G6PD

glucose-6-phosphate dehydrogenase

Basic information

Region (hg38): X:154517825-154547572

Links

ENSG00000160211 ∙ NCBI:2539 ∙ OMIM:305900 ∙ HGNC:4057 ∙ Uniprot:P11413 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• anemia, nonspherocytic hemolytic, due to G6PD deficiency (Definitive), mode of inheritance: XL
• anemia, nonspherocytic hemolytic, due to G6PD deficiency (Strong), mode of inheritance: XL
• class I glucose-6-phosphate dehydrogenase deficiency (Supportive), mode of inheritance: XL
• G6PD deficiency (Definitive), mode of inheritance: XL
• anemia, nonspherocytic hemolytic, due to G6PD deficiency (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Glucose-6-phosphate dehydrogenase deficiency	XL	Allergy/Immunology/Infectious; Hematologic; Pharmacogenomic	Hemolytic reactions can result from a variety of triggers, such as infections, dietary items, and medications, and avoidance of precipitating agents (or redosing in order to decreased the chance of certain medication reactions, as well as prompt removal in the case of a reaction) can be beneficial; Individuals are also susceptible to neonatal jaundice; Complete G6PD deficiency can result in immunodeficiency, and prophylactic measures, as well as prompt and aggressive treatment of infections, can be beneficial	Allergy/Immunology/Infectious; Hematologic	13360274; 13500095; 14014720; 14158057; 4388132; 5369703; 5305539; 4401271; 4125296; 5448; 3681550; 3446582; 2836867; 2912069; 2910917; 2602358; 2248331; 2263506; 2157298; 2321910; 1999409; 2005960; 1303182; 1611091; 1551674; 1536798; 1562739; 8471773; 8490627; 8364584; 7949118; 8533762; 7617034; 8627445; 8807322; 8826878; 8579052; 8956035; 9427729; 9674740; 10666231; 11048840; 11433050; 11803413; 11857737; 12028056; 15349799; 16204390; 15724035; 16155737; 16493607; 16607506; 16528451; 17444323; 18177777; 19112496; 18379570; 19177059; 20007901; 20701405; 21641489; 22573495; 22795224; 23237606; 23384623; 23573906; 23714236; 23815264; 23834949; 23860572; 23874116; 23874768
The condition involves predisposition to anemia, which can be precipitated by, among other things, certain medications; Complete G6PD deficiency can result in chronic granulamotous disease secondary to neutrophil deficiency

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the G6PD gene.

• Anemia, nonspherocytic hemolytic, due to G6PD deficiency (65 variants)
• Malaria, susceptibility to (11 variants)
• not provided (11 variants)
• G6PD deficiency (7 variants)
• not specified (3 variants)
• Anemia, nonspherocytic hemolytic, due to G6PD deficiency;Malaria, susceptibility to (3 variants)
• Malaria, susceptibility to;Anemia, nonspherocytic hemolytic, due to G6PD deficiency (2 variants)
• Inborn genetic diseases (2 variants)
• G6PD ORISSA (1 variants)
• G6PD PORTICI (1 variants)
• G6PD COIMBRA (1 variants)
• G6PD METAPONTO (1 variants)
• G6PD-related disorder (1 variants)
• G6PD TOMAH (1 variants)
• G6PD BEVERLY HILLS (1 variants)
• G6PD MODENA (1 variants)
• G6PD COSENZA (1 variants)
• G6PD AGRIGENTO (1 variants)
• G6PD ANDALUS (1 variants)
• G6PD IERAPETRA (1 variants)
• G6PD ZURICH (1 variants)
• G6PD KAIPING (1 variants)
• G6PD CHATHAM (1 variants)
• G6PD PETRICH-LIKE (1 variants)
• G6PD GUADALAJARA (1 variants)
• G6PD NANKANG (1 variants)
• G6PD SAPPORO-LIKE (1 variants)
• G6PD JAPAN (1 variants)
• G6PD CANTON (1 variants)
• G6PD NASHVILLE (1 variants)
• G6PD GIFU (1 variants)
• G6PD SEATTLE-LIKE (1 variants)
• G6PD ANAHEIM (1 variants)
• G6PD DHON (1 variants)
• G6PD ANANT (1 variants)
• G6PD TAIWAN-HAKKA (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the G6PD 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		2	3	140	3	148
missense	51	134	89	4	1	279
nonsense	5					5
start loss						0
frameshift	5	1				6
inframe indel	3	4	2			9
splice donor/acceptor (+/-2bp)	2		1			3
splice region		1	7	33		41
non coding		5	22	79	22	128
Total	66	146	117	223	26

Highest pathogenic variant AF is 0.000718

Variants in G6PD

This is a list of pathogenic ClinVar variants found in the G6PD region.

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

Position	Type	Phenotype	Significance	ClinVar
X-154518193-C-T			Likely benign (Jan 01, 2024)
X-154531401-G-A		G6PD deficiency	Uncertain significance (Jan 12, 2018)
X-154531452-G-A		G6PD deficiency	Uncertain significance (Jan 13, 2018)
X-154531465-C-A		G6PD deficiency	Uncertain significance (Jan 12, 2018)
X-154531480-C-T		G6PD deficiency	Conflicting classifications of pathogenicity (Dec 01, 2022)
X-154531534-G-C		G6PD deficiency	Uncertain significance (Jan 13, 2018)
X-154531635-C-T		G6PD deficiency	Conflicting classifications of pathogenicity (Mar 01, 2023)
X-154531643-C-T		Anemia, nonspherocytic hemolytic, due to G6PD deficiency	Uncertain significance (Aug 12, 2022)
X-154531643-C-C		G6PD deficiency • Anemia, nonspherocytic hemolytic, due to G6PD deficiency	Benign/Likely benign (Jan 15, 2024)
X-154531696-A-G		Anemia, nonspherocytic hemolytic, due to G6PD deficiency	Benign (Aug 12, 2022)
X-154531719-G-A		G6PD deficiency	Uncertain significance (Jan 13, 2018)
X-154531728-C-T		Anemia, nonspherocytic hemolytic, due to G6PD deficiency	Likely benign (Aug 12, 2022)
X-154531925-G-A		G6PD deficiency	Uncertain significance (Jan 13, 2018)
X-154531928-GTCC-G			Benign (Jul 09, 2018)
X-154531950-C-T			Uncertain significance (Sep 14, 2012)
X-154531953-C-T			Uncertain significance (Sep 14, 2012)
X-154531975-G-A		G6PD deficiency	Uncertain significance (Jan 13, 2018)
X-154532003-G-A		Anemia, nonspherocytic hemolytic, due to G6PD deficiency	Likely benign (Jul 30, 2023)
X-154532011-G-A			Uncertain significance (Jun 25, 2022)
X-154532011-G-T		Inborn genetic diseases	Uncertain significance (Jun 07, 2024)
X-154532012-G-A		Anemia, nonspherocytic hemolytic, due to G6PD deficiency	Likely benign (Dec 12, 2021)
X-154532012-G-C		Anemia, nonspherocytic hemolytic, due to G6PD deficiency	Likely benign (Nov 21, 2023)
X-154532031-G-C		Anemia, nonspherocytic hemolytic, due to G6PD deficiency	Uncertain significance (Sep 25, 2022)
X-154532042-C-T		Anemia, nonspherocytic hemolytic, due to G6PD deficiency	Likely benign (Jan 23, 2023)
X-154532046-A-C		-	no classification for the single variant (-)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
G6PD	protein_coding	protein_coding	ENST00000393562	13	16182

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.972	0.0284	125715	0	2	125717	0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.00	174	266	0.655	0.0000244	3575
Missense in Polyphen		46	116.1	0.3962		1598
Synonymous	-0.0326	113	113	1.00	0.0000110	1056
Loss of Function	3.71	2	19.8	0.101	0.00000136	309

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	0.0000625	0.0000462
European (Non-Finnish)	0.0000122	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the rate-limiting step of the oxidative pentose-phosphate pathway, which represents a route for the dissimilation of carbohydrates besides glycolysis. The main function of this enzyme is to provide reducing power (NADPH) and pentose phosphates for fatty acid and nucleic acid synthesis. {ECO:0000269|PubMed:15858258, ECO:0000269|PubMed:24769394}.
• Disease: DISEASE: Anemia, non-spherocytic hemolytic, due to G6PD deficiency (NSHA) [MIM:300908]: A disease characterized by G6PD deficiency, acute hemolytic anemia, fatigue, back pain, and jaundice. In most patients, the disease is triggered by an exogenous agent, such as some drugs, food, or infection. Increased unconjugated bilirubin, lactate dehydrogenase, and reticulocytosis are markers of the disorder. Although G6PD deficiency can be life-threatening, most patients are asymptomatic throughout their life. {ECO:0000269|PubMed:12524354, ECO:0000269|PubMed:1303180, ECO:0000269|PubMed:1303182, ECO:0000269|PubMed:1536798, ECO:0000269|PubMed:1611091, ECO:0000269|PubMed:1889820, ECO:0000269|PubMed:1945893, ECO:0000269|PubMed:20007901, ECO:0000269|PubMed:26479991, ECO:0000269|PubMed:2836867, ECO:0000269|PubMed:2912069, ECO:0000269|PubMed:7858267, ECO:0000269|PubMed:7959695, ECO:0000269|PubMed:8193373, ECO:0000269|PubMed:8490627, ECO:0000269|PubMed:8533762, ECO:0000269|PubMed:8733135, ECO:0000269|PubMed:9452072}. Note=The disease is caused by mutations affecting the gene represented in this entry. Deficiency of G6PD is associated with hemolytic anemia in two different situations. First, in areas in which malaria has been endemic, G6PD-deficiency alleles have reached high frequencies (1% to 50%) and deficient individuals, though essentially asymptomatic in the steady state, have a high risk of acute hemolytic attacks. Secondly, sporadic cases of G6PD deficiency occur at a very low frequencies, and they usually present a more severe phenotype. Several types of NSHA are recognized. Class-I variants are associated with severe NSHA; class-II have an activity <10% of normal; class-III have an activity of 10% to 60% of normal; class-IV have near normal activity.
• Pathway: Central carbon metabolism in cancer - Homo sapiens (human);Glutathione metabolism - Homo sapiens (human);Pentose phosphate pathway - Homo sapiens (human);Pentose Phosphate Pathway (Erythrocyte);Methylene Blue Pathway, Pharmacodynamics;Warburg Effect;Pentose Phosphate Pathway;Glucose-6-phosphate dehydrogenase deficiency;Ribose-5-phosphate isomerase deficiency;Transaldolase deficiency;Glutathione metabolism;Pentose Phosphate Pathway;Cori Cycle;miR-targeted genes in epithelium - TarBase;miR-targeted genes in leukocytes - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;Vitamin D Receptor Pathway;Nuclear Receptors Meta-Pathway;NRF2 pathway;ATM Signaling Network in Development and Disease;fig-met-1-last-solution;Sulfation Biotransformation Reaction;Gene expression (Transcription);Generic Transcription Pathway;Pentose phosphate pathway (hexose monophosphate shunt);Metabolism of carbohydrates;pentose phosphate pathway (oxidative branch);RNA Polymerase II Transcription;TCR;Metabolism;Pentose phosphate cycle;pentose phosphate pathway;TP53 Regulates Metabolic Genes;Transcriptional Regulation by TP53 (Consensus)

Recessive Scores

• pRec: 0.990

Intolerance Scores

• loftool: 0.0169
• rvis_EVS: -0.14
• rvis_percentile_EVS: 43.77

Haploinsufficiency Scores

• pHI: 0.379
• hipred: Y
• hipred_score: 0.747
• ghis: 0.522

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.987

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: G6pdx
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); embryo phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system 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)

Zebrafish Information Network

• Gene name: g6pd
• Affected structure: nucleate erythrocyte
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: glucose metabolic process;pentose-phosphate shunt;lipid metabolic process;cholesterol biosynthetic process;NADP metabolic process;NADPH regeneration;glutathione metabolic process;pentose-phosphate shunt, oxidative branch;response to iron(III) ion;negative regulation of protein glutathionylation;response to organic cyclic compound;pentose biosynthetic process;substantia nigra development;response to food;cellular response to oxidative stress;erythrocyte maturation;regulation of neuron apoptotic process;response to ethanol;ribose phosphate biosynthetic process;glucose 6-phosphate metabolic process;oxidation-reduction process;negative regulation of cell growth involved in cardiac muscle cell development;positive regulation of calcium ion transmembrane transport via high voltage-gated calcium channel;negative regulation of reactive oxygen species metabolic process
• Cellular component: nucleus;cytoplasm;cytosol;cytoplasmic side of plasma membrane;membrane;extracellular exosome
• Molecular function: glucose-6-phosphate dehydrogenase activity;protein binding;glucose binding;identical protein binding;protein homodimerization activity;NADP binding