GLRX5

glutaredoxin 5, the group of Mitochondrial iron-sulfur assembly components|Glutaredoxin domain containing

Basic information

Region (hg38): 14:95533502-95544724

Previous symbols: [ "C14orf87" ]

Links

ENSG00000182512 ∙ NCBI:51218 ∙ OMIM:609588 ∙ HGNC:20134 ∙ Uniprot:Q86SX6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• sideroblastic anemia 3 (Supportive), mode of inheritance: AR
• spasticity-ataxia-gait anomalies syndrome (Supportive), mode of inheritance: AR
• sideroblastic anemia 3 (Strong), mode of inheritance: AR
• spasticity-ataxia-gait anomalies syndrome (Strong), mode of inheritance: AR
• spasticity-ataxia-gait anomalies syndrome (Strong), mode of inheritance: AR
• sideroblastic anemia 3 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Anemia, sideroblastic 3, pyridoxine-refractory	AR	Hematologic	Individuals with Anemia, sideroblastic, pyridoxine-refractory, autosomal recessive have been reported who required RBC transfusions, as well as management with folate and iron chelation	Biochemical; Hematologic; Neurologic	17485548; 24334290; 30660387

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GLRX5 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GLRX5 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				27	2	29
missense			33		2	35
nonsense						0
start loss						0
frameshift						0
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding				11	6	17
Total	0	0	34	38	10

Variants in GLRX5

This is a list of pathogenic ClinVar variants found in the GLRX5 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
14-95534813-T-A			Likely benign (Jun 16, 2018)
14-95534834-G-A			Benign (Jul 07, 2018)
14-95534887-A-C			Likely benign (Jul 15, 2018)
14-95535046-A-C		not specified	Benign (Dec 02, 2015)
14-95535073-C-A		not specified	Benign (Feb 15, 2018)
14-95535074-C-T		not specified	Likely benign (Dec 01, 2017)
14-95535081-C-T		not specified	Likely benign (Nov 04, 2016)
14-95535084-G-A		GLRX5-related disorder	Conflicting classifications of pathogenicity (Oct 23, 2023)
14-95535098-G-T			Likely benign (May 25, 2023)
14-95535103-T-C			Benign (Nov 28, 2023)
14-95535104-C-T			Likely benign (Aug 04, 2023)
14-95535105-GG-CT			Uncertain significance (Jul 11, 2022)
14-95535109-G-A			Uncertain significance (Aug 22, 2022)
14-95535112-C-G		not specified	Uncertain significance (Oct 24, 2023)
14-95535114-G-A		not specified	Uncertain significance (Feb 21, 2022)
14-95535117-G-C		not specified	Uncertain significance (May 24, 2024)
14-95535121-C-T			Uncertain significance (Jul 25, 2022)
14-95535130-G-T		not specified	Uncertain significance (Aug 14, 2022)
14-95535148-G-A			Uncertain significance (May 04, 2022)
14-95535149-C-T			Likely benign (Nov 22, 2022)
14-95535152-C-T			Likely benign (Aug 09, 2022)
14-95535155-T-C			Likely benign (Jan 19, 2022)
14-95535156-G-A		not specified	Uncertain significance (Apr 22, 2024)
14-95535157-G-A		not specified	Uncertain significance (Jun 02, 2023)
14-95535161-T-C			Likely benign (Feb 18, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GLRX5	protein_coding	protein_coding	ENST00000331334	2	11222

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.746	0.245	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.216	68	73.2	0.929	0.00000343	984
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• 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.
• Pathway: Mitochondrial iron-sulfur cluster biogenesis;Metabolism (Consensus)

Recessive Scores

• pRec: 0.199

Haploinsufficiency Scores

• pHI: 0.112
• hipred: N
• hipred_score: 0.429
• ghis: 0.399

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.801

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Glrx5

Zebrafish Information Network

• Gene name: glrx5
• Affected structure: nucleate erythrocyte
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: protein lipoylation;electron transport chain;hemopoiesis;small molecule metabolic process;cell redox homeostasis
• Cellular component: nucleus;mitochondrion;mitochondrial matrix;dendrite;neuronal cell body
• Molecular function: protein binding;electron transfer activity;protein disulfide oxidoreductase activity;glutathione disulfide oxidoreductase activity;metal ion binding;2 iron, 2 sulfur cluster binding