Chromosome 16p13.3 duplication syndrome

Summary

Chromosome 16p13.3 duplication syndrome (MONDO:0013273) is a disease with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 2
• ClinVar variants: 2

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		27	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	chromosome 16p13.3 duplication syndrome
Mondo ID	MONDO:0013273
OMIM	613458
Orphanet	96078
DOID	DOID:0060431
SNOMED CT	733473000
UMLS	C3150708
MedGen	462058
GARD	0010755
Is cancer (heuristic)	no

Also known as: 16p13.3 duplication · 16p13.3 microduplication syndrome · chromosome 16p13.3 duplication · chromosome 16p13.3 duplication syndrome · chromosome 16p13.3 duplication syndrome, isolated cases · distal duplication 16p · distal trisomy 16p · dup(16)(p13.3) · interstitial 16p13.3 duplication · telomeric duplication 16p · trisomy 16pter

Data availability: 2 ClinVar variants.

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 › chromosome 16p13.3 duplication syndrome

Related subtypes (5): congenital cataracts-facial dysmorphism-neuropathy syndrome, chromosome 16p11.2 duplication syndrome, 16p11.2p12.2 microduplication 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

2 retrieved; paginated sample, class counts are floors:

1 likely pathogenic, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
625723	GRCh37/hg19 16p13.3(chr16:109978-4316797)	ABCA3	Pathogenic	criteria provided, single submitter
1703617	GRCh37/hg19 16p13.3-13.2(chr16:5381584-10067952)	ABAT	Likely pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

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

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ABAT	Orphanet:2066	Gamma-aminobutyric acid transaminase deficiency
ABCA3	Orphanet:2032	Idiopathic pulmonary fibrosis
ABCA3	Orphanet:217563	Neonatal acute respiratory distress syndrome
ABCA3	Orphanet:440402	Interstitial lung disease due to ABCA3 deficiency
ABCA3	Orphanet:685082	Pediatric acute respiratory distress syndrome

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ABAT	HGNC:23	ENSG00000183044	P80404	4-aminobutyrate aminotransferase, mitochondrial	clinvar
ABCA3	HGNC:33	ENSG00000167972	Q99758	Phospholipid-transporting ATPase ABCA3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ABAT	4-aminobutyrate aminotransferase, mitochondrial	Catalyzes the conversion of gamma-aminobutyrate and L-beta-aminoisobutyrate to succinate semialdehyde and methylmalonate semialdehyde, respectively.
ABCA3	Phospholipid-transporting ATPase ABCA3	Catalyzes the ATP-dependent transport of phospholipids such as phosphatidylcholine and phosphoglycerol from the cytoplasm into the lumen side of lamellar bodies, in turn participates in the lamellar bodies biogenesis and homeostasis of pul…

Protein-family classification

Druggable: 2 · 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
Transporter	1	38.9×	0.051
Enzyme (other)	1	6.0×	0.160

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ABAT	Enzyme (other)	yes	2.6.1.19	4NH2But_aminotransferase_euk, Aminotrans_3, PyrdxlP-dep_Trfase_major
ABCA3	Transporter	yes		ABC_transporter-like_ATP-bd, AAA+_ATPase, ABC2_TM

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
Brodmann (1909) area 23	1
endothelial cell	1
middle temporal gyrus	1
lower lobe of lung	1
upper lobe of left lung	1
upper lobe of lung	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ABAT	289	ubiquitous	marker	Brodmann (1909) area 23, endothelial cell, middle temporal gyrus
ABCA3	222	ubiquitous	marker	lower lobe of lung, upper lobe of lung, upper lobe of left lung

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ABAT	1,711
ABCA3	1,436

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ABCA3	Q99758	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ABAT	P80404	93.91

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 13. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective ABCA3 causes SMDP3	1	5710.0×	0.001	ABCA3
Degradation of GABA	1	2855.0×	0.002	ABAT
Diseases associated with surfactant metabolism	1	1427.5×	0.002	ABCA3
ABC transporters in lipid homeostasis	1	300.5×	0.009	ABCA3
ABC transporter disorders	1	219.6×	0.010	ABCA3
Surfactant metabolism	1	184.2×	0.010	ABCA3
Disorders of transmembrane transporters	1	69.6×	0.023	ABCA3
ABC-family protein mediated transport	1	60.7×	0.024	ABCA3
Diseases of metabolism	1	40.2×	0.032	ABCA3
Transport of small molecules	1	12.6×	0.092	ABCA3
Disease	1	6.5×	0.155	ABCA3
Metabolism of proteins	1	6.2×	0.155	ABCA3

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 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 protein homooligomerization	1	8426.0×	0.001	ABCA3
copulation	1	4213.0×	0.001	ABAT
obsolete GABA metabolic process	1	4213.0×	0.001	ABAT
GABA catabolic process	1	4213.0×	0.001	ABAT
negative regulation of gamma-aminobutyric acid secretion	1	4213.0×	0.001	ABAT
regulation of phosphatidylcholine metabolic process	1	4213.0×	0.001	ABCA3
positive regulation of prolactin secretion	1	4213.0×	0.001	ABAT
positive regulation of aspartate secretion	1	4213.0×	0.001	ABAT
response to xenobiotic stimulus	2	69.1×	0.001	ABAT, ABCA3
xenobiotic export from cell	1	2808.7×	0.001	ABCA3
negative regulation of dopamine secretion	1	2106.5×	0.002	ABAT
positive regulation of dopamine metabolic process	1	2106.5×	0.002	ABAT
positive regulation of phospholipid efflux	1	2106.5×	0.002	ABCA3
positive regulation of heat generation	1	1685.2×	0.002	ABAT
regulation of lipid biosynthetic process	1	1404.3×	0.002	ABCA3
organelle assembly	1	1404.3×	0.002	ABCA3
positive regulation of inhibitory postsynaptic potential	1	1404.3×	0.002	ABAT
positive regulation of phospholipid transport	1	1203.7×	0.002	ABCA3
GABA biosynthetic process	1	1053.2×	0.002	ABAT
positive regulation of uterine smooth muscle contraction	1	1053.2×	0.002	ABAT
phosphatidylglycerol metabolic process	1	702.2×	0.003	ABCA3
nervous system process	1	601.9×	0.003	ABAT
phospholipid homeostasis	1	495.6×	0.004	ABCA3
xenobiotic transmembrane transport	1	468.1×	0.004	ABCA3
response to iron ion	1	468.1×	0.004	ABAT
xenobiotic transport	1	421.3×	0.004	ABCA3
surfactant homeostasis	1	401.2×	0.004	ABCA3
phosphatidylcholine metabolic process	1	401.2×	0.004	ABCA3
phospholipid transport	1	351.1×	0.004	ABCA3
exploration behavior	1	324.1×	0.004	ABAT

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ABAT	0	0
ABCA3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
ABAT	41	Binding:41

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ABAT	2.6.1.19	4-aminobutyrate-2-oxoglutarate transaminase

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	ABCA3
D	Druggable family + AlphaFold only, no drug	1	ABAT
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ABAT	41	—
ABCA3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.