CREB3

cAMP responsive element binding protein 3, the group of MicroRNA protein coding host genes|CREB3 transcription factor family

Basic information

Region (hg38): 9:35732598-35736999

Links

ENSG00000107175 ∙ NCBI:10488 ∙ OMIM:606443 ∙ HGNC:2347 ∙ Uniprot:O43889 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CREB3 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CREB3 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				1	1	2
missense			25	1		26
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	0	0	25	2	1

Variants in CREB3

This is a list of pathogenic ClinVar variants found in the CREB3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
9-35732789-A-G		not specified	Uncertain significance (Aug 20, 2024)
9-35732843-G-A		not specified	Uncertain significance (Nov 15, 2024)
9-35732891-C-T		not specified	Uncertain significance (Apr 22, 2022)
9-35733025-G-T		not specified	Likely benign (Jan 24, 2023)
9-35733119-C-T		not specified	Uncertain significance (Jul 26, 2022)
9-35733128-G-C		not specified	Uncertain significance (Jun 28, 2024)
9-35733244-C-G		not specified	Uncertain significance (Feb 17, 2024)
9-35733265-G-C		not specified	Uncertain significance (Feb 26, 2025)
9-35733280-C-G		not specified	Uncertain significance (Feb 12, 2024)
9-35733432-A-G		not specified	Uncertain significance (Dec 22, 2024)
9-35733444-A-G		not specified	Uncertain significance (Aug 12, 2021)
9-35735122-T-C		not specified	Uncertain significance (Sep 16, 2021)
9-35735136-C-T		not specified	Uncertain significance (Feb 16, 2023)
9-35735170-A-C		not specified	Uncertain significance (Jan 04, 2024)
9-35735175-C-T		not specified	Uncertain significance (Aug 02, 2021)
9-35735198-T-C			Likely benign (Jul 01, 2022)
9-35735202-G-A		not specified	Uncertain significance (Jun 02, 2023)
9-35735314-A-C		not specified	Uncertain significance (Jan 11, 2023)
9-35735316-T-C		not specified	Uncertain significance (Feb 28, 2023)
9-35735367-C-A		not specified	Uncertain significance (Feb 08, 2025)
9-35736102-C-T			Benign (Dec 31, 2019)
9-35736116-G-C		not specified	Uncertain significance (Jun 17, 2024)
9-35736222-T-C			Benign (Jul 15, 2018)
9-35736233-C-G		not specified	Uncertain significance (Feb 15, 2023)
9-35736400-C-T		not specified	Uncertain significance (Dec 01, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CREB3	protein_coding	protein_coding	ENST00000353704	9	4670

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000185	0.895	125695	0	53	125748	0.000211

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0392	194	196	0.992	0.00000941	2401
Missense in Polyphen		56	59.074	0.94796		782
Synonymous	-0.268	81	78.0	1.04	0.00000360	750
Loss of Function	1.54	10	16.8	0.595	7.78e-7	198

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000368	0.000366
Ashkenazi Jewish	0.000992	0.000993
East Asian	0.00120	0.00120
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000792	0.0000791
Middle Eastern	0.00120	0.00120
South Asian	0.0000694	0.0000653
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Endoplasmic reticulum (ER)-bound sequence-specific transcription factor that directly binds DNA and activates transcription (PubMed:9271389, PubMed:19779205, PubMed:10984507, PubMed:15845366, PubMed:16940180). Plays a role in the unfolded protein response (UPR), promoting cell survival versus ER stress- induced apoptotic cell death (PubMed:15845366, PubMed:16940180). Also involved in cell proliferation, migration and differentiation, tumor suppression and inflammatory gene expression. Acts as a positive regulator of LKN-1/CCL15-induced chemotaxis signaling of leukocyte cell migration (PubMed:19779205, PubMed:15001559, PubMed:17296613). Associates with chromatin to the HERPUD1 promoter (PubMed:16940180). Also induces transcriptional activation of chemokine receptors (PubMed:18587271, PubMed:17296613). {ECO:0000269|PubMed:10984507, ECO:0000269|PubMed:15001559, ECO:0000269|PubMed:15845366, ECO:0000269|PubMed:16940180, ECO:0000269|PubMed:17296613, ECO:0000269|PubMed:18587271, ECO:0000269|PubMed:19779205, ECO:0000269|PubMed:9271389}.; FUNCTION: Isoform 2: Functions as a negative transcriptional regulator in ligand-induced transcriptional activation of the glucocorticoid receptor NR3C1 by recruiting and activating histone deacetylases (HDAC1, HDAC2 and HDAC6). Also decreases the acetylation level of histone H4. Does not promote the chemotactic activity of leukocyte cells. {ECO:0000269|PubMed:19779205}.; FUNCTION: (Microbial infection) Isoform 1: Plays a role in herpes simplex virus-1 (HSV-1) latent infection and reactivation from latency. Represses the VP16-mediated transactivation of immediate early genes of the HSV-1 virus by sequestering host cell factor-1 HCFC1 in the ER membrane of sensory neurons, thereby preventing the initiation of the replicative cascade leading to latent infection. {ECO:0000269|PubMed:10623756, ECO:0000269|PubMed:15705566}.; FUNCTION: (Microbial infection) Processed cyclic AMP-responsive element-binding protein 3: Activates transcription of genes required for reactivation of the latent HSV-1 virus. It's transcriptional activity is inhibited by CREBZF in a HCFC1- dependent manner, by the viral transactivator protein VP16. Binds DNA to the cAMP response element (CRE) (consensus: 5'- GTGACGT[AG][AG]-3') and C/EBP sequences present in many viral promoters. {ECO:0000269|PubMed:10623756}.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);Cortisol synthesis and secretion - Homo sapiens (human);Relaxin signaling pathway - Homo sapiens (human);Aldosterone synthesis and secretion - 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);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);Amphetamine addiction - Homo sapiens (human);Viral carcinogenesis - Homo sapiens (human);Hepatitis B - 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);Myometrial Relaxation and Contraction Pathways;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PI3K-Akt Signaling Pathway;G1 to S cell cycle control;Unfolded Protein Response (UPR);Metabolism of proteins;CREB3 factors activate genes (Consensus)

Recessive Scores

• pRec: 0.0871

Intolerance Scores

• loftool: 0.612
• rvis_EVS: -0.25
• rvis_percentile_EVS: 35.99

Haploinsufficiency Scores

• pHI: 0.213
• hipred: N
• hipred_score: 0.147
• ghis: 0.533

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.983

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Creb3

Gene ontology

• Biological process: chemotaxis;positive regulation of transcription from RNA polymerase II promoter involved in unfolded protein response;viral process;endoplasmic reticulum unfolded protein response;positive regulation of transcription by RNA polymerase II;positive regulation of monocyte chemotaxis;negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway
• Cellular component: Golgi membrane;nucleus;nucleoplasm;endoplasmic reticulum;endoplasmic reticulum membrane;cytosol;integral component of membrane
• Molecular function: RNA polymerase II regulatory region sequence-specific DNA binding;RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;protein binding;cAMP response element binding