GLRX3
Chr 10glutaredoxin 3
Also known as: GLRX4, GRX3, GRX4, PICOT, TXNL2, TXNL3
This protein functions as a cytosolic iron-sulfur cluster assembly factor that facilitates [2Fe-2S] cluster insertion into cytosolic proteins and is required for hemoglobin maturation. Mutations cause autosomal recessive myopathy with lactic acidosis and sideroblastic anemia, typically presenting in infancy with severe anemia and muscle weakness. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.477), reflecting its essential role in cellular iron-sulfur metabolism.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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
176 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 92 | 0 | 92 |
Likely Pathogenic | 0 | 0 | 5 | 0 | 5 |
VUS | 0 | 46 | 8 | 0 | 54 |
Likely Benign | 0 | 1 | 0 | 0 | 1 |
Benign | 0 | 0 | 0 | 1 | 1 |
| Total | 0 | 47 | 105 | 1 | 153 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
GLRX3 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools