TXNDC8
protein-codingthioredoxin domain containing 8, the group of Thioredoxin domain containing
Gene summary
Involved in spermatogenesis. Located in Golgi apparatus. Biomarker of male infertility. [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 ~34.4 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 TXNDC8 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001424031.1. 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 | 0 | |||||
| missense | 16 | 1 | 17 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 16 | 1 | 0 | 17 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001410960.1 | 6 | MANE Select | |
| Ensembl | ENSP00000363635.3 | 6 | MANE Select | |
| RefSeq | NP_001003936.1 | 6 | Standard | |
| RefSeq | NP_001273875.1 | 5 | 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
- protein disulfide oxidoreductase activity
Cellular Component
- cytoplasm
- Golgi apparatus
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000374510
- Coding exons
- 6
- Length
- 34327
- Individuals with no LoFs
- 125450
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 5
- Defined
- 125455
- p
- 0.0000199
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.409 | 70 | 61.0 | 1.15 | 0.00000310 | 764 |
| Missense (PolyPhen) | 25 | 17.28 | 1.4467 | 232 | ||
| Synonymous | -0.00255 | 20 | 20.0 | 1.00 | 0.00000108 | 188 |
| Loss of Function | 1.01 | 4 | 6.86 | 0.583 | 2.91e-7 | 85 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000062 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000058 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000018 | 0.000018 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May be required for post-translational modifications of proteins required for acrosomal biogenesis. May act by reducing disulfide bonds within the sperm.;
Intolerance Scores
- LoFtool
- 0.439
- RVIS EVS
- 0.66
- RVIS percentile EVS
- 84.35
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.145
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |