PDIA5
protein-codingprotein disulfide isomerase family A member 5, the group of MicroRNA protein coding host genes|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, three catalytically active thioredoxin (TRX) domains, a TRX-like domain, and a C-terminal ER-retention sequence. The N-terminal TRX-like domain is the primary binding site for the major ER chaperone calreticulin and possibly other proteins and substrates as well. Alternative splicing results in multiple protein- and non-protein-coding transcript variants. [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 ~158.2 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 PDIA5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006810.4. 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 | 1 | 1 | ||||
| missense | 86 | 2 | 88 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 8 | 8 | ||||
| Total | 0 | 0 | 97 | 2 | 0 | 99 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006801.1 | 17 | MANE Select | |
| Ensembl | ENSP00000323313.7 | 17 | MANE Select | |
| Ensembl | ENSP00000417199.1 | 4 | Standard | |
| Ensembl | ENSP00000419946.1 | 3 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| pdia5 | Danio rerio | Structure: thrombocyte Quality: decreased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- XBP1(S) activates chaperone genes
Biological Process
- protein folding
- IRE1-mediated unfolded protein response
- cell redox homeostasis
- oxidation-reduction process
Molecular Function
- protein disulfide isomerase activity
- protein binding
- peptide disulfide oxidoreductase activity
- oxidoreductase activity
Cellular Component
- endoplasmic reticulum lumen
- endoplasmic reticulum membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000316218
- Coding exons
- 17
- Length
- 158166
- Individuals with no LoFs
- 125676
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 72
- Defined
- 125748
- p
- 0.000286
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.238 | 283 | 295 | 0.961 | 0.0000167 | 3428 |
| Missense (PolyPhen) | 92 | 101.41 | 0.90719 | 1201 | ||
| Synonymous | -0.422 | 127 | 121 | 1.05 | 0.00000780 | 942 |
| Loss of Function | 2.32 | 20 | 34.7 | 0.576 | 0.00000190 | 404 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00037 | 0.00037 | rare |
| Latino/Admixed American | 0.00061 | 0.00061 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00016 | 0.00016 | rare |
| South Asian | 0.00079 | 0.00078 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
Recessive Scores
- pRec
- 0.134
Intolerance Scores
- LoFtool
- 0.790
- RVIS EVS
- -0.95
- RVIS percentile EVS
- 9.21
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.580
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |