CREBBPCREB binding protein
Autism Reports / Total Reports
17 / 42Rare Variants / Common Variants
114 / 5Aliases
CREBBP, CBP, KAT3A, RSTSAssociated Syndromes
Rubinstein-Taybi syndrome, Menke-Hennekam syndrome 1, Tourette syndrome, Menke-Hennekam syndrome 1, DD, ID, Rubinstein-Taybi syndrome 1, DD, IDChromosome Band
16p13.3Associated Disorders
DD/NDD, ID, EP, EPS, ASDGenetic Category
Rare Single Gene Mutation, Syndromic, Genetic AssociationRelevance 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
SFARI Genomic Platforms
Reports related to CREBBP (42 Reports)
# | Type | Title | Author, Year | Autism Report | Associated Disorders |
---|---|---|---|---|---|
1 | Support | Molecular analysis of the CBP gene in 60 patients with Rubinstein-Taybi syndrome | Coupry I , et al. (2002) | No | ASD |
2 | Primary | Candidate-gene screening and association analysis at the autism-susceptibility locus on chromosome 16p: evidence of association at GRIN2A and ABAT | Barnby G , et al. (2005) | Yes | - |
3 | Support | Genotype-phenotype correlations in Rubinstein-Taybi syndrome | Schorry EK , et al. (2008) | No | - |
4 | Support | Socio-behavioral characteristics of children with Rubinstein-Taybi syndrome | Galra C , et al. (2009) | No | - |
5 | Support | Multiplex ligation-dependent probe amplification detection of an unknown large deletion of the CREB-binding protein gene in a patient with Rubinstein-Taybi syndrome | Cal F , et al. (2013) | No | DD |
6 | Support | Massively parallel sequencing of patients with intellectual disability, congenital anomalies and/or autism spectrum disorders with a targeted gene panel | Brett M , et al. (2014) | Yes | MCA |
7 | Support | The contribution of de novo coding mutations to autism spectrum disorder | Iossifov I et al. (2014) | Yes | - |
8 | Support | Large-scale discovery of novel genetic causes of developmental disorders | Deciphering Developmental Disorders Study (2014) | No | - |
9 | Support | Whole exome sequencing for a patient with Rubinstein-Taybi syndrome reveals de novo variants besides an overt CREBBP mutation | Yoo HJ , et al. (2015) | No | ASD, ID |
10 | Support | Excess of rare, inherited truncating mutations in autism | Krumm N , et al. (2015) | Yes | - |
11 | Recent Recommendation | Low load for disruptive mutations in autism genes and their biased transmission | Iossifov I , et al. (2015) | Yes | - |
12 | Support | CREBBP and EP300 mutational spectrum and clinical presentations in a cohort of Swedish patients with Rubinstein-Taybi syndrome | Wincent J , et al. (2016) | No | - |
13 | Support | CREBBP mutations in individuals without Rubinstein-Taybi syndrome phenotype | Menke LA , et al. (2016) | No | DD, ID, ASD or autistic features |
14 | Support | Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability | Lelieveld SH et al. (2016) | No | - |
15 | Support | Clinical exome sequencing: results from 2819 samples reflecting 1000 families | Trujillano D , et al. (2016) | No | DD |
16 | Positive Association | De Novo Coding Variants Are Strongly Associated with Tourette Disorder | Willsey AJ , et al. (2017) | No | - |
17 | Support | Genomic diagnosis for children with intellectual disability and/or developmental delay | Bowling KM , et al. (2017) | No | Epilepsy/seizures, macrocephaly |
18 | Support | Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder | Lim ET , et al. (2017) | Yes | - |
19 | Support | Expanding the genetic heterogeneity of intellectual disability | Anazi S , et al. (2017) | No | - |
20 | Support | Further delineation of an entity caused by CREBBP and EP300 mutations but not resembling Rubinstein-Taybi syndrome | Menke LA , et al. (2018) | No | DD, ID, ASD or autistic behavior |
21 | Recent Recommendation | Opposing Effects of CREBBP Mutations Govern the Phenotype of Rubinstein-Taybi Syndrome and Adult SHH Medulloblastoma | Merk DJ , et al. (2018) | No | - |
22 | Support | Rubinstein-Taybi syndrome: New neuroradiological and neuropsychiatric insights from a multidisciplinary approach | Ajmone PF , et al. (2018) | No | - |
23 | Support | Genotype-phenotype specificity in Menke-Hennekam syndrome caused by missense variants in exon 30 or 31 of CREBBP | Banka S , et al. (2019) | No | Autistic features |
24 | Support | Lessons Learned from Large-Scale, First-Tier Clinical Exome Sequencing in a Highly Consanguineous Population | Monies D , et al. (2019) | No | Stereotypies |
25 | Support | Characterization of intellectual disability and autism comorbidity through gene panel sequencing | Aspromonte MC , et al. (2019) | Yes | - |
26 | Support | Impact of on-site clinical genetics consultations on diagnostic rate in children and young adults with autism spectrum disorder | Munnich A , et al. (2019) | Yes | - |
27 | Support | Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes | Feliciano P et al. (2019) | Yes | - |
28 | Support | Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism | Satterstrom FK et al. (2020) | Yes | - |
29 | Support | Excess of de novo variants in genes involved in chromatin remodelling in patients with marfanoid habitus and intellectual disability | Chevarin M et al. (2020) | No | Marfanoid habitus |
30 | Support | - | Mahjani B et al. (2021) | Yes | - |
31 | Support | - | Nishi E et al. (2021) | No | ASD, epilepsy/seizures |
32 | Support | - | Elalaoui SC et al. (2021) | No | - |
33 | Support | - | Brea-Fernández AJ et al. (2022) | No | - |
34 | Support | - | Zhou X et al. (2022) | Yes | - |
35 | Support | - | Kipkemoi P et al. (2023) | No | ID |
36 | Support | - | Sheth F et al. (2023) | Yes | DD, ID |
37 | Support | - | Amerh S Alqahtani et al. (2023) | Yes | - |
38 | Support | - | Ana Karen Sandoval-Talamantes et al. (2023) | Yes | - |
39 | Support | - | Marketa Wayhelova et al. (2024) | Yes | - |
40 | Support | - | Tamam Khalaf et al. (2024) | No | - |
41 | Support | - | Yasser Al-Sarraj et al. (2024) | Yes | - |
42 | Support | Rubinstein-Taybi syndrome caused by mutations in the transcriptional co-activator CBP | Petrij F , et al. (1995) | No | ASD |
Rare Variants (114)
Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
---|---|---|---|---|---|---|---|---|
A>T | - | intron_variant | - | - | - | 12070251 | Coupry I , et al. (2002) | |
C>G | - | intron_variant | - | - | - | 12070251 | Coupry I , et al. (2002) | |
T>C | - | intron_variant | - | - | - | 12070251 | Coupry I , et al. (2002) | |
- | - | copy_number_loss | De novo | - | - | 23315884 | Cal F , et al. (2013) | |
- | - | copy_number_loss | Unknown | - | - | 26788536 | Wincent J , et al. (2016) | |
- | - | copy_number_loss | Unknown | - | - | 31406558 | Munnich A , et al. (2019) | |
C>T | p.Arg413Ter | stop_gained | - | - | - | 12070251 | Coupry I , et al. (2002) | |
- | - | copy_number_loss | De novo | - | - | 34795756 | Elalaoui SC et al. (2021) | |
A>T | p.Lys1269Ter | stop_gained | - | - | - | 12070251 | Coupry I , et al. (2002) | |
C>T | p.Arg1498Ter | stop_gained | - | - | - | 12070251 | Coupry I , et al. (2002) | |
- | - | copy_number_loss | Unknown | - | - | 38438125 | Tamam Khalaf et al. (2024) | |
c.3096insT | - | frameshift_variant | - | - | - | 12070251 | Coupry I , et al. (2002) | |
C>A | p.Ser23Ter | stop_gained | De novo | - | - | 12070251 | Coupry I , et al. (2002) | |
A>G | p.Lys1520Arg | missense_variant | - | - | - | 12070251 | Coupry I , et al. (2002) | |
C>T | p.Arg370Ter | stop_gained | De novo | - | - | 12070251 | Coupry I , et al. (2002) | |
c.4398T>A | p.Tyr1466Ter | stop_gained | - | - | - | 12070251 | Coupry I , et al. (2002) | |
c.6127C>T | p.Gln2043Ter | stop_gained | - | - | - | 12070251 | Coupry I , et al. (2002) | |
del7bp+ins2bp | - | splice_site_variant | - | - | - | 12070251 | Coupry I , et al. (2002) | |
138delA+ins13bp | - | stop_gained | De novo | - | - | 12070251 | Coupry I , et al. (2002) | |
c.406C>T | p.Gln136Ter | stop_gained | Unknown | - | - | 7630403 | Petrij F , et al. (1995) | |
c.1069C>T | p.Gln357Ter | stop_gained | De novo | - | - | 7630403 | Petrij F , et al. (1995) | |
c.2941G>A | p.Ala981Thr | missense_variant | - | - | - | 12070251 | Coupry I , et al. (2002) | |
c.5933A>G | p.Asn1978Ser | missense_variant | - | - | - | 12070251 | Coupry I , et al. (2002) | |
c.6661A>C | p.Met2221Leu | missense_variant | - | - | - | 12070251 | Coupry I , et al. (2002) | |
c.6728C>T | p.Ala2243Val | missense_variant | - | - | - | 12070251 | Coupry I , et al. (2002) | |
c.840dup | p.Ser281Ter | frameshift_variant | - | - | - | 12070251 | Coupry I , et al. (2002) | |
c.2113+1G>A | - | splice_site_variant | Unknown | - | - | 34615535 | Mahjani B et al. (2021) | |
c.778C>T | p.Gln260Ter | stop_gained | De novo | - | - | 26788536 | Wincent J , et al. (2016) | |
c.1827+1G>A | - | splice_site_variant | De novo | - | - | 26788536 | Wincent J , et al. (2016) | |
c.3610-2A>G | - | splice_site_variant | Unknown | - | - | 29637745 | Ajmone PF , et al. (2018) | |
c.1825_1827+9del | - | splice_site_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
c.5635C>T | p.Gln1879Ter | stop_gained | Unknown | - | - | 34615535 | Mahjani B et al. (2021) | |
c.3665+1G>A | - | splice_site_variant | De novo | - | - | 28554332 | Bowling KM , et al. (2017) | |
c.3452G>A | p.Trp1151Ter | stop_gained | De novo | - | - | 26788536 | Wincent J , et al. (2016) | |
c.3517C>T | p.Arg1173Ter | stop_gained | Unknown | - | - | 26788536 | Wincent J , et al. (2016) | |
c.4078C>T | p.Arg1360Ter | stop_gained | De novo | - | - | 26788536 | Wincent J , et al. (2016) | |
c.5635C>T | p.Gln1879Ter | stop_gained | De novo | - | - | 26788536 | Wincent J , et al. (2016) | |
c.6211C>G | p.Leu2071Val | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
c.7082C>G | p.Ser2361Cys | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
c.2044+1G>A | - | splice_site_variant | Unknown | - | - | 27848944 | Trujillano D , et al. (2016) | |
c.4140G>C | p.Val1380%3D | synonymous_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
c.5354G>A | p.Cys1785Tyr | missense_variant | De novo | - | - | 30892814 | Banka S , et al. (2019) | |
c.5357G>A | p.Arg1786His | missense_variant | De novo | - | - | 30892814 | Banka S , et al. (2019) | |
c.5602C>T | p.Pro1868Ser | missense_variant | De novo | - | - | 30892814 | Banka S , et al. (2019) | |
c.1780G>A | p.Glu594Lys | missense_variant | Unknown | - | - | 34615535 | Mahjani B et al. (2021) | |
c.5877del | p.Val1960Ter | stop_gained | De novo | - | Simplex | 34652060 | Nishi E et al. (2021) | |
c.6188C>G | p.Ser2063Ter | stop_gained | De novo | - | Simplex | 34652060 | Nishi E et al. (2021) | |
c.6241C>T | p.Gln2081Ter | stop_gained | De novo | - | Simplex | 34652060 | Nishi E et al. (2021) | |
c.5128T>C | p.Cys1710Arg | missense_variant | De novo | - | - | 27311832 | Menke LA , et al. (2016) | |
c.5240T>G | p.Leu1747Arg | missense_variant | De novo | - | - | 27311832 | Menke LA , et al. (2016) | |
c.5357G>C | p.Arg1786Pro | missense_variant | De novo | - | - | 27311832 | Menke LA , et al. (2016) | |
c.5456G>T | p.Cys1819Phe | missense_variant | De novo | - | - | 27311832 | Menke LA , et al. (2016) | |
c.5488C>T | p.Arg1830Trp | missense_variant | De novo | - | - | 27311832 | Menke LA , et al. (2016) | |
c.5513G>A | p.Cys1838Tyr | missense_variant | De novo | - | - | 27311832 | Menke LA , et al. (2016) | |
c.5599C>T | p.Pro1867Ser | missense_variant | De novo | - | - | 27311832 | Menke LA , et al. (2016) | |
c.5602C>T | p.Arg1868Trp | missense_variant | De novo | - | - | 27311832 | Menke LA , et al. (2016) | |
c.5614A>G | p.Met1872Val | missense_variant | De novo | - | - | 27311832 | Menke LA , et al. (2016) | |
c.5155C>G | p.His1719Asp | missense_variant | De novo | - | - | 29460469 | Menke LA , et al. (2018) | |
c.5345C>T | p.Ala1782Val | missense_variant | De novo | - | - | 29460469 | Menke LA , et al. (2018) | |
c.5485C>G | p.Arg1829Gly | missense_variant | De novo | - | - | 29460469 | Menke LA , et al. (2018) | |
c.5600G>A | p.Arg1867Gln | missense_variant | Unknown | - | - | 29460469 | Menke LA , et al. (2018) | |
c.5602C>T | p.Arg1868Trp | missense_variant | De novo | - | - | 29460469 | Menke LA , et al. (2018) | |
c.5602C>T | p.Pro1868Ser | missense_variant | De novo | - | - | 29460469 | Menke LA , et al. (2018) | |
c.5603G>A | p.Arg1868Gln | missense_variant | De novo | - | - | 29460469 | Menke LA , et al. (2018) | |
c.5608G>A | p.Ala1870Thr | missense_variant | De novo | - | - | 29460469 | Menke LA , et al. (2018) | |
c.5614A>G | p.Met1872Val | missense_variant | De novo | - | - | 29460469 | Menke LA , et al. (2018) | |
c.4378C>T | p.Arg1460Ter | stop_gained | De novo | - | Simplex | 28940097 | Anazi S , et al. (2017) | |
c.4613C>G | p.Pro1538Arg | missense_variant | De novo | - | - | 26788536 | Wincent J , et al. (2016) | |
c.3514T>C | p.Ser1172Pro | missense_variant | Unknown | - | - | 29637745 | Ajmone PF , et al. (2018) | |
c.2456C>T | p.Pro819Leu | missense_variant | De novo | - | - | 31452935 | Feliciano P et al. (2019) | |
c.5237G>T | p.Gly1746Val | missense_variant | De novo | - | - | 28554332 | Bowling KM , et al. (2017) | |
c.3410A>G | p.Tyr1137Cys | missense_variant | De novo | - | - | 31452935 | Feliciano P et al. (2019) | |
c.3868+5G>A | - | splice_site_variant | De novo | - | Simplex | 34795756 | Elalaoui SC et al. (2021) | |
c.3800+3G>T | - | splice_region_variant | De novo | - | Simplex | 37463579 | Kipkemoi P et al. (2023) | |
c.3374A>G | p.Tyr1125Cys | missense_variant | De novo | - | - | 27479843 | Lelieveld SH et al. (2016) | |
c.5066T>C | p.Leu1689Pro | missense_variant | De novo | - | - | 27479843 | Lelieveld SH et al. (2016) | |
c.5170G>A | p.Glu1724Lys | missense_variant | Unknown | - | - | 38438125 | Tamam Khalaf et al. (2024) | |
c.2080G>A | p.Val694Met | missense_variant | Unknown | - | Simplex | 37543562 | Sheth F et al. (2023) | |
c.3160G>T | p.Glu1054Ter | stop_gained | De novo | - | Simplex | 34795756 | Elalaoui SC et al. (2021) | |
c.4350C>A | p.Tyr1450Ter | stop_gained | De novo | - | Simplex | 34795756 | Elalaoui SC et al. (2021) | |
c.6169C>T | p.Gln2057Ter | stop_gained | De novo | - | Simplex | 34795756 | Elalaoui SC et al. (2021) | |
c.4597G>T | p.Ala1533Ser | missense_variant | De novo | - | Simplex | 28714951 | Lim ET , et al. (2017) | |
c.5614A>G | p.Met1872Val | missense_variant | De novo | - | Simplex | 34652060 | Nishi E et al. (2021) | |
c.1238G>A | p.Arg413Gln | missense_variant | De novo | - | Simplex | 25961944 | Krumm N , et al. (2015) | |
c.5597_5599del | p.Gln1866del | inframe_deletion | De novo | - | - | 29460469 | Menke LA , et al. (2018) | |
c.4393G>A | p.Gly1465Arg | missense_variant | Unknown | - | - | 31209962 | Aspromonte MC , et al. (2019) | |
c.4616A>G | p.Tyr1539Cys | missense_variant | De novo | - | Simplex | 25961944 | Krumm N , et al. (2015) | |
c.2635C>T | p.Pro879Ser | missense_variant | Familial | Maternal | - | 24690944 | Brett M , et al. (2014) | |
c.1069C>T | p.Gln357Ter | stop_gained | Unknown | Not maternal | - | 26788536 | Wincent J , et al. (2016) | |
c.1585A>G | p.Met529Val | missense_variant | De novo | - | Simplex | 32277047 | Chevarin M et al. (2020) | |
c.1931dup | p.Pro645AlafsTer43 | frameshift_variant | De novo | - | - | 12070251 | Coupry I , et al. (2002) | |
c.4705A>G | p.Thr1569Ala | missense_variant | De novo | - | Simplex | 25363768 | Iossifov I et al. (2014) | |
c.5558A>C | p.Gln1853Pro | missense_variant | De novo | - | Simplex | 37463579 | Kipkemoi P et al. (2023) | |
c.1109G>C | p.Arg370Pro | missense_variant | De novo | - | Simplex | 28472652 | Willsey AJ , et al. (2017) | |
c.3014dup | p.Glu1006ArgfsTer7 | frameshift_variant | De novo | - | - | 26788536 | Wincent J , et al. (2016) | |
c.2617dup | p.Gln873ProfsTer59 | frameshift_variant | Unknown | - | - | 29637745 | Ajmone PF , et al. (2018) | |
c.3609G>C | p.Lys1203Asn | missense_variant | De novo | - | Simplex | 34795756 | Elalaoui SC et al. (2021) | |
c.6244C>T | p.Gln2082Ter | stop_gained | Unknown | - | Unknown | 37799141 | Amerh S Alqahtani et al. (2023) | |
c.5366A>G | p.Asn1789Ser | missense_variant | De novo | - | - | 35322241 | Brea-Fernández AJ et al. (2022) | |
c.2085del | p.Gln695HisfsTer15 | frameshift_variant | De novo | - | Simplex | 25768348 | Yoo HJ , et al. (2015) | |
c.881dup | p.Asn294LysfsTer56 | frameshift_variant | De novo | - | Simplex | 28940097 | Anazi S , et al. (2017) | |
c.4650G>C | p.Lys1550Asn | missense_variant | De novo | - | Multiplex | 31981491 | Satterstrom FK et al. (2020) | |
c.4409A>G | p.His1470Arg | missense_variant | De novo | - | Unknown | 38572415 | Yasser Al-Sarraj et al. (2024) | |
c.2713del | p.Gln905SerfsTer55 | frameshift_variant | Unknown | - | Unknown | 12070251 | Coupry I , et al. (2002) | |
c.3559C>T | p.Gln1187Ter | stop_gained | Unknown | - | - | 38003033 | Ana Karen Sandoval-Talamantes et al. (2023) | |
c.4831del | p.Ile1611SerfsTer95 | frameshift_variant | Unknown | - | Unknown | 12070251 | Coupry I , et al. (2002) | |
c.5131A>G | p.Lys1711Glu | missense_variant | Familial | Paternal | - | 38321498 | Marketa Wayhelova et al. (2024) | |
c.5570_5590del | p.His1857_Gln1863del | inframe_deletion | De novo | - | Simplex | 34652060 | Nishi E et al. (2021) | |
c.4400_4401insATGT | p.Met1468CysfsTer14 | frameshift_variant | De novo | - | - | 26788536 | Wincent J , et al. (2016) | |
c.2416_2417insGCTA | p.Pro806ArgfsTer127 | frameshift_variant | - | - | Multiplex | 31130284 | Monies D , et al. (2019) | |
c.5478C>G | p.Leu1826= | missense_variant | De novo | - | Possible multi-generational | 27311832 | Menke LA , et al. (2016) | |
c.5600G>A | p.Arg1867Gln | missense_variant | De novo | - | Possible multi-generational | 27311832 | Menke LA , et al. (2016) | |
c.5371C>G | p.His1791Asp | missense_variant | De novo | - | Simplex | 25533962 | Deciphering Developmental Disorders Study (2014) | |
c.5485C>T | p.His1829Tyr | missense_variant | De novo | - | Simplex | 25533962 | Deciphering Developmental Disorders Study (2014) |
Common Variants (5)
Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Paternal Transmission | Family Type | PubMed ID | Author, Year |
---|---|---|---|---|---|---|---|---|
c.3723-8C>T;c.3837-8C>T;c.3792-8C>T;c.3420-8C>T | N/A | intron_variant | - | - | - | 15830322 | Barnby G , et al. (2005) | |
c.3137-2583T>C;c.3251-2583T>C;c.3206-2583T>C;c.2834-2583T>C | N/A | intron_variant | - | - | - | 15830322 | Barnby G , et al. (2005) | |
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 | - | intron_variant | - | - | - | 15830322 | Barnby G , et al. (2005) | |
c.1217-32G>T;c.1331-32G>T | - | intron_variant | - | - | - | 15830322 | Barnby G , et al. (2005) | |
c.1459+214T>C;c.1573+214T>C | - | intron_variant | - | - | - | 15830322 | Barnby G , et al. (2005) |
SFARI Gene score
High Confidence, Syndromic
Score Delta: Score remained at 1S
criteria met
See SFARI Gene'scoring criteriaWe considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.
The syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."
4/1/2020
Score remained at 1
Description
Rare mutations in the CREBBP gene are associated with two distinct syndromes: Rubinstein-Taybi syndrome, which is frequently caused by either loss-of-function variants or submicroscopic 16p13.3 deletions; and Menke-Hennekam syndrome, which is caused by missense variants in exon 30 or 31 of the gene. A subset of individuals with either of these syndromes has been shown to display autism or autistic behaviors (Schorry et al., 2008; Wincent et al., 2015; Menke et al., 2016; Menke et al., 2018; Banka et al., 2019), although Galera et al., 2009 failed to validate the original findings of Schorry et al., 2008 for individuals with Rubinstein-Taybi syndrome. Genetic association between the CREBBP gene and ASD was observed in an IMGSAC cohort, but this association was not replicated in a second stage (Barnby et al., 2005). De novo missense variants in the CREBBP gene have also been identified in ASD probands from the Simons Simplex Collection (Iossifov et al., 2014; Krumm et al., 2015), as well as in a male ASD proband in Lim et al., 2017.
1/1/2020
Score remained at 1
Description
Rare mutations in the CREBBP gene are associated with two distinct syndromes: Rubinstein-Taybi syndrome, which is frequently caused by either loss-of-function variants or submicroscopic 16p13.3 deletions; and Menke-Hennekam syndrome, which is caused by missense variants in exon 30 or 31 of the gene. A subset of individuals with either of these syndromes has been shown to display autism or autistic behaviors (Schorry et al., 2008; Wincent et al., 2015; Menke et al., 2016; Menke et al., 2018; Banka et al., 2019), although Galera et al., 2009 failed to validate the original findings of Schorry et al., 2008 for individuals with Rubinstein-Taybi syndrome. Genetic association between the CREBBP gene and ASD was observed in an IMGSAC cohort, but this association was not replicated in a second stage (Barnby et al., 2005). De novo missense variants in the CREBBP gene have also been identified in ASD probands from the Simons Simplex Collection (Iossifov et al., 2014; Krumm et al., 2015), as well as in a male ASD proband in Lim et al., 2017.
10/1/2019
Decreased from 4S to 1
New Scoring Scheme
Description
Rare mutations in the CREBBP gene are associated with two distinct syndromes: Rubinstein-Taybi syndrome, which is frequently caused by either loss-of-function variants or submicroscopic 16p13.3 deletions; and Menke-Hennekam syndrome, which is caused by missense variants in exon 30 or 31 of the gene. A subset of individuals with either of these syndromes has been shown to display autism or autistic behaviors (Schorry et al., 2008; Wincent et al., 2015; Menke et al., 2016; Menke et al., 2018; Banka et al., 2019), although Galera et al., 2009 failed to validate the original findings of Schorry et al., 2008 for individuals with Rubinstein-Taybi syndrome. Genetic association between the CREBBP gene and ASD was observed in an IMGSAC cohort, but this association was not replicated in a second stage (Barnby et al., 2005). De novo missense variants in the CREBBP gene have also been identified in ASD probands from the Simons Simplex Collection (Iossifov et al., 2014; Krumm et al., 2015), as well as in a male ASD proband in Lim et al., 2017.
7/1/2019
Decreased from 5 to 4S
Description
Rare mutations in the CREBBP gene are associated with two distinct syndromes: Rubinstein-Taybi syndrome, which is frequently caused by either loss-of-function variants or submicroscopic 16p13.3 deletions; and Menke-Hennekam syndrome, which is caused by missense variants in exon 30 or 31 of the gene. A subset of individuals with either of these syndromes has been shown to display autism or autistic behaviors (Schorry et al., 2008; Wincent et al., 2015; Menke et al., 2016; Menke et al., 2018; Banka et al., 2019), although Galera et al., 2009 failed to validate the original findings of Schorry et al., 2008 for individuals with Rubinstein-Taybi syndrome. Genetic association between the CREBBP gene and ASD was observed in an IMGSAC cohort, but this association was not replicated in a second stage (Barnby et al., 2005). De novo missense variants in the CREBBP gene have also been identified in ASD probands from the Simons Simplex Collection (Iossifov et al., 2014; Krumm et al., 2015), as well as in a male ASD proband in Lim et al., 2017.
Reports Added
[Lessons Learned from Large-Scale, First-Tier Clinical Exome Sequencing in a Highly Consanguineous Population.2019] [Characterization of intellectual disability and autism comorbidity through gene panel sequencing.2019] [Impact of on-site clinical genetics consultations on diagnostic rate in children and young adults with autism spectrum disorder.2019]4/1/2019
Decreased from 5 to 5
Description
Genetic association has been found between the CREBBP gene and ASD in an IMGSAC cohort, but was not replicated in a second stage (Barnby et al., 2005). Rare mutations of the CREBBP gene have been identified in studies of patients with Rubinstein-Taybi syndrome (RTS), with some suggestion for increased autistic behavior (Schorry et al., 2008), that was not validated in a subsequent study (Galera et al., 2009).
10/1/2017
Decreased from 5 to 5
Description
Genetic association has been found between the CREBBP gene and ASD in an IMGSAC cohort, but was not replicated in a second stage (Barnby et al., 2005). Rare mutations of the CREBBP gene have been identified in studies of patients with Rubinstein-Taybi syndrome (RTS), with some suggestion for increased autistic behavior (Schorry et al., 2008), that was not validated in a subsequent study (Galera et al., 2009).
7/1/2017
Decreased from 5 to 5
Description
Genetic association has been found between the CREBBP gene and ASD in an IMGSAC cohort, but was not replicated in a second stage (Barnby et al., 2005). Rare mutations of the CREBBP gene have been identified in studies of patients with Rubinstein-Taybi syndrome (RTS), with some suggestion for increased autistic behavior (Schorry et al., 2008), that was not validated in a subsequent study (Galera et al., 2009).
4/1/2017
Decreased from 5 to 5
Description
Genetic association has been found between the CREBBP gene and ASD in an IMGSAC cohort, but was not replicated in a second stage (Barnby et al., 2005). Rare mutations of the CREBBP gene have been identified in studies of patients with Rubinstein-Taybi syndrome (RTS), with some suggestion for increased autistic behavior (Schorry et al., 2008), that was not validated in a subsequent study (Galera et al., 2009).
Reports Added
[Candidate-gene screening and association analysis at the autism-susceptibility locus on chromosome 16p: evidence of association at GRIN2A and ABAT.2005] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [Massively parallel sequencing of patients with intellectual disability, congenital anomalies and/or autism spectrum disorders with a targeted gene ...2014] [Multiplex ligation-dependent probe amplification detection of an unknown large deletion of the CREB-binding protein gene in a patient with Rubinste...2013] [Rubinstein-Taybi syndrome caused by mutations in the transcriptional co-activator CBP.1995] [Molecular analysis of the CBP gene in 60 patients with Rubinstein-Taybi syndrome.2002] [Whole exome sequencing for a patient with Rubinstein-Taybi syndrome reveals de novo variants besides an overt CREBBP mutation.2015] [Excess of rare, inherited truncating mutations in autism.2015] [Low load for disruptive mutations in autism genes and their biased transmission.2015] [The contribution of de novo coding mutations to autism spectrum disorder2014] [CREBBP and EP300 mutational spectrum and clinical presentations in a cohort of Swedish patients with Rubinstein-Taybi syndrome.2016] [CREBBP mutations in individuals without Rubinstein-Taybi syndrome phenotype.2016] [Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability2016] [Clinical exome sequencing: results from 2819 samples reflecting 1000 families.2016] [De Novo Coding Variants Are Strongly Associated with Tourette Disorder.2017] [Genomic diagnosis for children with intellectual disability and/or developmental delay.2017]10/1/2016
Decreased from 5 to 5
Description
Genetic association has been found between the CREBBP gene and ASD in an IMGSAC cohort, but was not replicated in a second stage (Barnby et al., 2005). Rare mutations of the CREBBP gene have been identified in studies of patients with Rubinstein-Taybi syndrome (RTS), with some suggestion for increased autistic behavior (Schorry et al., 2008), that was not validated in a subsequent study (Galera et al., 2009).
7/1/2016
Decreased from 5 to 5
Description
Genetic association has been found between the CREBBP gene and ASD in an IMGSAC cohort, but was not replicated in a second stage (Barnby et al., 2005). Rare mutations of the CREBBP gene have been identified in studies of patients with Rubinstein-Taybi syndrome (RTS), with some suggestion for increased autistic behavior (Schorry et al., 2008), that was not validated in a subsequent study (Galera et al., 2009).
1/1/2016
Decreased from 5 to 5
Description
Genetic association has been found between the CREBBP gene and ASD in an IMGSAC cohort, but was not replicated in a second stage (Barnby et al., 2005). Rare mutations of the CREBBP gene have been identified in studies of patients with Rubinstein-Taybi syndrome (RTS), with some suggestion for increased autistic behavior (Schorry et al., 2008), that was not validated in a subsequent study (Galera et al., 2009).
Reports Added
[Candidate-gene screening and association analysis at the autism-susceptibility locus on chromosome 16p: evidence of association at GRIN2A and ABAT.2005] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [Massively parallel sequencing of patients with intellectual disability, congenital anomalies and/or autism spectrum disorders with a targeted gene ...2014] [Multiplex ligation-dependent probe amplification detection of an unknown large deletion of the CREB-binding protein gene in a patient with Rubinste...2013] [Rubinstein-Taybi syndrome caused by mutations in the transcriptional co-activator CBP.1995] [Molecular analysis of the CBP gene in 60 patients with Rubinstein-Taybi syndrome.2002] [Whole exome sequencing for a patient with Rubinstein-Taybi syndrome reveals de novo variants besides an overt CREBBP mutation.2015] [Excess of rare, inherited truncating mutations in autism.2015] [Low load for disruptive mutations in autism genes and their biased transmission.2015] [The contribution of de novo coding mutations to autism spectrum disorder2014] [CREBBP and EP300 mutational spectrum and clinical presentations in a cohort of Swedish patients with Rubinstein-Taybi syndrome.2016]4/1/2015
Decreased from 5 to 5
Description
Genetic association has been found between the CREBBP gene and ASD in an IMGSAC cohort, but was not replicated in a second stage (Barnby et al., 2005). Rare mutations of the CREBBP gene have been identified in studies of patients with Rubinstein-Taybi syndrome (RTS), with some suggestion for increased autistic behavior (Schorry et al., 2008), that was not validated in a subsequent study (Galera et al., 2009).
1/1/2015
Decreased from 5 to 5
Description
Genetic association has been found between the CREBBP gene and ASD in an IMGSAC cohort, but was not replicated in a second stage (Barnby et al., 2005). Rare mutations of the CREBBP gene have been identified in studies of patients with Rubinstein-Taybi syndrome (RTS), with some suggestion for increased autistic behavior (Schorry et al., 2008), that was not validated in a subsequent study (Galera et al., 2009).
7/1/2014
Increased from No data to 5
Description
Genetic association has been found between the CREBBP gene and ASD in an IMGSAC cohort, but was not replicated in a second stage (Barnby et al., 2005). Rare mutations of the CREBBP gene have been identified in studies of patients with Rubinstein-Taybi syndrome (RTS), with some suggestion for increased autistic behavior (Schorry et al., 2008), that was not validated in a subsequent study (Galera et al., 2009).
4/1/2014
Increased from No data to 5
Description
Genetic association has been found between the CREBBP gene and ASD in an IMGSAC cohort, but was not replicated in a second stage (Barnby et al., 2005). Rare mutations of the CREBBP gene have been identified in studies of patients with Rubinstein-Taybi syndrome (RTS), with some suggestion for increased autistic behavior (Schorry et al., 2008), that was not validated in a subsequent study (Galera et al., 2009).
Krishnan Probability Score
Score 0.59757463566427
Ranking 425/25841 scored genes
[Show Scoring Methodology]
ExAC Score
Score 0.99999999999979
Ranking 31/18225 scored genes
[Show Scoring Methodology]
Iossifov Probability Score
Score 0.926
Ranking 116/239 scored genes
[Show Scoring Methodology]
Sanders TADA Score
Score 0.72057276341926
Ranking 1299/18665 scored genes
[Show Scoring Methodology]
Larsen Cumulative Evidence Score
Score 5
Ranking 278/461 scored genes
[Show Scoring Methodology]
Zhang D Score
Score 0.56836094114003
Ranking 182/20870 scored genes
[Show Scoring Methodology]
CNVs associated with CREBBP(1 CNVs)
Sort By:
16p13.3 | 69 | Deletion-Duplication | 99 / 539 |
Interactome
- Protein Binding
- DNA Binding
- RNA Binding
- Protein Modification
- Direct Regulation
- ASD-Linked Genes
Interaction Table
Interactor Symbol | Interactor Name | Interactor Organism | Interactor Type | Entrez ID | Uniprot ID |
---|---|---|---|---|---|
BRCA2 | breast cancer 2, early onset | Human | Protein Binding | 675 | P51587 |
C3ORF62 | chromosome 3 open reading frame 62 | Human | Protein Binding | 375341 | Q6ZUJ4 |
CCND3 | cyclin D3 | Human | Protein Binding | 896 | P30281 |
CTGF | Connective tissue growth factor | Human | Protein Binding | 1490 | P29279 |
RPS6KA2 | ribosomal protein S6 kinase polypeptide 2 | Rat | Protein Binding | 117269 | F1M7N7 |
STAT2 | Signal transducer and activator of transcription 2 | Human | Protein Binding | 6773 | P52630 |
TXNDC11 | thioredoxin domain containing 11 | Human | Protein Binding | 51061 | Q6PKC3 |