Central precocious puberty 1

Summary

Central precocious puberty 1 (MONDO:0008302) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 8

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	central precocious puberty 1
Mondo ID	MONDO:0008302
OMIM	176400
DOID	DOID:0112310
UMLS	C3805879
MedGen	812209
GARD	0024615
Is cancer (heuristic)	no

Also known as: central precocious puberty caused by mutation in KISS1R · CPPB1 · KISS1R central precocious puberty · precocious puberty, central, 1 · precocious puberty, central, type 1

Data availability: 8 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › reproductive system disorder › gonadal disorder › precocious puberty › central precocious puberty › central precocious puberty 1

Related subtypes (6): precocious puberty, central, 2, idiopathic central precocious puberty, secondary central precocious puberty, central precocious puberty in male, genetic central precocious puberty in female, secondary central precocious puberty in female

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

8 retrieved; paginated sample, class counts are floors:

2 benign/likely benign, 2 conflicting classifications of pathogenicity, 2 uncertain significance, 1 benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
5759	NM_032551.5(KISS1R):c.305T>C (p.Leu102Pro)	KISS1R	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
281944	NM_032551.5(KISS1R):c.890G>T (p.Arg297Leu)	KISS1R	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
5760	NM_032551.5(KISS1R):c.1157G>C (p.Arg386Pro)	KISS1R	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3584223	NM_032551.5(KISS1R):c.244+6del	KISS1R	Uncertain significance	criteria provided, single submitter
800826	NM_032551.5(KISS1R):c.439C>T (p.Pro147Ser)	KISS1R	Uncertain significance	criteria provided, single submitter
1590131	NM_032551.5(KISS1R):c.18G>A (p.Thr6=)	KISS1R	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
379860	NM_032551.5(KISS1R):c.1155G>A (p.Ala385=)	KISS1R	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
447660	NM_032551.5(KISS1R):c.1091T>A (p.Leu364His)	KISS1R	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
KISS1R	Limited	Autosomal dominant	central precocious puberty 1	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
KISS1R	Orphanet:432	Normosmic congenital hypogonadotropic hypogonadism
KISS1R	Orphanet:650077	Genetic central precocious puberty in female
KISS1R	Orphanet:650097	Genetic central precocious puberty in male

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
KISS1R	HGNC:4510	ENSG00000116014	Q969F8	KiSS-1 receptor	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KISS1R	KiSS-1 receptor	Receptor for kisspeptins (kisspeptin-10, kisspeptin-13, kisspeptin-14 and metastin/kisspeptin-54).

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

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

Family	Genes	Fold	FDR
GPCR	1	23.9×	0.042

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KISS1R	GPCR	yes		GPCR_Rhodpsn, KiSS_1_rcpt, GPCR_Rhodpsn_7TM

Expression context

Cohort genes with no expression data: 0.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
buccal mucosa cell	1
endothelial cell	1
pons	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KISS1R	109	broad	yes	pons, buccal mucosa cell, endothelial cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KISS1R	811

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KISS1R	Q969F8	6

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. Enrichment computed across 1 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.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Class A/1 (Rhodopsin-like receptors)	1	74.2×	0.029	KISS1R
Peptide ligand-binding receptors	1	74.2×	0.029	KISS1R
GPCR ligand binding	1	64.2×	0.029	KISS1R
G alpha (q) signalling events	1	57.4×	0.029	KISS1R
GPCR downstream signalling	1	43.4×	0.029	KISS1R
Signaling by GPCR	1	40.1×	0.029	KISS1R
Signal Transduction	1	10.2×	0.098	KISS1R

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of hormone secretion	1	1685.2×	0.002	KISS1R
neuropeptide signaling pathway	1	172.0×	0.009	KISS1R
G protein-coupled receptor signaling pathway	1	36.2×	0.028	KISS1R

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
KISS1R	3	3

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
KISSPEPTIN-10	3	KISS1R
BENZETHONIUM CHLORIDE	2	KISS1R
TAK-448	2	KISS1R

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
KISS1R	48	Binding:24, Functional:24

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

3 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.

Compound	Max phase	Cohort target (bioactivity)
KISSPEPTIN-10	3	KISS1R
BENZETHONIUM CHLORIDE	2	KISS1R
TAK-448	2	KISS1R

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	1	KISS1R
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.