G6PD deficiency

Summary

G6PD deficiency (MONDO:0005775) is a disease with 1 cohort gene and 30 clinical trials. Top therapeutic interventions include primaquine, chloroquine, and tafenoquine.

At a glance

• Cohort genes: 1
• ClinVar variants: 65
• Clinical trials: 30

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	G6PD deficiency
Mondo ID	MONDO:0005775
EFO	EFO:0007287
MeSH	D005955
DOID	DOID:2862
NCIT	C98933
SNOMED CT	62403005
UMLS	C2939465
MedGen	473706
Is cancer (heuristic)	no

Also known as: G-6-PD variant enzyme deficiency Anaemia · G-6-PD variant enzyme deficiency Anemia · G6PD · G6PD deficiency · glucose-6-phosphate dehydrogenase deficiency · glucosephosphate dehydrogenase deficiency · inborn error of glucose-6-phosphate dehydrogenase activity · inborn glucose-6-phosphate dehydrogenase activity disorder · rare inborn error of glucose-6-phosphate dehydrogenase activity

Data availability: 65 ClinVar variants · 21 cell lines.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › inborn carbohydrate metabolic disorder › G6PD deficiency

Related subtypes (17): GLUT1 deficiency syndrome, disorder of glycogen metabolism, primary hyperoxaluria, hyperinsulinemic hypoglycemia, multiple carboxylase deficiency, disorder of glycolysis, disorder of fructose metabolism, disorder of galactose metabolism, disorder of carbohydrate transmembrane transport and absorption, disorders of pentose/polyol metabolism, pyruvate dehydrogenase deficiency, disorder of gluconeogenesis, mucopolysaccharidosis, oligosaccharidosis, lactose intolerance, congenital disorder of deglycosylation 1, disorder of galactose and fructose metabolism

Subtypes (3): favism, anemia, nonspherocytic hemolytic, due to G6PD deficiency, class V glucose-6-phosphate dehydrogenase deficiency

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

65 retrieved; paginated sample, class counts are floors:

18 conflicting classifications of pathogenicity, 15 pathogenic/likely pathogenic, 13 uncertain significance, 8 pathogenic, 5 benign/likely benign, 4 likely pathogenic, 1 likely pathogenic/established risk allele, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
100057	NM_000402.4(G6PD):c.653C>T (p.Ser218Phe)	G6PD	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
100058	NM_000402.4(G6PD):c.1466G>T (p.Arg489Leu)	G6PD	Pathogenic	criteria provided, multiple submitters, no conflicts
100059	NM_000402.4(G6PD):c.1478G>A (p.Arg493His)	G6PD	Pathogenic	criteria provided, multiple submitters, no conflicts
10362	NM_000402.4(G6PD):c.944G>A (p.Arg315His)	G6PD	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
10367	NM_000402.4(G6PD):c.577G>A (p.Gly193Ser)	G6PD	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
10372	NM_000402.4(G6PD):c.934G>C (p.Asp312His)	G6PD	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
10385	NM_000402.4(G6PD):c.1147C>T (p.Pro383Ser)	G6PD	Pathogenic	criteria provided, multiple submitters, no conflicts
10386	NM_000402.4(G6PD):c.961G>A (p.Val321Met)	G6PD	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
10387	NM_001360016.2(G6PD):c.680G>T (p.Arg227Leu)	G6PD	Pathogenic	no assertion criteria provided
10388	NM_001360016.2(G6PD):c.968T>C (p.Leu323Pro)	G6PD	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
10401	NM_000402.4(G6PD):c.1039G>A (p.Glu347Lys)	G6PD	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
10402	NM_000402.4(G6PD):c.233T>C (p.Ile78Thr)	G6PD	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
10403	NM_000402.4(G6PD):c.185A>G (p.His62Arg)	G6PD	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
10406	NM_000402.4(G6PD):c.221C>G (p.Ala74Gly)	G6PD	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
10417	NM_000402.4(G6PD):c.683G>A (p.Arg228His)	G6PD	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
10422	NM_000402.4(G6PD):c.1466G>C (p.Arg489Pro)	G6PD	Pathogenic	criteria provided, multiple submitters, no conflicts
1722656	NM_001360016.2(G6PD):c.519C>G (p.Phe173Leu)	G6PD	Pathogenic	criteria provided, multiple submitters, no conflicts
1722659	NM_001360016.2(G6PD):c.679C>T (p.Arg227Trp)	G6PD	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
37123	NM_000402.4(G6PD):c.292G>A (p.Val98Met)	G6PD	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
37203	NM_000402.4(G6PD):c.632A>T (p.Asp211Val)	G6PD	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
854215	NM_001360016.2(G6PD):c.404A>C (p.Asn135Thr)	G6PD	Pathogenic	criteria provided, multiple submitters, no conflicts
93493	NM_001360016.2(G6PD):c.1360C>T (p.Arg454Cys)	G6PD	Pathogenic	criteria provided, multiple submitters, no conflicts
93499	NM_001360016.2(G6PD):c.383T>C (p.Leu128Pro)	G6PD	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
10361	G6PD A-		Likely pathogenic/Established risk allele	criteria provided, multiple submitters, no conflicts
1722634	NM_001360016.2(G6PD):c.1375C>G (p.Arg459Gly)	G6PD	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1722637	NM_001360016.2(G6PD):c.1387C>A (p.Arg463Ser)	G6PD	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1722704	NM_001360016.2(G6PD):c.148C>T (p.Pro50Ser)	G6PD	Likely pathogenic	criteria provided, multiple submitters, no conflicts
4072319	NM_001360016.2(G6PD):c.404A>T (p.Asn135Ile)	G6PD	Likely pathogenic	criteria provided, single submitter
100055	NM_000402.4(G6PD):c.466A>G (p.Asn156Asp)	G6PD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
10395	NM_000402.4(G6PD):c.770G>A (p.Arg257Gln)	G6PD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
G6PD	Orphanet:466026	Class I glucose-6-phosphate dehydrogenase deficiency

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
G6PD	HGNC:4057	ENSG00000160211	P11413	Glucose-6-phosphate 1-dehydrogenase	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
G6PD	Glucose-6-phosphate 1-dehydrogenase	Catalyzes the rate-limiting step of the oxidative pentose-phosphate pathway, which represents a route for the dissimilation of carbohydrates besides glycolysis.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
G6PD	Enzyme (other)	yes	1.1.1.49	G6P_DH, G6P_DH_AS, G6P_DH_NAD-bd

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
granulocyte	1
right testis	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
G6PD	218	ubiquitous	marker	stromal cell of endometrium, granulocyte, right testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
G6PD	4,226

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
G6PD	P11413	25

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
NFE2L2 regulates pentose phosphate pathway genes	1	1427.5×	0.002	G6PD
Pentose phosphate pathway	1	951.7×	0.002	G6PD
TP53 Regulates Metabolic Genes	1	129.8×	0.008	G6PD

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
ribose phosphate biosynthetic process	1	16852.0×	6e-04	G6PD
response to iron(III) ion	1	8426.0×	6e-04	G6PD
pentose biosynthetic process	1	8426.0×	6e-04	G6PD
positive regulation of calcium ion transmembrane transport via high voltage-gated calcium channel	1	8426.0×	6e-04	G6PD
pentose-phosphate shunt, oxidative branch	1	4213.0×	9e-04	G6PD
pentose-phosphate shunt	1	1532.0×	0.002	G6PD
NADP+ metabolic process	1	1532.0×	0.002	G6PD
negative regulation of cell growth involved in cardiac muscle cell development	1	1404.3×	0.002	G6PD
glucose 6-phosphate metabolic process	1	1296.3×	0.002	G6PD
negative regulation of reactive oxygen species metabolic process	1	936.2×	0.002	G6PD
erythrocyte maturation	1	842.6×	0.002	G6PD
regulation of neuron apoptotic process	1	702.2×	0.002	G6PD
response to food	1	495.6×	0.003	G6PD
cholesterol biosynthetic process	1	421.3×	0.003	G6PD
substantia nigra development	1	366.4×	0.004	G6PD
glutathione metabolic process	1	351.1×	0.004	G6PD
glucose metabolic process	1	255.3×	0.005	G6PD
cellular response to oxidative stress	1	154.6×	0.007	G6PD
response to ethanol	1	146.5×	0.007	G6PD
lipid metabolic process	1	91.6×	0.011	G6PD

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
G6PD	BREXANOLONE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
G6PD	8	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BREXANOLONE	4	G6PD
APOMORPHINE HYDROCHLORIDE	4	G6PD
PRASTERONE	4	G6PD
EBSELEN	3	G6PD
PICEID	2	G6PD
SEPRANOLONE	2	G6PD
PREGNENOLONE	1	G6PD
16.ALPHA.-BROMOEPIANDROSTERONE	1	G6PD

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
G6PD	49	Binding:46, ADMET:2, Functional:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
G6PD	1.1.1.49	glucose-6-phosphate dehydrogenase (NADP+)

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 1.

Cohort genes with a CPIC/DPWG dosing guideline

Symbol	CPIC guidelines
G6PD	1

Chemical tractability of cohort targets

8 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
BREXANOLONE	4	G6PD
APOMORPHINE HYDROCHLORIDE	4	G6PD
PRASTERONE	4	G6PD
EBSELEN	3	G6PD
PICEID	2	G6PD
SEPRANOLONE	2	G6PD
PREGNENOLONE	1	G6PD
16.ALPHA.-BROMOEPIANDROSTERONE	1	G6PD

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	G6PD
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 30.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	19
PHASE4	4
PHASE1	3
PHASE2	2
PHASE2/PHASE3	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07468513	PHASE4	RECRUITING	Primaquine for Vivax Malaria in G6PD Intermediate and Deficient Cases.
NCT02434952	PHASE4	COMPLETED	Safety and Tolerability of Low Dose Primaquine
NCT03337152	PHASE4	TERMINATED	Assessing a Risk Model for G6PD Deficiency
NCT04088513	PHASE4	UNKNOWN	Safety and Efficacy of Aspirin in Stroke Patients With Glucose-6-phosphate Dehydrogenase Deficiency (SAST)
NCT02498340	PHASE2/PHASE3	UNKNOWN	Diet Challenge in G6PD Deficient Egyptian Children: A One- Year Prospective Single Center Study With Genotype - Phenotype Correlation
NCT00004381	PHASE2	COMPLETED	Phase II Randomized Study of Tin Mesoporphyrin for Neonatal Hyperbilirubinemia
NCT03529396	PHASE2	COMPLETED	Safety and Efficacy of Different Regimens of Primaquine on Vivax Malaria Treatment in G6PD Deficient Patients
NCT07612345	PHASE1	NOT_YET_RECRUITING	High-Dose Vitamin C in G6PDA and Pyruvate Kinase Deficiency: A Safety Study
NCT03934450	PHASE1	COMPLETED	Metabolism and Pharmacokinetics of Primaquine Enantiomers in Human Volunteers Receiving a Seven Day Dose Regimen
NCT04073953	PHASE1	COMPLETED	Primaquine Enantiomers in G6PD Deficient Human Volunteers
NCT02937376	EARLY_PHASE1	UNKNOWN	Effects of N-acetyl Cystein (NAC) Supplementation in G6PD Deficient Individuals After Acute Exercise
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns
NCT00076323	Not specified	COMPLETED	A Test to Predict the Hemolytic Potential of Drugs in G6PD Deficiency
NCT01931644	Not specified	COMPLETED	At-Home Research Study for Patients With Autoimmune, Inflammatory, Genetic, Hematological, Infectious, Neurological, CNS, Oncological, Respiratory, Metabolic Conditions
NCT02069236	Not specified	COMPLETED	Comparing G6PD Tests Using Capillary Blood Versus Venous Blood
NCT02104518	Not specified	COMPLETED	Evaluation of Different G6PD Testing Platforms
NCT02937363	Not specified	COMPLETED	Effects of Alpha Lipoic Acid Supplementation in G6PD Deficient Individuals After Acute Exercise
NCT04010695	Not specified	COMPLETED	Validation of Diagnostics to Identify Glucose-6-phosphate Dehydrogenase Activity in the US
NCT04033640	Not specified	COMPLETED	Evaluation of a Diagnostic to Identify Glucose-6-phosphate Dehydrogenase (G6PD) Deficiency in Brazil
NCT04054661	Not specified	COMPLETED	Validation of a Diagnostic Test for Glucose-6-phosphate Dehydrogenase (G6PD) Deficiency in Anti-coagulated Blood
NCT04081272	Not specified	COMPLETED	Effect of G6PD Deficiency on Red Blood Cell Storage
NCT04146246	Not specified	COMPLETED	Comparative Evaluation of the FINDER Instrument and FINDER G6PD Cartridge in Adults and Neonates
NCT05026489	Not specified	UNKNOWN	G6PD Deficiency in Infarction Patients in Shaanxi Province
NCT05096702	Not specified	UNKNOWN	Operational Feasibility of Appropriate Radical Cure of Plasmodium Vivax With Tafenoquine or Primaquine After Quantitative G6PD Testing in Brazil
NCT05571748	Not specified	UNKNOWN	Oxidative Stress, Carbohydrate Metabolism Disorders and G6PD Deficiency
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening
NCT05753150	Not specified	COMPLETED	Operational Feasibility of Appropriate Plasmodium Vivax Radical Cure After G6PD Testing in Thailand
NCT05874271	Not specified	COMPLETED	Short Course Primaquine for the Radical Cure of P. Vivax - Papua New Guinea
NCT05879224	Not specified	COMPLETED	Short Course Primaquine for the Radical Cure of P. Vivax Malaria - Indonesia
NCT07037706	Not specified	COMPLETED	Use of Macrolides in Acute Chest Syndrome: A Multicenter Retrospective Study

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
PRIMAQUINE	4	19
CHLOROQUINE	4	2
TAFENOQUINE	4	2
CYSTEINE	4	1
SODIUM CHROMATE CR 51	4	1
LIPOIC ACID, ALPHA	3	2
STANNSOPORFIN	3	1