Chromosome 16p12.2-p11.2 deletion syndrome

Summary

Chromosome 16p12.2-p11.2 deletion syndrome (MONDO:0013320) 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): 43

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		8	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

43 HPO clinical features (Orphanet curated; top 43 by frequency):

HPO ID	Term	Frequency
HP:0000389	Chronic otitis media	Very frequent (80-99%)
HP:0000494	Downslanted palpebral fissures	Very frequent (80-99%)
HP:0001263	Global developmental delay	Very frequent (80-99%)
HP:0001511	Intrauterine growth retardation	Very frequent (80-99%)
HP:0002020	Gastroesophageal reflux	Very frequent (80-99%)
HP:0002342	Intellectual disability, moderate	Very frequent (80-99%)
HP:0011968	Feeding difficulties	Very frequent (80-99%)
HP:0000194	Open mouth	Frequent (30-79%)
HP:0000286	Epicanthus	Frequent (30-79%)
HP:0000308	Microretrognathia	Frequent (30-79%)
HP:0000369	Low-set ears	Frequent (30-79%)
HP:0000377	Abnormal pinna morphology	Frequent (30-79%)
HP:0000490	Deeply set eye	Frequent (30-79%)
HP:0000581	Blepharophimosis	Frequent (30-79%)
HP:0000750	Delayed speech and language development	Frequent (30-79%)
HP:0000752	Hyperactivity	Frequent (30-79%)
HP:0001252	Hypotonia	Frequent (30-79%)
HP:0001770	Toe syndactyly	Frequent (30-79%)
HP:0002007	Frontal bossing	Frequent (30-79%)
HP:0004322	Short stature	Frequent (30-79%)
HP:0007328	Impaired pain sensation	Frequent (30-79%)
HP:0007565	Multiple cafe-au-lait spots	Frequent (30-79%)
HP:0007598	Bilateral single transverse palmar creases	Frequent (30-79%)
HP:0012368	Flat face	Frequent (30-79%)
HP:0100490	Camptodactyly of finger	Frequent (30-79%)
HP:0000202	Orofacial cleft	Occasional (5-29%)
HP:0000276	Long face	Occasional (5-29%)
HP:0000348	High forehead	Occasional (5-29%)
HP:0000365	Hearing impairment	Occasional (5-29%)
HP:0000414	Bulbous nose	Occasional (5-29%)
HP:0000463	Anteverted nares	Occasional (5-29%)
HP:0000486	Strabismus	Occasional (5-29%)
HP:0000601	Hypotelorism	Occasional (5-29%)
HP:0002360	Sleep abnormality	Occasional (5-29%)
HP:0003189	Long nose	Occasional (5-29%)
HP:0003196	Short nose	Occasional (5-29%)
HP:0004279	Short palm	Occasional (5-29%)
HP:0005180	Tricuspid regurgitation	Occasional (5-29%)
HP:0005285	Absent nasal bridge	Occasional (5-29%)
HP:0009623	Proximal placement of thumb	Occasional (5-29%)
HP:0010535	Sleep apnea	Occasional (5-29%)
HP:0011675	Arrhythmia	Occasional (5-29%)
HP:0100033	Tics	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	chromosome 16p12.2-p11.2 deletion syndrome
Mondo ID	MONDO:0013320
OMIM	613604
Orphanet	261211
DOID	DOID:0060400
SNOMED CT	719576009
UMLS	C3150858
MedGen	462208
GARD	0017243
Is cancer (heuristic)	no

Also known as: 16p11.2-p12.2 microdeletion syndrome · 16p11.2p12.2 microdeletion syndrome · chromosome 16p12.2-p11.2 deletion syndrome, isolated cases · Del(16)(p11.2p12.2) · monosomy 16p11.2-p12.2 · monosomy 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 deletion › partial deletion of chromosome 16 › partial deletion of the short arm of chromosome 16 › chromosome 16p12.2-p11.2 deletion syndrome

Related subtypes (8): chromosome 16p12.1 deletion syndrome, 520kb, alpha thalassemia-intellectual disability syndrome type 1, autosomal dominant polycystic kidney disease type 1 with tuberous sclerosis, proximal 16p11.2 microdeletion syndrome, distal 16p11.2 microdeletion syndrome, 16p13.11 microdeletion syndrome, chromosome 16p13.3 deletion syndrome, Hao-Fountain syndrome due to 16p13.2 microdeletion

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
2573121	GRCh37/hg19 16p12.2-11.2(chr16:21475039-29043958)x1	APOBR	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
APOBR	HGNC:24087	ENSG00000184730	Q0VD83	Apolipoprotein B receptor	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
APOBR	Apolipoprotein B receptor	Macrophage receptor that binds to the apolipoprotein B48 (APOB) of dietary triglyceride (TG)-rich lipoproteins (TRL) or to a like domain of APOB in hypertriglyceridemic very low density lipoprotein (HTG-VLDL).

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)
APOBR	Other/Unknown	no		ApolipoprotB_rcpt

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
granulocyte	1
monocyte	1
mononuclear cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
APOBR	160	broad	marker	monocyte, mononuclear cell, granulocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
APOBR	1,258

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
APOBR	Q0VD83	41.14

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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
VLDL clearance	1	1903.3×	0.002	APOBR
Plasma lipoprotein clearance	1	475.8×	0.004	APOBR
Plasma lipoprotein assembly, remodeling, and clearance	1	228.4×	0.006	APOBR
Transport of small molecules	1	25.1×	0.040	APOBR

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
foam cell differentiation	1	8426.0×	5e-04	APOBR
triglyceride metabolic process	1	443.5×	0.005	APOBR
lipid transport	1	263.3×	0.005	APOBR
cholesterol metabolic process	1	195.9×	0.005	APOBR

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
APOBR	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	APOBR

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)
APOBR	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.