20p12.3 microdeletion syndrome

Summary

20p12.3 microdeletion syndrome (MONDO:0016841) 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): 23

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		3	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

23 HPO clinical features (Orphanet curated; top 23 by frequency):

HPO ID	Term	Frequency
HP:0000316	Hypertelorism	Very frequent (80-99%)
HP:0001263	Global developmental delay	Very frequent (80-99%)
HP:0000160	Narrow mouth	Frequent (30-79%)
HP:0000256	Macrocephaly	Frequent (30-79%)
HP:0000272	Malar flattening	Frequent (30-79%)
HP:0000286	Epicanthus	Frequent (30-79%)
HP:0000327	Hypoplasia of the maxilla	Frequent (30-79%)
HP:0000494	Downslanted palpebral fissures	Frequent (30-79%)
HP:0001716	Wolff-Parkinson-White syndrome	Frequent (30-79%)
HP:0004322	Short stature	Frequent (30-79%)
HP:0000293	Full cheeks	Occasional (5-29%)
HP:0000343	Long philtrum	Occasional (5-29%)
HP:0000391	Thickened helices	Occasional (5-29%)
HP:0000431	Wide nasal bridge	Occasional (5-29%)
HP:0000768	Pectus carinatum	Occasional (5-29%)
HP:0001250	Seizure	Occasional (5-29%)
HP:0001252	Hypotonia	Occasional (5-29%)
HP:0001631	Atrial septal defect	Occasional (5-29%)
HP:0002119	Ventriculomegaly	Occasional (5-29%)
HP:0005280	Depressed nasal bridge	Occasional (5-29%)
HP:0008551	Microtia	Occasional (5-29%)
HP:0010059	Broad hallux phalanx	Occasional (5-29%)
HP:0011304	Broad thumb	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	20p12.3 microdeletion syndrome
Mondo ID	MONDO:0016841
Orphanet	261295
SNOMED CT	719650004
UMLS	C4304539
MedGen	930208
GARD	0012492
Is cancer (heuristic)	no

Also known as: Del(20)(p12.3) · monosomy 20p12.3

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 deletion › partial deletion of chromosome 20 › partial monosomy of the short arm of chromosome 20 › 20p12.3 microdeletion syndrome

Related subtypes (2): Alagille syndrome due to 20p12 microdeletion, 20p13 microdeletion syndrome

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
1703638	GRCh37/hg19 20p13-12.2(chr20:3178539-11848383)	ADAM33	Pathogenic	no assertion criteria provided

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, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ADAM33	HGNC:15478	ENSG00000149451	Q9BZ11	Disintegrin and metalloproteinase domain-containing protein 33	clinvar

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
Protease	1	36.6×	0.027

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ADAM33	Protease	yes		EGF, Peptidase_M12B, Disintegrin_dom

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
body of uterus	1
endocervix	1
left uterine tube	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ADAM33	240	broad	marker	endocervix, body of uterus, left uterine tube

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ADAM33	988

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ADAM33	Q9BZ11	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. 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
Regulation of CDH11 function	1	1038.2×	0.003	ADAM33
Regulation of CDH11 Expression and Function	1	815.7×	0.003	ADAM33
Regulation of Homotypic Cell-Cell Adhesion	1	671.8×	0.003	ADAM33
Regulation of Expression and Function of Type II Classical Cadherins	1	671.8×	0.003	ADAM33
Adherens junctions interactions	1	248.3×	0.005	ADAM33
Cell-cell junction organization	1	248.3×	0.005	ADAM33
Cell junction organization	1	187.2×	0.006	ADAM33
Cell-Cell communication	1	137.6×	0.007	ADAM33

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
proteolysis	1	34.2×	0.029	ADAM33

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
ADAM33	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
ADAM33	2	Binding:2

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	1	ADAM33
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
ADAM33	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.