CREB1
cAMP responsive element binding protein 1, the group of Basic leucine zipper proteins
Basic information
Region (hg38): 2:207529736-207605988
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- Inborn genetic diseases (8 variants)
- not provided (5 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the CREB1 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 5 | |||||
| missense | 8 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region ? | 0 | |||||
| non coding ? | 0 | |||||
| Total | 0 | 0 | 8 | 1 | 4 |
Variants in CREB1
This is a list of pathogenic ClinVar variants found in the CREB1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 2-207555657-G-A | not specified | Uncertain significance (Feb 15, 2023) | ||
| 2-207555702-C-G | not specified | Uncertain significance (Feb 11, 2022) | ||
| 2-207555724-A-G | not specified | Uncertain significance (May 08, 2023) | ||
| 2-207560248-C-G | not specified | Uncertain significance (May 23, 2023) | ||
| 2-207560248-C-T | not specified | Uncertain significance (Apr 28, 2022) | ||
| 2-207560327-G-A | Benign (Sep 25, 2018) | |||
| 2-207560354-A-G | Likely benign (Aug 04, 2017) | |||
| 2-207567506-A-G | Variant of unknown significance | Uncertain significance (Apr 01, 2012) | ||
| 2-207570258-G-A | not specified | Uncertain significance (Jan 03, 2022) | ||
| 2-207570264-G-T | not specified | Uncertain significance (Sep 01, 2021) | ||
| 2-207575293-C-A | not specified | Uncertain significance (Oct 04, 2022) | ||
| 2-207575339-A-G | Benign (May 03, 2018) | |||
| 2-207575348-C-G | Benign (Dec 31, 2019) | |||
| 2-207577591-G-A | not specified | Uncertain significance (Dec 22, 2023) | ||
| 2-207577597-C-A | not specified | Uncertain significance (Jan 10, 2022) | ||
| 2-207597017-C-T | Benign (May 03, 2018) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| CREB1 | protein_coding | protein_coding | ENST00000432329 | 8 | 73695 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.997 | 0.00327 | 0 | 0 | 0 | 0 | 0.00 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.91 | 73 | 184 | 0.397 | 0.00000922 | 2181 |
| Missense in Polyphen | 10 | 62.478 | 0.16006 | 753 | ||
| Synonymous | 0.904 | 58 | 67.4 | 0.860 | 0.00000361 | 705 |
| Loss of Function | 4.07 | 1 | 21.3 | 0.0470 | 0.00000116 | 219 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00 | 0.00 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- 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-133 phosphorylation. Involved in different cellular processes including the synchronization of circadian rhythmicity and the differentiation of adipose cells.;
- Disease
- DISEASE: 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. Note=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.; DISEASE: Note=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. {ECO:0000269|PubMed:22267179}.;
- Pathway
- PI3K-Akt signaling pathway - Homo sapiens (human);Antigen processing and presentation - Homo sapiens (human);Cortisol synthesis and secretion - Homo sapiens (human);Relaxin signaling pathway - Homo sapiens (human);Aldosterone synthesis and secretion - Homo sapiens (human);Circadian rhythm - Homo sapiens (human);Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human);Dopaminergic synapse - Homo sapiens (human);Insulin resistance - Homo sapiens (human);Cushing,s syndrome - Homo sapiens (human);Thyroid hormone synthesis - Homo sapiens (human);Vasopressin-regulated water reabsorption - Homo sapiens (human);Huntington,s disease - Homo sapiens (human);TNF signaling pathway - Homo sapiens (human);HTLV-I infection - Homo sapiens (human);Circadian entrainment - Homo sapiens (human);AMPK signaling pathway - Homo sapiens (human);Thermogenesis - Homo sapiens (human);Glucagon signaling pathway - Homo sapiens (human);Adrenergic signaling in cardiomyocytes - Homo sapiens (human);Prostate cancer - Homo sapiens (human);Longevity regulating pathway - Homo sapiens (human);cAMP signaling pathway - Homo sapiens (human);Estrogen signaling pathway - Homo sapiens (human);Renin secretion - Homo sapiens (human);Tuberculosis - Homo sapiens (human);Amphetamine addiction - Homo sapiens (human);Viral carcinogenesis - Homo sapiens (human);Hepatitis B - Homo sapiens (human);Osteoclast differentiation - Homo sapiens (human);cGMP-PKG signaling pathway - Homo sapiens (human);Cholinergic synapse - Homo sapiens (human);Alcoholism - Homo sapiens (human);Cocaine addiction - Homo sapiens (human);Insulin secretion - Homo sapiens (human);Melanogenesis - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Excitatory Neural Signalling Through 5-HTR 4 and Serotonin;Intracellular Signalling Through Adenosine Receptor A2b and Adenosine;Intracellular Signalling Through Adenosine Receptor A2a and Adenosine;Excitatory Neural Signalling Through 5-HTR 7 and Serotonin ;Excitatory Neural Signalling Through 5-HTR 6 and Serotonin ;Intracellular Signalling Through LHCGR Receptor and Luteinizing Hormone/Choriogonadotropin;Intracellular Signalling Through FSH Receptor and Follicle Stimulating Hormone;Intracellular Signalling Through Histamine H2 Receptor and Histamine;EGF-Core;IGF-Core;WNT-Core;TGF-Core;Androgen receptor signaling pathway;miRNA Regulation of DNA Damage Response;Energy Metabolism;miRNAs involved in DNA damage response;Folate-Alcohol and Cancer Pathway Hypotheses;Sterol Regulatory Element-Binding Proteins (SREBP) signalling;Integrated Breast Cancer Pathway;Leptin signaling pathway;Human Thyroid Stimulating Hormone (TSH) signaling pathway;Follicle Stimulating Hormone (FSH) signaling pathway;White fat cell differentiation;B Cell Receptor Signaling Pathway;Interleukin-11 Signaling Pathway;Corticotropin-releasing hormone signaling pathway;Adipogenesis;Oncostatin M Signaling Pathway;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;ATM Signaling Pathway;JAK-STAT;Common Pathways Underlying Drug Addiction;Myometrial Relaxation and Contraction Pathways;MFAP5-mediated ovarian cancer cell motility and invasiveness;MECP2 and Associated Rett Syndrome;Transcription factor regulation in adipogenesis;BDNF-TrkB Signaling;ERK Pathway in Huntington,s Disease;VEGFA-VEGFR2 Signaling Pathway;Mitochondrial Gene Expression;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;Prion disease pathway;p38 MAPK Signaling Pathway;NO-cGMP-PKG mediated Neuroprotection;White fat cell differentiation;PI3K-Akt Signaling Pathway;Phosphodiesterases in neuronal function;EGF-EGFR Signaling Pathway;G1 to S cell cycle control;Interferon type I signaling pathways;T-Cell antigen Receptor (TCR) Signaling Pathway;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;DNA Damage Response;Estrogen signaling pathway;Serotonin HTR1 Group and FOS Pathway;Serotonin Receptor 4-6-7 and NR3C Signaling;Developmental Biology;Signaling by GPCR;Toll Like Receptor 7/8 (TLR7/8) Cascade;Interleukin-17 signaling;Disease;Signal Transduction;Signaling by Interleukins;hypoxia-inducible factor in the cardivascular system;role of erk5 in neuronal survival pathway;oxidative stress induced gene expression via nrf2;repression of pain sensation by the transcriptional regulator dream;human cytomegalovirus and map kinase pathways;transcription factor creb and its extracellular signals;erythropoietin mediated neuroprotection through nf-kb;p38 mapk signaling pathway;melanocyte development and pigmentation pathway;transcription regulation by methyltransferase of carm1;signaling pathway from g-protein families;calcium signaling by hbx of hepatitis b virus;mapkinase signaling pathway;Cytokine Signaling in Immune system;Toll Like Receptor 9 (TLR9) Cascade;GPCR Dopamine D1like receptor;MyD88 cascade initiated on plasma membrane;Toll Like Receptor 10 (TLR10) Cascade;Toll Like Receptor 3 (TLR3) Cascade;Toll Like Receptor 5 (TLR5) Cascade;Toll-Like Receptors Cascades;GPCR Adenosine A2A receptor;TCR;Innate Immune System;Immune System;Ghrelin;PKA-mediated phosphorylation of CREB;CaMK IV-mediated phosphorylation of CREB;Calmodulin induced events;CaM pathway;ATF-2 transcription factor network;AKT phosphorylates targets in the nucleus;NOTCH2 intracellular domain regulates transcription;Signaling by NOTCH2;Nuclear Events (kinase and transcription factor activation);Neuronal System;BCR;Signaling by NOTCH;AndrogenReceptor;CRH;Signaling by NTRK1 (TRKA);inhibition of huntingtons disease neurodegeneration by histone deacetylase inhibitors;CREB phosphorylation;Signaling by NTRKs;BDNF;EGFR1;MAPK targets/ Nuclear events mediated by MAP kinases;MAP kinase activation;TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation;Glucocorticoid receptor regulatory network;ErbB1 downstream signaling;DAG and IP3 signaling;MyD88 dependent cascade initiated on endosome;PIP3 activates AKT signaling;IL2;NCAM signaling for neurite out-growth;VEGFR3 signaling in lymphatic endothelium;Signaling events regulated by Ret tyrosine kinase;IL3;Gastrin;Ca-dependent events;PLC beta mediated events;Neurotransmitter receptors and postsynaptic signal transmission;Transmission across Chemical Synapses;G-protein mediated events;Opioid Signalling;G alpha (i) signalling events;Axon guidance;CREB phosphorylation through the activation of CaMKK;CREB phosphorylation through the activation of Adenylate Cyclase;CREB phosphorylation through the activation of Ras;Constitutive Signaling by AKT1 E17K in Cancer;PI3K/AKT Signaling in Cancer;CREB phosphorylation through the activation of CaMKII;Post NMDA receptor activation events;Activation of NMDA receptor and postsynaptic events;Transcriptional activation of mitochondrial biogenesis;Mitochondrial biogenesis;TSH;TNFalpha;Integrin-linked kinase signaling;TRIF(TICAM1)-mediated TLR4 signaling ;MyD88-independent TLR4 cascade ;Toll Like Receptor 4 (TLR4) Cascade;Signaling by Receptor Tyrosine Kinases;Gastrin-CREB signalling pathway via PKC and MAPK;G alpha (q) signalling events;GPCR downstream signalling;ca-calmodulin-dependent protein kinase activation;Intracellular signaling by second messengers;MyD88:Mal cascade initiated on plasma membrane;Toll Like Receptor TLR1:TLR2 Cascade;Toll Like Receptor TLR6:TLR2 Cascade;Toll Like Receptor 2 (TLR2) Cascade;LPA4-mediated signaling events;Signaling mediated by p38-alpha and p38-beta;Diseases of signal transduction;Validated targets of C-MYC transcriptional repression;AP-1 transcription factor network;HIF-1-alpha transcription factor network;Nongenotropic Androgen signaling;p38 signaling mediated by MAPKAP kinases;Trk receptor signaling mediated by PI3K and PLC-gamma;FOXA2 and FOXA3 transcription factor networks;Trk receptor signaling mediated by the MAPK pathway;Regulation of nuclear SMAD2/3 signaling;LKB1 signaling events;Organelle biogenesis and maintenance
(Consensus)
Recessive Scores
- pRec
- 0.949
Intolerance Scores
- loftool
- rvis_EVS
- 0.08
- rvis_percentile_EVS
- 59.76
Haploinsufficiency Scores
- pHI
- 0.994
- hipred
- Y
- hipred_score
- 0.783
- ghis
- 0.610
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.996
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Creb1
- Phenotype
- muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; reproductive system phenotype; growth/size/body region phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); skeleton phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; embryo phenotype;
Gene ontology
- Biological process
- response to hypoxia;transcription by RNA polymerase II;protein phosphorylation;signal transduction;transforming growth factor beta receptor signaling pathway;axonogenesis;aging;lactation;memory;circadian rhythm;regulation of cell size;visual learning;response to organic substance;negative regulation of transcription by competitive promoter binding;response to activity;viral process;pituitary gland development;positive regulation of transforming growth factor beta3 production;secretory granule organization;response to glucagon;chemotaxis to arachidonic acid;response to nicotine;cellular response to hepatocyte growth factor stimulus;cellular response to platelet-derived growth factor stimulus;positive regulation of multicellular organism growth;regulation of circadian rhythm;positive regulation of apoptotic process;positive regulation of fat cell differentiation;positive regulation of osteoclast differentiation;positive regulation of transcription, DNA-templated;positive regulation of RNA polymerase II transcriptional preinitiation complex assembly;positive regulation of transcription by RNA polymerase II;positive regulation of hormone secretion;positive regulation of lipid biosynthetic process;regulation of fibroblast proliferation;protein stabilization;positive regulation of cardiac muscle tissue development;regulation of glial cell proliferation;lung saccule development;type I pneumocyte differentiation;cellular response to zinc ion;cellular response to retinoic acid;cellular response to fatty acid;positive regulation of long-term synaptic potentiation;negative regulation of neuron death;response to L-glutamate;cellular response to nerve growth factor stimulus;cellular response to insulin-like growth factor stimulus;cellular response to leukemia inhibitory factor
- Cellular component
- nucleus;nucleoplasm;transcription factor complex;nuclear euchromatin;mitochondrial matrix;axon;ATF4-CREB1 transcription factor complex
- Molecular function
- RNA polymerase II proximal promoter sequence-specific DNA binding;RNA polymerase II distal enhancer sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;RNA polymerase II activating transcription factor binding;RNA polymerase II transcription coactivator binding;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA-binding transcription factor activity;transcription coregulator activity;protein binding;enzyme binding;Hsp70 protein binding;histone acetyltransferase binding;cAMP response element binding;identical protein binding;arrestin family protein binding