TXNRD1
protein-codingthioredoxin reductase 1, the group of Selenoproteins|Glutaredoxin domain containing
Gene summary
The protein encoded by this gene belongs to the pyridine nucleotide-disulfide oxidoreductase family, and is a member of the thioredoxin (Trx) system. Three thioredoxin reductase (TrxR) isozymes are found in mammals. TrxRs are selenocysteine-containing flavoenzymes, which reduce thioredoxins, as well as other substrates, and play a key role in redox homoeostasis. This gene encodes an ubiquitously expressed, cytosolic form of TrxR, which functions as a homodimer containing FAD, and selenocysteine (Sec) at the active site. Sec is encoded by UGA codon that normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, the Sec insertion sequence (SECIS) element, which is necessary for the recognition of UGA as a Sec codon rather than as a stop signal. Alternative splicing, primarily at the 5' end, results in transcript variants encoding same or different isoforms, including a glutaredoxin-containing isoform that is predominantly expressed in testis. [provided by RefSeq, May 2017]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~134.5 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 TXNRD1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001093771.3. 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 | 4 | 3 | 2 | 9 | ||
| missense | 92 | 4 | 96 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 6 | 6 | ||||
| Total | 0 | 0 | 102 | 7 | 2 | 111 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001087240.1 | 17 | MANE Select | |
| Ensembl | ENSP00000434516.1 | 17 | MANE Select | |
| RefSeq | NP_001248374.1 | 15 | Standard | |
| RefSeq | NP_001248375.1 | 12 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Selenocompound metabolism - Homo sapiens (human)
- Hepatocellular carcinoma - Homo sapiens (human)
- Pathways in cancer - Homo sapiens (human)
- Oxidative Stress Regulatory Pathway (Erythrocyte)
- Selenium Micronutrient Network
Biological Process
- mesoderm formation
- selenium compound metabolic process
- signal transduction
- cell population proliferation
- nucleobase-containing small molecule interconversion
Molecular Function
- thioredoxin-disulfide reductase activity
- protein binding
- electron transfer activity
- protein disulfide oxidoreductase activity
- flavin adenine dinucleotide binding
Cellular Component
- fibrillar center
- nucleoplasm
- cytoplasm
- mitochondrion
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000525566
- Coding exons
- 17
- Length
- 134505
- Individuals with no LoFs
- 124610
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 44
- Defined
- 124655
- p
- 0.000181
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.32 | 271 | 340 | 0.798 | 0.0000171 | 4169 |
| Missense (PolyPhen) | 118 | 164.88 | 0.71565 | 2021 | ||
| Synonymous | 0.889 | 110 | 123 | 0.898 | 0.00000633 | 1260 |
| Loss of Function | 2.79 | 15 | 32.0 | 0.468 | 0.00000152 | 440 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00013 | 0.00013 | rare |
| Latino/Admixed American | 0.00032 | 0.00029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00012 | 0.00011 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00023 | 0.00023 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Isoform 1 may possess glutaredoxin activity as well as thioredoxin reductase activity and induces actin and tubulin polymerization, leading to formation of cell membrane protrusions. Isoform 4 enhances the transcriptional activity of estrogen receptors alpha and beta while isoform 5 enhances the transcriptional activity of the beta receptor only. Isoform 5 also mediates cell death induced by a combination of interferon-beta and retinoic acid. {ECO:0000269|PubMed:15199063, ECO:0000269|PubMed:18042542, ECO:0000269|PubMed:8577704, ECO:0000269|PubMed:9774665}.;
Recessive Scores
- pRec
- 0.238
Intolerance Scores
- LoFtool
- 0.757
- RVIS EVS
- -0.87
- RVIS percentile EVS
- 10.8
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.987
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |