TXNDC5
protein-codingthioredoxin domain containing 5, the group of Protein disulfide isomerases|Thioredoxin domain containing
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 endoplasmic reticulum (ER)-signal sequence, three catalytically active thioredoxin domains and a C-terminal ER-retention sequence. Its expression is induced by hypoxia and its role may be to protect hypoxic cells from apoptosis. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the neighboring upstream BLOC1S5 gene. [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 ~29.3 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 TXNDC5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_030810.5. 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 | 3 | 1 | 88 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 84 | 4 | 1 | 89 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_110437.2 | 10 | MANE Select | |
| Ensembl | ENSP00000369081.4 | 10 | MANE Select | |
| RefSeq | NP_001139021.1 | 9 | Standard | |
| Ensembl | ENSP00000420784.1 | 9 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Protein processing in endoplasmic reticulum - Homo sapiens (human)
- Golgi Associated Vesicle Biogenesis
- Lysosome Vesicle Biogenesis
- Clathrin derived vesicle budding
- Neutrophil degranulation
Biological Process
- negative regulation of apoptotic process
- apoptotic cell clearance
- neutrophil degranulation
- cell redox homeostasis
Molecular Function
- protein binding
- isomerase activity
Cellular Component
- extracellular region
- endoplasmic reticulum
- endoplasmic reticulum lumen
- azurophil granule lumen
- lysosomal lumen
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000379757
- Coding exons
- 10
- Length
- 145164
- Individuals with no LoFs
- 125673
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 75
- Defined
- 125748
- p
- 0.000298
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.416 | 244 | 226 | 1.08 | 0.0000136 | 2759 |
| Missense (PolyPhen) | 96 | 96.351 | 0.99636 | 1089 | ||
| Synonymous | 0.386 | 90 | 94.8 | 0.950 | 0.00000638 | 857 |
| Loss of Function | 0.654 | 21 | 24.5 | 0.857 | 0.00000141 | 257 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00098 | 0.00098 | rare |
| Latino/Admixed American | 0.00046 | 0.00046 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.0011 | 0.00098 | notable |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00015 | 0.00015 | rare |
| South Asian | 0.00023 | 0.00023 | rare |
| Other | 0.00017 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Possesses thioredoxin activity. Has been shown to reduce insulin disulfide bonds. Also complements protein disulfide- isomerase deficiency in yeast (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.258
Intolerance Scores
- LoFtool
- 0.977
- RVIS EVS
- 0.02
- RVIS percentile EVS
- 55.69
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.341
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |