Gene Report

Basic information

Related studies

Functional annotation

Related other genetic factors

Overlap with SZ and MDD

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Basic Info

Approved Symbol	CREB1
Approved Name	cAMP responsive element binding protein 1
Location	2q34
Position	chr2:207529737-207603431, 1
External Links	HGNC: 2345 Entrez Gene: 1385 Ensembl: ENSG00000118260 UCSC: uc002vcc.3
No. of Studies	2 (Positive: 1; Negative: 1; trend: 0)
Overlap with SZ?	NO
Overlap with MDD?	YES

Gene related studies (count: 2)

Reference	Tested Markers	Statistical Values/Author Comments	Result Category	Comment on Study
Crisafulli, C.,2012	SNP: rs6740584	We failed to observe any association of the 14 SNPs genotypes or alleles with clinical improvement, response and remission rates as well as final outcomes in any of such disorders. Our findings suggest that 14 SNPs under investigation in our study do not influence diagnosis and treatment response in patients with MDD and BD.	Negative	Comment on Study
Li M, 2013	SNP: rs6785, rs2709370	Here, we studied the MDD-related gene CREB1 in a set of independent BD sample groups of European ancestry (a total of 64 888 subjects) and identified multiple SNPs significantly associated with BD.	Positive	Comment on Study

Gene functional annotation

Gene related GO terms (count: 65)

GO terms by PBA (count: 5)

ID	Name	Type	Evidence[PMID]	No. of Genes in BDgene
GO:0003700	sequence-specific DNA binding transcription factor activity	molecular function	IDA[8798441]	66
GO:0005634	nucleus	cellular component	IDA[8798441]	283
GO:0045087	innate immune response	biological process	TAS	49
GO:0007268	synaptic transmission	biological process	TAS	116
GO:0007411	axon guidance	biological process	TAS	60

GO terms by database search (count: 60)

ID	Name	Type	Evidence[PMID]	No. of Genes in BDgene
GO:0002224	toll-like receptor signaling pathway	biological process	TAS	10
GO:0005515	protein binding	molecular function	IPI[10722738]	563
GO:0038123	toll-like receptor TLR1:TLR2 signaling pathway	biological process	TAS	8
GO:0034138	toll-like receptor 3 signaling pathway	biological process	TAS	7
GO:0001190	RNA polymerase II transcription factor binding transcription factor activity involved in positive regulation of transcription	molecular function	IDA[19861239]	4
GO:0071294	cellular response to zinc ion	biological process	IEA	2
GO:0038095	Fc-epsilon receptor signaling pathway	biological process	TAS	19
GO:0007165	signal transduction	biological process	TAS	136
GO:0021983	pituitary gland development	biological process	IEA	4
GO:0034162	toll-like receptor 9 signaling pathway	biological process	TAS	7
GO:0034166	toll-like receptor 10 signaling pathway	biological process	TAS	6
GO:0046887	positive regulation of hormone secretion	biological process	IEA	2
GO:0034134	toll-like receptor 2 signaling pathway	biological process	TAS	8
GO:0045944	positive regulation of transcription from RNA polymerase II promoter	biological process	IDA[1655749]	91
GO:0033363	secretory granule organization	biological process	IEA	1
GO:0042493	response to drug	biological process	IEA	57
GO:0034142	toll-like receptor 4 signaling pathway	biological process	TAS	8
GO:0010033	response to organic substance	biological process	IDA[8798441]	3
GO:0045893	positive regulation of transcription, DNA-templated	biological process	ISS	58
GO:0003712	transcription cofactor activity	molecular function	TAS[8552098]	4
GO:0001077	RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription	molecular function	IC	18
GO:0051403	stress-activated MAPK cascade	biological process	TAS	8
GO:0006366	transcription from RNA polymerase II promoter	biological process	IDA[19861239]	31
GO:0003705	RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity	molecular function	IDA[19861239]	7
GO:0006468	protein phosphorylation	biological process	IDA[8798441]	42
GO:0048015	phosphatidylinositol-mediated signaling	biological process	TAS	17
GO:0007613	memory	biological process	IEA	22
GO:0034146	toll-like receptor 5 signaling pathway	biological process	TAS	6
GO:0007202	activation of phospholipase C activity	biological process	TAS	15
GO:0035497	cAMP response element binding	molecular function	IDA[19861239]	1
GO:0050821	protein stabilization	biological process	ISS	12
GO:0008543	fibroblast growth factor receptor signaling pathway	biological process	TAS	21
GO:0002755	MyD88-dependent toll-like receptor signaling pathway	biological process	TAS	8
GO:0045672	positive regulation of osteoclast differentiation	biological process	IEA	5
GO:0000980	RNA polymerase II distal enhancer sequence-specific DNA binding	molecular function	IDA[19861239]	5
GO:0006996	organelle organization	biological process	TAS	23
GO:0048011	neurotrophin TRK receptor signaling pathway	biological process	TAS	33
GO:0005654	nucleoplasm	cellular component	IDA; TAS	163
GO:0046889	positive regulation of lipid biosynthetic process	biological process	ISS	5
GO:1990589	ATF4-CREB1 transcription factor complex	cellular component	IDA[12871976]	2
GO:0060430	lung saccule development	biological process	IEA	1
GO:0033762	response to glucagon	biological process	ISS	3
GO:0005719	nuclear euchromatin	cellular component	IDA[19861239]	5
GO:0035666	TRIF-dependent toll-like receptor signaling pathway	biological process	TAS	7
GO:0010944	negative regulation of transcription by competitive promoter binding	biological process	IDA[19861239]	2
GO:0007595	lactation	biological process	IEA	5
GO:0007219	Notch signaling pathway	biological process	TAS	14
GO:0008361	regulation of cell size	biological process	IEA	2
GO:0040018	positive regulation of multicellular organism growth	biological process	IEA	8
GO:0045600	positive regulation of fat cell differentiation	biological process	ISS	9
GO:0007005	mitochondrion organization	biological process	TAS	8
GO:0019899	enzyme binding	molecular function	IPI[23382074]	34
GO:0007173	epidermal growth factor receptor signaling pathway	biological process	TAS	22
GO:0016032	viral process	biological process	IEA	26
GO:0002756	MyD88-independent toll-like receptor signaling pathway	biological process	TAS	7
GO:0038124	toll-like receptor TLR6:TLR2 signaling pathway	biological process	TAS	8
GO:0060509	Type I pneumocyte differentiation	biological process	IEA	3
GO:0001102	RNA polymerase II activating transcription factor binding	molecular function	IPI[19861239]	5
GO:0007623	circadian rhythm	biological process	ISS	40
GO:0000978	RNA polymerase II core promoter proximal region sequence-specific DNA binding	molecular function	IDA[9065434]	23

Gene related KEGG pathways (count: 3)

KEGG pathways by PBA (count: 0)

KEGG pathways by database search (count: 3)

ID	Name	No. of Genes in BDgene
hsa05215	Prostate cancer	18
hsa04916	Melanogenesis	16
hsa04612	Antigen processing and presentation	7

Gene related BioCarta pathways (count: 14)

BioCarta pathways by PBA (count: 1)

ID	Name	No. of Genes in BDgene	Brief Description
HuntingtonPathway	Inhibition of Huntington's disease neurodegeneration by histone deacetylase inhibitors	3

BioCarta pathways by database search (count: 13)

ID	Name	No. of Genes in BDgene
CaCaMPathway	Ca++/ Calmodulin-dependent Protein Kinase Activation	3
HBxPathway	Calcium Signaling by HBx of Hepatitis B virus	1
dreampathway	Repression of Pain Sensation by the Transcriptional Regulator DREAM	4
gpcrPathway	Signaling Pathway from G-Protein Families	7
carm1Pathway	Transcription Regulation by Methyltransferase of CARM1	4
arenrf2Pathway	Oxidative Stress Induced Gene Expression Via Nrf2	1
p38mapkPathway	p38 MAPK Signaling Pathway	3
erk5Pathway	Role of Erk5 in Neuronal Survival	5
hifPathway	Hypoxia-Inducible Factor in the Cardiovascular System	3
mapkPathway	MAPKinase Signaling Pathway	4
melanocytepathway	Melanocyte Development and Pigmentation Pathway	2
crebPathway	Transcription factor CREB and its extracellular signals	8
hcmvPathway	Human Cytomegalovirus and Map Kinase Pathways	5

Gene related interactors from protein-protein interactions data in HPRD (count: 34)

Gene	Interactor	Interactor in BDgene?	Experiment Type	PMID
CREB1	SMARCA4	NO	in vivo	16675956
CREB1	SGK1	NO	in vitro;in vivo	15733869
CREB1	ATM	NO	in vitro	16293623 , 15073328
CREB1	C14orf1	NO	yeast 2-hybrid	16169070
CREB1	PDX1	NO	in vivo	7505393
CREB1	VIM	NO	yeast 2-hybrid	16169070
CREB1	TSSK4	NO	in vitro;yeast 2-hybrid	15964553
CREB1	RPS6KA3	NO	in vitro;in vivo	9687510 , 11175347 , 9829964 , 8688081 , 11160957
CREB1	GTF2F2	NO	in vivo	8628277
CREB1	ATF1	NO	in vitro;in vivo	8384217 , 1655749
CREB1	MAPKAPK2	NO	in vitro	8887554
CREB1	NR3C1	YES	in vitro	7621901 , 8449898
CREB1	EDF1	NO	in vitro	10567391
CREB1	RPS6KA1	NO	in vitro	9687510 , 11175347 , 9829964 , 8688081 , 12235136
CREB1	CHD3	NO	yeast 2-hybrid	16169070
CREB1	RECQL5	NO	yeast 2-hybrid	16169070
CREB1	HPS6	NO	yeast 2-hybrid	16169070
CREB1	KCNIP3	NO	in vitro;in vivo	12198160
CREB1	DYRK1A	NO	in vivo	15694837
CREB1	PRKG1	NO	in vitro	9687510 , 11175347 , 9829964 , 8688081
CREB1	SMARCA5	NO	in vivo	16675956
CREB1	RPS6KA2	YES	in vitro;in vivo	9687510 , 11175347 , 9829964 , 8688081 , 11698596
CREB1	GLI2	YES	in vitro;in vivo	10074179
CREB1	RAB1A	NO	yeast 2-hybrid	16169070
CREB1	MAPK14	NO	in vivo	11377386
CREB1	SRF	NO	in vitro;in vivo	9388250 , 7551568
CREB1	SOX9	NO	in vivo	19113914
CREB1	CEBPB	NO	in vitro;in vivo;yeast 2-hybrid	12773552
CREB1	FHL5	NO	in vivo;yeast 2-hybrid	11046156
CREB1	AKT1	YES	in vitro	9829964
CREB1	THRA	YES	in vitro;in vivo	12805224
CREB1	RPS6KA4	NO	in vitro	9792677 , 9687510 , 11175347 , 9829964 , 8688081
CREB1	ABL1	NO	in vivo	7565761
CREB1	RPS6KA5	NO	in vitro;in vivo	9687510 , 11018520 , 11909979 , 16223362

Related other genetic factors

Gene related SNPs (count: 32)

Literature-origin SNPs (count: 3)

rs_ID	Location	Functional Annotation	No. of Studies (Positive/Negative/Trend)
rs6740584	chr2:207564627 - 207564627(1)	downstream_gene_variant; intron_variant; NMD_transcript_variant; non_coding_transcript_variant	1(0/1/0)
rs2709370	chr2:207517878 - 207517878(1)	intron_variant; non_coding_transcript_variant	1(1/0/0)
rs6785	chr2:207603273 - 207603273(1)	3_prime_UTR_variant; downstream_gene_variant; intron_variant	1(1/0/0)

LD-proxies (count: 29)

rs_ID	Location	Functional Annotation
rs2551921	chr2:207570831 - 207570831(1)	downstream_gene_variant; intron_variant; NMD_transcript_variant; non_coding_transcript_variant; upstream_gene_variant
rs2551923	chr2:207577052 - 207577052(1)	downstream_gene_variant; intron_variant; NMD_transcript_variant; non_coding_transcript_variant
rs2709387	chr2:207577371 - 207577371(1)	downstream_gene_variant; intron_variant; NMD_transcript_variant; non_coding_transcript_variant
rs2709392	chr2:207589915 - 207589915(1)	intron_variant; NMD_transcript_variant; non_coding_transcript_variant
rs2464978	chr2:207593194 - 207593194(1)	intron_variant; NMD_transcript_variant; non_coding_transcript_variant; upstream_gene_variant
rs13029936	chr2:207600820 - 207600820(1)	3_prime_UTR_variant; downstream_gene_variant; intron_variant
rs2551928	chr2:207601054 - 207601054(1)	3_prime_UTR_variant; downstream_gene_variant; intron_variant
rs1806584	chr2:207601546 - 207601546(1)	3_prime_UTR_variant; downstream_gene_variant; intron_variant
rs2551640	chr2:207543169 - 207543169(1)	intron_variant; non_coding_transcript_variant
rs1045780	chr2:207602426 - 207602426(1)	3_prime_UTR_variant; downstream_gene_variant; intron_variant
rs10932201	chr2:207561533 - 207561533(1)	downstream_gene_variant; intron_variant; NMD_transcript_variant; non_coding_transcript_variant
rs2551929	chr2:207603748 - 207603748(1)	downstream_gene_variant; intron_variant
rs11904814	chr2:207562074 - 207562074(1)	downstream_gene_variant; intron_variant; NMD_transcript_variant; non_coding_transcript_variant
rs2256941	chr2:207604460 - 207604460(1)	downstream_gene_variant; intron_variant
rs2254137	chr2:207579304 - 207579304(1)	downstream_gene_variant; intron_variant; NMD_transcript_variant; non_coding_transcript_variant
rs2709396	chr2:207605724 - 207605724(1)	downstream_gene_variant; intron_variant
rs2551931	chr2:207606756 - 207606756(1)	downstream_gene_variant; intron_variant
rs2253206	chr2:207527254 - 207527254(1)	intron_variant; non_coding_transcript_variant; upstream_gene_variant
rs889895	chr2:207534205 - 207534205(1)	intron_variant; non_coding_transcript_variant; upstream_gene_variant
rs2551639	chr2:207531463 - 207531463(1)	intron_variant; non_coding_transcript_variant; upstream_gene_variant
rs2709356	chr2:207547368 - 207547368(1)	intron_variant; non_coding_transcript_variant; upstream_gene_variant
rs2551641	chr2:207545543 - 207545543(1)	intron_variant; non_coding_transcript_variant; upstream_gene_variant
rs2551642	chr2:207548773 - 207548773(1)	intron_variant; non_coding_transcript_variant; upstream_gene_variant
rs2709357	chr2:207547808 - 207547808(1)	intron_variant; non_coding_transcript_variant; upstream_gene_variant
rs2709402	chr2:207556253 - 207556253(1)	intron_variant; non_coding_transcript_variant; upstream_gene_variant
rs2709399	chr2:207553377 - 207553377(1)	intron_variant; non_coding_transcript_variant
rs2551920	chr2:207567106 - 207567106(1)	intron_variant; NMD_transcript_variant; non_coding_transcript_variant
rs2551919	chr2:207565659 - 207565659(1)	intron_variant; NMD_transcript_variant; non_coding_transcript_variant
rs2551645	chr2:207586064 - 207586064(1)	intron_variant; NMD_transcript_variant; non_coding_transcript_variant

Gene related CNVs (count: 0)

Gene related other variants (count: 0)

Gene related regions (count: 5)

Region Name	Position	No. of Studies (Positive/Negative/Trend)
2q21-q33	chr2:129100000-208200000	1 (0/0/1)
2q33.3	chr2:204100000-208200000	1 (0/1/0)
Chr 2	chr2:0-242193529	3 (0/3/0)
2q24-33	chr2:154000000-208200000	1 (1/0/0)
2q32.3-q33	chr2:191100000-208200000	1 (0/1/0)

Overlap with schizophrenia (SZ) and major depressive disorder (MDD)

Gene relationship with SZ

Gene relationship with MDD

Overlap with MDD from cross-disorder studies (count: 1)

Reference	Description	Category in MDD
22386572	We failed to observe any association of the 14 SNPs genotypes or alleles with clinical improvement, response and remission rates as well as final outcomes in any of such disorders. Our findings suggest that 14 SNPs under investigation in our study do not influence diagnosis and treatment response in patients with MDD and BD.	Negative

Overlap with MDD from candidate gene intersection analysis (count: 9)

Reference	Description	Category in MDD	Link in MK4MDD
12457397	The region between the markers that yielded the peak LOD score includes the CREB1 gene	Pos	CREB1
12851637	Sequence variations in the CREB1 promoter and intron 8 have been detected that cosegregate with Mood Disorders, or their absence, in women from these families, identifying CREB1 as a sex-limited susceptibility gene for unipolar Mood Disorders.	Pos	CREB1
20533262	There was strong positive association between the rs10932201-rs6740584 haplotype of the CREB1 and MDD (P=0.00003241), and both haplotypes of A-C and A-T were significantly associated with MDD (P=0.020 and P=0.00022)	Pos	CREB1
19194961	None of these markers were significant in stage 2 in either sex individually or combined	Neg	CREB1
20471034	We also observed that variations in other mRNA expression were associated with treatment efficacy or clinical improvement (CREB1, HDAC5, HSPA2, HTR1B, HTR2A, and SLC6A4/5HTT).	Pos	CREB1
17258370	Levels of HDAC5 and CREB mRNA were significantly higher in drug-free depressive patients than those of controls	Pos	CREB1
14582139	The highest maximum LOD score observed, 8.19 (genome-wide adjusted P << 0.0001), occurred for Recurrent Major Depressive Disorder (R-MDD) at D2S2321 (205 cM), located 121 kb proximal to CREB1	Pos	CREB1
19517574	The results continue to support sex-specific linkage of the CREB1 region to mood disorders among women from families with RE-MDD.	Pos	CREB1

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Region: chr2:207529737..207603431 View in gBrowse