16p13.11 microdeletion syndrome

Summary

16p13.11 microdeletion syndrome (MONDO:0016836) is a disease with 2 cohort genes and 1 clinical trial.

At a glance

• Prevalence: <1 / 1 000 000 (Europe) [Orphanet-validated]
• Cohort genes: 2
• ClinVar variants: 5
• Phenotypes (HPO): 40
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	<1 / 1 000 000		Europe	Validated
Prevalence at birth	1-9 / 100 000	7	Worldwide	Not yet validated

Signs & symptoms

Clinical features (HPO)

40 HPO clinical features (Orphanet curated; top 40 by frequency):

HPO ID	Term	Frequency
HP:0000750	Delayed speech and language development	Very frequent (80-99%)
HP:0001263	Global developmental delay	Very frequent (80-99%)
HP:0001328	Specific learning disability	Very frequent (80-99%)
HP:0010864	Intellectual disability, severe	Very frequent (80-99%)
HP:0000252	Microcephaly	Frequent (30-79%)
HP:0000463	Anteverted nares	Frequent (30-79%)
HP:0002197	Generalized-onset seizure	Frequent (30-79%)
HP:0003196	Short nose	Frequent (30-79%)
HP:0004322	Short stature	Frequent (30-79%)
HP:0000028	Cryptorchidism	Occasional (5-29%)
HP:0000154	Wide mouth	Occasional (5-29%)
HP:0000175	Cleft palate	Occasional (5-29%)
HP:0000204	Cleft upper lip	Occasional (5-29%)
HP:0000219	Thin upper lip vermilion	Occasional (5-29%)
HP:0000319	Smooth philtrum	Occasional (5-29%)
HP:0000369	Low-set ears	Occasional (5-29%)
HP:0000384	Preauricular skin tag	Occasional (5-29%)
HP:0000407	Sensorineural hearing impairment	Occasional (5-29%)
HP:0000413	Atresia of the external auditory canal	Occasional (5-29%)
HP:0000494	Downslanted palpebral fissures	Occasional (5-29%)
HP:0000722	Compulsive behaviors	Occasional (5-29%)
HP:0000767	Pectus excavatum	Occasional (5-29%)
HP:0001274	Agenesis of corpus callosum	Occasional (5-29%)
HP:0001276	Hypertonia	Occasional (5-29%)
HP:0001360	Holoprosencephaly	Occasional (5-29%)
HP:0001629	Ventricular septal defect	Occasional (5-29%)
HP:0001631	Atrial septal defect	Occasional (5-29%)
HP:0001762	Talipes equinovarus	Occasional (5-29%)
HP:0002020	Gastroesophageal reflux	Occasional (5-29%)
HP:0002119	Ventriculomegaly	Occasional (5-29%)
HP:0002263	Exaggerated cupid’s bow	Occasional (5-29%)
HP:0002269	Abnormality of neuronal migration	Occasional (5-29%)
HP:0002353	EEG abnormality	Occasional (5-29%)
HP:0005280	Depressed nasal bridge	Occasional (5-29%)
HP:0009914	Cyclopia	Occasional (5-29%)
HP:0010508	Metatarsus valgus	Occasional (5-29%)
HP:0011968	Feeding difficulties	Occasional (5-29%)
HP:0100490	Camptodactyly of finger	Occasional (5-29%)
HP:0100716	Self-injurious behavior	Occasional (5-29%)
HP:0100753	Schizophrenia	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	16p13.11 microdeletion syndrome
Mondo ID	MONDO:0016836
Orphanet	261236
SNOMED CT	719577000
UMLS	C4304596
MedGen	930265
GARD	0020774
Is cancer (heuristic)	no

Also known as: 16p13.11 recurrent microdeletion (neurocognitive disorder susceptibility locus) · Del(16)(p13.11) · monosomy 16p13.11

Data availability: 5 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 deletion › partial deletion of chromosome 16 › partial deletion of the short arm of chromosome 16 › 16p13.11 microdeletion 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, chromosome 16p12.2-p11.2 deletion 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

5 retrieved; paginated sample, class counts are floors:

4 pathogenic, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
1703612	GRCh37/hg19 16p13.11(chr16:14897625-16494783)	ABCC1	Pathogenic	no assertion criteria provided
2580341	GRCh37/hg19 16p13.11(chr16:14853752-16666672)x1	ABCC1	Pathogenic	criteria provided, single submitter
2580346	GRCh37/hg19 16p13.11-12.3(chr16:15489453-18321582)x1	ABCC1	Pathogenic	criteria provided, single submitter
4819207	Single allele	LOC125146420	Pathogenic	criteria provided, single submitter
973045	GRCh37/hg19 16p13.11-12.3(chr16:15494600-18141051)x1	MARF1	not provided	no classification provided

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
ABCC1	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA

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
MARF1	HGNC:29562	ENSG00000166783	Q9Y4F3	Meiosis regulator and mRNA stability factor 1	clinvar
ABCC1	HGNC:51	ENSG00000103222	P33527	Multidrug resistance-associated protein 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MARF1	Meiosis regulator and mRNA stability factor 1	Essential regulator of oogenesis required for female meiotic progression to repress transposable elements and preventing their mobilization, which is essential for the germline integrity.
ABCC1	Multidrug resistance-associated protein 1	Mediates export of organic anions and drugs from the cytoplasm.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MARF1	Other/Unknown	no		RRM_dom, Nucleotide-bd_a/b_plait_sf, NYN
ABCC1	Transporter	yes	7.6.2.2	ABC_transporter-like_ATP-bd, AAA+_ATPase, MRP

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
blood	1
bone marrow cell	1
colonic epithelium	1
lower esophagus	1
lower esophagus mucosa	1
lower esophagus muscularis layer	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MARF1	134	ubiquitous	marker	colonic epithelium, bone marrow cell, blood
ABCC1	134	ubiquitous	marker	lower esophagus mucosa, lower esophagus, lower esophagus muscularis layer

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ABCC1	3,018
MARF1	1,655

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ABCC1	P33527	5
MARF1	Q9Y4F3	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 24. Enrichment computed across 2 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
Metabolism of porphyrins	1	1427.5×	0.006	ABCC1
Transport of RCbl within the body	1	1427.5×	0.006	ABCC1
NFE2L2 regulating MDR associated enzymes	1	1427.5×	0.006	ABCC1
Heme degradation	1	815.7×	0.006	ABCC1
Cobalamin (Cbl, vitamin B12) transport and metabolism	1	634.4×	0.006	ABCC1
Synthesis of Leukotrienes (LT) and Eoxins (EX)	1	571.0×	0.006	ABCC1
Arachidonate metabolism	1	571.0×	0.006	ABCC1
Paracetamol ADME	1	423.0×	0.007	ABCC1
Nuclear events mediated by NFE2L2	1	335.9×	0.008	ABCC1
Sphingolipid de novo biosynthesis	1	285.5×	0.008	ABCC1
Drug ADME	1	228.4×	0.010	ABCC1
Cytoprotection by HMOX1	1	184.2×	0.010	ABCC1
Metabolism of water-soluble vitamins and cofactors	1	181.3×	0.010	ABCC1
Sphingolipid metabolism	1	167.9×	0.010	ABCC1
Cellular response to chemical stress	1	142.8×	0.011	ABCC1
Fatty acid metabolism	1	131.3×	0.011	ABCC1
ABC-family protein mediated transport	1	121.5×	0.011	ABCC1
KEAP1-NFE2L2 pathway	1	120.2×	0.011	ABCC1
Metabolism of vitamins and cofactors	1	116.5×	0.011	ABCC1
Cellular responses to stress	1	36.8×	0.033	ABCC1
Metabolism of lipids	1	31.6×	0.035	ABCC1
Cellular responses to stimuli	1	31.5×	0.035	ABCC1
Transport of small molecules	1	25.1×	0.041	ABCC1
Metabolism	1	11.6×	0.086	ABCC1

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
antigen processing and presentation of lipid antigen via MHC class Ib	1	8426.0×	0.002	ABCC1
cyclic nucleotide transport	1	8426.0×	0.002	ABCC1
sphingolipid translocation	1	8426.0×	0.002	ABCC1
intracellular nitrogen homeostasis	1	8426.0×	0.002	ABCC1
pigment accumulation	1	4213.0×	0.003	ABCC1
granuloma formation	1	2808.7×	0.003	ABCC1
glutathione transmembrane transport	1	2106.5×	0.003	ABCC1
neural tissue regeneration	1	2106.5×	0.003	ABCC1
glucocorticoid metabolic process	1	1404.3×	0.003	ABCC1
amygdala development	1	1404.3×	0.003	ABCC1
NK T cell activation	1	1404.3×	0.003	ABCC1
carboxylic acid transmembrane transport	1	1404.3×	0.003	ABCC1
xenobiotic transport across blood-brain barrier	1	1404.3×	0.003	ABCC1
leukotriene transport	1	1203.7×	0.003	ABCC1
lymphocyte migration	1	1203.7×	0.003	ABCC1
cobalamin transport	1	936.2×	0.004	ABCC1
response to fluid shear stress	1	936.2×	0.004	ABCC1
female meiotic nuclear division	1	842.6×	0.004	MARF1
export across plasma membrane	1	842.6×	0.004	ABCC1
heme catabolic process	1	766.0×	0.004	ABCC1
amyloid-beta metabolic process	1	766.0×	0.004	ABCC1
hydrogen peroxide biosynthetic process	1	702.2×	0.004	ABCC1
endothelium development	1	648.1×	0.004	ABCC1
leukotriene metabolic process	1	648.1×	0.004	ABCC1
leukotriene biosynthetic process	1	648.1×	0.004	ABCC1
endothelial cell apoptotic process	1	648.1×	0.004	ABCC1
transepithelial transport	1	601.9×	0.004	ABCC1
inflammatory response to antigenic stimulus	1	468.1×	0.005	ABCC1
amyloid-beta clearance	1	468.1×	0.005	ABCC1
xenobiotic transport	1	421.3×	0.005	ABCC1

Therapeutics

Drug target analysis

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

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

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
ABCC1	RIMONABANT

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ABCC1	23	4
MARF1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
RIMONABANT	4	ABCC1
VINBLASTINE	4	ABCC1
CYCLOSPORINE	4	ABCC1
DAUNORUBICIN	4	ABCC1
ETRAVIRINE	4	ABCC1
BENZBROMARONE	4	ABCC1
ESTRONE SULFURIC ACID	4	ABCC1
DOXORUBICIN	4	ABCC1
MITOXANTRONE	4	ABCC1
INDOMETHACIN	4	ABCC1
IVERMECTIN	4	ABCC1
VERAPAMIL	4	ABCC1
VINCRISTINE	4	ABCC1
VALSPODAR	3	ABCC1
TARIQUIDAR	3	ABCC1
QUERCETIN	3	ABCC1
DEXVERAPAMIL	2	ABCC1
VEDROPREVIR	2	ABCC1
VERLUKAST	2	ABCC1
BIRICODAR	2	ABCC1
CLESACOSTAT	2	ABCC1
BMS-754807	2	ABCC1
KAEMPFEROL	1	ABCC1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
ABCC1	459	Binding:270, Functional:166, ADMET:23

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ABCC1	7.6.2.2, 7.6.2.3	ABC-type xenobiotic transporter, ABC-type glutathione-S-conjugate transporter

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
ABCC1	459

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

23 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)
RIMONABANT	4	ABCC1
VINBLASTINE	4	ABCC1
CYCLOSPORINE	4	ABCC1
DAUNORUBICIN	4	ABCC1
ETRAVIRINE	4	ABCC1
BENZBROMARONE	4	ABCC1
ESTRONE SULFURIC ACID	4	ABCC1
DOXORUBICIN	4	ABCC1
MITOXANTRONE	4	ABCC1
INDOMETHACIN	4	ABCC1
IVERMECTIN	4	ABCC1
VERAPAMIL	4	ABCC1
VINCRISTINE	4	ABCC1
VALSPODAR	3	ABCC1
TARIQUIDAR	3	ABCC1
QUERCETIN	3	ABCC1
DEXVERAPAMIL	2	ABCC1
VEDROPREVIR	2	ABCC1
VERLUKAST	2	ABCC1
BIRICODAR	2	ABCC1
CLESACOSTAT	2	ABCC1
BMS-754807	2	ABCC1
KAEMPFEROL	1	ABCC1

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	ABCC1
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	MARF1

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)
MARF1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01238250	Not specified	RECRUITING	Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight