AGR3
protein-codinganterior gradient 3, 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 gene is expressed in ciliated airway epithelial cells and, in mouse, plays a role in ciliary beat frequency in multiciliated cells. This gene is also over-expressed in breast, ovarian, and prostrate cancers. [provided by RefSeq, Dec 2016]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~22.6 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 AGR3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_176813.5. 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 | 1 | 1 | ||||
| missense | 25 | 1 | 26 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 29 | 1 | 0 | 30 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_789783.1 | 7 | MANE Select | |
| Ensembl | ENSP00000308606.2 | 7 | MANE Select | |
| Ensembl | ENSP00000386016.3 | 6 | Standard | |
| Ensembl | ENSP00000386016.3 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- biological_process
- negative regulation of cell death
Molecular Function
- dystroglycan binding
- protein binding
Cellular Component
- cellular_component
- endoplasmic reticulum
- intracellular membrane-bounded organelle
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000310398
- Coding exons
- 7
- Length
- 22583
- Individuals with no LoFs
- 125347
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 391
- Defined
- 125738
- p
- 0.00156
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.897 | 106 | 83.0 | 1.28 | 0.00000377 | 1072 |
| Missense (PolyPhen) | 37 | 28.93 | 1.279 | 392 | ||
| Synonymous | 0.337 | 25 | 27.2 | 0.918 | 0.00000123 | 293 |
| Loss of Function | -3.07 | 22 | 11.0 | 2.00 | 4.66e-7 | 140 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00068 | 0.00068 | rare |
| Latino/Admixed American | 0.00099 | 0.00098 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.00049 | 0.00049 | rare |
| Finnish | 0.00097 | 0.00097 | rare |
| European (Non-Finnish) | 0.0023 | 0.0023 | notable |
| South Asian | 0.0013 | 0.0012 | notable |
| Other | 0.0028 | 0.0028 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Required for calcium-mediated regulation of ciliary beat frequency and mucociliary clearance in the airway. Might be involved in the regulation of intracellular calcium in tracheal epithelial cells. {ECO:0000250|UniProtKB:Q8R3W7}.;
Recessive Scores
- pRec
- 0.119
Intolerance Scores
- RVIS EVS
- -0.19
- RVIS percentile EVS
- 39.68
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.224
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |