Rubinstein-Taybi syndrome

Summary

Rubinstein-Taybi syndrome (MONDO:0019188) is a disease caused by variants in CREBBP and EP300, with 6 cohort genes and 4 clinical trials. Top therapeutic interventions include valproate sodium and lufenuron.

At a glance

• Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
• Causal genes: CREBBP (GenCC Definitive), EP300 (GenCC Definitive)
• Cohort genes: 6
• ClinVar variants: 1,631
• Phenotypes (HPO): 66
• Clinical trials: 4

Clinical features

Epidemiology

Prevalence records

4 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000		Europe	Validated
Prevalence at birth	1-9 / 1 000 000	0.7	Europe	Validated
Point prevalence	1-9 / 100 000		Netherlands	Validated
Prevalence at birth	1-9 / 1 000 000	0.9	Netherlands	Validated

Signs & symptoms

Clinical features (HPO)

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

HPO ID	Term	Frequency
HP:0000218	High palate	Very frequent (80-99%)
HP:0000316	Hypertelorism	Very frequent (80-99%)
HP:0000369	Low-set ears	Very frequent (80-99%)
HP:0000444	Convex nasal ridge	Very frequent (80-99%)
HP:0000494	Downslanted palpebral fissures	Very frequent (80-99%)
HP:0000506	Telecanthus	Very frequent (80-99%)
HP:0000750	Delayed speech and language development	Very frequent (80-99%)
HP:0001156	Brachydactyly	Very frequent (80-99%)
HP:0001249	Intellectual disability	Very frequent (80-99%)
HP:0001263	Global developmental delay	Very frequent (80-99%)
HP:0001382	Joint hypermobility	Very frequent (80-99%)
HP:0001531	Failure to thrive in infancy	Very frequent (80-99%)
HP:0004322	Short stature	Very frequent (80-99%)
HP:0008872	Feeding difficulties in infancy	Very frequent (80-99%)
HP:0010059	Broad hallux phalanx	Very frequent (80-99%)
HP:0011087	Talon cusp	Very frequent (80-99%)
HP:0011304	Broad thumb	Very frequent (80-99%)
HP:0000028	Cryptorchidism	Frequent (30-79%)
HP:0000119	Abnormality of the genitourinary system	Frequent (30-79%)
HP:0000164	Abnormality of the dentition	Frequent (30-79%)
HP:0000252	Microcephaly	Frequent (30-79%)
HP:0000286	Epicanthus	Frequent (30-79%)
HP:0000347	Micrognathia	Frequent (30-79%)
HP:0000431	Wide nasal bridge	Frequent (30-79%)
HP:0000486	Strabismus	Frequent (30-79%)
HP:0000501	Glaucoma	Frequent (30-79%)
HP:0000518	Cataract	Frequent (30-79%)
HP:0000579	Nasolacrimal duct obstruction	Frequent (30-79%)
HP:0000589	Coloboma	Frequent (30-79%)
HP:0000670	Carious teeth	Frequent (30-79%)
HP:0000708	Atypical behavior	Frequent (30-79%)
HP:0000729	Autistic behavior	Frequent (30-79%)
HP:0000737	Irritability	Frequent (30-79%)
HP:0000739	Anxiety	Frequent (30-79%)
HP:0001273	Abnormal corpus callosum morphology	Frequent (30-79%)
HP:0001627	Abnormal heart morphology	Frequent (30-79%)
HP:0002019	Constipation	Frequent (30-79%)
HP:0002093	Respiratory insufficiency	Frequent (30-79%)
HP:0002098	Respiratory distress	Frequent (30-79%)
HP:0002230	Generalized hirsutism	Frequent (30-79%)
HP:0002553	Highly arched eyebrow	Frequent (30-79%)
HP:0002719	Recurrent infections	Frequent (30-79%)
HP:0004209	Clinodactyly of the 5th finger	Frequent (30-79%)
HP:0006817	Aplasia/Hypoplasia of the cerebellar vermis	Frequent (30-79%)
HP:0007018	Attention deficit hyperactivity disorder	Frequent (30-79%)
HP:0009832	Abnormal distal phalanx morphology of finger	Frequent (30-79%)
HP:0010535	Sleep apnea	Frequent (30-79%)
HP:0030434	Pilomatrixoma	Frequent (30-79%)
HP:0030680	Abnormal cardiovascular system morphology	Frequent (30-79%)
HP:0031087	Absent pubertal growth spurt	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Rubinstein-Taybi syndrome
Mondo ID	MONDO:0019188
MeSH	D012415
OMIM	180849
Orphanet	783
DOID	DOID:1933
ICD-11	692585833
NCIT	C75466
SNOMED CT	45582004
UMLS	C0035934
MedGen	48517
GARD	0007593
MedDRA	10039281
NORD	1682
Is cancer (heuristic)	no

Also known as: Broad thumb-hallux syndrome · Broad thumbs-halluces syndrome · RSTS · Rubinstein-Taybi Syndrome

Data availability: 1,631 ClinVar variants · 2 GenCC gene-disease records · 6 cell lines.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › neurodevelopmental disorder › intellectual disability › syndromic intellectual disability › Rubinstein-Taybi syndrome

Related subtypes (16): Smith-Magenis syndrome, intellectual disability, Buenos-Aires type, intellectual disability, Wolff type, CK syndrome, AHDC1-related intellectual disability - obstructive sleep apnea - mild dysmorphism syndrome, 7p22.1 microduplication syndrome, 9p13 microdeletion syndrome, 3q27.3 microdeletion syndrome, 9q31.1q31.3 microdeletion syndrome, X-linked syndromic intellectual disability, 9q33.3q34.11 microdeletion syndrome, autosomal recessive syndromic intellectual disability, autosomal dominant syndromic intellectual disability, aplasia cutis-enamel dysplasia syndrome, 2p25.3 microduplication syndrome, dyneinopathy

Subtypes (3): Rubinstein-Taybi syndrome due to CREBBP mutations, Rubinstein-Taybi syndrome due to EP300 haploinsufficiency, chromosome 16p13.3 deletion 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

600 retrieved; paginated sample, class counts are floors:

233 likely benign, 119 uncertain significance, 105 conflicting classifications of pathogenicity, 49 benign/likely benign, 42 pathogenic, 42 benign, 6 likely pathogenic, 4 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1067259	NM_004380.3(CREBBP):c.4561-1G>A	CREBBP	Pathogenic	criteria provided, single submitter
1068836	NM_004380.3(CREBBP):c.2574dup (p.Pro859fs)	CREBBP	Pathogenic	criteria provided, single submitter
1069172	NC_000016.9:g.(?3827594)(3832947_?)del	CREBBP	Pathogenic	criteria provided, single submitter
1070983	NM_004380.3(CREBBP):c.3676del (p.Ala1226fs)	CREBBP	Pathogenic	criteria provided, single submitter
1071243	NM_004380.3(CREBBP):c.4679_4683del (p.Glu1560fs)	CREBBP	Pathogenic	criteria provided, multiple submitters, no conflicts
1071591	NM_004380.3(CREBBP):c.802G>T (p.Gly268Ter)	CREBBP	Pathogenic	criteria provided, single submitter
1073076	NC_000016.9:g.(?3900278)(3901030_?)del	CREBBP	Pathogenic	criteria provided, single submitter
1076909	NM_004380.3(CREBBP):c.4944dup (p.Ile1649fs)	CREBBP	Pathogenic	criteria provided, multiple submitters, no conflicts
1201902	NM_004380.3(CREBBP):c.4340C>T (p.Thr1447Ile)	CREBBP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1362462	NM_004380.3(CREBBP):c.581del (p.Gly194fs)	CREBBP	Pathogenic	criteria provided, single submitter
1388252	NM_004380.3(CREBBP):c.4480C>T (p.Pro1494Ser)	CREBBP	Pathogenic	criteria provided, single submitter
1397911	NM_004380.3(CREBBP):c.2881-13G>A	CREBBP	Pathogenic	criteria provided, multiple submitters, no conflicts
1417982	NM_004380.3(CREBBP):c.3425T>C (p.Leu1142Pro)	CREBBP	Pathogenic	criteria provided, single submitter
1451776	NM_004380.3(CREBBP):c.5782C>T (p.Gln1928Ter)	CREBBP	Pathogenic	criteria provided, single submitter
1452058	NM_004380.3(CREBBP):c.1618C>T (p.Gln540Ter)	CREBBP	Pathogenic	criteria provided, single submitter
1454532	NM_004380.3(CREBBP):c.5296_5297insCCCAC (p.Glu1766fs)	CREBBP	Pathogenic	criteria provided, single submitter
1455967	NC_000016.9:g.(?3841962)(3843647_?)del	CREBBP	Pathogenic	criteria provided, single submitter
1458408	NC_000016.9:g.(?3900278)(3929917_?)del	CREBBP	Pathogenic	criteria provided, single submitter
1459112	NM_004380.3(CREBBP):c.4561-2A>T	CREBBP	Pathogenic	criteria provided, single submitter
1460099	NC_000016.9:g.(?3817701)(3860800_?)del	CREBBP	Pathogenic	criteria provided, single submitter
1510381	NM_004380.3(CREBBP):c.3610-1G>A	CREBBP	Pathogenic	criteria provided, single submitter
158359	NM_004380.3(CREBBP):c.3779+1G>A	CREBBP	Pathogenic	criteria provided, multiple submitters, no conflicts
158361	NM_004380.3(CREBBP):c.3836+1G>A	CREBBP	Pathogenic	criteria provided, multiple submitters, no conflicts
158384	NM_004380.3(CREBBP):c.5036CCT[1] (p.Ser1680del)	CREBBP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
158391	NM_004380.3(CREBBP):c.5837del (p.Pro1946fs)	CREBBP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
158403	NM_004380.3(CREBBP):c.953C>A (p.Ser318Ter)	CREBBP	Pathogenic	criteria provided, multiple submitters, no conflicts
1994881	NM_004380.3(CREBBP):c.521del (p.Gly174fs)	CREBBP	Pathogenic	criteria provided, single submitter
2000642	NM_004380.3(CREBBP):c.4482del (p.Lys1495fs)	CREBBP	Pathogenic	criteria provided, single submitter
2002948	NM_004380.3(CREBBP):c.4232del (p.Gly1411fs)	CREBBP	Pathogenic	criteria provided, single submitter
2004442	NM_004380.3(CREBBP):c.2526_2529dup (p.Pro844fs)	CREBBP	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 13 · Orphanet: 5 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
CREBBP	Definitive	Autosomal dominant	Rubinstein-Taybi syndrome due to CREBBP mutations	6
EP300	Definitive	Autosomal dominant	Rubinstein-Taybi syndrome due to EP300 haploinsufficiency	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CREBBP	Orphanet:353277	Rubinstein-Taybi syndrome due to CREBBP mutations
CREBBP	Orphanet:353281	Rubinstein-Taybi syndrome due to 16p13.3 microdeletion
CREBBP	Orphanet:370026	Acute myeloid leukemia with t(8;16)(p11;p13) translocation
CREBBP	Orphanet:592574	Menke-Hennekam syndrome
EP300	Orphanet:353284	Rubinstein-Taybi syndrome due to EP300 haploinsufficiency

Cohort genes → proteins

6 cohort genes, 6 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	6

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CREBBP	HGNC:2348	ENSG00000005339	Q92793	CREB-binding protein	gencc,clinvar
EP300	HGNC:3373	ENSG00000100393	Q09472	Histone acetyltransferase p300	gencc,clinvar
HSP90B2P	HGNC:12099	ENSG00000259706	Q58FF3	Putative endoplasmin-like protein	clinvar
TRAP1	HGNC:16264	ENSG00000126602	Q12931	Heat shock protein 75 kDa, mitochondrial	clinvar
ADCY9	HGNC:240	ENSG00000162104	O60503	Adenylate cyclase type 9	clinvar
NLRC3	HGNC:29889	ENSG00000167984	Q7RTR2	NLR family CARD domain-containing protein 3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CREBBP	CREB-binding protein	Acetylates histones, giving a specific tag for transcriptional activation.
EP300	Histone acetyltransferase p300	Functions as a histone acetyltransferase and regulates transcription via chromatin remodeling.
HSP90B2P	Putative endoplasmin-like protein	Putative molecular chaperone.
TRAP1	Heat shock protein 75 kDa, mitochondrial	Chaperone that expresses an ATPase activity.
ADCY9	Adenylate cyclase type 9	Adenylyl cyclase that catalyzes the formation of the signaling molecule cAMP in response to activation of G protein-coupled receptors.
NLRC3	NLR family CARD domain-containing protein 3	Negative regulator of the innate immune response.

Protein-family classification

Druggable: 0 · Difficult: 2 · Unknown: 4 · 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
Transcription factor	2	2.8×	0.316
Other/Unknown	4	1.2×	0.458

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CREBBP	Transcription factor	no	2.3.1.48	Znf_TAZ, Znf_ZZ, Bromodomain
EP300	Transcription factor	no	2.3.1.48	Znf_TAZ, Znf_ZZ, Bromodomain
HSP90B2P	Other/Unknown	no		Hsp90_fam, Ribosomal_Su5_D2-typ_SF, HSP90_C
TRAP1	Other/Unknown	no		Hsp90_fam, HATPase_dom, Ribosomal_Su5_D2-typ_SF
ADCY9	Other/Unknown	no		A/G_cyclase, A/G_cyclase_CS, Nucleotide_cyclase
NLRC3	Other/Unknown	no		Leu-rich_rpt, NACHT_NTPase, P-loop_NTPase

Expression context

Cohort genes with no expression data: 0.

6 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)	6
unknown	0

Top tissues across cohort

Tissue	Cohort genes
sural nerve	2
amniotic fluid	1
tibia	1
adrenal tissue	1
bone marrow cell	1
colonic epithelium	1
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1
gastrocnemius	1
hindlimb stylopod muscle	1
right uterine tube	1
choroid plexus epithelium	1
secondary oocyte	1
vastus lateralis	1
granulocyte	1
ileal mucosa	1
thymus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CREBBP	297	ubiquitous	marker	sural nerve, tibia, amniotic fluid
EP300	292	ubiquitous	marker	colonic epithelium, adrenal tissue, bone marrow cell
HSP90B2P	108	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, sural nerve
TRAP1	294	ubiquitous	marker	hindlimb stylopod muscle, right uterine tube, gastrocnemius
ADCY9	296	ubiquitous	marker	secondary oocyte, choroid plexus epithelium, vastus lateralis
NLRC3	181	broad	marker	thymus, granulocyte, ileal mucosa

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
EP300	10,122
CREBBP	6,959
TRAP1	5,216
ADCY9	1,492
NLRC3	1,212
HSP90B2P	8

Intra-cohort edges

A	B	Sources
CREBBP	EP300	string_interaction

Structural data

PDB: 4 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CREBBP	Q92793	144
EP300	Q09472	60
TRAP1	Q12931	24
ADCY9	O60503	6

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
NLRC3	Q7RTR2	86.91
HSP90B2P	Q58FF3	82.17

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 188. Enrichment computed across 6 evidence-associated genes (5 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 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production	2	913.6×	1e-04	CREBBP, EP300
NFE2L2 regulating inflammation associated genes	2	913.6×	1e-04	CREBBP, EP300
NFE2L2 regulating ER-stress associated genes	2	913.6×	1e-04	CREBBP, EP300
NFE2L2 regulates pentose phosphate pathway genes	2	571.0×	1e-04	CREBBP, EP300
NFE2L2 regulating MDR associated enzymes	2	571.0×	1e-04	CREBBP, EP300
Regulation of NFE2L2 gene expression	2	571.0×	1e-04	CREBBP, EP300
Regulation of FOXO transcriptional activity by acetylation	2	456.8×	2e-04	CREBBP, EP300
Regulation of gene expression by Hypoxia-inducible Factor	2	380.7×	2e-04	CREBBP, EP300
Activation of the TFAP2 (AP-2) family of transcription factors	2	380.7×	2e-04	CREBBP, EP300
NFE2L2 regulating tumorigenic genes	2	380.7×	2e-04	CREBBP, EP300
RUNX3 regulates NOTCH signaling	2	326.3×	2e-04	CREBBP, EP300
TRAF3-dependent IRF activation pathway	2	304.5×	2e-04	CREBBP, EP300
Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells	2	285.5×	2e-04	CREBBP, EP300
FOXO-mediated transcription of cell death genes	2	285.5×	2e-04	CREBBP, EP300
Zygotic genome activation (ZGA)	2	268.7×	3e-04	CREBBP, EP300
NOTCH4 Intracellular Domain Regulates Transcription	2	228.4×	3e-04	CREBBP, EP300
NFE2L2 regulating anti-oxidant/detoxification enzymes	2	217.5×	4e-04	CREBBP, EP300
CD209 (DC-SIGN) signaling	2	207.6×	4e-04	CREBBP, EP300
NOTCH3 Intracellular Domain Regulates Transcription	2	175.7×	5e-04	CREBBP, EP300
Attenuation phase	2	163.1×	5e-04	CREBBP, EP300
Formation of paraxial mesoderm	2	163.1×	5e-04	CREBBP, EP300
RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression	2	163.1×	5e-04	CREBBP, EP300
TRAF6 mediated IRF7 activation	2	152.3×	5e-04	CREBBP, EP300
Nuclear events mediated by NFE2L2	2	134.3×	7e-04	CREBBP, EP300
Evasion by RSV of host interferon responses	2	130.5×	7e-04	CREBBP, EP300
Expression of BMAL (ARNTL), CLOCK, and NPAS2	2	117.1×	8e-04	CREBBP, EP300
SUMOylation of transcription cofactors	2	97.2×	0.001	CREBBP, EP300
NOTCH1 Intracellular Domain Regulates Transcription	2	95.2×	0.001	CREBBP, EP300
Heme signaling	2	86.2×	0.001	CREBBP, EP300
Constitutive Signaling by NOTCH1 PEST Domain Mutants	2	78.8×	0.002	CREBBP, EP300

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
N-terminal peptidyl-lysine acetylation	2	1872.4×	2e-05	CREBBP, EP300
canonical NF-kappaB signal transduction	3	183.2×	2e-05	CREBBP, EP300, NLRC3
protein acetylation	2	468.1×	2e-04	CREBBP, EP300
regulation of cellular response to heat	2	351.1×	3e-04	CREBBP, EP300
stimulatory C-type lectin receptor signaling pathway	2	244.2×	5e-04	CREBBP, EP300
positive regulation of transforming growth factor beta receptor signaling pathway	2	175.5×	9e-04	CREBBP, EP300
cellular response to nutrient levels	2	156.0×	1e-03	CREBBP, EP300
cellular response to UV	2	98.5×	0.002	CREBBP, EP300
protein destabilization	2	96.8×	0.002	CREBBP, EP300
behavioral defense response	1	2808.7×	0.002	EP300
negative regulation of protein oligomerization	1	2808.7×	0.002	EP300
swimming	1	2808.7×	0.002	EP300
peptidyl-lysine propionylation	1	2808.7×	0.002	EP300
regulation of tubulin deacetylation	1	2808.7×	0.002	EP300
peptidyl-lysine crotonylation	1	2808.7×	0.002	EP300
peptidyl-lysine butyrylation	1	2808.7×	0.002	EP300
internal protein amino acid acetylation	1	1404.3×	0.004	EP300
translational attenuation	1	1404.3×	0.004	TRAP1
negative regulation of cellular respiration	1	1404.3×	0.004	TRAP1
thigmotaxis	1	702.2×	0.007	EP300
negative regulation of chromosome condensation	1	702.2×	0.007	EP300
protein folding	2	34.5×	0.007	HSP90B2P, TRAP1
response to hypoxia	2	31.9×	0.007	CREBBP, EP300
internal peptidyl-lysine acetylation	1	561.7×	0.007	EP300
negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide	1	561.7×	0.007	TRAP1
negative regulation of interferon-alpha production	1	468.1×	0.008	NLRC3
negative regulation of brown fat cell differentiation	1	468.1×	0.008	EP300
negative regulation of transcription by RNA polymerase I	1	401.2×	0.009	CREBBP
positive regulation of TORC2 signaling	1	351.1×	0.010	EP300
positive regulation of T-helper 17 cell lineage commitment	1	351.1×	0.010	EP300

Therapeutics

Drug target analysis

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

Druggability breadth: 4 of 6 evidence-associated genes (67%) 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
CREBBP	COLCHICINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CREBBP	13	4
EP300	9	3
TRAP1	9	3
HSP90B2P	0	0
ADCY9	0	0
NLRC3	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
COLCHICINE	4	CREBBP
ALTRETAMINE	4	CREBBP
CURCUMIN	3	CREBBP, EP300
PAPAVERINE	3	CREBBP
EPIGALOCATECHIN GALLATE	3	CREBBP, EP300
COENZYME_A	3	EP300
TANESPIMYCIN	3	TRAP1
GANETESPIB	3	TRAP1
MOLIBRESIB	2	CREBBP, EP300
FISETIN	2	CREBBP
ETAZOLATE	2	CREBBP
LUNRESERTIB	2	CREBBP
TRACAZOLATE	2	CREBBP
NOCODAZOLE	2	CREBBP
MIVEBRESIB	2	EP300
STREPTONIGRIN	2	EP300
MITOQUINONE CATION	2	TRAP1
ADENOSINE TRIPHOSPHATE	2	TRAP1
PU-H71	2	TRAP1
LUMINESPIB	2	TRAP1
GELDANAMYCIN	2	TRAP1
BIIB021	2	TRAP1
INOBRODIB	1	CREBBP, EP300
AZD-5153	1	CREBBP
BERBERINE CHLORIDE	1	EP300
PLUMBAGIN	1	EP300
CUDC-305	1	TRAP1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
EP300	767	Binding:763, Functional:3, ADMET:1
CREBBP	687	Binding:644, Functional:43
TRAP1	94	Binding:94
ADCY9	18	Binding:16, Functional:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CREBBP	2.3.1.48	histone acetyltransferase
EP300	2.3.1.48	histone acetyltransferase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
CREBBP	687
EP300	767

Pharmacogenomics

Cohort genes with a PharmGKB record: 6; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

27 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)
COLCHICINE	4	CREBBP
ALTRETAMINE	4	CREBBP
CURCUMIN	3	CREBBP, EP300
PAPAVERINE	3	CREBBP
EPIGALOCATECHIN GALLATE	3	CREBBP, EP300
COENZYME_A	3	EP300
TANESPIMYCIN	3	TRAP1
GANETESPIB	3	TRAP1
MOLIBRESIB	2	CREBBP, EP300
FISETIN	2	CREBBP
ETAZOLATE	2	CREBBP
LUNRESERTIB	2	CREBBP
TRACAZOLATE	2	CREBBP
NOCODAZOLE	2	CREBBP
MIVEBRESIB	2	EP300
STREPTONIGRIN	2	EP300
MITOQUINONE CATION	2	TRAP1
ADENOSINE TRIPHOSPHATE	2	TRAP1
PU-H71	2	TRAP1
LUMINESPIB	2	TRAP1
GELDANAMYCIN	2	TRAP1
BIIB021	2	TRAP1
INOBRODIB	1	CREBBP, EP300
AZD-5153	1	CREBBP
BERBERINE CHLORIDE	1	EP300
PLUMBAGIN	1	EP300
CUDC-305	1	TRAP1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	CREBBP
B	Phased (≥1) drug, not yet approved	2	EP300, TRAP1
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	3	HSP90B2P, ADCY9, NLRC3

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
HSP90B2P	0	—
ADCY9	18	—
NLRC3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 4.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	3
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01619644	PHASE2	COMPLETED	Rubinstein-Taybi Syndrome: Functional Imaging and Therapeutic Trial
NCT06740162	Not specified	RECRUITING	Physical Activity and Community EmPOWERment Project
NCT04122742	Not specified	UNKNOWN	Diagnosis of RSTS: Identification of the Acetylation Profiles as Epigenetic Markers for Assessing Causality of CREBBP and EP300 Variants.
NCT05696912	Not specified	UNKNOWN	Functional Tests to Resolve Unsolved Rare Diseases. Rares.

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
VALPROATE SODIUM	4	1
LUFENURON	2	1