GLRX2
protein-codingglutaredoxin 2, the group of Glutaredoxin domain containing
Gene summary
The protein encoded by this gene is a member of the glutaredoxin family of proteins, which maintain cellular thiol homeostasis. These proteins are thiol-disulfide oxidoreductases that use a glutathione-binding site and one or two active cysteines in their active site. This gene undergoes alternative splicing to produce multiple isoforms, one of which is ubiquitously expressed and localizes to mitochondria, where it functions in mitochondrial redox homeostasis and is important for the protection against and recovery from oxidative stress. Other isoforms, which have more restrictive expression patterns, show cytosolic and nuclear localization, and are thought to function in cellular differentiation and transformation, possibly with a role in tumor progression. [provided by RefSeq, Aug 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~15.2 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 GLRX2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_197962.3. 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 | 16 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 17 | 0 | 0 | 17 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_932066.1 | 4 | MANE Select | |
| Ensembl | ENSP00000356409.3 | 4 | MANE Select | |
| RefSeq | NP_001230328.1 | 3 | Standard | |
| RefSeq | NP_057150.2 | 4 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| glrx2 | Danio rerio | Structure: dopaminergic neuron Quality: decreased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- regulation of transcription, DNA-templated
- glutathione metabolic process
- apoptotic process
- aging
- response to temperature stimulus
Molecular Function
- protein disulfide isomerase activity
- arsenate reductase (glutaredoxin) activity
- electron transfer activity
- protein disulfide oxidoreductase activity
- glutathione disulfide oxidoreductase activity
Cellular Component
- nucleus
- nucleoplasm
- mitochondrion
- mitochondrial matrix
- dendrite
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000367440
- Coding exons
- 4
- Length
- 9647
- Individuals with no LoFs
- 125709
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 10
- Defined
- 125719
- p
- 0.0000398
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.387 | 71 | 80.8 | 0.879 | 0.00000372 | 1070 |
| Missense (PolyPhen) | 17 | 22.159 | 0.76717 | 311 | ||
| Synonymous | -1.15 | 39 | 30.9 | 1.26 | 0.00000158 | 309 |
| Loss of Function | 0.448 | 5 | 6.20 | 0.806 | 2.62e-7 | 86 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000059 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.0000088 | 0.0000088 | rare |
| South Asian | 0.000066 | 0.000065 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Glutathione-dependent oxidoreductase that facilitates the maintenance of mitochondrial redox homeostasis upon induction of apoptosis by oxidative stress. Involved in response to hydrogen peroxide and regulation of apoptosis caused by oxidative stress. Acts as a very efficient catalyst of monothiol reactions because of its high affinity for protein glutathione-mixed disulfides. Can receive electrons not only from glutathione (GSH), but also from thioredoxin reductase supporting both monothiol and dithiol reactions. Efficiently catalyzes both glutathionylation and deglutathionylation of mitochondrial complex I, which in turn regulates the superoxide production by the complex. Overexpression decreases the susceptibility to apoptosis and prevents loss of cardiolipin and cytochrome c release. {ECO:0000269|PubMed:11297543, ECO:0000269|PubMed:14676218, ECO:0000269|PubMed:15328416, ECO:0000269|PubMed:15649413}.;
Recessive Scores
- pRec
- 0.113
Intolerance Scores
- LoFtool
- 0.681
- RVIS EVS
- 0.39
- RVIS percentile EVS
- 75.87
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.958
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |