CREB3L2
protein-codingcAMP responsive element binding protein 3 like 2, the group of CREB3 transcription factor family
Gene summary
This gene encodes a member of the oasis bZIP transcription factor family. Members of this family can dimerize but form homodimers only. The encoded protein is a transcriptional activator. Translocations between this gene on chromosome 7 and the gene fused in sarcoma on chromosome 16 can be found in some tumors. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~127.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CREB3L2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_194071.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 2 | ||||
| missense | 64 | 2 | 66 | |||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 70 | 2 | 0 | 72 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_919047.2 | 12 | MANE Select | |
| Ensembl | ENSP00000329140.6 | 12 | MANE Select | |
| RefSeq | NP_001240704.1 | 4 | Standard | |
| RefSeq | NP_001305175.1 | 11 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| creb3l2 | Danio rerio | Structure: melanocyte Quality: immature abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- 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)
Biological Process
- chondrocyte differentiation
- endoplasmic reticulum to Golgi vesicle-mediated transport
- response to wounding
- positive regulation of neuron projection development
- endoplasmic reticulum unfolded protein response
Molecular Function
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA-binding transcription activator activity, RNA polymerase II-specific
- cAMP response element binding
- transcription regulatory region DNA binding
Cellular Component
- chromatin
- nucleus
- nucleoplasm
- endoplasmic reticulum
- endoplasmic reticulum membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000330387
- Coding exons
- 12
- Length
- 127089
- Individuals with no LoFs
- 125708
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 40
- Defined
- 125748
- p
- 0.000159
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.0304 | 260 | 261 | 0.995 | 0.0000140 | 3339 |
| Missense (PolyPhen) | 125 | 127.74 | 0.97853 | 1675 | ||
| Synonymous | 0.401 | 112 | 118 | 0.953 | 0.00000731 | 1067 |
| Loss of Function | 2.83 | 9 | 23.9 | 0.376 | 0.00000108 | 312 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00025 | 0.00025 | rare |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000059 | 0.000054 | rare |
| Finnish | 0.000047 | 0.000046 | rare |
| European (Non-Finnish) | 0.00011 | 0.00011 | rare |
| South Asian | 0.00056 | 0.00056 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Transcription factor involved in unfolded protein response (UPR). In the absence of endoplasmic reticulum (ER) stress, inserted into ER membranes, with N-terminal DNA-binding and transcription activation domains oriented toward the cytosolic face of the membrane. In response to ER stress, transported to the Golgi, where it is cleaved in a site-specific manner by resident proteases S1P/MBTPS1 and S2P/MBTPS2. The released N-terminal cytosolic domain is translocated to the nucleus to effect transcription of specific target genes. Plays a critical role in chondrogenesis by activating the transcription of SEC23A, which promotes the transport and secretion of cartilage matrix proteins, and possibly that of ER biogenesis-related genes (By similarity). In a neuroblastoma cell line, protects cells from ER stress- induced death (PubMed:17178827). In vitro activates transcription of target genes via direct binding to the CRE site (PubMed:17178827). {ECO:0000250|UniProtKB:Q8BH52, ECO:0000269|PubMed:17178827}.;
- Disease
- DISEASE: Note=A chromosomal aberration involving CREB3L2 is found in low grade fibromyxoid sarcoma (LGFMS). Translocation t(7;16)(q33;p11) with FUS.;
Recessive Scores
- pRec
- 0.136
Intolerance Scores
- LoFtool
- 0.640
- RVIS EVS
- -0.69
- RVIS percentile EVS
- 15.2
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.831
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |