TXNDC2

Chr 18

thioredoxin domain containing 2

Also known as: SPTRX, SPTRX1

NCBI Gene: 84203ENSG00000168454UniProt: Q86VQ3

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]

Research Assistant →
0
Active trials
1
Pubs (1 yr)
103
P/LP submissions
0%
P/LP missense
0.92
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— TXNDC2
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.63) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
98 unique Pathogenic / Likely Pathogenic· 79 VUS of 205 total submissions
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.92LOEUF
pLI 0.634
Z-score 1.66
OE 0.00 (0.00–0.92)
Moderately constrained

Typical tolerance to LoF variation

Missense Constraint
-0.06Z-score
OE missense 1.01 (0.92–1.11)
282 obs / 279.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.00 (0.00–0.92)
0≤0.351.4
Missense OE1.01 (0.92–1.11)
0≤0.61.4
Synonymous OE1.05
0≤1.21.6
LoF obs/exp: 0 / 3.2Missense obs/exp: 282 / 279.1Syn Z: -0.43
DN
0.77top 25%
GOF
0.83top 10%
LOF
0.4135th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

205 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic96
Likely Pathogenic2
VUS79
Likely Benign24
Benign2
96
Pathogenic
2
Likely Pathogenic
79
VUS
24
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
96
0
96
Likely Pathogenic
0
0
2
0
2
VUS
0
72
7
0
79
Likely Benign
0
13
0
11
24
Benign
0
0
1
1
2
Total08510612203

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TXNDC2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 4 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients