protein
CREB-binding protein
Gene
CREBBP
Organism
Homo sapiens(9606)
Length
2442 aa
Mass
265,351 Da
# CREB-Binding Protein (CREBBP)
CREBBP encodes CREB-binding protein, a 2442-amino acid acetyltransferase that functions as a key transcriptional coactivator (UniProt: Q92793). The protein acetylates histones at specific lysine residues (H3K18ac and H3K27ac) to activate transcription, and modifies numerous non-histone substrates including DDX21, FBL, IRF2, FOXO1, and others to regulate their activity. Beyond acetylation, CREBBP can mediate protein lactylation using alternative acyl-CoA substrates, catalyzing lactylation of MRE11 in DNA damage responses. It also acts as a coactivator for circadian transcription factors and the TGF-β signaling pathway.
CREBBP mutations cause two distinct developmental disorders: Rubinstein-Taybi syndrome 1 (RSTS1), characterized by craniofacial abnormalities, intellectual disability, and growth deficiency, and Menke-Hennekam syndrome 1 (MKHK1), which presents with developmental delay, intellectual disability of variable severity, speech delay, short stature, and microcephaly. Both conditions feature broad thumbs/toes in RSTS1 or distinctive facial features in MKHK1.
CREBBP is classified as a syndromic autism-associated gene (SFARI Cat S; UniProt: Q92793). Notably, autistic behavior is documented as a clinical feature in Menke-Hennekam syndrome 1, consistent with CREBBP's role in neurodevelopmental pathways.
Generated from the curated entity record below. May contain errors — verify against source links.
Genetic Evidence · ASD
Source: SFARI Gene database · gene.sfari.org
Related Publications
Browse all →Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.
Ruzzo Elizabeth K et al.Cell2019PMID 31398340Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model.
Guo Hui et al.Molecular autism2018PMID 30564305Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder.
C Yuen Ryan K et al.Nature neuroscience2017PMID 28263302Identification of common genetic risk variants for autism spectrum disorder.
Grove Jakob et al.Nature genetics2019PMID 30804558Synaptic, transcriptional and chromatin genes disrupted in autism.
De Rubeis Silvia et al.Nature2014PMID 25363760
Function
Acetylates histones, giving a specific tag for transcriptional activation (PubMed:21131905, PubMed:24616510). Mediates acetylation of histone H3 at 'Lys-18' and 'Lys-27' (H3K18ac and H3K27ac, respectively) (PubMed:21131905). Also acetylates non-histone proteins, like DDX21, FBL, IRF2, MAFG, NCOA3, POLR1E/PAF53 and FOXO1 (PubMed:10490106, PubMed:11154691, PubMed:12738767, PubMed:12929931, PubMed:24207024, PubMed:28790157, PubMed:30540930, PubMed:35675826, PubMed:9707565). Binds specifically to phosphorylated CREB and enhances its transcriptional activity toward cAMP-responsive genes. Acts as a coactivator of ALX1. Acts as a circadian transcriptional coactivator which enhances the activity of the circadian transcriptional activators: NPAS2-BMAL1 and CLOCK-BMAL1 heterodimers (PubMed:14645221). Acetylates PCNA; acetylation promotes removal of chromatin-bound PCNA and its degradation during nucleotide excision repair (NER) (PubMed:24939902). Acetylates POLR1E/PAF53, leading to decreased association of RNA polymerase I with the rDNA promoter region and coding region (PubMed:24207024). Acetylates DDX21, thereby inhibiting DDX21 helicase activity (PubMed:28790157). Acetylates FBL, preventing methylation of 'Gln-105' of histone H2A (H2AQ104me) (PubMed:30540930). In addition to protein acetyltransferase, can use different acyl-CoA substrates, such as lactoyl-CoA, and is able to mediate protein lactylation (PubMed:38128537). Catalyzes lactylation of MRE11 in response to DNA damage, thereby promoting DNA double-strand breaks (DSBs) via homologous recombination (HR) (PubMed:38128537). Functions as a transcriptional coactivator for SMAD4 in the TGF-beta signaling pathway (PubMed:25514493)
Disease associations
Rubinstein-Taybi syndrome 1RSTS1
A disorder characterized by craniofacial abnormalities, postnatal growth deficiency, broad thumbs, broad big toes, intellectual disability and a propensity for development of malignancies.
Menke-Hennekam syndrome 1MKHK1
A form of Menke-Hennekam syndrome, a congenital autosomal dominant disease characterized by developmental delay, growth retardation, and craniofacial dysmorphism. Patients have intellectual disability of variable severity, speech delay, autistic behavior, short stature and microcephaly. Main facial characteristics include short palpebral fissures, telecanthi, depressed nasal ridge, short nose, anteverted nares, short columella and long philtrum.
Sources
Last updated 5/6/2026, 5:24:40 AM