marie-Tooth disease, axonal, type 2HH (CMT2HH) [MIM:619574] An autosomal dominant, axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. CMT2HH is characterized by vocal fold paresis that remains throughout life and may be severe. Additional features include pes cavus, scoliosis, distal sensory impairment with hyporeflexia, mild distal muscle weakness and atrophy primarily affecting the lower limbs, although the upper limbs may also be involved. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The second EGF-like domain is atypical.

Isoforms (2)

UniProt ID	Names	Canonical?
P78504-1	1	yes
P78504-2	2

RefSeq proteins (1): NP_000205* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000152	EGF-type_Asp/Asn_hydroxyl_site	PTM
IPR000742	EGF	Domain
IPR001007	VWF_dom	Domain
IPR001774	DSL	Domain
IPR001881	EGF-like_Ca-bd_dom	Domain
IPR009030	Growth_fac_rcpt_cys_sf	Homologous_superfamily
IPR011651	Notch_ligand_N	Domain
IPR013032	EGF-like_CS	Conserved_site
IPR018097	EGF_Ca-bd_CS	Conserved_site
IPR026219	Jagged/Serrate	Family
IPR056986	JAG1_1/2_dom	Domain

Pfam: PF00008, PF01414, PF07657, PF12661, PF21700, PF23575, PF25024

UniProt features (191 total): sequence variant 71, disulfide bond 51, strand 23, domain 17, glycosylation site 9, turn 6, sequence conflict 3, topological domain 2, region of interest 2, signal peptide 1, chain 1, mutagenesis site 1, helix 1, compositionally biased region 1, transmembrane region 1, splice variant 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
4XI7	X-RAY DIFFRACTION	2.05
4CC0	X-RAY DIFFRACTION	2.32
2VJ2	X-RAY DIFFRACTION	2.5
4CBZ	X-RAY DIFFRACTION	2.5
5BO1	X-RAY DIFFRACTION	2.56
4CC1	X-RAY DIFFRACTION	2.84
2KB9	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P78504-F1	73.02	0.14

Antibody-complex structures (SAbDab): 1 — 5BO1

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (51): 187–196, 200–212, 220–229, 234–245, 238–251, 253–262, 265–276, 271–282, 284–293, 300–312, 306–322, 324–333, 340–351, 345–360, 362–371, 378–389, 383–398, 400–409, 416–427, 421–436 …

Glycosylation sites (9): 143, 217, 382, 559, 745, 960, 991, 1045, 1064

Mutagenesis-validated functional residues (1):

Position	Phenotype
207	strongly reduced notch1 binding.

Function

Pathways and Gene Ontology

Reactome pathways

34 pathways

ID	Pathway
R-HSA-2122948	Activated NOTCH1 Transmits Signal to the Nucleus
R-HSA-2644606	Constitutive Signaling by NOTCH1 PEST Domain Mutants
R-HSA-2660826	Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant
R-HSA-2691232	Constitutive Signaling by NOTCH1 HD Domain Mutants
R-HSA-2894862	Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
R-HSA-2979096	NOTCH2 Activation and Transmission of Signal to the Nucleus
R-HSA-8941856	RUNX3 regulates NOTCH signaling
R-HSA-9013149	RAC1 GTPase cycle
R-HSA-9013423	RAC3 GTPase cycle
R-HSA-9013507	NOTCH3 Activation and Transmission of Signal to the Nucleus
R-HSA-9013700	NOTCH4 Activation and Transmission of Signal to the Nucleus
R-HSA-9831926	Nephron development
R-HSA-1266738	Developmental Biology
R-HSA-157118	Signaling by NOTCH
R-HSA-162582	Signal Transduction
R-HSA-1643685	Disease
R-HSA-194315	Signaling by Rho GTPases
R-HSA-1980143	Signaling by NOTCH1
R-HSA-1980145	Signaling by NOTCH2
R-HSA-212436	Generic Transcription Pathway
R-HSA-2644602	Signaling by NOTCH1 PEST Domain Mutants in Cancer
R-HSA-2644603	Signaling by NOTCH1 in Cancer
R-HSA-2660825	Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant
R-HSA-2691230	Signaling by NOTCH1 HD Domain Mutants in Cancer
R-HSA-2894858	Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-8878159	Transcriptional regulation by RUNX3
R-HSA-9012852	Signaling by NOTCH3

MSigDB gene sets: 875 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_CARDIAC_CHAMBER_DEVELOPMENT, AHRARNT_01, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, LI_CISPLATIN_RESISTANCE_DN, MYAATNNNNNNNGGC_UNKNOWN, REACTOME_SIGNALING_BY_NOTCH, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, MODULE_516, GOBP_EPITHELIUM_DEVELOPMENT, ZHAN_LATE_DIFFERENTIATION_GENES_UP, GOBP_REGULATION_OF_FAT_CELL_DIFFERENTIATION, TAATAAT_MIR126, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_NEGATIVE_REGULATION_OF_NEURON_DIFFERENTIATION

GO Biological Process (54): angiogenesis (GO:0001525), cell fate determination (GO:0001709), negative regulation of cell-matrix adhesion (GO:0001953), blood vessel remodeling (GO:0001974), morphogenesis of an epithelial sheet (GO:0002011), inhibition of neuroepithelial cell differentiation (GO:0002085), T cell mediated immunity (GO:0002456), aortic valve morphogenesis (GO:0003180), pulmonary valve morphogenesis (GO:0003184), cardiac right ventricle morphogenesis (GO:0003215), Notch signaling pathway (GO:0007219), nervous system development (GO:0007399), negative regulation of cell-cell adhesion (GO:0022408), hemopoiesis (GO:0030097), keratinocyte differentiation (GO:0030216), negative regulation of cell migration (GO:0030336), response to muramyl dipeptide (GO:0032495), aorta morphogenesis (GO:0035909), regulation of cell population proliferation (GO:0042127), inner ear auditory receptor cell differentiation (GO:0042491), myoblast differentiation (GO:0045445), endothelial cell differentiation (GO:0045446), negative regulation of fat cell differentiation (GO:0045599), negative regulation of endothelial cell differentiation (GO:0045602), positive regulation of myeloid cell differentiation (GO:0045639), negative regulation of neuron differentiation (GO:0045665), positive regulation of osteoblast differentiation (GO:0045669), positive regulation of Notch signaling pathway (GO:0045747), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of epithelial cell proliferation (GO:0050678), cardiac septum morphogenesis (GO:0060411), ciliary body morphogenesis (GO:0061073), neuroendocrine cell differentiation (GO:0061101), pulmonary artery morphogenesis (GO:0061156), cardiac neural crest cell development involved in outflow tract morphogenesis (GO:0061309), endocardial cushion cell development (GO:0061444), positive regulation of cardiac epithelial to mesenchymal transition (GO:0062043), nephron development (GO:0072006), podocyte development (GO:0072015), distal tubule development (GO:0072017)

GO Molecular Function (7): Notch binding (GO:0005112), structural molecule activity (GO:0005198), calcium ion binding (GO:0005509), phospholipid binding (GO:0005543), growth factor activity (GO:0008083), molecular adaptor activity (GO:0060090), protein binding (GO:0005515)

GO Cellular Component (6): extracellular region (GO:0005576), plasma membrane (GO:0005886), adherens junction (GO:0005912), membrane (GO:0016020), apical plasma membrane (GO:0016324), apical part of cell (GO:0045177)

Reactome top-level categories

Rollup of top-15 pathways:

Category	Pathways
RHO GTPase cycle	2
Signaling by NOTCH	2
Signaling by NOTCH1	1
Signaling by NOTCH1 PEST Domain Mutants in Cancer	1
Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant	1
Signaling by NOTCH1 HD Domain Mutants in Cancer	1
Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer	1
Signaling by NOTCH2	1
Transcriptional regulation by RUNX3	1
Signaling by NOTCH3	1
Signaling by NOTCH4	1
Kidney development	1
Signal Transduction	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
RNA Polymerase II Transcription	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
heart valve morphogenesis	2
molecular_function	2
binding	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
cell fate commitment	1
cellular developmental process	1
regulation of cell-matrix adhesion	1
cell-matrix adhesion	1
negative regulation of cell-substrate adhesion	1
tissue remodeling	1
morphogenesis of an epithelium	1
regulation of anatomical structure morphogenesis	1
negative regulation of epithelial cell differentiation	1
regulation of embryonic development	1
regulation of timing of cell differentiation	1
neuroepithelial cell differentiation	1
lymphocyte mediated immunity	1
adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains	1
aortic valve development	1
pulmonary valve development	1
cardiac ventricle morphogenesis	1
cell surface receptor signaling pathway	1
system development	1
negative regulation of cell adhesion	1
regulation of cell-cell adhesion	1
cell-cell adhesion	1
cell development	1
epidermal cell differentiation	1
skin development	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
response to nitrogen compound	1
response to oxygen-containing compound	1
aorta development	1
artery morphogenesis	1
cell population proliferation	1
regulation of cellular process	1

Protein interactions and networks

STRING

4189 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
JAG1	NOTCH2	Q04721	991
JAG1	NOTCH4	Q99466	991
JAG1	NOTCH1	P46531	988
JAG1	NOTCH3	Q9UM47	988
JAG1	HEY1	Q9Y5J3	918
JAG1	RBPJ	Q06330	917
JAG1	SRRT	Q9BXP5	915
JAG1	HEY2	Q9UBP5	915
JAG1	MAML1	Q92585	874
JAG1	EGF	P01133	867
JAG1	HES5	Q5TA89	836
JAG1	EPHA1	P21709	811
JAG1	MAML2	Q8IZL2	792
JAG1	AFDN	P55196	790
JAG1	CTNNB1	P35222	775

IntAct

157 interactions, top by confidence:

A	B	Type	Score
NOTCH1	JAG1	psi-mi:“MI:0407”(direct interaction)	0.730
JAG1	CD46	psi-mi:“MI:0407”(direct interaction)	0.730
CD46	JAG1	psi-mi:“MI:0407”(direct interaction)	0.730
JAG1	CD46	psi-mi:“MI:0403”(colocalization)	0.730
NOTCH1	JAG1	psi-mi:“MI:0403”(colocalization)	0.730
HTRA1	JAG1	psi-mi:“MI:0915”(physical association)	0.610
JAG1	HTRA1	psi-mi:“MI:0407”(direct interaction)	0.610
JAG1	VASN	psi-mi:“MI:0407”(direct interaction)	0.600
JAG1	VASN	psi-mi:“MI:0403”(colocalization)	0.600
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
LGALS1	LAMA5	psi-mi:“MI:0914”(association)	0.530
LGALS1	PODXL	psi-mi:“MI:0914”(association)	0.530
JAG1	ADAM17	psi-mi:“MI:0407”(direct interaction)	0.440
JAG1	LNX2	psi-mi:“MI:0407”(direct interaction)	0.440
JAG1	PATJ	psi-mi:“MI:0407”(direct interaction)	0.440
JAG1	GORASP2	psi-mi:“MI:0407”(direct interaction)	0.440
JAG1	RADIL	psi-mi:“MI:0407”(direct interaction)	0.440
JAG1	MAGI3	psi-mi:“MI:0407”(direct interaction)	0.440
JAG1	GORASP1	psi-mi:“MI:0407”(direct interaction)	0.440
JAG1	GRIP2	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (59): JAG1 (Affinity Capture-Western), JAG1 (Co-crystal Structure), JAG1 (Affinity Capture-Western), JAG1 (Reconstituted Complex), MIB1 (Affinity Capture-Western), JAG1 (Biochemical Activity), JAG1 (Proximity Label-MS), JAG1 (Affinity Capture-RNA), JAG1 (Protein-RNA), JAG1 (Proximity Label-MS), JAG1 (Proximity Label-MS), JAG1 (Proximity Label-MS), JAG1 (Proximity Label-MS), JAG1 (Proximity Label-MS), JAG1 (Proximity Label-MS)

ESM2 similar proteins: A0A096LNW5, B8JI71, D3ZHH1, G3I6Z6, O00548, O35516, O57409, P0DPK3, P0DPK4, P35442, P46531, P78504, P97677, Q01705, Q04721, Q05793, Q07008, Q08E66, Q2QI47, Q5G872, Q5ZQU0, Q61483, Q63722, Q66PY1, Q6DI48, Q6NZL8, Q70E20, Q7TQN3, Q7Z3S9, Q8IWY4, Q8IX30, Q8JZM4, Q8K3K1, Q8NFT8, Q8TER0, Q8TEU8, Q8UWJ4, Q8VHS2, Q90Y54, Q90Y57

Diamond homologs: A0A1F4, D3ZHH1, G5EDK5, O35474, O43854, O88277, P10040, P13508, P14585, P18168, P78504, P97607, Q06561, Q19319, Q20911, Q501P1, Q53RD9, Q5R7K9, Q5ZQU0, Q63722, Q6R8J2, Q70E20, Q8TER0, Q90Y54, Q90Y57, Q9JLB4, Q9QXX0, Q9QYE5, Q9W332, Q9Y219, A0A2K5V015, A8X481, B8JI71, P21956, P70490, Q5R6R1, Q5T1H1, Q8JZM4, Q8NFT8, Q9NL29

SIGNOR signaling

19 interactions.

A	Effect	B	Mechanism
LFNG	down-regulates	JAG1	binding
MIB1	“up-regulates activity”	JAG1	ubiquitination
JAG1	up-regulates	NOTCH2	binding
JAG1	up-regulates	NOTCH3	binding
NOTCH	“up-regulates quantity by expression”	JAG1	“transcriptional regulation”
KDM4C	“up-regulates quantity by expression”	JAG1	“transcriptional regulation”
SNAI2	“up-regulates quantity by expression”	JAG1	“transcriptional regulation”
JAG1	up-regulates	NOTCH	binding
AKT1	“up-regulates quantity by expression”	JAG1	“transcriptional regulation”
AKT2	“up-regulates quantity by expression”	JAG1	“transcriptional regulation”
AKT3	“up-regulates quantity by expression”	JAG1	“transcriptional regulation”
NEURL1	“down-regulates quantity by destabilization”	JAG1	ubiquitination
JAG2	up-regulates	JAG1
“A4/b1 integrin”	“up-regulates quantity by expression”	JAG1
“A5/b1 integrin”	“up-regulates quantity by expression”	JAG1
JAG1	“up-regulates activity”	NOTCH1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 101 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Ras activation upon Ca2+ influx through NMDA receptor	5	46.0×	4e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	43.9×	4e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	43.9×	4e-06
Long-term potentiation	5	38.4×	6e-06
Assembly and cell surface presentation of NMDA receptors	9	36.8×	2e-10
Neurexins and neuroligins	10	31.8×	1e-10
Protein-protein interactions at synapses	6	25.7×	5e-06
RHOB GTPase cycle	5	12.4×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	10	63.9×	2e-13
protein localization to synapse	6	50.5×	2e-07
receptor clustering	7	48.0×	3e-08
regulation of postsynaptic membrane neurotransmitter receptor levels	7	38.1×	1e-07
cell-cell adhesion	11	12.3×	2e-07
protein-containing complex assembly	8	10.0×	1e-04
protein localization to plasma membrane	7	8.4×	1e-03
chemical synaptic transmission	7	6.0×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

2698 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	344
Likely pathogenic	110
Uncertain significance	788
Likely benign	591
Benign	112

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1028619	NM_000214.3(JAG1):c.2372+1G>T	Pathogenic
1032929	NM_000214.3(JAG1):c.3001_3002dup (p.Cys1002fs)	Pathogenic
1065116	NM_000214.3(JAG1):c.1485del (p.Cys496fs)	Pathogenic
1069512	NM_000214.3(JAG1):c.3203del (p.Phe1068fs)	Pathogenic
1069646	NM_000214.3(JAG1):c.273del (p.Cys92fs)	Pathogenic
1070550	NM_000214.3(JAG1):c.734dup (p.Cys245fs)	Pathogenic
1070837	NM_000214.3(JAG1):c.1779T>A (p.Tyr593Ter)	Pathogenic
1070945	NM_000214.3(JAG1):c.3049-2A>G	Pathogenic
1071570	NC_000020.11:g.10641783dup	Pathogenic
1071992	NM_000214.3(JAG1):c.1312dup (p.Cys438fs)	Pathogenic
1072898	NM_000214.3(JAG1):c.2917-1G>T	Pathogenic
1073158	NM_000214.3(JAG1):c.655dup (p.Thr219fs)	Pathogenic
1073270	NM_000214.3(JAG1):c.1101dup (p.Gly368fs)	Pathogenic
1074174	NM_000214.3(JAG1):c.1829del (p.Gly610fs)	Pathogenic
1074592	NM_000214.3(JAG1):c.1308C>A (p.Cys436Ter)	Pathogenic
1074995	NM_000214.3(JAG1):c.682G>T (p.Glu228Ter)	Pathogenic
1075491	NM_000214.3(JAG1):c.2318del (p.Gly773fs)	Pathogenic
1191321	NM_000214.3(JAG1):c.1955dup (p.Cys653fs)	Pathogenic
1210293	NM_000214.3(JAG1):c.2358C>A (p.Cys786Ter)	Pathogenic
1251969	NM_000214.2:c.(755+1_756-1)_(1120+1_1121-1)del	Pathogenic
1300241	NM_000214.3(JAG1):c.1731C>G (p.Ser577Arg)	Pathogenic
1300242	NM_000214.3(JAG1):c.1948T>C (p.Ser650Pro)	Pathogenic
1319943	NM_000214.3(JAG1):c.1007-2A>G	Pathogenic
1323131	NM_000214.3(JAG1):c.384G>A (p.Trp128Ter)	Pathogenic
1323132	NM_000214.3(JAG1):c.1228C>T (p.Gln410Ter)	Pathogenic
1333228	NM_000214.3(JAG1):c.2650C>T (p.Gln884Ter)	Pathogenic
1341895	NM_000214.3(JAG1):c.1653C>A (p.Cys551Ter)	Pathogenic
1353005	NM_000214.3(JAG1):c.622G>T (p.Gly208Ter)	Pathogenic
1353877	NM_000214.3(JAG1):c.1139del (p.Pro380fs)	Pathogenic
1354095	NM_000214.3(JAG1):c.1687del (p.His562_Leu563insTer)	Pathogenic

SpliceAI

3573 predictions. Top by Δscore:

Variant	Effect	Δscore
20:10639900:C:CT	acceptor_gain	1.0000
20:10639901:A:T	acceptor_gain	1.0000
20:10639937:A:T	acceptor_gain	1.0000
20:10639951:GAAAT:G	acceptor_gain	1.0000
20:10639956:C:CC	acceptor_gain	1.0000
20:10639957:T:G	acceptor_loss	1.0000
20:10640779:CTAC:C	donor_loss	1.0000
20:10640780:TACC:T	donor_loss	1.0000
20:10640781:A:AC	donor_gain	1.0000
20:10640781:AC:A	donor_gain	1.0000
20:10640782:C:CC	donor_gain	1.0000
20:10640782:CC:C	donor_gain	1.0000
20:10640929:GCAGA:G	acceptor_gain	1.0000
20:10640930:CAGA:C	acceptor_gain	1.0000
20:10640930:CAGAC:C	acceptor_gain	1.0000
20:10640931:AGA:A	acceptor_gain	1.0000
20:10640932:GA:G	acceptor_gain	1.0000
20:10640933:ACT:A	acceptor_loss	1.0000
20:10640934:C:CC	acceptor_gain	1.0000
20:10640934:CTGG:C	acceptor_loss	1.0000
20:10640935:T:C	acceptor_loss	1.0000
20:10641455:CATA:C	donor_gain	1.0000
20:10641456:ATACT:A	donor_loss	1.0000
20:10641457:TAC:T	donor_loss	1.0000
20:10641458:A:AC	donor_gain	1.0000
20:10641459:C:CA	donor_gain	1.0000
20:10641459:CT:C	donor_gain	1.0000
20:10641459:CTG:C	donor_gain	1.0000
20:10641508:AT:A	donor_gain	1.0000
20:10641689:CAGAC:C	acceptor_gain	1.0000

AlphaMissense

8171 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:10643785:G:C	C817W	1.000
20:10643786:C:G	C817S	1.000
20:10643786:C:T	C817Y	1.000
20:10643787:A:G	C817R	1.000
20:10643787:A:T	C817S	1.000
20:10643801:A:C	F812C	1.000
20:10643846:C:G	C797S	1.000
20:10643847:A:T	C797S	1.000
20:10646946:G:C	C626W	1.000
20:10646947:C:G	C626S	1.000
20:10646948:A:T	C626S	1.000
20:10652583:C:A	W257C	1.000
20:10652583:C:G	W257C	1.000
20:10658490:C:A	W224C	1.000
20:10658490:C:G	W224C	1.000
20:10658515:C:A	G216V	1.000
20:10658515:C:T	G216D	1.000
20:10658516:C:A	G216C	1.000
20:10658527:C:G	C212S	1.000
20:10658527:C:T	C212Y	1.000
20:10658528:A:T	C212S	1.000
20:10658563:C:G	C200S	1.000
20:10658563:C:T	C200Y	1.000
20:10658564:A:T	C200S	1.000
20:10658574:G:C	C196W	1.000
20:10658575:C:A	C196F	1.000
20:10658575:C:G	C196S	1.000
20:10658575:C:T	C196Y	1.000
20:10658576:A:G	C196R	1.000
20:10658576:A:T	C196S	1.000

dbSNP variants (sampled 300 via entrez): RS1000010346 (20:10672968 C>G,T), RS1000027018 (20:10669709 T>C), RS1000063379 (20:10644498 A>G,T), RS1000248724 (20:10669991 C>A,T), RS1000251336 (20:10655616 A>C), RS1000294886 (20:10658211 C>T), RS1000301837 (20:10663739 G>A), RS1000317264 (20:10640566 G>A,T), RS1000456134 (20:10647643 C>A,T), RS1000492607 (20:10675802 A>G), RS1000501370 (20:10651361 C>A,G), RS1000536981 (20:10644706 A>G), RS1000593724 (20:10664073 G>A,T), RS1000709156 (20:10655326 T>C,G), RS1000909416 (20:10667012 G>C)

Disease associations

OMIM: gene MIM:601920 | disease phenotypes: MIM:118450, MIM:187500, MIM:619574, MIM:617992, MIM:236700, MIM:209900, MIM:607086, MIM:610805, MIM:217095

GenCC curated gene-disease

Disease	Classification	Inheritance
Alagille syndrome due to a JAG1 point mutation	Definitive	Autosomal dominant
Charcot-Marie-Tooth disease, axonal, Type 2HH	Strong	Autosomal dominant
tetralogy of fallot	Supportive	Autosomal dominant

Mondo (17): Alagille syndrome due to a JAG1 point mutation (MONDO:0016862), tetralogy of fallot (MONDO:0008542), Charcot-Marie-Tooth disease, axonal, Type 2HH (MONDO:0030458), deafness, congenital heart defects, and posterior embryotoxon (MONDO:0060713), inherited retinal dystrophy (MONDO:0019118), Alagille syndrome (MONDO:0007318), McKusick-Kaufman syndrome (MONDO:0009367), Bardet-Biedl syndrome (MONDO:0015229), familial thoracic aortic aneurysm and aortic dissection (MONDO:0019625), atypical coarctation of aorta (MONDO:0015446), focal segmental glomerulosclerosis (MONDO:0100313), congenital heart disease (MONDO:0005453), congenital anomaly of kidney and urinary tract (MONDO:0019719), hepatoblastoma (MONDO:0018666), conotruncal heart malformations (MONDO:0016581)

Orphanet (13): Alagille syndrome due to a JAG1 point mutation (Orphanet:261619), Alagille syndrome (Orphanet:52), Tetralogy of Fallot (Orphanet:3303), OBSOLETE: Inherited retinal disorder (Orphanet:71862), Bardet-Biedl syndrome (Orphanet:110), McKusick-Kaufman syndrome (Orphanet:2473), Familial thoracic aortic aneurysm and aortic dissection (Orphanet:91387), Middle aortic syndrome (Orphanet:1456), Renal or urinary tract malformation (Orphanet:93545), Hepatoblastoma (Orphanet:449), Conotruncal heart malformations (Orphanet:2445), Common arterial trunk (Orphanet:3384), Double outlet right ventricle (Orphanet:3426)

HPO phenotypes

103 total (30 of 103 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000028	Cryptorchidism
HP:0000076	Vesicoureteral reflux
HP:0000081	Duplicated collecting system
HP:0000089	Renal hypoplasia
HP:0000097	Focal segmental glomerulosclerosis
HP:0000110	Renal dysplasia
HP:0000233	Thin vermilion border
HP:0000268	Dolichocephaly
HP:0000316	Hypertelorism
HP:0000325	Triangular face
HP:0000337	Broad forehead
HP:0000369	Low-set ears
HP:0000400	Macrotia
HP:0000407	Sensorineural hearing impairment
HP:0000414	Bulbous nose
HP:0000482	Microcornea
HP:0000486	Strabismus
HP:0000490	Deeply set eye
HP:0000518	Cataract
HP:0000520	Proptosis
HP:0000533	Chorioretinal atrophy
HP:0000545	Myopia
HP:0000580	Pigmentary retinopathy
HP:0000582	Upslanted palpebral fissure
HP:0000585	Band keratopathy
HP:0000593	Abnormal anterior chamber morphology
HP:0000627	Posterior embryotoxon
HP:0000750	Delayed speech and language development
HP:0000772	Abnormal rib morphology

GWAS associations

59 associations (top):

Study	Trait	p-value
GCST000572_1	Bone mineral density	5.000000e-08
GCST000960_19	Cardiac hypertrophy	9.000000e-06
GCST001227_12	Systolic blood pressure	2.000000e-08
GCST001228_10	Diastolic blood pressure	1.000000e-15
GCST001236_8	Blood pressure	4.000000e-08
GCST001482_1	Lumbar spine bone mineral density	3.000000e-19
GCST002460_2	Urinary bladder cancer	2.000000e-11
GCST002630_15	Systolic blood pressure	1.000000e-08
GCST002631_4	Diastolic blood pressure	2.000000e-08
GCST003273_14	Diastolic blood pressure	1.000000e-06
GCST003273_20	Diastolic blood pressure	6.000000e-08
GCST003720_39	Migraine	2.000000e-09
GCST004278_69	Pulse pressure	5.000000e-25
GCST004279_40	Systolic blood pressure	6.000000e-08
GCST004280_63	Diastolic blood pressure	8.000000e-08
GCST004280_73	Diastolic blood pressure	4.000000e-16
GCST004776_26	Systolic blood pressure	9.000000e-07
GCST004777_57	Diastolic blood pressure	1.000000e-07
GCST004782_1	Type 2 diabetes	1.000000e-08
GCST005146_38	Birth weight	7.000000e-09
GCST005796_33	Lumbar spine bone mineral density	6.000000e-09
GCST006020_13	Diastolic blood pressure	5.000000e-16
GCST006147_4	Frontotemporal dementia (age at onset)	3.000000e-07
GCST006149_5	Frontotemporal dementia with GRN mutation (age at onset)	7.000000e-07
GCST006187_44	Diastolic blood pressure (cigarette smoking interaction)	3.000000e-36
GCST006188_14	Systolic blood pressure (cigarette smoking interaction)	4.000000e-22
GCST006258_56	Diastolic blood pressure	2.000000e-17
GCST006259_16	Systolic blood pressure	2.000000e-11
GCST006288_403	Heel bone mineral density	7.000000e-10
GCST006288_404	Heel bone mineral density	7.000000e-08

EFO canonical traits (18, from GWAS)

EFO ID	Trait name
EFO:0002503	cardiac hypertrophy
EFO:0006335	systolic blood pressure
EFO:0006336	diastolic blood pressure
EFO:0006340	mean arterial pressure
EFO:0005763	pulse pressure measurement
EFO:0004344	birth weight
EFO:0007701	spine bone mineral density
EFO:0004847	age at onset
EFO:0006527	smoking status measurement
EFO:0009270	heel bone mineral density
EFO:0005939	parental genotype effect measurement
EFO:0004531	urate measurement
EFO:0004346	neuroimaging measurement
EFO:0004980	appendicular lean mass
EFO:0004842	eosinophil count
EFO:0007986	reticulocyte count
EFO:0004587	lymphocyte count
EFO:0004305	erythrocyte count

MeSH disease descriptors (12)

Descriptor	Name	Tree numbers
D016738	Alagille Syndrome	C06.130.120.135.250.125; C06.552.150.125; C14.240.400.044; C16.131.077.065; C16.131.240.400.044; C16.320.051
D020788	Bardet-Biedl Syndrome	C10.228.140.617.200; C11.270.684.624; C16.131.077.245.125; C16.320.184.125
D005413	Flatfoot	C05.330.488.655.250; C05.330.495.681.250; C05.660.585.512.380.813.250; C16.131.621.585.512.500.681.250
D005923	Glomerulosclerosis, Focal Segmental	C12.050.351.968.419.570.363.640; C12.200.777.419.570.363.660; C12.950.419.570.363.640
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400
D018197	Hepatoblastoma	C04.557.435.380
D058499	Retinal Dystrophies	C11.768.585.658
D012600	Scoliosis	C05.116.900.800.875
D013771	Tetralogy of Fallot	C14.240.400.849; C14.280.400.849; C16.131.240.400.849
C566906	Cakut (supp.)
C566604	Deafness, Congenital Heart Defects, and Posterior Embryotoxon (supp.)
C538159	McKusick Kaufman syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3217396 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

132 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, decreases expression	8
Valproic Acid	affects cotreatment, decreases expression, decreases reaction, increases expression	6
Estradiol	affects cotreatment, decreases expression, increases expression	5
Tretinoin	decreases expression, affects cotreatment, increases expression	5
bisphenol A	affects expression, decreases expression, increases expression, affects cotreatment	4
trichostatin A	affects cotreatment, decreases expression, increases expression	4
sodium arsenite	increases abundance, decreases expression, affects cotreatment	4
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression	4
Aflatoxin B1	affects expression, increases expression	3
arsenite	affects binding, decreases reaction, decreases expression	2
Acetylcysteine	decreases reaction, increases expression, decreases expression	2
Arsenic	affects cotreatment, decreases expression, increases abundance	2
Doxorubicin	increases expression	2
Cyclosporine	increases expression	2
Particulate Matter	decreases reaction, increases expression, decreases expression, affects reaction	2
GSK-J4	increases expression	1
napabucasin	decreases expression	1
N-((3,5-difluorophenyl)acetyl)alanyl-2-phenylglycine-1,1-dimethylethyl ester	decreases expression	1
TL8-506	affects cotreatment, increases expression	1
dicrotophos	increases expression	1
N(6)-(delta(2)-isopentenyl)adenine	increases expression	1
quinone	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
HT-2 toxin	increases expression	1
beta-lapachone	increases expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
9,10-dihydro-9,10-dihydroxybenzo(a)pyrene	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3225623	Binding	Binding affinity to human Jagged-1 (amino acid residues S32 to S1046) at 0.125 to 2 uM by surface plasmon resonance assay	Binding region and interaction properties of sulfoquinovosylacylglycerol (SQAG) with human vascular endothelial growth factor 165 revealed by biosensor-based assays — Medchemcomm

Cellosaurus cell lines

26 cell lines: 11 induced pluripotent stem cell, 7 cancer cell line, 4 embryonic stem cell, 2 transformed cell line, 2 finite cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A3I9	SEES3-1V human JAG1, clone1	Embryonic stem cell	Male
CVCL_A3J0	SEES3-1V human JAG1, clone2	Embryonic stem cell	Male
CVCL_A3J1	SEES3-1V human JAG1, clone3	Embryonic stem cell	Male
CVCL_A4XH	SDQLCHi037-A	Induced pluripotent stem cell	Male
CVCL_A8NS	TRNDi029-A	Induced pluripotent stem cell	Female
CVCL_A8PE	TRNDi031-A	Induced pluripotent stem cell	Female
CVCL_B3XM	UCSFi001-A-58	Induced pluripotent stem cell	Male
CVCL_B3XN	UCSFi001-A-59	Induced pluripotent stem cell	Male
CVCL_B7XR	Abcam Raji JAG1 KO	Cancer cell line	Male
CVCL_B9YG	Abcam THP-1 JAG1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

152 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT01971593	PHASE4	TERMINATED	The Effects of Eplerenone on Markers of Myocardial Fibrosis in Adult Congenital Heart Disease
NCT05488067	PHASE4	COMPLETED	Atorvastatin Therapy on Xanthoma in Alagille Syndrome
NCT07290257	PHASE4	RECRUITING	Long-Term Low-Intervention SafEty and Clinical Outcomes Clinical Study of LivmArli® in Patients With Alagille Syndrome in the European Union (LEAP-EU)
NCT00564993	PHASE3	TERMINATED	Cardiac Function Under Stress for Early Detection of the Right Ventricular Insufficiency After Repair of Tetralogy of Fallot
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT04674761	PHASE3	COMPLETED	Efficacy and Safety of Odevixibat in Patients With Alagille Syndrome
NCT05035030	PHASE3	RECRUITING	Long-term Safety and Efficacy of Odevixibat in Patients With Alagille Syndrome
NCT05543174	PHASE3	COMPLETED	A Study of TAK-625 for the Treatment of Alagille Syndrome (ALGS)
NCT03746522	PHASE3	COMPLETED	Setmelanotide (RM-493), Melanocortin-4 Receptor (MC4R) Agonist, in Bardet-Biedl Syndrome (BBS) and Alström Syndrome (AS) Participants With Moderate to Severe Obesity
NCT04966741	PHASE3	COMPLETED	Setmelanotide in Pediatric Participants With Rare Genetic Diseases of Obesity
NCT05194124	PHASE3	COMPLETED	Phase 3 Crossover Trial of Two Formulations of Setmelanotide in Participants With Specific Gene Defects in the MC4R Pathway
NCT00848393	PHASE2	COMPLETED	Measures to Lower the Stress Response in Pediatric Cardiac Surgery
NCT02010905	PHASE2	UNKNOWN	Right Ventricular Dysfunction in Tetralogy of Fallot: Inhibition of the Renin-angiotensin-aldosterone System
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT01903460	PHASE2	COMPLETED	Safety and Efficacy Study of LUM001 in the Treatment of Cholestatic Liver Disease in Patients With Alagille Syndrome
NCT02047318	PHASE2	COMPLETED	An Extension Study to Evaluate the Long-Term Safety and Durability of Effect of LUM001 in the Treatment of Cholestatic Liver Disease in Subjects With Alagille Syndrome (ALGS)
NCT02057692	PHASE2	COMPLETED	Evaluation of LUM001 in the Reduction of Pruritus in Alagille Syndrome
NCT02117713	PHASE2	COMPLETED	An Extension Study to Evaluate the Long-Term Safety and Durability of Effect of LUM001 in the Treatment of Cholestatic Liver Disease in Pediatric Subjects With Alagille Syndrome
NCT02160782	PHASE2	COMPLETED	Safety and Efficacy Study of LUM001 (Maralixibat) With a Drug Withdrawal Period in Participants With Alagille Syndrome (ALGS)
NCT04729751	PHASE2	COMPLETED	A Study to Evaluate the Safety and Tolerability of Maralixibat in Infant Participants With Cholestatic Liver Diseases Including Progressive Familial Intrahepatic Cholestasis (PFIC) and Alagille Syndrome (ALGS).
NCT03490019	PHASE2	WITHDRAWN	Treatment of Bardet-Biedl-Syndrome With Metformin for Evaluation of a Possible Visual Improvement
NCT00573066	PHASE1	COMPLETED	Understanding Dexmedetomidine In Infants Post-Operative From Cardiac Surgery
NCT01915277	PHASE1	COMPLETED	A Phase I Study of Dexmedetomidine Bolus and Infusion in Corrective Infant Cardiac Surgery: Safety and Pharmacokinetics
NCT04713657	PHASE1	RECRUITING	Beta-blocker Administration for Cardiomyocyte Division
NCT05902962	PHASE1	COMPLETED	SAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects
NCT06319872	PHASE1	RECRUITING	The Effects of Disulfiram (Antabuse®) on Visual Acuity in Patients With Retinal Degeneration
NCT06455826	PHASE1	COMPLETED	MAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects (Wallaby)
NCT02963077	PHASE1	COMPLETED	A Safety and Pharmakokinetic Study of A4250 Alone or in Combination With A3384
NCT03082937	PHASE1	COMPLETED	An Open Label, Single-dose, Single Period ADME Study of A4250 in Healthy Subjects
NCT02590679	PHASE2/PHASE3	UNKNOWN	Multi-center Trial of Percutaneous Pulmonary Valve Implantation With Venus-p
NCT05579964	PHASE2/PHASE3	COMPLETED	The Role of Dexmedetomidine as Myocardial Protector in Pediatric Cardiac Surgery Total Correction of Tetralogy of Fallot
NCT05186415	PHASE1/PHASE2	COMPLETED	Contrast Enhanced 3D Echocardiographic Quantification of Right Ventricular Volumes in Repaired CHD
NCT07194304	EARLY_PHASE1	COMPLETED	Effect of Parenteral Alpha-Tocopherol in the Definitive Surgery of Tetralogy of Fallot
NCT00004361	Not specified	COMPLETED	Study of the Relationship Between Calcium Levels and Intact Parathyroid Hormone (iPTH) in Adults With Repaired or Palliated Conotruncal Cardiac Defects
NCT00005190	Not specified	COMPLETED	Reproduction and Survival After Cardiac Defect Repair
NCT00112320	Not specified	COMPLETED	Comparison of Two Pulmonary Valve Replacement Methods to Treat Tetralogy of Fallot
NCT00155428	Not specified	UNKNOWN	Biomodel in Tetralogy of Fallot