CREBBP
Homo sapiens
Gene Name: CREB binding protein
Aliases: CBP, KAT3A, RSTS
Chromosome No: 16
Chromosome Band: 16p13.3
Genetic Category: Syndromic-Genetic Association-Rare single gene variant-
Associated Syndrome(s): Menke-Hennekam syndrome 1,Rubinstein-Taybi syndrome
Aliases: CBP, KAT3A, RSTS
Chromosome No: 16
Chromosome Band: 16p13.3
Genetic Category: Syndromic-Genetic Association-Rare single gene variant-
Associated Syndrome(s): Menke-Hennekam syndrome 1,Rubinstein-Taybi syndrome
Summary Statistics:
ASD Reports: 41
Recent Reports: 2
Annotated variants: 120
Associated CNVs: 4
Evidence score: 4
ASD Reports: 41
Recent Reports: 2
Annotated variants: 120
Associated CNVs: 4
Evidence score: 4
| Associated Disorders: |
|
Relevance to Autism
Genetic association has been found between the CREBBP gene and ASD in an IMGSAC cohort (Barnby et al., 2005). This gene has also been associated with syndromic autism, where a subpopulation of individuals with a given syndrome develop autism. In particular, rare mutations of the CREBBP gene have been identified in studies of patients with Rubinstein-Taybi syndrome (RTS).
Molecular Function
This gene is ubiquitously expressed and is involved in the transcriptional coactivation of many different transcription factors. First isolated as a nuclear protein that binds to cAMP-response element binding protein (CREB), this gene is now known to play critical roles in embryonic development, growth control, and homeostasis by coupling chromatin remodeling to transcription factor recognition. Mutations in this gene cause Rubinstein-Taybi syndrome (RTS). Chromosomal translocations involving this gene have been associated with acute myeloid leukemia. Alternative splicing results in multiple transcript variants encoding different isoforms.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Candidate-gene screening and association analysis at the autism-susceptibility locus on chromosome 16p: evidence of association at GRIN2A and ABAT.
ASD
Positive Association
De Novo Coding Variants Are Strongly Associated with Tourette Disorder.
Tourette syndrome
Support
Impact of on-site clinical genetics consultations on diagnostic rate in children and young adults with autism spectrum disorder.
ASD
Support
Clinical description and mutational profile of a Moroccan series of patients with Rubinstein Taybi syndrome
Rubinstein-Taybi syndrome 1, DD, ID
Support
Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder.
ASD
Support
Genotype-phenotype correlations in Rubinstein-Taybi syndrome.
Rubinstein-Taybi syndrome
Support
Characterization of intellectual disability and autism comorbidity through gene panel sequencing.
ID, ASD or autistic traits
Support
Whole exome sequencing for a patient with Rubinstein-Taybi syndrome reveals de novo variants besides an overt CREBBP mutation.
Rubinstein-Taybi syndrome
ASD, ID
Support
The novel and recurrent variants in exon 31 of CREBBP in Japanese patients with Menke-Hennekam syndrome
Menke-Hennekam syndrome 1, DD, ID
ASD, epilepsy/seizures
Support
Genomic diagnosis for children with intellectual disability and/or developmental delay.
ID
Epilepsy/seizures, macrocephaly
Support
Molecular analysis of the CBP gene in 60 patients with Rubinstein-Taybi syndrome.
Rubinstein-Taybi syndrome
ASD
Support
Lessons Learned from Large-Scale, First-Tier Clinical Exome Sequencing in a Highly Consanguineous Population.
DD, ID
Stereotypies
Support
Large-scale discovery of novel genetic causes of developmental disorders.
DD
Support
Prevalence and phenotypic impact of rare potentially damaging variants in autism spectrum disorder
ASD
Support
Clinical exome sequencing: results from 2819 samples reflecting 1000 families.
Rubinstein-Taybi syndrome
DD
Support
Genotype-phenotype specificity in Menke-Hennekam syndrome caused by missense variants in exon 30 or 31 of CREBBP.
Menke-Hennekam syndrome 1
Autistic features
Support
The contribution of de novo coding mutations to autism spectrum disorder
ASD
Support
Excess of de novo variants in genes involved in chromatin remodelling in patients with marfanoid habitus and intellectual disability
ID
Marfanoid habitus
Support
Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability
ID
Support
Rubinstein-Taybi syndrome: New neuroradiological and neuropsychiatric insights from a multidisciplinary approach.
Rubinstein-Taybi syndrome
Support
Massively parallel sequencing of patients with intellectual disability, congenital anomalies and/or autism spectrum disorders with a targeted gene ...
DD, ID, ASD
MCA
Support
Rubinstein-Taybi syndrome caused by mutations in the transcriptional co-activator CBP.
Rubinstein-Taybi syndrome
ASD
Support
Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism
ASD
Support
CREBBP mutations in individuals without Rubinstein-Taybi syndrome phenotype.
Menke-Hennekam syndrome 1
DD, ID, ASD or autistic features
Support
Further delineation of an entity caused by CREBBP and EP300 mutations but not resembling Rubinstein-Taybi syndrome.
Menke-Hennekam syndrome 1
DD, ID, ASD or autistic behavior
Support
Multiplex ligation-dependent probe amplification detection of an unknown large deletion of the CREB-binding protein gene in a patient with Rubinste...
ID
DD
Support
Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes
ASD
Support
CREBBP and EP300 mutational spectrum and clinical presentations in a cohort of Swedish patients with Rubinstein-Taybi syndrome.
Rubinstein-Taybi syndrome
Support
Trio-based exome sequencing reveals a high rate of the de novo variants in intellectual disability
ID
Support
Socio-behavioral characteristics of children with Rubinstein-Taybi syndrome.
Rubinstein-Taybi syndrome
Recent Recommendation
Opposing Effects of CREBBP Mutations Govern the Phenotype of Rubinstein-Taybi Syndrome and Adult SHH Medulloblastoma.
Rubinstein-Taybi syndrome
Recent Recommendation
Low load for disruptive mutations in autism genes and their biased transmission.
ASD
Rare
Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
GEN285R027
missense_variant
c.5371C>G
p.His1791Asp
De novo
Simplex
GEN285R028
missense_variant
c.5485C>T
p.His1829Tyr
De novo
Simplex
GEN285R041
frameshift_variant
c.4400_4401insATGT
p.Met1468CysfsTer14
De novo
GEN285R048
missense_variant
c.5478C>G
p.Leu1826=
De novo
Possible multi-generational
GEN285R051
missense_variant
c.5600G>A
p.Arg1867Gln
De novo
Possible multi-generational
GEN285R083
frameshift_variant
c.2416_2417insGCTA
p.Pro806ArgfsTer127
Multiplex
Common
Variant ID
Polymorphism
SNP ID
Allele Change
Residue Change
Population Origin
Population Stage
Author, Year
GEN285C001
intron_variant
rs130021
c.1459+214T>C;c.1573+214T>C
IMGSAC
Discovery
GEN285C002
intron_variant
rs886528
c.3137-2583T>C;c.3251-2583T>C;c.3206-2583T>C;c.2834-2583T>C
N/A
IMGSAC
Discovery
GEN285C003
intron_variant
rs130025
c.1217-32G>T;c.1331-32G>T
IMGSAC
Discovery
GEN285C004
intron_variant
rs3025684
c.3723-8C>T;c.3837-8C>T;c.3792-8C>T;c.3420-8C>T
N/A
IMGSAC
Discovery
GEN285C005
intron_variant
rs130008
c.4615-14G>A;c.4615-14G>C;c.4729-14G>A;c.4729-14G>C;c.4684-14G>A;c.4684-14G>C;c.4312-14G>A;c.4312-14
IMGSAC
Discovery
