16p11.2p12.2 microduplication syndrome

Summary

16p11.2p12.2 microduplication syndrome (MONDO:0016834) 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): 14

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		7	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

14 HPO clinical features (Orphanet curated; top 14 by frequency):

HPO ID	Term	Frequency
HP:0000252	Microcephaly	Very frequent (80-99%)
HP:0000047	Hypospadias	Occasional (5-29%)
HP:0000175	Cleft palate	Occasional (5-29%)
HP:0000545	Myopia	Occasional (5-29%)
HP:0000709	Psychosis	Occasional (5-29%)
HP:0000717	Autism	Occasional (5-29%)
HP:0000767	Pectus excavatum	Occasional (5-29%)
HP:0001249	Intellectual disability	Occasional (5-29%)
HP:0001250	Seizure	Occasional (5-29%)
HP:0001263	Global developmental delay	Occasional (5-29%)
HP:0001332	Dystonia	Occasional (5-29%)
HP:0002463	Language impairment	Occasional (5-29%)
HP:0007018	Attention deficit hyperactivity disorder	Occasional (5-29%)
HP:0100753	Schizophrenia	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	16p11.2p12.2 microduplication syndrome
Mondo ID	MONDO:0016834
Orphanet	261204
SNOMED CT	733518000
UMLS	C4518821
MedGen	1377902
GARD	0020772
Is cancer (heuristic)	no

Also known as: 16p11.2 microduplication syndrome · 16p11.2-p12.2 microduplication syndrome · dup(16)(p11.2p12.2) · trisomy 16p11.2p12.2

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 16 › partial duplication of the short arm of chromosome 16 › 16p11.2p12.2 microduplication syndrome

Related subtypes (5): congenital cataracts-facial dysmorphism-neuropathy syndrome, chromosome 16p13.3 duplication syndrome, chromosome 16p11.2 duplication syndrome, 16p13.11 microduplication syndrome, 16p12.1p12.3 triplication 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
1330191	GRCh37/hg19 16p11.2(chr16:29675000-30200058)x3	ALDOA	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ALDOA	Orphanet:57	Glycogen storage disease due to aldolase A deficiency

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
ALDOA	HGNC:414	ENSG00000149925	P04075	Fructose-bisphosphate aldolase A	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ALDOA	Fructose-bisphosphate aldolase A	Catalyzes the reversible conversion of beta-D-fructose 1,6-bisphosphate (FBP) into two triose phosphate and plays a key role in glycolysis and gluconeogenesis.

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ALDOA	Enzyme (other)	yes	4.1.2.13	FBA_I, Aldolase_TIM, Aldolase_I_AS

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
gastrocnemius	1
hindlimb stylopod muscle	1
skeletal muscle tissue	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ALDOA	134	ubiquitous	marker	skeletal muscle tissue, gastrocnemius, hindlimb stylopod muscle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ALDOA	3,591

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ALDOA	P04075	8

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 12. 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
Glucose metabolism	1	878.5×	0.014	ALDOA
Gluconeogenesis	1	439.2×	0.014	ALDOA
Glycolysis	1	285.5×	0.014	ALDOA
Response to elevated platelet cytosolic Ca2+	1	163.1×	0.018	ALDOA
Metabolism of carbohydrates and carbohydrate derivatives	1	120.2×	0.019	ALDOA
Platelet activation, signaling and aggregation	1	105.7×	0.019	ALDOA
Platelet degranulation	1	87.8×	0.020	ALDOA
Hemostasis	1	36.0×	0.042	ALDOA
Innate Immune System	1	25.5×	0.052	ALDOA
Neutrophil degranulation	1	23.1×	0.052	ALDOA
Immune System	1	13.0×	0.084	ALDOA
Metabolism	1	11.6×	0.086	ALDOA

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
fructose 1,6-bisphosphate metabolic process	1	2106.5×	0.003	ALDOA
fructose metabolic process	1	1685.2×	0.003	ALDOA
ATP biosynthetic process	1	991.3×	0.003	ALDOA
striated muscle contraction	1	842.6×	0.003	ALDOA
canonical glycolysis	1	702.2×	0.003	ALDOA
muscle cell cellular homeostasis	1	648.1×	0.003	ALDOA
binding of sperm to zona pellucida	1	421.3×	0.004	ALDOA
glycolytic process	1	383.0×	0.004	ALDOA
positive regulation of insulin secretion involved in cellular response to glucose stimulus	1	374.5×	0.004	ALDOA
protein homotetramerization	1	237.3×	0.005	ALDOA
regulation of cell shape	1	123.0×	0.008	ALDOA
actin filament organization	1	118.7×	0.008	ALDOA

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · 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
ALDOA	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	ALDOA

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
ALDOA	9	Binding:9

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ALDOA	4.1.2.13	fructose-bisphosphate aldolase

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

1 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)
MOLIBRESIB	2	ALDOA

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	ALDOA
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.