TXNDC12
protein-codingthioredoxin domain containing 12, the group of Protein disulfide isomerases|Thioredoxin domain containing
Gene summary
This gene encodes a member of the thioredoxin superfamily. Members of this family are characterized by a conserved active motif called the thioredoxin fold that catalyzes disulfide bond formation and isomerization. This protein localizes to the endoplasmic reticulum and has a single atypical active motif. The encoded protein is mainly involved in catalyzing native disulfide bond formation and displays activity similar to protein-disulfide isomerases. This protein may play a role in defense against endoplasmic reticulum stress. Alternate splicing results in both coding and non-coding variants. [provided by RefSeq, Mar 2012]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~35.6 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 TXNDC12 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_015913.4. 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 | 2 | 2 | ||||
| missense | 18 | 18 | ||||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 22 | 0 | 0 | 22 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_056997.1 | 7 | MANE Select | |
| Ensembl | ENSP00000360688.4 | 7 | MANE Select | |
| Ensembl | ENSP00000477120.1 | 3 | Standard | |
| Ensembl | ENSP00000476401.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Glutathione metabolism - Homo sapiens (human)
Biological Process
- cell redox homeostasis
- oxidation-reduction process
- negative regulation of cell death
- negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway
Molecular Function
- protein binding
- peptide disulfide oxidoreductase activity
- protein-disulfide reductase (glutathione) activity
Cellular Component
- endoplasmic reticulum
- endoplasmic reticulum lumen
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000371626
- Coding exons
- 7
- Length
- 36041
- Individuals with no LoFs
- 125721
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 27
- Defined
- 125748
- p
- 0.000107
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.517 | 78 | 92.0 | 0.848 | 0.00000426 | 1136 |
| Missense (PolyPhen) | 23 | 34.059 | 0.67529 | 408 | ||
| Synonymous | 0.664 | 30 | 35.0 | 0.857 | 0.00000187 | 311 |
| Loss of Function | 0.801 | 8 | 10.8 | 0.738 | 5.58e-7 | 126 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00025 | 0.00025 | rare |
| Latino/Admixed American | 0.00026 | 0.00026 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000071 | 0.000070 | rare |
| South Asian | 0.00017 | 0.00016 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Possesses significant protein thiol-disulfide oxidase activity. {ECO:0000269|PubMed:12761212}.;
Recessive Scores
- pRec
- 0.147
Intolerance Scores
- LoFtool
- 0.594
- RVIS EVS
- 0.73
- RVIS percentile EVS
- 85.98
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.914
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |