CREBRF
protein-codingCREB3 regulatory factor
Gene summary
Enables DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Involved in several processes, including negative regulation of endoplasmic reticulum unfolded protein response; positive regulation of protein catabolic process; and regulation of transcription by RNA polymerase II. Located in cytoplasm and nuclear body. [provided by Alliance of Genome Resources, Jul 2025]
- C5orf41
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~82.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0019182
Submitter: Ambry Genetics
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CREBRF variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_153607.3. 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 | 4 | 3 | 2 | 9 | ||
| missense | 54 | 54 | ||||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 65 | 3 | 2 | 70 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_705835.2 | 8 | MANE Select | |
| Ensembl | ENSP00000296953.2 | 8 | MANE Select | |
| RefSeq | NP_001161865.1 | 3 | Standard | |
| RefSeq | NP_001161866.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Unfolded Protein Response (UPR)
- Metabolism of proteins
- CREB3 factors activate genes
Biological Process
- endoplasmic reticulum unfolded protein response
- maternal behavior
- positive regulation of transcription by RNA polymerase II
- negative regulation of glucocorticoid mediated signaling pathway
- positive regulation of prolactin signaling pathway
Molecular Function
- RNA polymerase II regulatory region sequence-specific DNA binding
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA-binding transcription activator activity, RNA polymerase II-specific
- protein binding
Cellular Component
- nucleus
- nucleoplasm
- nuclear body
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000296953
- Coding exons
- 8
- Length
- 82937
- Individuals with no LoFs
- 125399
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 2
- Defined
- 125401
- p
- 0.00000797
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.36 | 211 | 332 | 0.635 | 0.0000163 | 4223 |
| Missense (PolyPhen) | 58 | 140.19 | 0.41371 | 1744 | ||
| Synonymous | 1.71 | 98 | 122 | 0.804 | 0.00000609 | 1166 |
| Loss of Function | 5.06 | 0 | 29.8 | 0.00 | 0.00000150 | 380 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000018 | 0.000018 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Acts as a negative regulator of the endoplasmic reticulum stress response or unfolded protein response (UPR). Represses the transcriptional activity of CREB3 during the UPR. Recruits CREB3 into nuclear foci. {ECO:0000269|PubMed:18391022}.;
Recessive Scores
- pRec
- 0.0744
Intolerance Scores
- RVIS EVS
- -0.82
- RVIS percentile EVS
- 11.68
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.114
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |