TXNRD3
protein-codingthioredoxin reductase 3, the group of Glutaredoxin domain containing|Selenoproteins
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 the third TrxR, which unlike the other two isozymes, contains an additional N-terminal glutaredoxin (Grx) domain, and shows highest expression in testis. The Grx domain allows this isozyme to participate in both Trx and glutathione systems. It 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. Alternatively spliced transcript variants have been found for this gene. Experimental evidence suggests the use of a non-AUG (CUG) codon as a translation initiation codon (PMID:20018845). [provided by RefSeq, Aug 2017]
- TXNRD3NB
- TXNRD3IT1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~83.3 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 TXNRD3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_052883.3. 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 | 1 | 1 | 2 | |||
| missense | 96 | 6 | 102 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 97 | 7 | 0 | 104 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_443115.1 | 16 | MANE Select | |
| Ensembl | ENSP00000430031.4 | 16 | MANE Select | |
| RefSeq | NP_001166984.1 | 15 | Standard | |
| Ensembl | ENSP00000429584.3 | 15 | 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)
- Selenium Micronutrient Network
- Selenium Metabolism and Selenoproteins
Biological Process
- multicellular organism development
- spermatogenesis
- electron transport chain
- cell differentiation
- cell redox homeostasis
Molecular Function
- thioredoxin-disulfide reductase activity
- electron transfer activity
- protein disulfide oxidoreductase activity
- flavin adenine dinucleotide binding
Cellular Component
- nucleus
- cytoplasm
- mitochondrion
- endoplasmic reticulum
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000524230
- Coding exons
- 16
- Length
- 83377
- Individuals with no LoFs
- 0
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 0
- Defined
- 0
- p
- 0.00
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.60 | 184 | 256 | 0.719 | 0.0000130 | 4449 |
| Missense (PolyPhen) | 61 | 101.9 | 0.59861 | 1351 | ||
| Synonymous | 1.87 | 70 | 92.9 | 0.754 | 0.00000494 | 1395 |
| Loss of Function | 1.76 | 15 | 24.4 | 0.616 | 0.00000103 | 441 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Displays thioredoxin reductase, glutaredoxin and glutathione reductase activities. Catalyzes disulfide bond isomerization. Promotes disulfide bond formation between GPX4 and various sperm proteins and may play a role in sperm maturation by promoting formation of sperm structural components (By similarity). {ECO:0000250|UniProtKB:Q99MD6}.;
Recessive Scores
- pRec
- 0.107
Essentials
- Essential (CRISPR2)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.212
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |