PREB
protein-codingprolactin regulatory element binding, the group of WD repeat domain containing
Gene summary
This gene encodes a protein that specifically binds to a Pit1-binding element of the prolactin (PRL) promoter. This protein may act as a transcriptional regulator and is thought to be involved in some of the developmental abnormalities observed in patients with partial trisomy 2p. This gene overlaps the abhydrolase domain containing 1 (ABHD1) gene on the opposite strand. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~3.9 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 PREB variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_013388.6. 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 | 3 | 3 | ||||
| missense | 53 | 3 | 56 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 59 | 3 | 0 | 62 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_037520.1 | 9 | MANE Select | |
| Ensembl | ENSP00000260643.2 | 9 | MANE Select | |
| RefSeq | NP_001317413.1 | 8 | Standard | |
| RefSeq | NP_001317414.1 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Protein processing in endoplasmic reticulum - Homo sapiens (human)
- XBP1(S) activates chaperone genes
- Vesicle-mediated transport
- Membrane Trafficking
- Post-translational protein modification
Biological Process
- regulation of COPII vesicle coating
- endoplasmic reticulum to Golgi vesicle-mediated transport
- protein secretion
- protein exit from endoplasmic reticulum
- IRE1-mediated unfolded protein response
Molecular Function
- DNA binding
- guanyl-nucleotide exchange factor activity
- Sar guanyl-nucleotide exchange factor activity
- GTPase activator activity
- protein binding
Cellular Component
- Golgi membrane
- nucleus
- endoplasmic reticulum membrane
- membrane
- integral component of endoplasmic reticulum membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000260643
- Coding exons
- 9
- Length
- 3920
- Individuals with no LoFs
- 125717
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 31
- Defined
- 125748
- p
- 0.000123
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.431 | 217 | 236 | 0.921 | 0.0000135 | 2657 |
| Missense (PolyPhen) | 72 | 86.013 | 0.83708 | 973 | ||
| Synonymous | 0.823 | 88 | 98.4 | 0.894 | 0.00000566 | 892 |
| Loss of Function | 2.48 | 9 | 21.4 | 0.421 | 0.00000115 | 217 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00026 | 0.00026 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00065 | 0.00065 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000062 | 0.000062 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Guanine nucleotide exchange factor that specifically activates the small GTPase SAR1B. Mediates the recruitement of SAR1B and other COPII coat components to endoplasmic reticulum membranes and is therefore required for the formation of COPII transport vesicles from the ER. {ECO:0000250|UniProtKB:Q9WTV0, ECO:0000250|UniProtKB:Q9WUQ2}.;
Recessive Scores
- pRec
- 0.275
Intolerance Scores
- RVIS EVS
- -0.36
- RVIS percentile EVS
- 29.31
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.633
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |