CREBBP (CREB binding protein)

Alias_names	RSTS
	Rubinstein-Taybi syndrome
Alias_symbol (synonym)	RTS
	CBP
	KAT3A
Other alias	CBP (cAMP Response Element-Binding Protein (CREB)-binding protein)
	RSTS (Rubinstein-Taybi syndrome)
HGNC (Hugo)	CREBBP
LocusID (NCBI)	1387
Atlas_Id	42
Location	16p13.3  [Link to chromosome band 16p13]
Location_base_pair	Starts at 3725055 and ends at 3880120 bp from pter ( according to hg19-Feb_2009)  [Mapping CREBBP.png]
Local_order	centromere-ADCY9-CREBBP-TRAP1-telomere.
	A: CBP (16p22) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics. B: Map showing the position of BAC clone RP11-1072J2 (UCSC Genome Browser assembly Mar 2006), centered on CREBBP gene (top) and two images of partial metaphases from normal controls showing, after FISH, CREBBP-specific signals at 16p13.3 (bottom).

Note
Entity	t(8;16)(p11;p13)/M4 AML --> MOZ/ CREBBP
Disease	Acute non lymphocytic leukemia (AML) and treatment related AML (t-AML).
Prognosis	Poor: remission is obtained in half cases; survival is often less than 1yr.
Cytogenetics	+8 as an additional anomalies in half cases.
Hybrid/Mutated Gene	5' MOZ - 3' CBP.
Abnormal Protein	N-term finger motifs and acetyl transferase from MOZ fused to most of CBP, with a breakpoint in 5' of the CREB binding domain of CBP.
Entity	t(10;16)(q22;p13)/M4 AML --> MYST4/ CREBBP
Disease	Acute myeloid leukaemia (AML) M4/M5a and therapy-related myelodysplastic syndromes (MDS). Only 4 cases described.
Prognosis	Poor, bad response to chemotherapy.
Hybrid/Mutated Gene	5' MYST4 - 3' CBP.
Abnormal Protein	In-frame fusion between MYST4 exon 17 and CREBBP exon 3. Variants fusing MYST4 exon 16 and CREBBP exon 5; MYST4 exon 17 and CREBBP exon 7 have been also described. CREBBP-MYST4 transcripts have been detected.
Entity	t(11;16)(q23;p13)/t-AML --> KMT2A/ CREBBP
Disease	Therapy related AML (t-AML); should be very close to the t(11;22)(q23;q13).
Prognosis	Likely to be poor.
Hybrid/Mutated Gene	5' MLL - 3'CBP.
Abnormal Protein	N-term AT hook and DNA methyltransferase from MLL fused to most of CBP; variable brakpoint in CBP: either 5' to the CREB binding domain (like in the t(8;16)), or just upstream the bromodomain.
Entity	Rubinstein-Taybi syndrome
Note	Due to CBP haploinsufficiency.
Disease	Rare autosomal dominant congenital disorder characterized by postnatal growth retardation and psychomotor developmental delay, skeletal anomalies (broad and duplicated distal phalanges of thumbs and halluces are a landmark sign) and specific facial dysmorphisms. The latter include down-slanted palpebral fissures, broad nasal bridge, beaked nose and micrognathia. In addition, patients with RSTS have an increased, although not well documented, risk of tumor formation.
	Top: Ideogram of chromosome 16 and chromosomal localisation of the CREBBP gene. Middle: the genomic region including CREBBP (red) and flanking genes is zoomed. Deletions spanning CREBBP and adjacent sequences (accounting for about 10% of CREBBP mutations) are indicated by black lines. Mosaic deletions (only 3 so far detected) are asterisked; dotted lines target low-resolution mapped breakpoints. So far 22 deletions have been reported and the differently sized ones (21) are here diagrammed. Bottom: structure of CREBBP gene and protein. Different colours are used to link gene exons (pictured by rectangles) and corresponding protein domains. Different reported point mutations (n.108 in Leiden Open Variation Database) are shown: filled circles (nonsense) and dotted circles (frameshift), squares (missense) and triangles (splicing). Most mutations cluster to exons encoding the HAT domain. Known domains from the carbossi-terminal are: Q= poly Glutaminic stretch, Zn=zinc-finger, HAT= acetyl transferasic, Bromo= Bromodomain, KIX= CREB binding).

	Localization of breakpoints affecting CREBBP and partner genes in leukaemia-associated balanced translocations.

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