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8 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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TXNDC8
thioredoxin domain containing 8
Chromosome 9 · 9q31.3
NCBI Gene: 255220Ensembl: ENSG00000204193.12HGNC: HGNC:31454UniProt: A0AAA9YHJ3
10PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein-disulfide reductase activityspermatogenesisGolgi apparatuscytoplasmhypertensionheart diseaseplacental retentioncervical carcinoma
✦AI Summary

TXNDC8 (thioredoxin domain containing 8), also known as SPTRX3, is a germ line-specific thioredoxin localized to the Golgi apparatus of spermatocytes and spermatids 1. Its primary function involves reducing disulfide bonds and facilitating post-translational modifications of proteins required for acrosomal biogenesis 1. TXNDC8 is uniquely expressed during male germ cell development and becomes abnormally retained in the nuclear vacuoles and superfluous cytoplasm of defective spermatozoa 2. While related thioredoxins (Txndc2 and Txndc3) are critical for protecting mature spermatozoa against oxidative stress and age-related DNA damage 3, TXNDC8 serves as a biomarker of spermatogenic dysfunction. High semen levels of TXNDC8 (>15% positive spermatozoa) correlate with reduced pregnancy rates in assisted reproductive therapy, with affected couples experiencing nearly two-thirds reduction in conception likelihood compared to those with low TXNDC8 levels 4. TXNDC8 content also correlates positively with sperm DNA fragmentation and negatively with sperm concentration and motility 5. Notably, fathers of multiple births show significantly lower TXNDC8 levels than those conceiving singletons 5, suggesting TXNDC8 as a predictive marker for ART outcomes and pregnancy complications.

Sources cited
1
TXNDC8 (SPTRX-3) localizes to Golgi apparatus of spermatocytes and spermatids; involved in post-translational modifications for acrosomal biogenesis
PMID: 15181017
2
TXNDC8 is retained in nuclear vacuoles and superfluous cytoplasm of defective spermatozoa; high semen levels associated with reduced ART success
PMID: 25999356
3
Related thioredoxins (Txndc2/3) protect spermatozoa against oxidative stress and age-related DNA damage
PMID: 23707457
4
High TXNDC8 levels (>15% positive spermatozoa) reduce pregnancy rates in IVF/ICSI couples by nearly two-thirds
PMID: 23734172
5
TXNDC8 correlates with sperm DNA fragmentation index, sperm concentration, motility, and multiple birth outcomes after ART
PMID: 32851881
Disease Associationsⓘ20
hypertensionOpen Targets
0.35Weak
heart diseaseOpen Targets
0.33Weak
cervical carcinomaOpen Targets
0.31Weak
placental retentionOpen Targets
0.31Weak
gastritisOpen Targets
0.13Weak
ovarian neoplasmOpen Targets
0.12Weak
smoking initiationOpen Targets
0.10Weak
retinal drusenOpen Targets
0.07Suggestive
essential hypertensionOpen Targets
0.05Suggestive
coronary artery diseaseOpen Targets
0.05Suggestive
Increased blood pressureOpen Targets
0.04Suggestive
cardiovascular diseaseOpen Targets
0.03Suggestive
Abnormality of the skeletal systemOpen Targets
0.03Suggestive
coronary atherosclerosisOpen Targets
0.02Suggestive
male infertilityOpen Targets
0.02Suggestive
parasitic infectionOpen Targets
0.02Suggestive
ileostomyOpen Targets
0.02Suggestive
amyloidosisOpen Targets
0.02Suggestive
infertilityOpen Targets
0.02Suggestive
Abdominal Aortic AneurysmOpen Targets
0.02Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
ACRV1Shared pathway100%SPAG4Shared pathway100%SSX1Shared pathway100%SPAG11BShared pathway100%MYCBPShared pathway100%SPANXA1Shared pathway100%
Tissue Expression6 tissues
Brain
0%
Bone Marrow
0%
Heart
0%
Ovary
0%
Liver
0%
Lung
0%
Gene Interaction Network
Click a node to explore
TXNDC8ACRV1SPAG4SSX1SPAG11BMYCBPSPANXA1
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q6A555
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.75LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.03 [0.60–1.75]
RankingsWhere TXNDC8 stands among ~20K protein-coding genes
  • #17,212of 20,598
    Most Researched10
  • #16,317of 17,882
    Most Constrained (LOEUF)1.75
Genes detectedTXNDC8
Sources retrieved8 papers
Response time—
📄 Sources
8▼
1
Pathway analysis of a genome-wide gene by air pollution interaction study in asthmatic children.
PMID: 31028280
J Expo Sci Environ Epidemiol · 2019
1.00
2
Negative biomarker based male fertility evaluation: Sperm phenotypes associated with molecular-level anomalies.
PMID: 25999356
Asian J Androl · 2015
0.88
3
Functional deletion of Txndc2 and Txndc3 increases the susceptibility of spermatozoa to age-related oxidative stress.
PMID: 23707457
Free Radic Biol Med · 2013
0.75
4
Semen levels of spermatid-specific thioredoxin-3 correlate with pregnancy rates in ART couples.
PMID: 23734172
PLoS One · 2013
0.63
5
Sperm content of TXNDC8 reflects sperm chromatin structure, pregnancy establishment, and incidence of multiple births after ART.
PMID: 32851881
Syst Biol Reprod Med · 2020
0.50