AGR2
protein-codinganterior gradient 2, protein disulphide isomerase family member, the group of Protein disulfide isomerases
Gene summary
This gene encodes a member of the disulfide isomerase (PDI) family of endoplasmic reticulum (ER) proteins that catalyze protein folding and thiol-disulfide interchange reactions. The encoded protein has an N-terminal ER-signal sequence, a catalytically active thioredoxin domain, and a C-terminal ER-retention sequence. This protein plays a role in cell migration, cellular transformation and metastasis and is as a p53 inhibitor. As an ER-localized molecular chaperone, it plays a role in the folding, trafficking, and assembly of cysteine-rich transmembrane receptors and the cysteine-rich intestinal gylcoprotein mucin. This gene has been implicated in inflammatory bowel disease and cancer progression. [provided by RefSeq, Mar 2017]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~41.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0859370
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0859370
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0859370
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0859370
Submitter: Ambry Genetics
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to AGR2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006408.4. 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 | 0 | |||||
| missense | 1 | 2 | 21 | 1 | 25 | |
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | 1 | 3 | ||
| splice donor/acceptor (+/-2bp) | 1 | 3 | 1 | 5 | ||
| Total | 3 | 7 | 23 | 1 | 0 | 34 |
Highest pathogenic variant AF is 0.000021700931
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006399.1 | 7 | MANE Select | |
| Ensembl | ENSP00000391490.2 | 7 | MANE Select | |
| Ensembl | ENSP00000386025.1 | 6 | Standard | |
| Ensembl | ENSP00000386025.1 | 6 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| agr2 | Danio rerio | Structure: goblet cell Quality: immature abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- positive regulation of gene expression
- positive regulation of cell-substrate adhesion
- response to endoplasmic reticulum stress
- positive regulation of epidermal growth factor receptor signaling pathway
- digestive tract morphogenesis
Molecular Function
- dystroglycan binding
- epidermal growth factor receptor binding
- protein binding
- protein homodimerization activity
Cellular Component
- extracellular space
- endoplasmic reticulum
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000419304
- Coding exons
- 7
- Length
- 41623
- Individuals with no LoFs
- 125729
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 19
- Defined
- 125748
- p
- 0.0000756
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.844 | 67 | 89.5 | 0.749 | 0.00000414 | 1131 |
| Missense (PolyPhen) | 20 | 33.73 | 0.59294 | 429 | ||
| Synonymous | 0.730 | 28 | 33.4 | 0.839 | 0.00000162 | 328 |
| Loss of Function | 0.103 | 11 | 11.4 | 0.967 | 5.45e-7 | 140 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00013 | 0.00013 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Required for MUC2 post-transcriptional synthesis and secretion. May play a role in the production of mucus by intestinal cells (By similarity). Proto-oncogene that may play a role in cell migration, cell differentiation and cell growth. Promotes cell adhesion (PubMed:23274113). {ECO:0000250, ECO:0000269|PubMed:18199544, ECO:0000269|PubMed:23274113}.;
Recessive Scores
- pRec
- 0.102
Intolerance Scores
- LoFtool
- 0.625
- RVIS EVS
- -0.14
- RVIS percentile EVS
- 42.88
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0406
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |