Trisomy 12p

Summary

Trisomy 12p (MONDO:0015723) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 1
• Phenotypes (HPO): 31

Clinical features

Epidemiology

Prevalence records

3 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		40	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated
Prevalence at birth	1-9 / 100 000	2	Worldwide	Not yet validated

Signs & symptoms

Clinical features (HPO)

31 HPO clinical features (Orphanet curated; top 31 by frequency):

HPO ID	Term	Frequency
HP:0000232	Everted lower lip vermilion	Very frequent (80-99%)
HP:0000262	Turricephaly	Very frequent (80-99%)
HP:0000272	Malar flattening	Very frequent (80-99%)
HP:0000286	Epicanthus	Very frequent (80-99%)
HP:0000293	Full cheeks	Very frequent (80-99%)
HP:0000316	Hypertelorism	Very frequent (80-99%)
HP:0000347	Micrognathia	Very frequent (80-99%)
HP:0000431	Wide nasal bridge	Very frequent (80-99%)
HP:0000470	Short neck	Very frequent (80-99%)
HP:0000474	Thickened nuchal skin fold	Very frequent (80-99%)
HP:0000574	Thick eyebrow	Very frequent (80-99%)
HP:0001176	Large hands	Very frequent (80-99%)
HP:0001249	Intellectual disability	Very frequent (80-99%)
HP:0001263	Global developmental delay	Very frequent (80-99%)
HP:0002714	Downturned corners of mouth	Very frequent (80-99%)
HP:0002916	Abnormality of chromosome segregation	Very frequent (80-99%)
HP:0003196	Short nose	Very frequent (80-99%)
HP:0004209	Clinodactyly of the 5th finger	Very frequent (80-99%)
HP:0009738	Abnormality of the antihelix	Very frequent (80-99%)
HP:0012368	Flat face	Very frequent (80-99%)
HP:0000369	Low-set ears	Frequent (30-79%)
HP:0000520	Proptosis	Frequent (30-79%)
HP:0002750	Delayed skeletal maturation	Frequent (30-79%)
HP:0004322	Short stature	Frequent (30-79%)
HP:0030680	Abnormal cardiovascular system morphology	Frequent (30-79%)
HP:0000079	Abnormality of the urinary system	Occasional (5-29%)
HP:0000175	Cleft palate	Occasional (5-29%)
HP:0002023	Anal atresia	Occasional (5-29%)
HP:0002558	Supernumerary nipple	Occasional (5-29%)
HP:0008053	Aplasia/Hypoplasia of the iris	Occasional (5-29%)
HP:0008056	Aplasia/Hypoplasia affecting the eye	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	trisomy 12p
Mondo ID	MONDO:0015723
MeSH	C538299
Orphanet	1699
UMLS	C0795845
MedGen	162880
GARD	0005305
Is cancer (heuristic)	no

Also known as: 12p duplication · 12p trisomy · chromosome 12p duplication · Duplication 12p · partial trisomy 12p · trisomy type 12p

Data availability: 1 ClinVar variant.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › chromosomal disorder › syndrome caused by partial chromosomal duplication › partial duplication of chromosome 12 › partial trisomy/tetrasomy of the short arm of chromosome 12 › trisomy 12p

Related subtypes (1): tetrasomy 12p

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

1 retrieved; paginated sample, class counts are floors:

1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2664871	GRCh38/hg38 1p36.33-35.1(chr1:99125-34026935)x3	A2ML1-AS2	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

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

Cohort genes → proteins

1 cohort genes, 0 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
A2ML1-AS2	HGNC:41523	ENSG00000256904		A2ML1 antisense RNA 2	clinvar

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
A2ML1-AS2	Other/Unknown	no

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
male germ line stem cell (sensu Vertebrata) in testis	1
skeletal muscle tissue	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
A2ML1-AS2	86		marker	male germ line stem cell (sensu Vertebrata) in testis, skeletal muscle tissue, ventricular zone

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
A2ML1-AS2	0

Structural data

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

Function

Pathway analysis

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

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
A2ML1-AS2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 0; 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	A2ML1-AS2

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)
A2ML1-AS2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.