Rubinstein-Taybi syndrome due to 16p13.3 microdeletion

Summary

Rubinstein-Taybi syndrome due to 16p13.3 microdeletion (MONDO:0012519) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 3
• Phenotypes (HPO): 88

Clinical features

Signs & symptoms

Clinical features (HPO)

88 HPO clinical features (Orphanet curated; top 50 by frequency):

HPO ID	Term	Frequency
HP:0000750	Delayed speech and language development	Very frequent (80-99%)
HP:0001249	Intellectual disability	Very frequent (80-99%)
HP:0001999	Abnormal facial shape	Very frequent (80-99%)
HP:0000028	Cryptorchidism	Frequent (30-79%)
HP:0000079	Abnormality of the urinary system	Frequent (30-79%)
HP:0000189	Narrow palate	Frequent (30-79%)
HP:0000444	Convex nasal ridge	Frequent (30-79%)
HP:0000708	Atypical behavior	Frequent (30-79%)
HP:0000712	Emotional lability	Frequent (30-79%)
HP:0000722	Compulsive behaviors	Frequent (30-79%)
HP:0000733	Abnormal repetitive mannerisms	Frequent (30-79%)
HP:0000756	Agoraphobia	Frequent (30-79%)
HP:0001508	Failure to thrive	Frequent (30-79%)
HP:0001513	Obesity	Frequent (30-79%)
HP:0001627	Abnormal heart morphology	Frequent (30-79%)
HP:0002019	Constipation	Frequent (30-79%)
HP:0002020	Gastroesophageal reflux	Frequent (30-79%)
HP:0002205	Recurrent respiratory infections	Frequent (30-79%)
HP:0002353	EEG abnormality	Frequent (30-79%)
HP:0002750	Delayed skeletal maturation	Frequent (30-79%)
HP:0002870	Obstructive sleep apnea	Frequent (30-79%)
HP:0004322	Short stature	Frequent (30-79%)
HP:0005484	Secondary microcephaly	Frequent (30-79%)
HP:0007086	Social and occupational deterioration	Frequent (30-79%)
HP:0009765	Low hanging columella	Frequent (30-79%)
HP:0009834	Abnormal proximal phalanx morphology of the hand	Frequent (30-79%)
HP:0009836	Broad distal phalanx of finger	Frequent (30-79%)
HP:0010055	Broad hallux	Frequent (30-79%)
HP:0011087	Talon cusp	Frequent (30-79%)
HP:0011304	Broad thumb	Frequent (30-79%)
HP:0012760	Reduced social responsiveness	Frequent (30-79%)
HP:0025269	Panic attack	Frequent (30-79%)
HP:0100710	Impulsivity	Frequent (30-79%)
HP:0100852	Abnormal fear/anxiety-related behavior	Frequent (30-79%)
HP:0000010	Recurrent urinary tract infections	Occasional (5-29%)
HP:0000047	Hypospadias	Occasional (5-29%)
HP:0000076	Vesicoureteral reflux	Occasional (5-29%)
HP:0000126	Hydronephrosis	Occasional (5-29%)
HP:0000388	Otitis media	Occasional (5-29%)
HP:0000405	Conductive hearing impairment	Occasional (5-29%)
HP:0000407	Sensorineural hearing impairment	Occasional (5-29%)
HP:0000488	Retinopathy	Occasional (5-29%)
HP:0000501	Glaucoma	Occasional (5-29%)
HP:0000539	Abnormality of refraction	Occasional (5-29%)
HP:0000668	Hypodontia	Occasional (5-29%)
HP:0000670	Carious teeth	Occasional (5-29%)
HP:0000678	Dental crowding	Occasional (5-29%)
HP:0000689	Dental malocclusion	Occasional (5-29%)
HP:0000718	Aggressive behavior	Occasional (5-29%)
HP:0000752	Hyperactivity	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Rubinstein-Taybi syndrome due to 16p13.3 microdeletion
Mondo ID	MONDO:0012519
OMIM	610543
Orphanet	353281
UMLS	C1864648
MedGen	350477
GARD	0010754
Is cancer (heuristic)	no

Also known as: 16p13.3 deletion syndrome

Data availability: 3 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 › chromosome 16p13.3 deletion syndrome › Rubinstein-Taybi syndrome due to 16p13.3 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

3 retrieved; paginated sample, class counts are floors:

2 not provided, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
4795131	NC_000002.12:g.(238325285_239352719)del		Pathogenic	criteria provided, single submitter
684459	Single allele	ABCC1	not provided	no classification provided
973048	GRCh37/hg19 16p13.11(chr16:15154115-16276115)	ABCC1	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

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
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)
ABCC1	Multidrug resistance-associated protein 1	Mediates export of organic anions and drugs from the cytoplasm.

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
Transporter	1	77.8×	0.013

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ABCC1	Transporter	yes	7.6.2.2	ABC_transporter-like_ATP-bd, AAA+_ATPase, MRP

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
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
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

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ABCC1	P33527	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 24. 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
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 1 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	16852.0×	9e-04	ABCC1
cyclic nucleotide transport	1	16852.0×	9e-04	ABCC1
sphingolipid translocation	1	16852.0×	9e-04	ABCC1
intracellular nitrogen homeostasis	1	16852.0×	9e-04	ABCC1
pigment accumulation	1	8426.0×	0.001	ABCC1
granuloma formation	1	5617.3×	0.002	ABCC1
glutathione transmembrane transport	1	4213.0×	0.002	ABCC1
neural tissue regeneration	1	4213.0×	0.002	ABCC1
glucocorticoid metabolic process	1	2808.7×	0.002	ABCC1
amygdala development	1	2808.7×	0.002	ABCC1
NK T cell activation	1	2808.7×	0.002	ABCC1
carboxylic acid transmembrane transport	1	2808.7×	0.002	ABCC1
xenobiotic transport across blood-brain barrier	1	2808.7×	0.002	ABCC1
leukotriene transport	1	2407.4×	0.002	ABCC1
lymphocyte migration	1	2407.4×	0.002	ABCC1
cobalamin transport	1	1872.4×	0.002	ABCC1
response to fluid shear stress	1	1872.4×	0.002	ABCC1
export across plasma membrane	1	1685.2×	0.002	ABCC1
heme catabolic process	1	1532.0×	0.002	ABCC1
amyloid-beta metabolic process	1	1532.0×	0.002	ABCC1
hydrogen peroxide biosynthetic process	1	1404.3×	0.002	ABCC1
endothelium development	1	1296.3×	0.002	ABCC1
leukotriene metabolic process	1	1296.3×	0.002	ABCC1
leukotriene biosynthetic process	1	1296.3×	0.002	ABCC1
endothelial cell apoptotic process	1	1296.3×	0.002	ABCC1
transepithelial transport	1	1203.7×	0.002	ABCC1
inflammatory response to antigenic stimulus	1	936.2×	0.002	ABCC1
amyloid-beta clearance	1	936.2×	0.002	ABCC1
xenobiotic transport	1	842.6×	0.002	ABCC1
macrophage activation	1	702.2×	0.003	ABCC1

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · 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).

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

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: 1; 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	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.