TXNDC2
protein-codingthioredoxin domain containing 2, the group of Thioredoxin domain containing
Gene summary
Enables thioredoxin-disulfide reductase (NADPH) activity. Predicted to be involved in cell redox homeostasis and spermatogenesis. Predicted to act upstream of or within cellular response to reactive oxygen species and flagellated sperm motility. Located in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~3.5 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 TXNDC2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_032243.6. 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 | 12 | 12 | ||||
| missense | 64 | 14 | 78 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 64 | 26 | 0 | 90 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_115619.4 | 1 | MANE Select | |
| Ensembl | ENSP00000350419.4 | 1 | MANE Select | |
| RefSeq | NP_001091999.1 | 2 | Standard | |
| Ensembl | ENSP00000304908.6 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- glycerol ether metabolic process
- multicellular organism development
- spermatogenesis
- cell differentiation
- cell redox homeostasis
Molecular Function
- thioredoxin-disulfide reductase activity
- protein disulfide oxidoreductase activity
Cellular Component
- cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000306084
- Coding exons
- 2
- Length
- 3510
- Individuals with no LoFs
- 125690
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 4
- Defined
- 125694
- p
- 0.0000159
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.0622 | 282 | 279 | 1.01 | 0.0000134 | 3585 |
| Missense (PolyPhen) | 63 | 66.958 | 0.94088 | 960 | ||
| Synonymous | -0.434 | 119 | 113 | 1.05 | 0.00000584 | 1053 |
| Loss of Function | 1.66 | 0 | 3.22 | 0.00 | 1.34e-7 | 49 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000055 | 0.000054 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.0000088 | 0.0000088 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Probably plays a regulatory role in sperm development. May participate in regulation of fibrous sheath (FS) assembly by supporting the formation of disulfide bonds during sperm tail morphogenesis. May also be required to rectify incorrect disulfide pairing and generate suitable pairs between the FS constituents. Can reduce disulfide bonds in vitro in the presence of NADP and thioredoxin reductase.;
Intolerance Scores
- LoFtool
- 0.826
- RVIS EVS
- 1.31
- RVIS percentile EVS
- 94.05
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0629
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |