CREB1

Summary

CREB1 (cAMP responsive element binding protein 1, HGNC:2345) is a protein-coding gene on chromosome 2q33.3, encoding Cyclic AMP-responsive element-binding protein 1 (P16220). Phosphorylation-dependent transcription factor that stimulates transcription upon binding to the DNA cAMP response element (CRE), a sequence present in many viral and cellular promoters.

This gene encodes a transcription factor that is a member of the leucine zipper family of DNA binding proteins. This protein binds as a homodimer to the cAMP-responsive element, an octameric palindrome. The protein is phosphorylated by several protein kinases, and induces transcription of genes in response to hormonal stimulation of the cAMP pathway. Alternate splicing of this gene results in several transcript variants encoding different isoforms.

Source: NCBI Gene 1385 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 37 total
• Phenotypes (HPO): 2
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Transcription factor: yes — 494 downstream targets (CollecTRI)
• MANE Select transcript: NM_004379

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2345
Approved symbol	CREB1
Name	cAMP responsive element binding protein 1
Location	2q33.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000118260
Ensembl biotype	protein_coding
OMIM	123810
Entrez	1385

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 16 protein_coding, 4 protein_coding_CDS_not_defined, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000353267, ENST00000414681, ENST00000418081, ENST00000421139, ENST00000430624, ENST00000432329, ENST00000445803, ENST00000446449, ENST00000448277, ENST00000451164, ENST00000452474, ENST00000455757, ENST00000457101, ENST00000464407, ENST00000480189, ENST00000494094, ENST00000494983, ENST00000896942, ENST00000896943, ENST00000915136, ENST00000961890, ENST00000961891, ENST00000961892

RefSeq mRNA: 6 — MANE Select: NM_004379 NM_001320793, NM_001371426, NM_001371427, NM_001371428, NM_004379, NM_134442

CCDS: CCDS2374, CCDS2375

Canonical transcript exons

ENST00000353267 — 8 exons

Exon	Start	End
ENSE00001887644	207529962	207530134
ENSE00003553318	207577505	207577655
ENSE00003594653	207560226	207560372
ENSE00003621510	207555628	207555749
ENSE00003656413	207575272	207575454
ENSE00003659734	207567463	207567563
ENSE00003784251	207570179	207570321
ENSE00003847639	207596914	207605988

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 95.90.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 48.2984 / max 585.8434, expressed in 1824 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
24877	26.2757	1818
24876	9.2033	1742
24880	7.8425	1523
24878	2.4492	1305
24879	1.5077	912
24881	0.5819	154
24875	0.1358	70
24882	0.0963	26
24874	0.0632	20
24885	0.0544	7

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	95.90	gold quality
calcaneal tendon	UBERON:0003701	95.06	gold quality
bone marrow cell	CL:0002092	94.26	gold quality
superficial temporal artery	UBERON:0001614	94.16	gold quality
trabecular bone tissue	UBERON:0002483	94.06	gold quality
cortical plate	UBERON:0005343	93.98	gold quality
left testis	UBERON:0004533	93.97	gold quality
ganglionic eminence	UBERON:0004023	93.94	gold quality
skin of hip	UBERON:0001554	93.83	gold quality
embryo	UBERON:0000922	93.70	gold quality
right testis	UBERON:0004534	93.57	gold quality
epithelium of nasopharynx	UBERON:0001951	93.56	gold quality
bone marrow	UBERON:0002371	93.28	gold quality
testis	UBERON:0000473	93.19	gold quality
tonsil	UBERON:0002372	93.18	gold quality
parietal pleura	UBERON:0002400	93.10	gold quality
visceral pleura	UBERON:0002401	92.93	gold quality
colonic epithelium	UBERON:0000397	92.91	gold quality
ventricular zone	UBERON:0003053	92.59	gold quality
islet of Langerhans	UBERON:0000006	92.25	gold quality
germinal epithelium of ovary	UBERON:0001304	92.23	gold quality
upper leg skin	UBERON:0004262	92.22	gold quality
palpebral conjunctiva	UBERON:0001812	92.12	gold quality
mucosa of paranasal sinus	UBERON:0005030	92.11	gold quality
tendon	UBERON:0000043	92.06	gold quality
pleura	UBERON:0000977	92.04	gold quality
blood	UBERON:0000178	91.73	gold quality
lower lobe of lung	UBERON:0008949	91.65	gold quality
penis	UBERON:0000989	91.49	gold quality
mammalian vulva	UBERON:0000997	91.23	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

494 targets.

Target	Regulation
AANAT	Activation
ABCA1	Activation
ABCB1	Unknown
ACACA	Activation
ACHE	Activation
ACSL4	Unknown
ADAM2
ADARB1	Repression
ADCYAP1	Unknown
ADIPOQ	Unknown
ADM	Activation
ADORA2A
ADRA1A	Unknown
AGER	Activation
AGT	Activation
AGTR1	Unknown
AICDA	Unknown
AKAP8L	Activation
AKT1	Unknown
ALAS2	Unknown
ANG	Activation
ANGPTL2	Repression
AP1	Repression
APEX1	Unknown
AQP2	Activation
AQP3	Unknown
AR	Unknown
AREG	Activation
ARG1	Activation
ARMCX1	Activation

JASPAR motifs

Motif	Name	Family
MA0018.1	CREB1	CREB-related factors
MA0018.2	CREB1	CREB-related factors
MA0018.3	CREB1	CREB-related factors
MA0018.4	CREB1	CREB-related factors
MA0018.5	CREB1	CREB-related factors

JASPAR matrix evidence (PMIDs): PMID:8264613, PMID:17916232

Upstream regulators (CollecTRI, top): AP1, ATF1, ATF4, ATF5, ATF6, CEBPA, CREB1, CREBBP, CREM, FOSB, FOXO4, HOXA9, LYL1, NFKB, NR3C1, RELA, SMAD3, SMAD4, SP1, SRF, THRB, TP53, USF1, YY1

miRNA regulators (miRDB)

437 targeting CREB1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997

Literature-anchored findings (GeneRIF, showing 40)

• review of CREB transcription factor involvment with spermatogenesis (PMID:11988318)
• Prostaglandin-E2 enhances EPO-mediated STAT5 transcriptional activity by serine phosphorylation of CREB. (PMID:12091337)
• CREB and sterol regulatory element binding protein cooperate in transactivating CYP51. (PMID:12145339)
• is co-expressed with CREB and CBP in extravillous cytotrophoblasts, revealing the in vivo relevance of this transactivation pathway (PMID:12183445)
• CREB-DNA binding by magnetic fields is dependent on calcium ions. (PMID:12200150)
• hGRP-R activation stimulated sustained cyclic AMP response element binding protein (CREB) phosphorylation and transactivation in duodenal cancer cells through a protein kinase C and partially p38 mitogen-activated protein kinase-dependent pathway. (PMID:12220644)
• Oct-1 potentiates CREB-dependent cyclin D1 transcriptional activity by a phospho-CREB and CREB binding protein-independent mechanism (PMID:12391146)
• CREB1 plays an important role in the trans-activation of the MHC class II trans-activator (CIITA) promoter III in B cells. (PMID:12391222)
• Structurally distinct modes of recognition of the KIX domain of CBP by Jun and CREB (PMID:12437352)
• CREB response to hypoxia is modified by small ubiquitin-related modifier-1 (SUMO-1) (PMID:12552083)
• Here we show that HDAC1 associates with and blocks Ser133 phosphorylation of CREB during pre-stimulus and attenuation phases of the cAMP response (PMID:12567184)
• CREB1 associates with TIF2 and is essential for cell transformation. (PMID:12676584)
• IL1beta and TNFalpha activation of MSK1 and CREB and cAMP-response element signaling cascades occurs via ERK/p38 MAP kinases and are crucial aspects of the intracellular mechanisms that mediate MUC5AC gene expression (PMID:12690113)
• Levels of CREB mRNA in thyroid carcinomas, but not in adenomas, were significantly lower than in corresponding normal tissue. (PMID:12720543)
• Tissue transglutaminase directly regulates adenylyl cyclase resulting in enhanced cAMP-response element-binding protein (CREB) activation. (PMID:12743114)
• The involvement of CREB in STAT5 transactivation was demonstrated by serine-133-mutated CREB, which completely blocked the SCF effect. In addition, the CREB-binding protein CBP/p300 was shown to be essential for EPO- and SCF-mediated STAT5 transactivation (PMID:12829027)
• 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. (PMID:12851637)
• observed CREB phosphorylation via signal pathways and binding of CREB to the cAMP-responsive element after treatment with oxidized phospholipids (PMID:14523007)
• role in assembly of CBP-CREB-HTLV-1 tax coactivator-activator complex (PMID:14580193)
• CREB-binding protein interacts preferentially with the glycosylated form of Stat5 (PMID:14597631)
• activation of BTK and the subsequent phosphorylation of CREB at Ser-133 are important in the neuronal differentiation of hippocampal progenitor cells. (PMID:14597636)
• chronic activation CREB and p90RSK in the epileptic hippocampus may be closely associated with the histopathological changes of Ammon’s horn sclerosis (PMID:14646589)
• CREB-1/CREM-1 have roles as regulators of macrophage differentiation (PMID:14754893)
• CREB is activated by TNF/TNFR1 signaling through a p38MAPK/MSK1 signaling pathway. (PMID:14761884)
• CREB has a role in PPARgamma2 inhibition of cyclin D1 transcription in hepatocytes (PMID:14764597)
• In VSMCs, LDL-induced mitogenesis involves NOR-1 upregulation through a CREB-dependent mechanism. CREB could play a role in the modulation by LDL of key genes (containing CRE sites) involved in atherogenesis. (PMID:14962944)
• CRH plays pathogenic role in modulating inflammatory joint disease with CREB/ATF family of transcription factors as principal effector molecules of proinflammatory mediator action in rheumatoid arthritis. (PMID:15077295)
• identified the in vivo binding sites of CREB1 across the entire human chromosome 22; a large number of potential gene targets for CREB1 have been identified, raising the possibility that it has important roles in a variety of cellular processes (PMID:15082775)
• CREB suppresses the glioblastoma proliferative effect of the stress-induced acetylcholinesterase variant, AChE-R (PMID:15153340)
• Resistance to various antifolates may potentially be associated with impaired activity of Galphas or their coupled receptors, resulting in loss of CREB-1 phosphorylation. (PMID:15340044)
• This review article highlights the current findings on the role of nucleus accumbal and amygdaloid CREB signaling in behavioral consequences of alcohol use and abuse. (PMID:15500908)
• SDF-1/CXCL12 enhanced cell survival in synergy with other cytokines involves activation of CREB and induction of Mcl-1 and c-Fos (PMID:15588513)
• p90 ribosomal S 6 protein kinase 1 (RSK1) mediates the PGE2-induced phosphorylation of cAMP-response element binding protein (PMID:15615708)
• affects the expression of 958 genes in myometrium (PMID:15691874)
• CREB phosphorylation alone is not a reliable predictor of target gene activation and that additional CREB regulatory partners are required for recruitment of the transcriptional apparatus to the promoter. (PMID:15753290)
• CREB promotes abnormal proliferation and survival of myeloid cells in vitro and in vivo through upregulation of specific target genes and thus is implicated in myeloid cell transformation. (PMID:15837624)
• The contribution of CREB to interferon(IFN)-gamma upregulation is demonstrated in T cells from normal tuberculin reactors, compared to T cells from tuberculosis patients with ineffective immunity, which show reduced CREB activity and low IFN-gamma levels. (PMID:15879136)
• the PI3-kinase/p38(MAPK)/CREB pathway contributes to the EGF activation of NF-IL6beta gene expression (PMID:15901830)
• Pellino3 is a novel upstream regulator of p38 MAPK and activates CREB in a p38-dependent manner (PMID:15917247)
• Results do not support the previous evidence for CREB1 as a major factor contributing to depression. (PMID:15999345)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	creb1b	ENSDARG00000093420
mus_musculus	Creb1	ENSMUSG00000025958
rattus_norvegicus	Creb1	ENSRNOG00000013412
drosophila_melanogaster	Atf6	FBGN0033010
drosophila_melanogaster	CrebB	FBGN0265784
caenorhabditis_elegans		WBGENE00000222
caenorhabditis_elegans		WBGENE00000793

Paralogs (9): CREB3L3 (ENSG00000060566), CREM (ENSG00000095794), CREB3 (ENSG00000107175), ATF6 (ENSG00000118217), ATF1 (ENSG00000123268), CREB3L4 (ENSG00000143578), CREB3L1 (ENSG00000157613), CREB3L2 (ENSG00000182158), ATF6B (ENSG00000213676)

Protein

Protein identifiers

Cyclic AMP-responsive element-binding protein 1 — P16220 (reviewed: P16220)

All UniProt accessions (11): C9J276, C9J4L5, C9J896, C9JBT4, C9JCI4, E7EWP8, P16220, H7C1R5, H7C3I0, Q53X93, Q5U0J5

UniProt curated annotations — full annotation on UniProt →

Function. Phosphorylation-dependent transcription factor that stimulates transcription upon binding to the DNA cAMP response element (CRE), a sequence present in many viral and cellular promoters. Transcription activation is enhanced by the TORC coactivators which act independently of Ser-119 phosphorylation. Involved in different cellular processes including the synchronization of circadian rhythmicity and the differentiation of adipose cells. Regulates the expression of apoptotic and inflammatory response factors in cardiomyocytes in response to ERFE-mediated activation of AKT signaling.

Subunit / interactions. Interacts with PPRC1. Binds DNA as a dimer. This dimer is stabilized by magnesium ions. Interacts, through the bZIP domain, with the coactivators CRTC1/TORC1, CRTC2/TORC2 and CRTC3/TORC3. When phosphorylated on Ser-119, binds CREBBP. Interacts with CREBL2; regulates CREB1 phosphorylation, stability and transcriptional activity. Interacts (phosphorylated form) with TOX3. Interacts with ARRB1. Binds to HIPK2. Interacts with SGK1. Interacts with TSSK4; this interaction facilitates phosphorylation on Ser-119. Forms a complex with KMT2A and CREBBP. Interacts with TOX4; CREB1 is required for full induction of TOX4-dependent activity and the interaction is increased by cAMP and inhibited by insulin. (Microbial infection) Interacts with hepatitis B virus/HBV protein X. (Microbial infection) Interacts with HTLV-1 protein Tax.

Subcellular location. Nucleus.

Post-translational modifications. Stimulated by phosphorylation. Phosphorylation of both Ser-119 and Ser-128 in the SCN regulates the activity of CREB and participates in circadian rhythm generation. Phosphorylation of Ser-119 allows CREBBP binding. In liver, phosphorylation is induced by fasting or glucagon in a circadian fashion. CREBL2 positively regulates phosphorylation at Ser-119 thereby stimulating CREB1 transcriptional activity. Phosphorylated upon calcium influx by CaMK4 and CaMK2 on Ser-119. CaMK4 is much more potent than CaMK2 in activating CREB. Phosphorylated by CaMK2 on Ser-128. Phosphorylation of Ser-128 blocks CREB-mediated transcription even when Ser-119 is phosphorylated. Phosphorylated by CaMK1. Phosphorylation of Ser-257 by HIPK2 in response to genotoxic stress promotes CREB1 activity, facilitating the recruitment of the coactivator CBP. Phosphorylated at Ser-119 by RPS6KA3, RPS6KA4 and RPS6KA5 in response to mitogenic or stress stimuli. Phosphorylated by TSSK4 on Ser-119. Sumoylated with SUMO1. Sumoylation on Lys-290, but not on Lys-271, is required for nuclear localization of this protein. Sumoylation is enhanced under hypoxia, promoting nuclear localization and stabilization.

Disease relevance. Angiomatoid fibrous histiocytoma (AFH) [MIM:612160] A distinct variant of malignant fibrous histiocytoma that typically occurs in children and adolescents and is manifest by nodular subcutaneous growth. Characteristic microscopic features include lobulated sheets of histiocyte-like cells intimately associated with areas of hemorrhage and cystic pseudovascular spaces, as well as a striking cuffing of inflammatory cells, mimicking a lymph node metastasis. The gene represented in this entry may be involved in disease pathogenesis. A chromosomal aberration involving CREB1 is found in a patient with angiomatoid fibrous histiocytoma. Translocation t(2;22)(q33;q12) with CREB1 generates a EWSR1/CREB1 fusion gene that is most common genetic abnormality in this tumor type. A CREB1 mutation has been found in a patient with multiple congenital anomalies consisting of agenesis of the corpus callosum, cerebellar hypoplasia, severe neonatal respiratory distress refractory to surfactant, thymus hypoplasia, and thyroid follicular hypoplasia.

Miscellaneous. Highly expressed in adult testis and sperm.

Similarity. Belongs to the bZIP family.

Isoforms (3)

UniProt ID	Names	Canonical?
P16220-2	1, CREB-B	yes
P16220-1	2, CREB-A
P16220-3	3, htCREB

RefSeq proteins (6): NP_001307722, NP_001358355, NP_001358356, NP_001358357, NP_004370, NP_604391 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001630	Leuzip_CREB	Family
IPR003102	CREB1-like_pKID	Domain
IPR004827	bZIP	Domain
IPR046347	bZIP_sf	Homologous_superfamily

Pfam: PF00170, PF02173

UniProt features (38 total): sequence conflict 11, mutagenesis site 6, region of interest 5, modified residue 3, cross-link 3, helix 3, domain 2, splice variant 2, chain 1, sequence variant 1, site 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
7TBH	ELECTRON MICROSCOPY	2.3
5ZK1	X-RAY DIFFRACTION	3.05
5ZKO	X-RAY DIFFRACTION	3.05
2LXT	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P16220-F1	62.38	0.18

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 300 (required for binding torcs)

Post-translational modifications (6): 128, 257, 122, 271, 290, 119

Mutagenesis-validated functional residues (6):

Position	Phenotype
119	does not interact with tox3 and inhibits induction of transcription by tox3. loss of phosphorylation by camk4. loss of p
141	no effect on sumoylation.
257	impaired phosphorylation by hipk2 and subsequent transactivation.
257	potentiated transactivation.
271	decreased sumoylation, in vivo and in vitro.
290	decreased sumoylation, in vivo and in vitro. loss of nuclear localization.

Function

Pathways and Gene Ontology

Reactome pathways

27 pathways

ID	Pathway
R-HSA-111931	PKA-mediated phosphorylation of CREB
R-HSA-111932	CaMK IV-mediated phosphorylation of CREB
R-HSA-198693	AKT phosphorylates targets in the nucleus
R-HSA-199920	CREB phosphorylation
R-HSA-2151201	Transcriptional activation of mitochondrial biogenesis
R-HSA-2197563	NOTCH2 intracellular domain regulates transcription
R-HSA-375165	NCAM signaling for neurite out-growth
R-HSA-442720	CREB1 phosphorylation through the activation of Adenylate Cyclase
R-HSA-442729	CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde
R-HSA-442742	CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling
R-HSA-5674400	Constitutive Signaling by AKT1 E17K in Cancer
R-HSA-881907	Gastrin-CREB signalling pathway via PKC and MAPK
R-HSA-9022692	Regulation of MECP2 expression and activity
R-HSA-9022699	MECP2 regulates neuronal receptors and channels
R-HSA-9022702	MECP2 regulates transcription of neuronal ligands
R-HSA-9022707	MECP2 regulates transcription factors
R-HSA-9031628	NGF-stimulated transcription
R-HSA-9609690	HCMV Early Events
R-HSA-9616222	Transcriptional regulation of granulopoiesis
R-HSA-9634638	Estrogen-dependent nuclear events downstream of ESR-membrane signaling
R-HSA-9660821	ADORA2B mediated anti-inflammatory cytokines production
R-HSA-9664323	FCGR3A-mediated IL10 synthesis
R-HSA-9707616	Heme signaling
R-HSA-9824585	Regulation of MITF-M-dependent genes involved in pigmentation
R-HSA-9856649	Transcriptional and post-translational regulation of MITF-M expression and activity
R-HSA-9931509	Expression of BMAL (ARNTL), CLOCK, and NPAS2
R-HSA-9931510	Phosphorylated BMAL1:CLOCK (ARNTL:CLOCK) activates expression of core clock genes

MSigDB gene sets: 795 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_CIRCADIAN_RHYTHM, GOBP_MEMORY, CREL_01, REACTOME_SIGNALING_BY_NOTCH, GOBP_MEMBRANE_DEPOLARIZATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_ETHANOL, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_FAT_CELL_DIFFERENTIATION, GOBP_LUNG_EPITHELIUM_DEVELOPMENT, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_REGULATION_OF_OSTEOCLAST_DIFFERENTIATION, GOBP_COGNITION

GO Biological Process (70): regulation of transcription by RNA polymerase II (GO:0006357), protein phosphorylation (GO:0006468), signal transduction (GO:0007165), transforming growth factor beta receptor signaling pathway (GO:0007179), axonogenesis (GO:0007409), lactation (GO:0007595), memory (GO:0007613), circadian rhythm (GO:0007623), regulation of cell size (GO:0008361), visual learning (GO:0008542), response to xenobiotic stimulus (GO:0009410), negative regulation of gene expression (GO:0010629), obsolete negative regulation of transcription by competitive promoter binding (GO:0010944), response to purine-containing compound (GO:0014074), response to activity (GO:0014823), pituitary gland development (GO:0021983), osteoclast differentiation (GO:0030316), positive regulation of transforming growth factor beta3 production (GO:0032916), secretory granule organization (GO:0033363), response to glucagon (GO:0033762), chemotaxis to arachidonate (GO:0034670), response to nicotine (GO:0035094), cellular response to hepatocyte growth factor stimulus (GO:0035729), response to erythropoietin (GO:0036017), cellular response to platelet-derived growth factor stimulus (GO:0036120), positive regulation of multicellular organism growth (GO:0040018), response to cocaine (GO:0042220), mRNA transcription by RNA polymerase II (GO:0042789), positive regulation of apoptotic process (GO:0043065), negative regulation of apoptotic process (GO:0043066), response to morphine (GO:0043278), response to ethanol (GO:0045471), positive regulation of fat cell differentiation (GO:0045600), positive regulation of osteoclast differentiation (GO:0045672), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of RNA polymerase II transcription preinitiation complex assembly (GO:0045899), positive regulation of transcription by RNA polymerase II (GO:0045944), hormone secretion (GO:0046879), positive regulation of hormone secretion (GO:0046887), positive regulation of lipid biosynthetic process (GO:0046889)

GO Molecular Function (19): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), transcription coactivator binding (GO:0001223), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA-binding transcription factor activity (GO:0003700), enzyme binding (GO:0019899), Hsp70 protein binding (GO:0030544), histone acetyltransferase binding (GO:0035035), cAMP response element binding (GO:0035497), identical protein binding (GO:0042802), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), arrestin family protein binding (GO:1990763), sequence-specific double-stranded DNA binding (GO:1990837), transcription cis-regulatory region binding (GO:0000976), RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), DNA binding (GO:0003677), double-stranded DNA binding (GO:0003690), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565)

GO Cellular Component (12): chromatin (GO:0000785), euchromatin (GO:0000791), nucleus (GO:0005634), nucleoplasm (GO:0005654), mitochondrial matrix (GO:0005759), centrosome (GO:0005813), cytosol (GO:0005829), axon (GO:0030424), ciliary basal body (GO:0036064), RNA polymerase II transcription regulator complex (GO:0090575), ATF4-CREB1 transcription factor complex (GO:1990589), transcription regulator complex (GO:0005667)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
Transcriptional Regulation by MECP2	4
Post NMDA receptor activation events	3
Calmodulin induced events	2
Nuclear Events (kinase and transcription factor activation)	2
PIP3 activates AKT signaling	1
MAPK targets/ Nuclear events mediated by MAP kinases	1
Mitochondrial biogenesis	1
Signaling by NOTCH2	1
Axon guidance	1
PI3K/AKT Signaling in Cancer	1
G alpha (q) signalling events	1
HCMV Infection	1
Developmental Biology	1
Extra-nuclear estrogen signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
protein binding	3
cellular anatomical structure	3
regulation of DNA-templated transcription	2
chromatin	2
transcription cis-regulatory region binding	2
DNA binding	2
microtubule organizing center	2
transcription by RNA polymerase II	1
phosphorylation	1
protein modification process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cellular response to transforming growth factor beta stimulus	1
transforming growth factor beta receptor superfamily signaling pathway	1
cell morphogenesis involved in neuron differentiation	1
neuron projection morphogenesis	1
axon development	1
body fluid secretion	1
mammary gland development	1
milk ejection reflex	1
learning or memory	1
rhythmic process	1
regulation of cellular component size	1
visual behavior	1
associative learning	1
response to chemical	1
gene expression	1
regulation of gene expression	1
negative regulation of macromolecule biosynthetic process	1
response to nitrogen compound	1
response to stimulus	1
diencephalon development	1
endocrine system development	1
gland development	1
myeloid leukocyte differentiation	1
transforming growth factor beta3 production	1

Protein interactions and networks

STRING

6686 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CREB1	CREBBP	Q92793	997
CREB1	EP300	Q09472	997
CREB1	CRTC2	Q53ET0	997
CREB1	JUN	P05412	997
CREB1	FOS	P01100	996
CREB1	TP53	P04637	992
CREB1	MECP2	P51608	988
CREB1	RFX1	P22670	986
CREB1	RELA	Q04206	986
CREB1	TAF4	O00268	985
CREB1	CRTC1	Q6UUV9	972
CREB1	PPARGC1A	Q9UBK2	963
CREB1	PRKACB	P22694	958
CREB1	BDNF	P23560	956
CREB1	PRKACG	P22612	945

IntAct

166 interactions, top by confidence:

A	B	Type	Score
ATF1	CREB1	psi-mi:“MI:0915”(physical association)	0.760
CREB1	ATF1	psi-mi:“MI:0915”(physical association)	0.760
CREB1	ATF1	psi-mi:“MI:0407”(direct interaction)	0.760
ATF1	CREB1	psi-mi:“MI:0407”(direct interaction)	0.760
CREB1	CREB1	psi-mi:“MI:0407”(direct interaction)	0.710
TSSK4	CREB1	psi-mi:“MI:0915”(physical association)	0.690
CREB1	TSSK4	psi-mi:“MI:0915”(physical association)	0.690
CREB1	TSSK4	psi-mi:“MI:0217”(phosphorylation reaction)	0.690
MEIS1	CREB1	psi-mi:“MI:0914”(association)	0.680
MEIS1	CREB1	psi-mi:“MI:0915”(physical association)	0.680
CREB1	MEIS1	psi-mi:“MI:0915”(physical association)	0.680
CREB1	MEIS1	psi-mi:“MI:0914”(association)	0.680
CREB1	CRTC1	psi-mi:“MI:0915”(physical association)	0.670
MIA2	RGPD8	psi-mi:“MI:0914”(association)	0.640
JUN	NFATC1	psi-mi:“MI:0914”(association)	0.610
CREB1	NFIL3	psi-mi:“MI:0407”(direct interaction)	0.590
NFIL3	CREB1	psi-mi:“MI:0407”(direct interaction)	0.590
CREBBP	CREB1	psi-mi:“MI:0915”(physical association)	0.590
CREB1	CREBBP	psi-mi:“MI:0915”(physical association)	0.590
CREB1	NFATC1	psi-mi:“MI:0915”(physical association)	0.580
HSPA4	CREB1	psi-mi:“MI:2364”(proximity)	0.570

BioGRID (350): HTT (Affinity Capture-Western), CREB1 (Far Western), CREB1 (Far Western), CREB1 (Far Western), CREB1 (Reconstituted Complex), CREB1 (Reconstituted Complex), CREB1 (Far Western), CREBBP (Reconstituted Complex), CREBBP (Far Western), CREB1 (Biochemical Activity), CREB1 (Reconstituted Complex), CTNNB1 (Affinity Capture-Western), CREB1 (Reconstituted Complex), CREB1 (Affinity Capture-MS), CREB1 (Affinity Capture-MS)

ESM2 similar proteins: A4IFD2, B0R0I6, E9Q7E2, G5ED89, O08949, O15409, O70494, O94842, P0CF24, P15337, P16220, P18576, P18846, P23511, P23708, P27699, P27925, P39769, P52654, P52655, P58462, P58463, P79145, Q01147, Q03060, Q03061, Q08DA8, Q0P5K4, Q1LZH5, Q498D1, Q4VYS1, Q58NQ4, Q5E9S2, Q5QL03, Q5R6A9, Q5RCU0, Q5W1J5, Q68CP9, Q7ZX03, Q86NP2

Diamond homologs: P15337, P16220, P18846, P27699, P27925, P51984, P51985, P79145, P81269, Q01147, Q03060, Q03061, Q08DA8, Q1LZH5, Q66HA2, Q96BA8, Q9U2I0, Q9VWW0, Q9Z125

SIGNOR signaling

88 interactions.

A	Effect	B	Mechanism
CAMK4	“up-regulates activity”	CREB1	phosphorylation
CAMK2A	down-regulates	CREB1	phosphorylation
ATM	“down-regulates activity”	CREB1	phosphorylation
ATM	down-regulates	CREB1	phosphorylation
ATR	down-regulates	CREB1	phosphorylation
CREB1	“down-regulates activity”	FOXO4	binding
TSSK4	up-regulates	CREB1	phosphorylation
CREB1	“up-regulates quantity by expression”	BCL2L1	“transcriptional regulation”
CREB1	“up-regulates quantity by expression”	PKM	“transcriptional regulation”
CAMK4	up-regulates	CREB1	phosphorylation
MAPKAPK2	up-regulates	CREB1	phosphorylation
CREB1	“up-regulates quantity by expression”	FOS	“transcriptional regulation”
CREB1	“up-regulates quantity by expression”	NR4A3	“transcriptional regulation”
RPS6KA4	up-regulates	CREB1	phosphorylation
HIPK2	up-regulates	CREB1	phosphorylation
MAPKAPK2	“up-regulates activity”	CREB1	phosphorylation
CREB1	“up-regulates quantity by expression”	MYF5	“transcriptional regulation”
CREB1	“up-regulates quantity by expression”	MYOD1	“transcriptional regulation”
CREB1	“up-regulates quantity by expression”	PAX3	“transcriptional regulation”
PRKACA	“up-regulates activity”	CREB1	phosphorylation
CREB1	up-regulates	Survival
HNF1B	“up-regulates activity”	CREB1	binding
AKT	“up-regulates activity”	CREB1	phosphorylation
RPS6KA3	“up-regulates activity”	CREB1	phosphorylation
CREB1	“up-regulates quantity by expression”	GCH1	“transcriptional regulation”
AKT1	“up-regulates activity”	CREB1	phosphorylation
RPS6K	“up-regulates activity”	CREB1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 139 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Activation of HOX genes during differentiation	5	24.7×	9e-04
Expression of BMAL (ARNTL), CLOCK, and NPAS2	5	16.4×	1e-03
Heme signaling	6	14.5×	1e-03
Regulation of PTEN gene transcription	6	12.0×	1e-03
Transcriptional activation of mitochondrial biogenesis	5	11.5×	4e-03
TP53 Regulates Transcription of DNA Repair Genes	5	10.2×	4e-03
SUMOylation of chromatin organization proteins	5	8.9×	7e-03
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	5	8.2×	9e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of miRNA transcription	6	13.6×	1e-03
chromatin remodeling	9	5.1×	5e-03
in utero embryonic development	9	5.1×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

37 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	23
Likely benign	1
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

1889 predictions. Top by Δscore:

Variant	Effect	Δscore
2:207555745:CCCAG:C	donor_loss	1.0000
2:207555746:CCAGG:C	donor_loss	1.0000
2:207555747:CAGG:C	donor_loss	1.0000
2:207555748:AG:A	donor_loss	1.0000
2:207555749:GG:G	donor_loss	1.0000
2:207555750:G:T	donor_loss	1.0000
2:207555751:T:A	donor_loss	1.0000
2:207560217:A:G	acceptor_gain	1.0000
2:207560219:A:AG	acceptor_gain	1.0000
2:207560223:TAGGT:T	acceptor_loss	1.0000
2:207560224:A:T	acceptor_loss	1.0000
2:207560372:GGT:G	donor_loss	1.0000
2:207560373:G:GA	donor_loss	1.0000
2:207560374:T:A	donor_loss	1.0000
2:207567458:TTCA:T	acceptor_loss	1.0000
2:207567459:TCA:T	acceptor_loss	1.0000
2:207567460:CAGAT:C	acceptor_loss	1.0000
2:207567461:A:AG	acceptor_gain	1.0000
2:207567461:AGAT:A	acceptor_loss	1.0000
2:207567462:G:GA	acceptor_gain	1.0000
2:207567559:TACAG:T	donor_loss	1.0000
2:207567560:ACAG:A	donor_loss	1.0000
2:207567561:CAGGT:C	donor_loss	1.0000
2:207567562:AG:A	donor_loss	1.0000
2:207567563:GG:G	donor_loss	1.0000
2:207567564:G:A	donor_loss	1.0000
2:207567565:T:A	donor_loss	1.0000
2:207570317:GTATA:G	donor_gain	1.0000
2:207570318:TATA:T	donor_gain	1.0000
2:207570320:TA:T	donor_gain	1.0000

AlphaMissense

2096 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:207567548:G:C	R116T	1.000
2:207567548:G:T	R116M	1.000
2:207567549:G:C	R116S	1.000
2:207567549:G:T	R116S	1.000
2:207567551:G:T	R117M	1.000
2:207567552:G:C	R117S	1.000
2:207567552:G:T	R117S	1.000
2:207567559:T:C	Y120H	1.000
2:207567559:T:G	Y120D	1.000
2:207570184:T:A	I123N	1.000
2:207570184:T:C	I123T	1.000
2:207570184:T:G	I123S	1.000
2:207570297:T:G	Y161D	1.000
2:207577639:C:A	R275S	1.000
2:207577643:T:C	L276P	1.000
2:207577648:A:G	K278E	1.000
2:207577650:G:C	K278N	1.000
2:207577650:G:T	K278N	1.000
2:207577651:A:G	N279D	1.000
2:207577652:A:C	N279T	1.000
2:207577652:A:G	N279S	1.000
2:207577652:A:T	N279I	1.000
2:207577653:C:A	N279K	1.000
2:207577653:C:G	N279K	1.000
2:207577654:A:T	R280W	1.000
2:207577655:G:C	R280T	1.000
2:207577655:G:T	R280M	1.000
2:207596914:G:C	R280S	1.000
2:207596914:G:T	R280S	1.000
2:207596918:G:C	A282P	1.000

dbSNP variants (sampled 300 via entrez): RS1000021094 (2:207568920 C>T), RS1000026484 (2:207546152 C>T), RS1000083791 (2:207552444 A>G), RS1000122076 (2:207532132 A>G), RS1000146686 (2:207598956 C>G,T), RS1000150707 (2:207572082 C>T), RS1000231466 (2:207572373 A>G), RS1000252996 (2:207542151 T>C), RS1000314897 (2:207529371 C>T), RS1000431350 (2:207564757 C>G,T), RS1000502749 (2:207586319 A>G), RS1000521796 (2:207552225 G>T), RS1000526328 (2:207566417 A>C,G), RS1000615870 (2:207528307 G>A), RS1000623323 (2:207570784 T>G)

Disease associations

OMIM: gene MIM:123810 | disease phenotypes: MIM:612160

GenCC curated gene-disease

Mondo (1): histiocytoma, Angiomatoid fibrous (MONDO:0012809)

Orphanet (1): Angiomatoid fibrous histiocytoma (Orphanet:569164)

HPO phenotypes

2 total (2 of 2 shown, HPO-id order):

HPO	Term
HP:0001442	Typified by somatic mosaicism
HP:0012315	Histiocytoma

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST002518_5	Food antigen IgG levels	1.000000e-06
GCST002783_296	Body mass index	3.000000e-08
GCST002783_552	Body mass index	8.000000e-08
GCST002783_63	Body mass index	6.000000e-06
GCST004904_152	Body mass index	3.000000e-10
GCST007094_36	Diastolic blood pressure	1.000000e-07
GCST007099_89	Systolic blood pressure	2.000000e-08
GCST010002_408	Refractive error	2.000000e-08
GCST90002390_465	Mean corpuscular hemoglobin	9.000000e-10

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0005844	response to dietary antigen
EFO:0004340	body mass index
EFO:0006336	diastolic blood pressure
EFO:0006335	systolic blood pressure
EFO:0004527	mean corpuscular hemoglobin

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C563181	Histiocytoma, Angiomatoid Fibrous (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5587 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 8,592 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL8260	BAICALEIN	2	8,592

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs7569963	Efficacy,Toxicity	3	antidepressants;citalopram	Depression
rs889895	Efficacy	3	antidepressants	Major Depressive Disorder

PharmGKB variants

5 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs889895	CREB1	3	0.50	1	antidepressants
rs4675690	CREB1	3	3.00	1	citalopram
rs6740584	CREB1		0.00	0
rs7569963	CREB1, METTL21A	3	5.00	1	antidepressants;citalopram
rs2551919	CREB1		0.00	0

ChEMBL bioactivities

4 potent at pChembl≥5 of 7 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.77	AC50	1700	nM	CHEMBL186490
5.66	AC50	2200	nM	OROXYLIN A
5.37	AC50	4300	nM	CHEMBL434537
5.09	AC50	8200	nM	CHEMBL189339

CTD chemical–gene interactions

233 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Colforsin	increases activity, decreases reaction, increases phosphorylation, affects binding	6
sodium arsenite	decreases reaction, increases phosphorylation, affects cotreatment, affects localization, decreases response to substance (+3 more)	5
N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide	decreases reaction, increases phosphorylation, increases expression, increases activity	5
SB 203580	decreases reaction, increases phosphorylation, decreases phosphorylation	5
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	decreases reaction, increases phosphorylation, decreases phosphorylation	5
Valproic Acid	decreases expression, increases methylation, affects expression, affects binding, increases reaction	5
Resveratrol	increases phosphorylation, affects binding, decreases reaction, decreases phosphorylation, increases activity	4
Tetradecanoylphorbol Acetate	decreases reaction, increases phosphorylation, increases activity	4
Particulate Matter	decreases phosphorylation, decreases reaction, affects cotreatment, increases abundance, increases expression (+1 more)	4
bisphenol A	affects binding, increases reaction, increases activity, increases phosphorylation, decreases reaction	3
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	increases phosphorylation, affects cotreatment, decreases phosphorylation, decreases reaction	3
4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole	decreases phosphorylation, decreases reaction, increases phosphorylation	3
Benzo(a)pyrene	affects activity, decreases expression, affects reaction, increases expression	3
Formaldehyde	decreases reaction, increases phosphorylation, increases expression, decreases expression	3
Hydrogen Peroxide	decreases expression, increases phosphorylation, affects cotreatment, decreases phosphorylation, decreases reaction (+1 more)	3
Rotenone	affects response to substance, decreases expression	3
Tobacco Smoke Pollution	decreases expression, increases expression, increases phosphorylation	3
Cadmium Chloride	decreases reaction, increases phosphorylation, affects phosphorylation, increases reaction	3
666-15 compound	decreases activity, decreases reaction, increases expression	2
methylmercuric chloride	affects cotreatment, affects phosphorylation, affects reaction, affects binding, decreases expression	2
o,p’-DDT	affects localization, increases activity, increases phosphorylation	2
manganese chloride	increases abundance, decreases phosphorylation, decreases reaction, decreases expression	2
4-hydroxy-2-nonenal	decreases expression, increases phosphorylation	2
nickel sulfate	affects cotreatment, increases reaction, increases secretion, affects expression, increases expression	2
epigallocatechin gallate	affects cotreatment, decreases phosphorylation, decreases reaction, affects reaction, decreases expression	2
cordycepin	decreases reaction, increases phosphorylation, increases expression	2
Ro 31-8220	increases phosphorylation, decreases reaction	2
bisindolylmaleimide I	decreases reaction, increases phosphorylation	2
4-tert-octylphenol	decreases reaction, affects cotreatment, increases phosphorylation	2
U 0126	decreases reaction, increases phosphorylation	2

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3816446	Binding	Induction of degradation of halo-tagged CREB1 (unknown origin) expressed in HEK293 cells at 10 uM by Western blot analysis	Efficient protein knockdown of HaloTag-fused proteins using hybrid molecules consisting of IAP antagonist and HaloTag ligand. — Bioorg Med Chem

Cellosaurus cell lines

12 cell lines: 8 cancer cell line, 3 embryonic stem cell, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A0S0	SEES3-1V human CREB1, clone1	Embryonic stem cell	Male
CVCL_A0S1	SEES3-1V human CREB1, clone2	Embryonic stem cell	Male
CVCL_A0S2	SEES3-1V human CREB1, clone3	Embryonic stem cell	Male
CVCL_B8E1	Abcam HCT 116 CREB1 KO	Cancer cell line	Male
CVCL_B8UA	Abcam MCF-7 CREB1 KO	Cancer cell line	Female
CVCL_B9G9	Abcam A-549 CREB1 KO	Cancer cell line	Male
CVCL_D7MU	Ubigene A-549 CREB1 KO	Cancer cell line	Male
CVCL_D9CA	Ubigene HEK293 CREB1 KO	Transformed cell line	Female
CVCL_E0AU	Ubigene HeLa CREB1 KO	Cancer cell line	Female
CVCL_KB18	HLR-CREB	Cancer cell line	Female

Clinical trials (associated diseases)

5 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT03600649	PHASE1	UNKNOWN	Clinical Trial of SP-2577 (Seclidemstat) in Patients With Relapsed or Refractory Ewing or Ewing-related Sarcomas
NCT02180867	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Radiation Therapy With or Without Combination Chemotherapy or Pazopanib Before Surgery in Treating Patients With Newly Diagnosed Non-rhabdomyosarcoma Soft Tissue Sarcomas That Can Be Removed by Surgery
NCT05266196	PHASE1/PHASE2	UNKNOWN	A Rollover Protocol to Allow for Continued Access to the LSD1 Inhibitor Seclidemstat (SP-2577)
NCT06239272	PHASE1/PHASE2	RECRUITING	NRSTS2021, A Risk Adapted Study Evaluating Maintenance Pazopanib, Limited Margin, Dose-Escalated Radiation Therapy and Selinexor in Non-Rhabdomyosarcoma Soft Tissue Sarcoma (NRSTS)
NCT03759327	Not specified	COMPLETED	Angiomatoid Fibrous Histiocytoma: a Single Institution Case-series