PDIA4
protein-codingprotein disulfide isomerase family A member 4, 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, three catalytically active thioredoxin (TRX) domains, two TRX-like domains and a C-terminal ER-retention sequence. This protein, when bound to cyclophilin B, enhances the rate of immunoglobulin G intermolecular disulfide bonding and antibody assembly. [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 ~25.6 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 PDIA4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004911.5. 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 | 84 | 6 | 90 | |||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 88 | 6 | 1 | 95 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004902.1 | 10 | MANE Select | |
| Ensembl | ENSP00000499129.1 | 10 | MANE Select | |
| RefSeq | NP_001358173.1 | 10 | Standard | |
| RefSeq | NP_001358174.1 | 10 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Thyroid hormone synthesis - Homo sapiens (human)
- Protein processing in endoplasmic reticulum - Homo sapiens (human)
- Vibrio cholerae infection - Homo sapiens (human)
- Ibuprofen Action Pathway
- Phenytoin (Antiarrhythmic) Action Pathway
Biological Process
- protein folding
- protein secretion
- response to endoplasmic reticulum stress
- cell redox homeostasis
- oxidation-reduction process
Molecular Function
- RNA binding
- protein disulfide isomerase activity
- protein binding
- peptide disulfide oxidoreductase activity
Cellular Component
- extracellular space
- endoplasmic reticulum
- endoplasmic reticulum lumen
- cell surface
- melanosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000286091
- Coding exons
- 10
- Length
- 25580
- Individuals with no LoFs
- 125732
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 16
- Defined
- 125748
- p
- 0.0000636
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.126 | 367 | 360 | 1.02 | 0.0000198 | 4256 |
| Missense (PolyPhen) | 116 | 135 | 0.85927 | 1584 | ||
| Synonymous | -0.743 | 167 | 155 | 1.08 | 0.0000104 | 1206 |
| Loss of Function | 3.43 | 7 | 25.8 | 0.271 | 0.00000119 | 341 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000089 | 0.000088 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
Intolerance Scores
- LoFtool
- 0.522
- RVIS EVS
- -0.19
- RVIS percentile EVS
- 39.25
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.859
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |