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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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GLRX5
glutaredoxin 5
Chromosome 14 Β· 14q32.13
NCBI Gene: 51218Ensembl: ENSG00000182512.6HGNC: HGNC:20134UniProt: A0A384MDT9
47PubMed Papers
22Diseases
0Drugs
9Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein binding[2Fe-2S] cluster assemblyprotein maturationmitochondrial matrixsideroblastic anemia 3spasticity-ataxia-gait anomalies syndromeAdult-onset autosomal recessive sideroblastic anemianeurodegenerative disease
✦AI Summary

GLRX5 is a monothiol glutaredoxin that functions as a critical mitochondrial iron-sulfur (Fe/S) cluster transfer protein 1. It receives 2Fe/2S clusters from the scaffold protein ISCU and mediates their transfer to apoproteins, the 4Fe/4S cluster biosynthesis machinery, or export from mitochondria 123. GLRX5 forms a tetrameric complex when bound to [2Fe-2S] clusters through coordination by conserved cysteine residues and glutathione molecules 4. The protein is essential for regulating hemoglobin synthesis through the iron-sulfur protein ACO1 and supporting lipoate-dependent enzyme function 15. Clinically, GLRX5 mutations cause sideroblastic anemia and childhood-onset spastic paraplegia with hyperglycinemia 637. In sideroblastic anemia patients, GLRX5 mutations impair heme biosynthetic enzymes ALAS2 and ferrochelatase activity, leading to oxidative stress and mitochondrial dysfunction 6. Additionally, GLRX5 has emerged as a prognostic marker in bladder cancer, where elevated expression correlates with malignant behavior and poor outcomes 8, and as a potential biomarker in acute kidney injury and suicide attempt risk 910.

Sources cited
1
GLRX5 receives 2Fe/2S clusters from ISCU and mediates transfer to apoproteins; required for hemoglobin synthesis regulation by ACO1
PMID: 20364084
2
GLRX5 role in mitochondrial Fe/S cluster transfer to apoproteins and biosynthesis machinery
PMID: 23615440
3
GLRX5 mutations cause variant nonketotic hyperglycinemia with childhood-onset spastic paraplegia and optic atrophy
PMID: 24334290
4
GLRX5 forms tetrameric organization when bound to [2Fe-2S] clusters; coordinates clusters through cysteine residues and GSH
PMID: 21029046
5
GLRX5 mutations impair ferrochelatase and ALAS2 activities in congenital sideroblastic anemia, causing oxidative stress and mitochondrial dysfunction
PMID: 30660387
6
GLRX5 defects impair lipoate-dependent enzyme function and can present with variant nonketotic hyperglycinemia phenotype
PMID: 24777537
7
GLRX5 mutations identified as genetic cause of hereditary spastic paraplegia
PMID: 33813722
8
GLRX5 high expression in bladder cancer correlates with poor prognosis and tumor malignancy
PMID: 41485701
9
GLRX5 identified as potential biomarker for acute kidney injury with AUC > 0.800
PMID: 39042632
10
GLRX5 identified as causal brain protein associated with suicide attempt risk
PMID: 38317018
Disease Associationsβ“˜22
sideroblastic anemia 3Open Targets
0.75Strong
spasticity-ataxia-gait anomalies syndromeOpen Targets
0.75Strong
Adult-onset autosomal recessive sideroblastic anemiaOpen Targets
0.74Strong
neurodegenerative diseaseOpen Targets
0.44Moderate
lymphatic system cancerOpen Targets
0.27Weak
non-Hodgkins lymphomaOpen Targets
0.27Weak
liver diseaseOpen Targets
0.27Weak
Waldenstrom macroglobulinemiaOpen Targets
0.11Weak
plasma protein metabolism diseaseOpen Targets
0.10Weak
ParaproteinemiaOpen Targets
0.10Suggestive
clonal hematopoiesisOpen Targets
0.09Suggestive
lymphoplasmacytic lymphomaOpen Targets
0.09Suggestive
amino acid metabolism diseaseOpen Targets
0.09Suggestive
ocular hypotensionOpen Targets
0.08Suggestive
immunoproliferative disorderOpen Targets
0.08Suggestive
injuryOpen Targets
0.07Suggestive
goutOpen Targets
0.06Suggestive
subarachnoid hemorrhageOpen Targets
0.06Suggestive
atrial fibrillationOpen Targets
0.06Suggestive
neoplasmOpen Targets
0.03Suggestive
Anemia, sideroblastic, 3, pyridoxine-refractoryUniProt
Spasticity, childhood-onset, with hyperglycinemiaUniProt
Pathogenic Variants9
NM_016417.3(GLRX5):c.148AAG[1] (p.Lys51del)Likely pathogenic
Spasticity-ataxia-gait anomalies syndrome|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 51
NM_016417.3(GLRX5):c.367G>C (p.Asp123His)Likely pathogenic
Spasticity-ataxia-gait anomalies syndrome
β˜…β˜†β˜†β˜†2023β†’ Residue 123
NM_016417.3(GLRX5):c.197A>C (p.Gln66Pro)Pathogenic
Spasticity-ataxia-gait anomalies syndrome
β˜†β˜†β˜†β˜†2021β†’ Residue 66
NM_016417.3(GLRX5):c.200G>A (p.Cys67Tyr)Pathogenic
Sideroblastic anemia 3
β˜†β˜†β˜†β˜†2020β†’ Residue 67
NM_016417.3(GLRX5):c.383T>A (p.Met128Lys)Pathogenic
Sideroblastic anemia 3
β˜†β˜†β˜†β˜†2020β†’ Residue 128
NM_016417.3(GLRX5):c.301A>C (p.Lys101Gln)Pathogenic
Sideroblastic anemia 3
β˜†β˜†β˜†β˜†2018β†’ Residue 101
NM_016417.3(GLRX5):c.443T>C (p.Leu148Ser)Pathogenic
Sideroblastic anemia 3
β˜†β˜†β˜†β˜†2018β†’ Residue 148
NM_016417.3(GLRX5):c.86_93dup (p.Ala32fs)Pathogenic
Spasticity-ataxia-gait anomalies syndrome
β˜†β˜†β˜†β˜†2018β†’ Residue 32
NM_016417.3(GLRX5):c.294A>G (p.Gln98=)Pathogenic
Sideroblastic anemia 3
β˜†β˜†β˜†β˜†2007β†’ Residue 98
View on ClinVar β†—
Related Genes
ABCB7Protein interaction94%GLRXProtein interaction92%LIASProtein interaction91%BOLA2BProtein interaction88%BOLA3Protein interaction87%TXNProtein interaction83%
Tissue Expression6 tissues
Bone Marrow
100%
Liver
76%
Heart
75%
Brain
65%
Ovary
35%
Lung
28%
Gene Interaction Network
Click a node to explore
GLRX5ABCB7GLRXLIASBOLA2BBOLA3TXN
PROTEIN STRUCTURE
Preparing viewer…
PDB2WUL Β· 2.40 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.74LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF1.05 [0.63–1.74]
RankingsWhere GLRX5 stands among ~20K protein-coding genes
  • #9,208of 20,598
    Most Researched47
  • #2,973of 5,498
    Most Pathogenic Variants9
  • #16,297of 17,882
    Most Constrained (LOEUF)1.74
Genes detectedGLRX5
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
HACE1, GLRX5, and ELP2 gene variant cause spastic paraplegies.
PMID: 33813722
Acta Neurol Belg Β· 2022
1.00
2
The crystal structure of human GLRX5: iron-sulfur cluster co-ordination, tetrameric assembly and monomer activity.
PMID: 21029046
Biochem J Β· 2011
0.90
3
GLRX5 mutations impair heme biosynthetic enzymes ALA synthase 2 and ferrochelatase in Human congenital sideroblastic anemia.
PMID: 30660387
Mol Genet Metab Β· 2019
0.80
4
GLRX5 is a prognostic marker in bladder cancer and correlates with activation of cancer-associated fibroblasts in the tumor microenvironment.
PMID: 41485701
Exp Cell Res Β· 2026
0.70
5
Lipoic acid biosynthesis defects.
PMID: 24777537
J Inherit Metab Dis Β· 2014
0.60