DLK1

Summary

DLK1 (delta like non-canonical Notch ligand 1, HGNC:2907) is a protein-coding gene on chromosome 14q32.2, encoding Protein delta homolog 1 (P80370). May have a role in neuroendocrine differentiation.

This gene encodes a transmembrane protein that contains multiple epidermal growth factor repeats that functions as a regulator of cell growth. The encoded protein is involved in the differentiation of several cell types including adipocytes. This gene is located in a region of chromosome 14 frequently showing unparental disomy, and is imprinted and expressed from the paternal allele. A single nucleotide variant in this gene is associated with child and adolescent obesity and shows polar overdominance, where heterozygotes carrying an active paternal allele express the phenotype, while mutant homozygotes are normal.

Source: NCBI Gene 8788 — RefSeq curated summary.

At a glance

• Gene–disease (curated): central precocious puberty (Strong, GenCC)
• GWAS associations: 20
• Clinical variants (ClinVar): 94 total — 2 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 169
• Druggable target: yes — 15 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_003836

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2907
Approved symbol	DLK1
Name	delta like non-canonical Notch ligand 1
Location	14q32.2
Locus type	gene with protein product
Status	Approved
Aliases	FA1, pG2, Pref-1, ZOG, Delta1
Ensembl gene	ENSG00000185559
Ensembl biotype	protein_coding
OMIM	176290
Entrez	8788

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 retained_intron

ENST00000331224, ENST00000341267, ENST00000392848, ENST00000555747, ENST00000556051, ENST00000942991

RefSeq mRNA: 2 — MANE Select: NM_003836 NM_001317172, NM_003836

CCDS: CCDS81852, CCDS9963

Canonical transcript exons

ENST00000341267 — 5 exons

Exon	Start	End
ENSE00001300094	100728936	100729066
ENSE00001315826	100732042	100732183
ENSE00001320288	100728396	100728459
ENSE00002436630	100734149	100738224
ENSE00003837497	100726892	100727135

Expression profiles

Bgee: expression breadth ubiquitous, 199 present calls, max score 99.81.

FANTOM5 (CAGE): breadth broad, TPM avg 54.8585 / max 9024.3477, expressed in 428 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
141482	52.0521	403
141483	1.5509	260
141484	0.6336	183
141485	0.2359	101
141488	0.1708	70
141489	0.1484	61
141486	0.0667	34

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right adrenal gland cortex	UBERON:0035827	99.81	gold quality
right adrenal gland	UBERON:0001233	99.78	gold quality
adrenal cortex	UBERON:0001235	99.78	gold quality
left adrenal gland	UBERON:0001234	99.76	gold quality
left adrenal gland cortex	UBERON:0035825	99.76	gold quality
adrenal tissue	UBERON:0018303	99.60	gold quality
adenohypophysis	UBERON:0002196	99.56	gold quality
pituitary gland	UBERON:0000007	99.40	gold quality
cartilage tissue	UBERON:0002418	98.99	gold quality
adrenal gland	UBERON:0002369	98.26	gold quality
type B pancreatic cell	CL:0000169	98.00	gold quality
gluteal muscle	UBERON:0002000	97.92	gold quality
left ovary	UBERON:0002119	96.49	gold quality
placenta	UBERON:0001987	95.00	gold quality
parotid gland	UBERON:0001831	93.33	gold quality
body of tongue	UBERON:0011876	93.28	gold quality
ovary	UBERON:0000992	93.15	gold quality
right ovary	UBERON:0002118	93.09	gold quality
islet of Langerhans	UBERON:0000006	91.65	gold quality
heart right ventricle	UBERON:0002080	91.45	gold quality
triceps brachii	UBERON:0001509	90.55	gold quality
biceps brachii	UBERON:0001507	88.83	gold quality
tongue	UBERON:0001723	88.09	gold quality
adult organism	UBERON:0007023	87.55	gold quality
right testis	UBERON:0004534	87.46	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	87.34	gold quality
testis	UBERON:0000473	87.27	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.85	gold quality
left testis	UBERON:0004533	86.59	gold quality
vastus lateralis	UBERON:0001379	86.33	gold quality

Single-cell (SCXA)

Detected in 22 experiment(s), a significant marker in 22.

Experiment	Marker?	Max mean expression
E-MTAB-9154	yes	17705.82
E-MTAB-6701	yes	14733.61
E-HCAD-24	yes	10193.41
E-MTAB-7407	yes	6467.20
E-MTAB-10018	yes	4815.72
E-CURD-112	yes	4613.40
E-MTAB-10042	yes	3113.81
E-HCAD-23	yes	2699.36
E-MTAB-5061	yes	2628.40
E-MTAB-8221	yes	2081.27
E-GEOD-81547	yes	1840.32
E-HCAD-31	yes	1562.91
E-GEOD-93593	yes	1505.83
E-GEOD-81608	yes	900.64
E-ENAD-27	yes	748.19

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
SOX9	Unknown

Upstream regulators (CollecTRI, top): BMP7, CEBPD, CTCF, E2F1, EGR1, FOXA2, FOXC1, KLF2, KLF6, MSX1, NEUROG2, NR4A2, PITX3, PPARG, RBPJ, SP1, SP3, SREBF1, TFAP2A

miRNA regulators (miRDB)

220 targeting DLK1, 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-5196-5P	100.00	67.98	2761
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-1468-3P	99.96	72.74	3797

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 40)

• DLK1 gene is imprinted, with preferential expression from the paternal allele. (PMID:11076856)
• Retroviral mediated expression of the human myeloid nuclear antigen in a null cell line upregulates Dlk1 expression (PMID:12112016)
• delta-like 1 expression in a subset of neuroblastoma cell lines corresponds to a differentiated chromaffin cell type (PMID:12672031)
• The mRNA expression level of the gene delta-like (Dlk) was measured using real-time PCR methodology in a large series of control biopsies and bone marrow trephines from patients with myelodysplastic syndrome and related myeloid disorders. (PMID:15289021)
• Dlk may regulate the endothelial function in neuroblastic tumors. (PMID:15605081)
• DLK1 has activity both as a soluble and a transmembrane expressed protein (PMID:15806146)
• Dlk1 is overexpressed in selected samples of MDS (especially RA and RAEB) and AML (particularly M6, M7), and it appears to be associated with normal development of megakaryocytes and B cells. (PMID:15959531)
• results suggest that DLK1 may play a role in the formation or progression of gliomas (PMID:16288219)
• DLK1 variants in pituitary- and neuroendocrine tumors include Secredeltin, Brevideltin and Brevideltinin (PMID:16403460)
• The regulation of expression, not splicing, is the most likely mechanism controlling the biological function of DLK1. (PMID:16901742)
• role for Dlk1 in regulating the multiple biological functions of hMSC by influencing the composition of their microenvironment “niche.” (PMID:17182623)
• the maternal UPD14 phenotype is due to aberrant gene expression within the imprinted domain at 14q32 (PMID:17601927)
• Delta-like protein seems to be a highly sensitive and specific marker for hepatoblastomas. (PMID:18236070)
• Monitoring dlk1 levels may be important to evaluate the metabolic and hormonal stage of child development. (PMID:18248640)
• DLK1 was expressed in liver neoplasms. DLK1-positive patients had a shorter survival time than DLK1-negative patients. Cox regression analysis also showed that DLK1 is a risk factor. (PMID:18352842)
• the novel prostate progenitor marker Dlk-1 is downregulated by Notch signalling in intermediate cells. The identification of Dlk-1-expressing candidate stem and neuroendocrine cells suggests a hierarchical relationship (PMID:18375047)
• Associated with extreme early-onset obesity. (PMID:18398438)
• four patients with clinical features of upd(14)mat who show a maternal-only methylation pattern, but biparental inheritance for chromosome 14. (PMID:18454453)
• The expression of Dlk1 was found to be up-regulated in CD34+ cells from patients with myelodysplastic syndrome (MDS) by analyzing the gene expression profiles determined by microarray. (PMID:18575777)
• Selective loss of MEG3 expression and intergenic differentially methylated region hypermethylation in the MEG3/DLK1 locus in human clinically nonfunctioning pituitary adenomas. (PMID:18628527)
• Pref-1 is modulated by both dexamethasone and 3-isobutyl-1methylxanthine (IBMX), two components of the adipogenic induction mixture during the adipogenesis in vitro. (PMID:19427405)
• PTTG1 and DLK1 are involved in cell differentiation and transformation. (PMID:19477929)
• Pref-1 has roles in adipogenesis and mesenchymal cell fate [review] (PMID:19541743)
• DLK is a novel immunohistochemical marker for adrenal gland tumors. (PMID:19685073)
• DLK1 gene may be involved in leukemia, but the mRNA level of DLK1 has no relation with some clinical characteristics of AL patients at onset. (PMID:19779261)
• designed allele-specific methylation study of the DLK1/GTL2 intergenic differentially methylated region allowed us to determine the parental origin of del(14q/IGH) in 9/20 analyzed cases. (PMID:19786834)
• Because elevated DLK1 expression is found in many tumor types, our observations suggest that hypoxia and DLK1 may constitute an important stem cell pathway for the regulation of cancer stem cell-like functionality and tumorigenicity. (PMID:19934310)
• Studies indicate the imprinted DLK1-MEG3 gene region of chromosome 14q32.2 contains a functional T1D candidate gene. (PMID:19966805)
• The imprinted DLK1-MEG3 gene region of chromosome 14q32.2 is robustly associated with paternally inherited risk of type 1 diabetes. DLK1 is the most likely functional T1D candidate gene in the region. (PMID:19966805)
• identified dlk1/FA1 as a novel marker of chondroprogenitor cells that undergo embryonic lineage progression from proliferation to the prehypertrophic stage. (PMID:20058200)
• An insulator located 18 kb upstream of DLK1 plays an important role in regulating DLK1 imprinting. (PMID:20089961)
• IFI16 may be an essential downstream target of DLK1 in hepatocellular carcinomas (HCC) cells and required for DLK1-induced cell proliferation. (PMID:20214740)
• Constitutive overexpression of DLK-1/PREF1 in CB MSC resulted in a reduced adipogenic differentiation, whereas silencing of DLK-1 in USSC resulted in adipogenic differentiation. (PMID:20331358)
• hDlk-1 is a cell surface protein expressed in many carcinomas. (PMID:20356822)
• mRNA expressions of DLK1, c-FLIPL and c-FLIPS are abnormal in bone marrow mononuclear cells of myelodysplastic syndrome patients. (PMID:20561424)
• dlk1’s expression in non-small cell lung cancers (PMID:20959062)
• Adipose tissue in metabolically healthy obese individuals had lower levels of Pref-1, a known inhibitor of preadipocyte differentiation, and a more favorable inflammatory profile. (PMID:21252254)
• coordinate up-regulation of the DLK1-DIO3 miRNA cluster at 14q32.2 may define a novel molecular (stem cell-like) subtype of hepatocellular carcinoma associated with poor prognosis (PMID:21737452)
• A regulatory role for DLK1 in human and mouse neural progenitor differentiation and an interaction between DLK1 and Hes1-mediated Notch signaling in these cells, are reported. (PMID:21761283)
• The DLK1-MEG3 locus plays a tumor suppressor role in human nonfunctioning adenomas. (PMID:21871428)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Dlk1	ENSMUSG00000040856
rattus_norvegicus	Dlk1	ENSRNOG00000019584
drosophila_melanogaster	NimA	FBGN0261514

Paralogs (1): PEAR1 (ENSG00000187800)

Protein

Protein identifiers

Protein delta homolog 1 — P80370 (reviewed: P80370)

Alternative names: pG2

All UniProt accessions (3): P80370, G3V2R7, G3XAH5

UniProt curated annotations — full annotation on UniProt →

Function. May have a role in neuroendocrine differentiation.

Subunit / interactions. Monomer. Interacts with SH3RF2.

Subcellular location. Membrane. Cytoplasm.

Tissue specificity. Found within the stromal cells in close contact to the vascular structure of placental villi, yolk sac, fetal liver, adrenal cortex and pancreas and in the beta cells of the islets of Langerhans in the adult pancreas. Found also in some forms of neuroendocrine lung tumor tissue.

Post-translational modifications. N- and O-glycosylated. O-glycosylated with core 1 or possibly core 8 glycans.

Isoforms (2)

UniProt ID	Names	Canonical?
P80370-1	Long	yes
P80370-2	Short

RefSeq proteins (2): NP_001304101, NP_003827* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000152	EGF-type_Asp/Asn_hydroxyl_site	PTM
IPR000742	EGF	Domain
IPR001881	EGF-like_Ca-bd_dom	Domain
IPR051022

Pfam: PF00008

UniProt features (50 total): disulfide bond 18, glycosylation site 11, domain 6, sequence variant 6, chain 2, topological domain 2, sequence conflict 2, signal peptide 1, transmembrane region 1, splice variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
9D20	X-RAY DIFFRACTION	2.67

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P80370-F1	70.55	0.14

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 (18): 26–37, 30–43, 45–54, 57–68, 63–74, 76–85, 92–103, 97–113, 115–124, 131–144, 138–156, 158–167, 174–185, 179–194, 196–205, 212–223, 217–233, 235–244

Glycosylation sites (11): 94, 100, 143, 163, 165, 172, 214, 222, 251, 256, 260

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-2122948	Activated NOTCH1 Transmits Signal to the Nucleus

MSigDB gene sets: 649 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, VERHAAK_AML_WITH_NPM1_MUTATED_DN, REACTOME_SIGNALING_BY_NOTCH, MODULE_52, LEE_NEURAL_CREST_STEM_CELL_DN, GOBP_REGULATION_OF_OSTEOCLAST_DIFFERENTIATION, BENPORATH_ES_WITH_H3K27ME3, TSENG_IRS1_TARGETS_UP, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, PID_HNF3B_PATHWAY, GOBP_OSTEOBLAST_DIFFERENTIATION, GOBP_MYELOID_LEUKOCYTE_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_NOTCH_SIGNALING_PATHWAY, MODULE_503, MODULE_66

GO Biological Process (7): cell differentiation (GO:0030154), negative regulation of ossification (GO:0030279), negative regulation of osteoblast differentiation (GO:0045668), positive regulation of osteoclast differentiation (GO:0045672), negative regulation of Notch signaling pathway (GO:0045746), positive regulation of bone resorption (GO:0045780), regulation of bone remodeling (GO:0046850)

GO Molecular Function (2): calcium ion binding (GO:0005509), protein binding (GO:0005515)

GO Cellular Component (3): obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Signaling by NOTCH1	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cellular developmental process	1
ossification	1
regulation of ossification	1
negative regulation of multicellular organismal process	1
osteoblast differentiation	1
negative regulation of cell differentiation	1
regulation of osteoblast differentiation	1
positive regulation of myeloid leukocyte differentiation	1
osteoclast differentiation	1
regulation of osteoclast differentiation	1
Notch signaling pathway	1
regulation of Notch signaling pathway	1
negative regulation of signal transduction	1
regulation of bone resorption	1
bone resorption	1
positive regulation of multicellular organismal process	1
regulation of tissue remodeling	1
bone remodeling	1
metal ion binding	1
binding	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

12 interactions, top by confidence:

A	B	Type	Score
GRN	DLK1	psi-mi:“MI:0915”(physical association)	0.560
DLK1	SPRED1	psi-mi:“MI:0915”(physical association)	0.560
DLK1	GRN	psi-mi:“MI:0915”(physical association)	0.560
DLK1	TCAF2	psi-mi:“MI:0914”(association)	0.530
DLK1	SCAMP3	psi-mi:“MI:0914”(association)	0.530
DND1	RPSA2	psi-mi:“MI:0914”(association)	0.350
DLK1	PLPP3	psi-mi:“MI:0914”(association)	0.350

BioGRID (174): DLK1 (Two-hybrid), TUBB8 (Affinity Capture-MS), DCAKD (Affinity Capture-MS), ACVR2B (Affinity Capture-MS), ZNF696 (Affinity Capture-MS), SMG8 (Affinity Capture-MS), ATP1A3 (Affinity Capture-MS), ATP12A (Affinity Capture-MS), NCLN (Affinity Capture-MS), TBC1D15 (Affinity Capture-MS), ATP13A1 (Affinity Capture-MS), TFRC (Affinity Capture-MS), NUP188 (Affinity Capture-MS), PTRH2 (Affinity Capture-MS), WDR44 (Affinity Capture-MS)

ESM2 similar proteins: A0JM12, A1A5Y0, A2VCU8, A6BM72, A6QR11, E9QJQ6, O42182, O70534, O88281, P23142, P35555, P35953, P80370, P97607, P98133, P98155, P98156, P98165, P98166, Q08879, Q09163, Q28832, Q2VWQ2, Q5R3Z7, Q5VY43, Q61220, Q61554, Q61555, Q62918, Q62919, Q6DIB5, Q7ZXL5, Q80T14, Q80T91, Q80V70, Q86XX4, Q8C088, Q8R4Y4, Q8VIK5, Q90827

Diamond homologs: A2RUV0, A4FV93, B2LW77, B8JI71, D3ZHH1, D3ZUK3, O35474, O70534, O88277, P10041, P21783, P31695, P78504, P80370, P97607, Q09163, Q2PZL6, Q5IJ48, Q5R6R1, Q5ZQU0, Q63722, Q6DCQ6, Q6QNF4, Q6UY11, Q6V0I7, Q70E20, Q8JZM4, Q8K1E3, Q8NFT8, Q8TER0, Q8VHS2, Q90Y54, Q90Y57, Q9JI71, Q9QXX0, Q9QYE5, Q9Y219, O43854, P18168, P82279

SIGNOR signaling

12 interactions.

A	Effect	B	Mechanism
KLF6	“down-regulates quantity by repression”	DLK1	“transcriptional regulation”
DLK1	up-regulates	FN1	binding
BMP7	“down-regulates quantity by repression”	DLK1	“transcriptional regulation”
DLK1	“up-regulates quantity by expression”	SOX9	“transcriptional regulation”
DLK1	down-regulates	Adipogenesis
DLK1	up-regulates	SOX9	“transcriptional regulation”
KLF6	down-regulates	DLK1	“transcriptional regulation”
BMP7	down-regulates	DLK1	“transcriptional regulation”
DLK1	“down-regulates activity”	NOTCH1	binding
FOXA2	“up-regulates quantity by expression”	DLK1	“transcriptional regulation”
E2F1	“up-regulates quantity by expression”	DLK1	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	56
Likely benign	20
Benign	12

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
162007	NC_000014.9:g.100720531_100829298del108768	Pathogenic
983280	GRCh37/hg19 14q32.2(chr14:101201380-101290903)x1	Pathogenic
2506570	NM_003836.7(DLK1):c.357C>G (p.Tyr119Ter)	Likely pathogenic

SpliceAI

554 predictions. Top by Δscore:

Variant	Effect	Δscore
14:100727136:G:GG	donor_gain	1.0000
14:100727137:T:A	donor_loss	1.0000
14:100732041:GAT:G	acceptor_gain	1.0000
14:100727134:TG:T	donor_gain	0.9900
14:100727135:GG:G	donor_gain	0.9900
14:100732033:A:AG	acceptor_gain	0.9900
14:100732034:C:G	acceptor_gain	0.9900
14:100732039:CAGAT:C	acceptor_loss	0.9900
14:100732040:A:AG	acceptor_gain	0.9900
14:100732040:AGAT:A	acceptor_gain	0.9900
14:100732041:G:A	acceptor_loss	0.9900
14:100732041:G:GA	acceptor_gain	0.9900
14:100732041:GATG:G	acceptor_gain	0.9900
14:100732182:GG:G	donor_gain	0.9900
14:100732183:GG:G	donor_gain	0.9900
14:100734147:A:AG	acceptor_gain	0.9900
14:100734148:G:GG	acceptor_gain	0.9900
14:100727131:CTATG:C	donor_gain	0.9800
14:100727132:TATG:T	donor_gain	0.9800
14:100727133:ATG:A	donor_gain	0.9800
14:100727138:GAGT:G	donor_loss	0.9800
14:100732037:C:A	acceptor_gain	0.9800
14:100732041:GA:G	acceptor_gain	0.9800
14:100732161:G:GT	donor_gain	0.9800
14:100732180:ACGGG:A	donor_loss	0.9800
14:100732184:GT:G	donor_loss	0.9800
14:100732185:TAAA:T	donor_loss	0.9800
14:100734148:GCTC:G	acceptor_gain	0.9800
14:100734148:GCTCC:G	acceptor_gain	0.9800
14:100732033:ACCCC:A	acceptor_gain	0.9700

AlphaMissense

2519 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:100734234:G:T	G164C	0.998
14:100734244:G:A	C167Y	0.998
14:100734243:T:A	C167S	0.997
14:100734244:G:C	C167S	0.997
14:100734297:T:A	C185S	0.997
14:100734298:G:C	C185S	0.997
14:100734298:G:A	C185Y	0.996
14:100734318:T:C	F192L	0.996
14:100734320:C:A	F192L	0.996
14:100734320:C:G	F192L	0.996
14:100734324:T:A	C194S	0.996
14:100734325:G:C	C194S	0.996
14:100734357:T:A	C205S	0.996
14:100734358:G:C	C205S	0.996
14:100734228:T:C	F162L	0.995
14:100734230:C:A	F162L	0.995
14:100734230:C:G	F162L	0.995
14:100734235:G:T	G164V	0.995
14:100734244:G:T	C167F	0.995
14:100734245:C:G	C167W	0.995
14:100734279:T:A	C179S	0.995
14:100734280:G:A	C179Y	0.995
14:100734280:G:C	C179S	0.995
14:100734297:T:C	C185R	0.995
14:100734319:T:G	F192C	0.995
14:100734342:T:C	F200L	0.995
14:100734344:C:A	F200L	0.995
14:100734344:C:G	F200L	0.995
14:100734358:G:A	C205Y	0.995
14:100734441:T:A	C233S	0.995

dbSNP variants (sampled 300 via entrez): RS1000048663 (14:100728089 T>C,G), RS1000099586 (14:100727376 G>C), RS1000244004 (14:100730825 A>C,G), RS1000316287 (14:100730642 G>C), RS1000348890 (14:100730345 C>A), RS1000401758 (14:100729471 G>A,C), RS1000491738 (14:100735552 C>G,T), RS1000841163 (14:100735787 A>G), RS1001215581 (14:100725082 G>A,T), RS1001464307 (14:100736797 A>C,T), RS1001525416 (14:100737989 G>C), RS1001526351 (14:100729827 C>T), RS1001717652 (14:100725214 C>A,G), RS1001832694 (14:100734979 C>A,T), RS1001888385 (14:100727813 A>G)

Disease associations

OMIM: gene MIM:176290 | disease phenotypes: MIM:180860, MIM:608149, MIM:176400

GenCC curated gene-disease

Disease	Classification	Inheritance
central precocious puberty	Strong	Autosomal dominant

Mondo (3): Silver-Russell syndrome 1 (MONDO:0020796), paternal uniparental disomy of chromosome 14 (MONDO:0011975), central precocious puberty (MONDO:0019165)

Orphanet (5): Silver-Russell syndrome (Orphanet:813), Kagami-Ogata syndrome (Orphanet:254519), Kagami-Ogata syndrome due to paternal uniparental disomy of chromosome 14 (Orphanet:96334), Rare central precocious puberty (Orphanet:650063), NON RARE IN EUROPE: Central precocious puberty (Orphanet:759)

HPO phenotypes

169 total (30 of 169 shown, HPO-id order):

HPO	Term
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000119	Abnormality of the genitourinary system
HP:0000126	Hydronephrosis
HP:0000158	Macroglossia
HP:0000160	Narrow mouth
HP:0000175	Cleft palate
HP:0000193	Bifid uvula
HP:0000194	Open mouth
HP:0000218	High palate
HP:0000252	Microcephaly
HP:0000260	Wide anterior fontanel
HP:0000278	Retrognathia
HP:0000286	Epicanthus
HP:0000293	Full cheeks
HP:0000303	Mandibular prognathia
HP:0000322	Short philtrum
HP:0000327	Hypoplasia of the maxilla
HP:0000337	Broad forehead
HP:0000341	Narrow forehead
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000403	Recurrent otitis media
HP:0000431	Wide nasal bridge
HP:0000445	Wide nose
HP:0000463	Anteverted nares
HP:0000470	Short neck
HP:0000490	Deeply set eye
HP:0000565	Esotropia

GWAS associations

20 associations (top):

Study	Trait	p-value
GCST000539_2	Type 1 diabetes	1.000000e-10
GCST001337_43	Platelet count	3.000000e-08
GCST002541_100	Menarche (age at onset)	6.000000e-09
GCST002541_99	Menarche (age at onset)	9.000000e-15
GCST005991_35	Platelet count	2.000000e-10
GCST008362_77	Birth weight	1.000000e-12
GCST008839_191	Height	1.000000e-18
GCST009066_42	Mosaic loss of chromosome Y (Y chromosome dosage)	4.000000e-33
GCST009067_33	Mosaic loss of chromosome Y (Y chromosome dosage)	1.000000e-52
GCST009356_14	Nonsyndromic cleft palate	7.000000e-10
GCST009357_4	Nonsyndromic cleft lip	3.000000e-08
GCST009375_10	Mosaic loss of chromosome Y (Y chromosome dosage)	4.000000e-15
GCST009391_186	Metabolite levels	3.000000e-07
GCST009646_3	Diastolic blood pressure response to thiazide and thiazide-like diuretics in hypertension	4.000000e-08
GCST010002_160	Refractive error	3.000000e-10
GCST010118_99	Type 2 diabetes	7.000000e-11
GCST010988_546	Adult body size	3.000000e-10
GCST010989_67	Body size at age 10	4.000000e-08
GCST012335_7	Hodgkin’s lymphoma	6.000000e-12
GCST90000025_201	Appendicular lean mass	5.000000e-11

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count
EFO:0004703	age at menarche
EFO:0004344	birth weight
EFO:0007783	mosaic loss of chromosome Y measurement
EFO:0003959	cleft lip
EFO:0010482	gamma-aminoisobutyric acid measurement
EFO:0006945	diastolic blood pressure change measurement
EFO:0009819	comparative body size at age 10, self-reported
EFO:0004980	appendicular lean mass

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C536471	Uniparental disomy, paternal, chromosome 14 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5671 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

15 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 150,507 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1289926	AXITINIB	4	15,732
CHEMBL180022	NERATINIB	4	9,404
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL535	SUNITINIB	4	79,020
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL290352	CEP-1347	3	359
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL1721885	SU-014813	2	363
CHEMBL572878	TOZASERTIB	2	2,998
CHEMBL607707	PELITINIB	2	6,340
CHEMBL1908397	KW-2449	1	622
CHEMBL3732012	GDC-0134	1	62
CHEMBL574738	AST-487	1	451

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

ChEMBL bioactivities

39 potent at pChembl≥5 of 39 total, top 35 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.77	Ki	0.17	nM	CHEMBL3355003
9.40	Ki	0.4	nM	CHEMBL3355005
9.00	IC50	1	nM	CHEMBL4207983
8.70	IC50	2	nM	CHEMBL5287658
8.40	IC50	4	nM	CHEMBL5403790
8.40	IC50	4	nM	CHEMBL5268969
8.20	Ki	6.3	nM	SUNITINIB
7.96	IC50	11	nM	GDC-0134
7.82	Ki	15	nM	CHEMBL5413922
7.60	Ki	25	nM	CHEMBL3393328
7.48	Ki	33	nM	CHEMBL3393324
7.45	Ki	35.8	nM	TOZASERTIB
7.38	Kd	42	nM	TAE-684
7.17	Kd	67	nM	KW-2449
7.16	Kd	70	nM	CHEMBL2436978
7.00	Kd	100	nM	SUNITINIB
6.96	Ki	110	nM	CHEMBL3355004
6.94	IC50	114	nM	CEP-1347
6.92	IC50	119	nM	CHEMBL4218417
6.84	Ki	145	nM	CHEMBL3629009
6.82	IC50	150	nM	CHEMBL2436978
6.77	Kd	170	nM	CRIZOTINIB
6.70	IC50	201	nM	CHEMBL5400272
6.57	Ki	270	nM	CHEMBL3355006
6.48	Kd	330	nM	CHEMBL1908842
6.43	Kd	370	nM	NERATINIB
6.25	Kd	560	nM	SU-014813
6.17	Kd	670	nM	BOSUTINIB
6.08	Kd	840	nM	LESTAURTINIB
5.77	Kd	1700	nM	AXITINIB
5.68	Kd	2100	nM	DOVITINIB
5.60	Kd	2500	nM	AST-487
5.58	Kd	2600	nM	PELITINIB
5.28	Kd	5200	nM	JNJ-7706621
5.20	Kd	6300	nM	FEDRATINIB

PubChem BioAssay actives

41 with measured affinity, of 108 total; 35 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
5-[5-(1-methylpiperidin-4-yl)-1-propan-2-ylpyrazol-3-yl]-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine	1177107: Inhibition of DLK (unknown origin) by RT-FRET assay	ki	0.0002	uM
5-[5-[(1R,5S)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl]-1-propan-2-ylpyrazol-3-yl]-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine	1177107: Inhibition of DLK (unknown origin) by RT-FRET assay	ki	0.0004	uM
2-[[6-(3,3-difluoropyrrolidin-1-yl)-4-[1-(oxetan-3-yl)piperidin-4-yl]-2-pyridinyl]amino]pyridine-4-carbonitrile	1970214: Binding affinity to DLK (unknown origin) assessed as inhibition constant	ki	0.0005	uM
19-methyl-3-propan-2-yl-7-pyrimidin-2-yloxy-3,13,19,20-tetrazahexacyclo[14.7.0.02,10.04,9.011,15.017,21]tricosa-1(16),2(10),4(9),5,7,11(15),17,20-octaen-14-one	1384628: Inhibition of DLK (unknown origin) using myelin basic protein as substrate preincubated for 15 mins measured after 30 mins in presence of [gamma-32P]ATP by scintillation counting	ic50	0.0010	uM
1-[4-[6-amino-5-(trifluoromethyl)-3-pyridinyl]-1-(3-morpholin-4-yl-1-bicyclo[1.1.1]pentanyl)imidazol-2-yl]-2-methylpropan-1-ol	1970215: Inhibition of DLK (unknown origin)	ic50	0.0020	uM
3-(difluoromethoxy)-5-[2-(3,3-difluoropyrrolidin-1-yl)-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]-4-pyridinyl]pyrazin-2-amine	1970215: Inhibition of DLK (unknown origin)	ic50	0.0040	uM
5-[2-(2-azabicyclo[2.1.1]hexan-2-yl)-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]-4-pyridinyl]-3-(difluoromethoxy)pyrazin-2-amine	1970215: Inhibition of DLK (unknown origin)	ic50	0.0040	uM
Sunitinib	1384629: Inhibition of DLK (unknown origin)	ki	0.0063	uM
3-(difluoromethoxy)-5-[2-(3,3-difluoropyrrolidin-1-yl)-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]pyridin-2-amine	1970215: Inhibition of DLK (unknown origin)	ic50	0.0110	uM
(1S)-1-[4-[6-amino-5-(trifluoromethyl)-3-pyridinyl]-1-(1-bicyclo[1.1.1]pentanyl)imidazol-2-yl]-2-methylpropan-1-ol	1970214: Binding affinity to DLK (unknown origin) assessed as inhibition constant	ki	0.0150	uM
2-[[4-(1-acetylpiperidin-4-yl)-6-(3,3-difluoropyrrolidin-1-yl)-2-pyridinyl]amino]pyridine-4-carbonitrile	2141504: Binding affinity to DLK (unknown origin) assessed as inhibition constant	ki	0.0250	uM
1-[4-[2-(3,3-difluoropyrrolidin-1-yl)-6-[[4-(trifluoromethyl)-2-pyridinyl]amino]pyrimidin-4-yl]piperidin-1-yl]ethanone	1970214: Binding affinity to DLK (unknown origin) assessed as inhibition constant	ki	0.0330	uM
N-[4-[4-(4-methylpiperazin-1-yl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]cyclopropanecarboxamide	1384629: Inhibition of DLK (unknown origin)	ki	0.0358	uM
5-chloro-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine	1970220: Binding affinity to DLK (unknown origin) assessed as dissociation constant	kd	0.0420	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	1970220: Binding affinity to DLK (unknown origin) assessed as dissociation constant	kd	0.0670	uM
3-(1H-indol-5-yl)-5-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]-1H-pyrrolo[2,3-b]pyridine	775371: Binding affinity to human wild type DLK by qPCR analysis	kd	0.0700	uM
3-fluoro-5-[5-[1-(oxetan-3-yl)pyrrolidin-3-yl]-1-propan-2-ylpyrazol-3-yl]-1H-pyrrolo[2,3-b]pyridine	1177107: Inhibition of DLK (unknown origin) by RT-FRET assay	ki	0.1100	uM
methyl (15S,16R,18R)-10,23-bis(ethylsulfanylmethyl)-16-hydroxy-15-methyl-3-oxo-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8(13),9,11,20(25),21,23,26-nonaene-16-carboxylate	1384628: Inhibition of DLK (unknown origin) using myelin basic protein as substrate preincubated for 15 mins measured after 30 mins in presence of [gamma-32P]ATP by scintillation counting	ic50	0.1140	uM
3-(2-hydroxyethyl)-7-(propan-2-yloxymethyl)-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17,19,21-nonaen-12-one	1384628: Inhibition of DLK (unknown origin) using myelin basic protein as substrate preincubated for 15 mins measured after 30 mins in presence of [gamma-32P]ATP by scintillation counting	ic50	0.1190	uM
N-(5-piperidin-4-yl-1-propan-2-ylpyrazol-3-yl)-4-(trifluoromethyl)pyridin-2-amine	1970214: Binding affinity to DLK (unknown origin) assessed as inhibition constant	ki	0.1450	uM
Crizotinib	1970220: Binding affinity to DLK (unknown origin) assessed as dissociation constant	kd	0.1700	uM
1-[4-[4-[[(2R,4S)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazin-1-yl]ethanone	1970214: Binding affinity to DLK (unknown origin) assessed as inhibition constant	ki	0.2000	uM
5-[2-(2-azabicyclo[2.1.1]hexan-2-yl)-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]-4-pyridinyl]pyrazin-2-amine	1970215: Inhibition of DLK (unknown origin)	ic50	0.2010	uM
7-[5-[(1R,5S)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl]-1-propan-2-ylpyrazol-3-yl]-1H-pyrazolo[4,5-c]pyridin-4-amine	1177107: Inhibition of DLK (unknown origin) by RT-FRET assay	ki	0.2700	uM
5-cyano-N-[2-(cyclohexen-1-yl)-4-[1-[2-(dimethylamino)acetyl]piperidin-4-yl]phenyl]-1H-imidazole-2-carboxamide	1970220: Binding affinity to DLK (unknown origin) assessed as dissociation constant	kd	0.3300	uM
Neratinib	1970220: Binding affinity to DLK (unknown origin) assessed as dissociation constant	kd	0.3700	uM
5-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-N-[(2S)-2-hydroxy-3-morpholin-4-ylpropyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	1970220: Binding affinity to DLK (unknown origin) assessed as dissociation constant	kd	0.5600	uM
Bosutinib	1970220: Binding affinity to DLK (unknown origin) assessed as dissociation constant	kd	0.6700	uM
(15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaen-3-one	1970220: Binding affinity to DLK (unknown origin) assessed as dissociation constant	kd	0.8400	uM
Axitinib	1970220: Binding affinity to DLK (unknown origin) assessed as dissociation constant	kd	1.7000	uM
4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one	1970220: Binding affinity to DLK (unknown origin) assessed as dissociation constant	kd	2.1000	uM
1-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea	1970220: Binding affinity to DLK (unknown origin) assessed as dissociation constant	kd	2.5000	uM
(E)-N-[4-(3-chloro-4-fluoroanilino)-3-cyano-7-ethoxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide	1970220: Binding affinity to DLK (unknown origin) assessed as dissociation constant	kd	2.6000	uM
4-[[5-amino-1-(2,6-difluorobenzoyl)-1,2,4-triazol-3-yl]amino]benzenesulfonamide	1970220: Binding affinity to DLK (unknown origin) assessed as dissociation constant	kd	5.2000	uM
Fedratinib	1970220: Binding affinity to DLK (unknown origin) assessed as dissociation constant	kd	6.3000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects expression, increases methylation, affects cotreatment	8
trichostatin A	decreases expression, affects cotreatment	3
Benzo(a)pyrene	decreases expression, affects methylation	3
Tetrachlorodibenzodioxin	affects methylation, decreases expression	3
Tretinoin	decreases expression	3
bisphenol A	decreases methylation, affects expression	2
entinostat	decreases expression, affects cotreatment	2
Decitabine	decreases methylation, increases expression, affects expression	2
Vorinostat	affects cotreatment, decreases expression	2
Panobinostat	affects cotreatment, decreases expression	2
Arsenic	affects expression, affects methylation	2
Fluorouracil	increases expression, affects reaction, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Silicon Dioxide	increases expression	2
methylmercuric chloride	increases expression	1
cobaltiprotoporphyrin	affects expression	1
bisphenol A diglycidyl ether	decreases expression	1
manganese chloride	decreases expression, increases methylation	1
benzo(e)pyrene	increases methylation	1
beta-methylcholine	affects expression	1
pentanal	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Rosiglitazone	decreases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Sunitinib	decreases expression	1
Arsenic Trioxide	affects response to substance	1
Atrazine	increases expression	1
Azacitidine	decreases methylation	1
Carbamazepine	affects expression	1

ChEMBL screening assays

51 unique, capped per target: 51 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1000438	Binding	Inhibition of human DLK expressed in baculovirus insect cell system	Mixed-lineage kinase 1 and mixed-lineage kinase 3 subtype-selective dihydronaphthyl[3,4-a]pyrrolo[3,4-c]carbazole-5-ones: optimization, mixed-lineage kinase 1 crystallography, and oral in vivo activity in 1-methyl-4-phenyltetrahydropyridine models. — J Med Chem

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A0X4	SEES3-1V human DLK1, clone1	Embryonic stem cell	Male
CVCL_A0X5	SEES3-1V human DLK1, clone2	Embryonic stem cell	Male
CVCL_A0X6	SEES3-1V human DLK1, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00438217	PHASE4	UNKNOWN	Analysis of Genetic and Environmental Parameters Influencing Growth Rate of Precocious Puberty Children
NCT01634321	PHASE4	COMPLETED	The Clinical Trial to Evaluate the Efficacy and Safety of Luphere Depot Inj. 3.75mg(Leuprolide Acetate 3.75mg) in Patients With Precocious Puberty
NCT02427958	PHASE4	COMPLETED	A Study to Assess the Safety and Efficacy of Leuprorelin in Central Precocious Puberty in Chinese Participants
NCT02920515	PHASE4	COMPLETED	Study of Comprehensive Diagnosis and Treatment for Children Precocious Puberty
NCT02974270	PHASE4	UNKNOWN	Analysis of Body Mass Index in Central Precocious Puberty Patients Treated With Leuprolide Acetate
NCT03316482	PHASE4	COMPLETED	Leuprorelin Acetate DPS (Leuplin DPS) Treatment Quarterly in Patients With Central Precocious Puberty
NCT05341115	PHASE4	COMPLETED	A Study of Leuprolide Acetate Depot in Children With Central Precocious Puberty
NCT06487143	PHASE4	NOT_YET_RECRUITING	Efficacy, Metabolism and BMD of the 3-month TP Compared to the 1-month TP in ICPP
NCT00667446	PHASE3	COMPLETED	Safety Extension Study Of Leuprolide Acetate (Lupron Depot) In The Treatment Of Central Precocious Puberty
NCT00779103	PHASE3	COMPLETED	Histrelin Subcutaneous Implant in Children With Central Precocious Puberty
NCT01278290	PHASE3	COMPLETED	Comparative Validation of the Triptorelin Test for the Diagnosis of CPP in Girls
NCT01467882	PHASE3	COMPLETED	Efficacy, Safety, and Pharmacokinetics (PK) of Triptorelin 6-month Formulation in Patients With Central Precocious Puberty
NCT02452931	PHASE3	COMPLETED	Study of Leuprolide Acetate Injectable Suspension in the Treatment of Central Precocious Puberty
NCT03695237	PHASE3	COMPLETED	A Study to Evaluate Leuprolide Acetate 45 mg 6-Month Formulation in Children With Central Precocious Puberty (CPP)
NCT04736602	PHASE3	COMPLETED	Efficacy and Safety Study of Triptorelin 3-Month Formulation in Chinese Children With Central Precocious Puberty.
NCT05029622	PHASE3	COMPLETED	A Study to Assess the Efficacy and Safety of the Triptorelin 6-month Formulation in Paediatric Participants With Central Precocious Puberty.
NCT06025409	PHASE3	UNKNOWN	Evaluate the Efficacy and Safety of DWJ108J
NCT06129539	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Assess the Efficacy, Safety, and Pharmacokinetics of Debio 4326 in Pediatric Participants With Central Precocious Puberty (LIBELULA™ Clinical Trial)
NCT02006680	Not specified	TERMINATED	Markers of Pubertal Suppression During Therapy for Precocious Puberty
NCT02993926	Not specified	COMPLETED	A Study to Assess the Safety and Efficacy of Enantone (Leuprorelin) in Central Precocious Puberty (CPP) Among Chinese Participants
NCT05341128	Not specified	COMPLETED	A Study of Medical Records From Children With Central Precocious Puberty (CPP) in China
NCT06720623	Not specified	COMPLETED	Diagnostic Power of Basal LH Compared to Peak LH After Stimulus Test in the Diagnosis of Central Precocious Puberty
NCT06720844	Not specified	RECRUITING	Idiopathic Central Precocious Puberty and Associated Neurodevelopmental Syndromes and Pathologies: Evaluation of Frequency and Comparison of Diagnostic and Developmental Characteristics
NCT07359092	Not specified	COMPLETED	Spexin and Phoenixin-20 in Girls With Central Precocious Puberty
NCT07411001	Not specified	ACTIVE_NOT_RECRUITING	Hypiend - Multicomponent Behavioral Intervention in Pre-puberal Children (Hypiend-PPC)