GSR

glutathione-disulfide reductase

Basic information

Region (hg38): 8:30678066-30727846

Links

ENSG00000104687 ∙ NCBI:2936 ∙ OMIM:138300 ∙ HGNC:4623 ∙ Uniprot:P00390 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hemolytic anemia due to glutathione reductase deficiency (Limited), mode of inheritance: AR
• hemolytic anemia due to glutathione reductase deficiency (Strong), mode of inheritance: AR
• hemolytic anemia due to glutathione reductase deficiency (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Anemia, congenital, nonspherocytic hemolytic, 10	AR	Hematologic	Individuals are susceptible to hemolytic anemia, and awareness may allow early management as well as avoidance of triggers of hemolysis (eg, fava beans)	Hematologic	6017801; 17185460

ClinVar

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

• Hemolytic_anemia_due_to_glutathione_reductase_deficiency (80 variants)
• not_provided (77 variants)
• not_specified (69 variants)
• GSR-related_disorder (17 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GSR gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000637.5. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	21	4	26
missense	1	1	113	9	4	128
nonsense	1	1	1			3
start loss						0
frameshift	1	1	1			3
splice donor/acceptor (+/-2bp)						0
Total	3	3	116	30	8

Highest pathogenic variant AF is 0.00009516082

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GSR	protein_coding	protein_coding	ENST00000221130	13	49861

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000129	0.954	125713	0	35	125748	0.000139

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.512	247	271	0.912	0.0000154	3360
Missense in Polyphen		115	127.17	0.90428		1477
Synonymous	0.585	95	103	0.927	0.00000640	1047
Loss of Function	1.89	13	22.7	0.572	0.00000114	290

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000119	0.000119
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000158	0.000158
Middle Eastern	0.0000544	0.0000544
South Asian	0.000294	0.000294
Other	0.000489	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Maintains high levels of reduced glutathione in the cytosol.
• Pathway: Thyroid hormone synthesis - Homo sapiens (human);Glutathione metabolism - Homo sapiens (human);Oxidative Stress Pathway (Erythrocyte);Pathway_PA165980337;Oxidative Stress Pathway (Erythrocyte);Oxidative Stress Regulatory Pathway (Erythrocyte);2-Hydroxyglutric Aciduria (D And L Form);Gamma-glutamyl-transpeptidase deficiency;5-oxoprolinase deficiency;Gamma-Glutamyltransferase Deficiency;Glutathione Metabolism;Homocarnosinosis;Hyperinsulinism-Hyperammonemia Syndrome;Glutathione Synthetase Deficiency;Succinic semialdehyde dehydrogenase deficiency;4-Hydroxybutyric Aciduria/Succinic Semialdehyde Dehydrogenase Deficiency;5-Oxoprolinuria;Glutamate Metabolism;Glutathione metabolism;Selenium Micronutrient Network;Nuclear Receptors Meta-Pathway;NRF2 pathway;Amino Acid metabolism;One carbon metabolism and related pathways;Oxidative Stress;Sulfation Biotransformation Reaction;Metapathway biotransformation Phase I and II;Detoxification of Reactive Oxygen Species;Gene expression (Transcription);Metabolism of ingested H2SeO4 and H2SeO3 into H2Se;glutathione redox reactions I;Generic Transcription Pathway;Metabolism of nucleotides;Cellular responses to stress;Glutamate Glutamine metabolism;Metabolism of amino acids and derivatives;Interconversion of nucleotide di- and triphosphates;RNA Polymerase II Transcription;Metabolism;Selenoamino acid metabolism;TP53 Regulates Metabolic Genes;Cellular responses to external stimuli;Urea cycle and metabolism of arginine, proline, glutamate, aspartate and asparagine;glutathione redox reactions II;Transcriptional Regulation by TP53 (Consensus)

Intolerance Scores

• loftool: 0.468
• rvis_EVS: -0.36
• rvis_percentile_EVS: 29.31

Haploinsufficiency Scores

• pHI: 0.160
• hipred: Y
• hipred_score: 0.589
• ghis: 0.521

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.909

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gsr
• Phenotype: normal phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); vision/eye phenotype

Gene ontology

• Biological process: glutathione metabolic process;nucleobase-containing small molecule interconversion;electron transport chain;cellular response to oxidative stress;cell redox homeostasis;cellular oxidant detoxification
• Cellular component: mitochondrion;mitochondrial matrix;cytosol;external side of plasma membrane;extracellular exosome
• Molecular function: glutathione-disulfide reductase activity;electron transfer activity;flavin adenine dinucleotide binding;NADP binding