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Atlas / Disease / Precocious puberty

Precocious puberty

disease
On this page

Also known as familial precocious pubertyidiopathic sexual precocitypubertas praecoxsexual precocity

Summary

Precocious puberty (MONDO:0000088) is a disease with 2 cohort genes (1 GWAS associations across 1 studies) and 23 clinical trials. Top therapeutic interventions include gonadorelin, testolactone, and triptorelin.

At a glance

  • Cohort genes: 2
  • GWAS associations: 1
  • ClinVar variants: 2
  • Clinical trials: 23

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical nameprecocious puberty
Mondo IDMONDO:0000088
MeSHD011629
Orphanet95708
ICD-10-CME30.1
NCITC79704
SNOMED CT400179000
UMLSC0034013
MedGen18752
MedDRA10044701, 10058084
Is cancer (heuristic)no

Also known as: familial precocious puberty · idiopathic sexual precocity · pubertas praecox · sexual precocity

Data availability: 2 ClinVar variants · 1 GWAS association (1 study) · 1 GenCC gene-disease record · 1 HPO phenotype.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › reproductive system disorder › gonadal disorder › precocious puberty

Related subtypes (5): disorder of sexual differentiation, hypogonadism, testicular disorder, ovarian disorder, gonadoblastoma

Subtypes (3): peripheral precocious puberty, precocious puberty in female, central precocious puberty

Genetics & variants

GWAS landscape

1 GWAS associations across 1 studies. Top hits map to 0 distinct genes (as reported by GWAS).

Top associations by p-value

rsIDp-valueGeneRisk alleleOdds ratio
rs1401703842e-08CARTPT - MAP1B?

Top studies (by case count)

StudyLead authorYearCasesControlsTitle
GCST90651564Liu TY20251,926224,577Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

TierVariants
Tier 1: coding0
Tier 2: splice/UTR0
Tier 3: regulatory0
Tier 4: intronic/intergenic1

MAF distribution

BucketVariants
common (>=0.05)0
low_freq (0.01-0.05)0
rare (<0.01)0
unknown1

Functional consequences

ConsequenceCount
intergenic_variant1

Top variants

rsIDChrPosAllelesMAFConsequenceGenep-valueTier
rs140170384571929064A>Gintergenic_variantCARTPT - MAP1B2e-08Tier 4: intronic/intergenic

ClinVar germline variants

2 retrieved; paginated sample, class counts are floors:

1 uncertain significance, 1 likely pathogenic

ClinVarVariant (HGVS)GeneClassificationReview
997831NM_000264.5(PTCH1):c.2265_2268del (p.Leu756fs)LOC100507346Likely pathogeniccriteria provided, single submitter
2571641NM_005428.4(VAV1):c.909del (p.Asp303fs)VAV1Uncertain significancecriteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · Orphanet: 4 · 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.

GeneClassificationInheritanceDiseaseRecords
CDKL5LimitedX-linkedprecocious puberty9

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
CDKL5Orphanet:1934Early infantile developmental and epileptic encephalopathy
CDKL5Orphanet:3095Atypical Rett syndrome
CDKL5Orphanet:505652CDKL5-deficiency disorder
CDKL5Orphanet:697160Infantile epileptic spasms syndrome

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

SubsetGenes
multi_evidence2

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
CDKL5HGNC:11411ENSG00000008086O76039Cyclin-dependent kinase-like 5gencc
VAV1HGNC:12657ENSG00000141968P15498Proto-oncogene vavclinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
CDKL5Cyclin-dependent kinase-like 5Mediates phosphorylation of MECP2.
VAV1Proto-oncogene vavCouples tyrosine kinase signals with the activation of the Rho/Rac GTPases, thus leading to cell differentiation and/or proliferation.

Protein-family classification

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

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

FamilyGenesFoldFDR
Kinase113.9×0.112
Scaffold/PPI18.6×0.112

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
CDKL5Kinaseyes2.7.11.22Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
VAV1Scaffold/PPInoDH_dom, SH2, GDS_CDC24_CS

Expression context

Cohort genes with no expression data: 0.

2 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

BucketGenes
narrow (1-5 tissues)0
moderate (6-20)0
broad (>20)2
unknown0

Top tissues across cohort

TissueCohort genes
Brodmann (1909) area 231
cortical plate1
frontal pole1
granulocyte1
leukocyte1
monocyte1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
CDKL5257ubiquitousmarkerfrontal pole, Brodmann (1909) area 23, cortical plate
VAV1188broadmarkergranulocyte, monocyte, leukocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

SymbolInteractor count
VAV13,042
CDKL51,357

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
VAV1P1549810
CDKL5O760393

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 24. Enrichment computed across 2 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
CD28 dependent Vav1 pathway1878.5×0.008VAV1
Erythropoietin activates RAS1761.3×0.008VAV1
Regulation of signaling by CBL1496.5×0.008VAV1
Azathioprine ADME1496.5×0.008VAV1
VEGFR2 mediated vascular permeability1407.9×0.008VAV1
FCERI mediated Ca+2 mobilization1356.9×0.008VAV1
Antigen activates B Cell Receptor (BCR) leading to generation of second messengers1356.9×0.008VAV1
FCERI mediated MAPK activation1346.1×0.008VAV1
Interleukin-3, Interleukin-5 and GM-CSF signaling1317.2×0.008VAV1
GPVI-mediated activation cascade1308.6×0.008VAV1
Signaling by SCF-KIT1248.3×0.009VAV1
FCGR3A-mediated phagocytosis1187.2×0.009VAV1
NRAGE signals death through JNK1184.2×0.009VAV1
Regulation of actin dynamics for phagocytic cup formation1184.2×0.009VAV1
RHOG GTPase cycle1148.3×0.010VAV1
VEGFA-VEGFR2 Pathway1139.3×0.010VAV1
G alpha (12/13) signalling events1137.6×0.010VAV1
Constitutive Signaling by Aberrant PI3K in Cancer1126.9×0.010VAV1
RAC2 GTPase cycle1126.9×0.010VAV1
Potential therapeutics for SARS1114.2×0.011VAV1
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling196.8×0.012VAV1
RHOA GTPase cycle174.6×0.015VAV1
PIP3 activates AKT signaling166.8×0.016VAV1
RAC1 GTPase cycle161.1×0.016VAV1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
immune response-regulating cell surface receptor signaling pathway1936.2×0.008VAV1
regulation of dendrite development1495.6×0.008CDKL5
positive regulation of dendrite morphogenesis1443.5×0.008CDKL5
regulation of cell size1383.0×0.008VAV1
Fc-epsilon receptor signaling pathway1366.4×0.008VAV1
Fc-gamma receptor signaling pathway involved in phagocytosis1351.1×0.008VAV1
positive regulation of Rac protein signal transduction1324.1×0.008CDKL5
regulation of cilium assembly1300.9×0.008CDKL5
natural killer cell activation1290.6×0.008VAV1
positive regulation of natural killer cell mediated cytotoxicity1280.9×0.008VAV1
regulation of postsynapse organization1263.3×0.008CDKL5
positive regulation of axon extension1255.3×0.008CDKL5
B cell proliferation1240.7×0.008VAV1
vascular endothelial growth factor receptor signaling pathway1240.7×0.008VAV1
reactive oxygen species metabolic process1234.1×0.008VAV1
natural killer cell mediated cytotoxicity1216.1×0.008VAV1
T cell differentiation1191.5×0.009VAV1
T cell costimulation1187.2×0.009VAV1
neutrophil chemotaxis1142.8×0.011VAV1
platelet activation1133.8×0.011VAV1
cellular response to xenobiotic stimulus1120.4×0.011VAV1
small GTPase-mediated signal transduction191.6×0.014VAV1
modulation of chemical synaptic transmission191.6×0.014CDKL5
integrin-mediated signaling pathway180.2×0.015VAV1
regulation of small GTPase mediated signal transduction172.0×0.016VAV1
neuron migration166.9×0.017CDKL5
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction139.2×0.027VAV1
cell migration130.8×0.033VAV1
G protein-coupled receptor signaling pathway118.1×0.054VAV1

Therapeutics

Drugs indicated for this disease

0 approved, 1 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

DrugDevelopment status
TriptorelinPhase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Anastrozole, Bicalutamide, Fulvestrant, Spironolactone, Testolactone.

Drug target analysis

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

Druggability breadth: 2 of 2 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

SymbolExample approved molecule
CDKL5FEDRATINIB

Top cohort targets by molecule count

SymbolMoleculesMax phase
CDKL5144
VAV100

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
FEDRATINIB4CDKL5
CAPMATINIB4CDKL5
DEFACTINIB3CDKL5
ALVOCIDIB3CDKL5
LESTAURTINIB3CDKL5
RUBOXISTAURIN3CDKL5
FORETINIB2CDKL5
RG-5472CDKL5
AT-75192CDKL5
TOZASERTIB2CDKL5
BMS-3870321CDKL5
PF-037583091CDKL5
5-(6-BENZOTHIAZOLYLMETHYLENE)-3,5-DIHYDRO-2-(((1S)-1-(METHOXYMETHYL)-3-METHYLBUTYL)AMINO)-4H-IMIDAZOL-4-ONE, (5Z)-1CDKL5
AST-4871CDKL5

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

SymbolAssaysType breakdown
CDKL574Binding:74
VAV11Binding:1

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
CDKL52.7.11.22cyclin-dependent kinase

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

14 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.

CompoundMax phaseCohort target (bioactivity)
FEDRATINIB4CDKL5
CAPMATINIB4CDKL5
DEFACTINIB3CDKL5
ALVOCIDIB3CDKL5
LESTAURTINIB3CDKL5
RUBOXISTAURIN3CDKL5
FORETINIB2CDKL5
RG-5472CDKL5
AT-75192CDKL5
TOZASERTIB2CDKL5
BMS-3870321CDKL5
PF-037583091CDKL5
5-(6-BENZOTHIAZOLYLMETHYLENE)-3,5-DIHYDRO-2-(((1S)-1-(METHOXYMETHYL)-3-METHYLBUTYL)AMINO)-4H-IMIDAZOL-4-ONE, (5Z)-1CDKL5
AST-4871CDKL5

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

TierDefinitionGenesSymbols
AApproved (phase 4 drug)1CDKL5
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug0
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug1VAV1

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
VAV11—

Clinical trials & evidence

Clinical trials

Clinical trials: 23.

Phase distribution (across all retrieved trials)

PhaseTrials
Not specified14
PHASE34
PHASE22
PHASE41
PHASE11
EARLY_PHASE11

Top trials by phase / activity

NCTPhaseStatusTitle
NCT03963752PHASE4COMPLETEDClinical Trial of Rapid Progressive Central Precocious Puberty With Integrative Chinese and Western Medicine
NCT06510764PHASE3RECRUITINGA Trial of Chinese Traditional Medicine Combining With Intradermal Acupuncture for Treating Precocious Puberty
NCT00564850PHASE3COMPLETEDEfficacy and Safety Study of Pamoate of Triptorelin in Children With Precocious Puberty
NCT00909844PHASE3COMPLETEDEffects of Triptorelin Pamoate in Children With Precocious Puberty - Follow up Study
NCT01278290PHASE3COMPLETEDComparative Validation of the Triptorelin Test for the Diagnosis of CPP in Girls
NCT00001181PHASE2COMPLETEDTestolactone for the Treatment of Girls With LHRH Resistant Precocious Puberty
NCT00001202PHASE2COMPLETEDTreatment of Boys With Precocious Puberty
NCT00006174PHASE1COMPLETEDEffects of Letrozole on Precocious Puberty Due to McCune Albright Syndrome
NCT00734279EARLY_PHASE1COMPLETEDFollicle-Stimulating Hormone (FSH) and the Onset of Puberty
NCT01601171Not specifiedRECRUITINGGenetics of Reproductive Disorders (Including Kallmann Syndrome) and Cleft Lip and/or Palate
NCT04113070Not specifiedRECRUITINGOverweight and Obesity and Puberty Development Cohort Study
NCT05945576Not specifiedRECRUITINGIDMet (RaDiCo Cohort) (RaDiCo-IDMet)
NCT06280807Not specifiedRECRUITINGObservation of Environment and Reproductive-Endocrine Effects
NCT00004335Not specifiedCOMPLETEDStudy of Gonadotropin-Releasing Hormone Pulse Frequency in Sexual Maturation and in the Menstrual Cycle
NCT00004344Not specifiedCOMPLETEDPurification of Testis-Stimulating Factor in Precocious Puberty
NCT01944475Not specifiedUNKNOWNFollow-up of Girls With Premature Thelarche and Precocious Puberty
NCT01944488Not specifiedUNKNOWNLH Response to GnRH Test in Prepubescent Girls Under 6 Years
NCT02199587Not specifiedCOMPLETEDThe Effect of Medical Clown on the Pain and Anxiety Perception During LRH Analog Treatment or GH Provocation Test
NCT02650141Not specifiedCOMPLETEDClinical Trial of Experienced Chinese Herbal Formulas on Different Types of Precocious Puberty
NCT04502836Not specifiedTERMINATEDEvaluation of the Correlation Between Psychological Intervention, Including Providing Knowledge and Tools for Problems Solving, and the Anxiety Level of Female Patients Arriving to ACTH LRH Test - Pilot Study
NCT04665713Not specifiedCOMPLETEDEffect of Prevalence of BMI on Efficacy of Herbal Medicines in Girls’ Sexual Precocity
NCT05338411Not specifiedUNKNOWNEffect of Exogenous Growth Hormone on Ocular Findings
NCT07141615Not specifiedTERMINATEDClinical Observation of Qingwei Huazhuo Decoction (Product: Jinsaiyu) in Improving Children With Precocious Puberty of Phlegm-Dampness Internal Accumulation Type

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
GONADORELIN42
TESTOLACTONE42
TRIPTORELIN42
MEGESTROL ACETATE41
SPIRONOLACTONE41
DESLORELIN21
CHEMBL16683902
CHEMBL407338702
CHEMBL407121501
CHEMBL156222301
CHEMBL3045801
CHEMBL237064401

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

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This page pulls from 71 datasets indexed by BioBTree:

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