GLRX5
protein-codingglutaredoxin 5, the group of Mitochondrial iron-sulfur assembly components|Glutaredoxin domain containing
Gene summary
This gene encodes a mitochondrial protein, which is evolutionarily conserved. It is involved in the biogenesis of iron-sulfur clusters, which are required for normal iron homeostasis. Mutations in this gene are associated with autosomal recessive pyridoxine-refractory sideroblastic anemia. [provided by RefSeq, May 2010]
- C14orf87
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~11.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0014803
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0014804
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0014803
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0014804
Submitter: Genomics England PanelApp
Inheritance Pattern: AR
Disease ID:MONDO:0014804
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0014803
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0014803
Submitter: Genomics England PanelApp
Inheritance Pattern: AR
Disease ID:MONDO:0014804
Submitter: PanelApp Australia
Clinical Genomic Database (CGD)
Manifestation: Biochemical; Hematologic; Neurologic
Intervention: Hematologic
Rationale: Individuals with Anemia, sideroblastic, pyridoxine-refractory, autosomal recessive have been reported who required RBC transfusions, as well as management with folate and iron chelation
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to GLRX5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_016417.3. 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 | 1 | 35 | 2 | 38 | ||
| missense | 5 | 1 | 60 | 1 | 1 | 68 |
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | 2 | 4 | ||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 7 | 2 | 62 | 36 | 3 | 110 |
Highest pathogenic variant AF is 0.0000313594
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_057501.2 | 2 | MANE Select | |
| Ensembl | ENSP00000328570.4 | 2 | MANE Select | |
| Ensembl | ENSP00000451800.1 | 2 | Standard | |
| Ensembl | ENSP00000573041.1 | 2 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| glrx5 | Danio rerio | Structure: nucleate erythrocyte Quality: decreased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Mitochondrial iron-sulfur cluster biogenesis
- Metabolism
Biological Process
- protein lipoylation
- electron transport chain
- hemopoiesis
- small molecule metabolic process
- cell redox homeostasis
Molecular Function
- protein binding
- electron transfer activity
- protein disulfide oxidoreductase activity
- glutathione disulfide oxidoreductase activity
- metal ion binding
Cellular Component
- nucleus
- mitochondrion
- mitochondrial matrix
- dendrite
- neuronal cell body
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000331334
- Coding exons
- 2
- Length
- 11222
- Individuals with no LoFs
- 0
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 0
- Defined
- 0
- p
- 0.00
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.216 | 68 | 73.2 | 0.929 | 0.00000343 | 984 |
| Missense (PolyPhen) | 22 | 25.55 | 0.86106 | 310 | ||
| Synonymous | 0.0409 | 34 | 34.3 | 0.991 | 0.00000185 | 323 |
| Loss of Function | 1.97 | 0 | 4.53 | 0.00 | 1.95e-7 | 51 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Monothiol glutaredoxin involved in the biogenesis of iron-sulfur clusters (PubMed:20364084). Involved in protein lipoylation, acting in the pathway that provides an iron-sulfur cluster to lipoate synthase (PubMed:24334290). Required for normal iron homeostasis. Required for normal regulation of hemoglobin synthesis by the iron-sulfur protein ACO1 (PubMed:20364084). May protect cells against apoptosis due to reactive oxygen species and oxidative stress (By similarity). {ECO:0000250|UniProtKB:Q80Y14, ECO:0000269|PubMed:20364084, ECO:0000269|PubMed:24334290}.;
- Disease
- DISEASE: Anemia, sideroblastic, 3, pyridoxine-refractory (SIDBA3) [MIM:616860]: A form of sideroblastic anemia, a bone marrow disorder defined by the presence of pathologic iron deposits in erythroblast mitochondria. Sideroblastic anemia is characterized by anemia of varying severity, hypochromic peripheral erythrocytes, systemic iron overload secondary to chronic ineffective erythropoiesis, and the presence of bone marrow ringed sideroblasts. Sideroblasts are characterized by iron-loaded mitochondria clustered around the nucleus. SIDBA3 is refractory to treatment with vitamin B6, while iron chelation therapy may result in clinical improvement. SIDBA3 inheritance is autosomal recessive. {ECO:0000269|PubMed:17485548, ECO:0000269|PubMed:20364084, ECO:0000269|PubMed:25342667, ECO:0000269|PubMed:26100117}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Spasticity, childhood-onset, with hyperglycinemia (SPAHGC) [MIM:616859]: An autosomal recessive disorder characterized by childhood-onset of spasticity, spinal lesions, leukodystrophy, optic atrophy in some patients, non-ketotic hyperglycinemia, and defective enzymatic glycine cleavage. Glycine levels in the cerebrospinal fluid are mildly increased in some but not all patients. The increase is less pronounced than in patients with classic non-ketotic hyperglycinemia. {ECO:0000269|PubMed:24334290}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.199
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- H
- Indispensability pred.
- E
- Indispensability score
- 0.801
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |