Precocious puberty, central, 2

disease

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Also known as central precocious puberty caused by mutation in MKRN3CPPB2MKRN3 central precocious pubertyprecocious puberty, central, type 2

Summary

Precocious puberty, central, 2 (MONDO:0014137) is a disease caused by MKRN3 (GenCC Strong), with 1 cohort gene.

At a glance

Causal gene: MKRN3 (GenCC Strong)
Cohort genes: 1
ClinVar variants: 12

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	precocious puberty, central, 2
Mondo ID	MONDO:0014137
OMIM	615346
DOID	DOID:0112309
UMLS	C3809199
MedGen	815529
GARD	0024975
Is cancer (heuristic)	no

Also known as: central precocious puberty caused by mutation in MKRN3 · CPPB2 · MKRN3 central precocious puberty · precocious puberty, central, 2 · precocious puberty, central, type 2

Data availability: 12 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › reproductive system disorder › gonadal disorder › precocious puberty › central precocious puberty › precocious puberty, central, 2

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

12 retrieved; paginated sample, class counts are floors:

5 uncertain significance, 5 pathogenic, 1 conflicting classifications of pathogenicity, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2431610	NM_005664.4(MKRN3):c.482del (p.Pro161fs)	MKRN3	Pathogenic	criteria provided, single submitter
438339	NM_005664.4(MKRN3):c.982C>T (p.Arg328Cys)	MKRN3	Pathogenic	no assertion criteria provided
56901	NM_005664.4(MKRN3):c.637del (p.Arg213fs)	MKRN3	Pathogenic	no assertion criteria provided
56902	NM_005664.4(MKRN3):c.1172dup (p.Tyr391Ter)	MKRN3	Pathogenic	no assertion criteria provided
56903	NM_005664.4(MKRN3):c.1095G>T (p.Arg365Ser)	MKRN3	Pathogenic	no assertion criteria provided
625144	NM_005664.4(MKRN3):c.326G>A (p.Cys109Tyr)	MKRN3	Likely pathogenic	criteria provided, single submitter
56904	NM_005664.4(MKRN3):c.482dup (p.Ala162fs)	MKRN3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1030007	NM_005664.4(MKRN3):c.103T>G (p.Cys35Gly)	MKRN3	Uncertain significance	criteria provided, single submitter
2433752	NM_005664.4(MKRN3):c.-81C>T	MKRN3	Uncertain significance	criteria provided, multiple submitters, no conflicts
3376562	NM_005664.4(MKRN3):c.1252dup (p.Tyr418fs)	MKRN3	Uncertain significance	criteria provided, single submitter
3891667	NM_005664.4(MKRN3):c.300C>G (p.Ile100Met)	MKRN3	Uncertain significance	criteria provided, single submitter
3891668	NM_005664.4(MKRN3):c.482C>T (p.Pro161Leu)	MKRN3	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 2 · 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
MKRN3	Strong	Autosomal dominant	precocious puberty, central, 2	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MKRN3	Orphanet:650077	Genetic central precocious puberty in female
MKRN3	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
MKRN3	HGNC:7114	ENSG00000179455	Q13064	E3 ubiquitin-protein ligase makorin-3	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MKRN3	E3 ubiquitin-protein ligase makorin-3	E3 ubiquitin ligase catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.0

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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MKRN3	Transcription factor	no		Znf_CCCH, Znf_RING, Znf_RING/FYVE/PHD

Expression context

Cohort genes with no expression data: 0.

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

Breadth distribution (Bgee present_calls)

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

Top tissues across cohort

Tissue	Cohort genes
cortical plate	1
ganglionic eminence	1
male germ line stem cell (sensu Vertebrata) in testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MKRN3	163	broad	marker	ganglionic eminence, cortical plate, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MKRN3	1,494

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MKRN3	Q13064	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
protein polyubiquitination	1	115.4×	0.017	MKRN3
protein ubiquitination	1	41.4×	0.024	MKRN3

Therapeutics

Drug target analysis

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

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
MKRN3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
MKRN3	1	Binding:1

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

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	MKRN3

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
MKRN3	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: MKRN3