G6PD

Summary

G6PD (glucose-6-phosphate dehydrogenase, HGNC:4057) is a protein-coding gene on chromosome Xq28, encoding Glucose-6-phosphate 1-dehydrogenase (P11413). Catalyzes the rate-limiting step of the oxidative pentose-phosphate pathway, which represents a route for the dissimilation of carbohydrates besides glycolysis. It is a selective cancer dependency (DepMap: 10.9% of cell lines).

This gene encodes glucose-6-phosphate dehydrogenase. This protein is a cytosolic enzyme encoded by a housekeeping X-linked gene whose main function is to produce NADPH, a key electron donor in the defense against oxidizing agents and in reductive biosynthetic reactions. G6PD is remarkable for its genetic diversity. Many variants of G6PD, mostly produced from missense mutations, have been described with wide ranging levels of enzyme activity and associated clinical symptoms. G6PD deficiency may cause neonatal jaundice, acute hemolysis, or severe chronic non-spherocytic hemolytic anemia. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 2539 — RefSeq curated summary.

At a glance

• Gene–disease (curated): G6PD deficiency (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 19
• Clinical variants (ClinVar): 883 total — 67 pathogenic, 122 likely-pathogenic
• Phenotypes (HPO): 22
• Druggable target: yes — 8 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 10.9% of screened cell lines
• MANE Select transcript: NM_001360016

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4057
Approved symbol	G6PD
Name	glucose-6-phosphate dehydrogenase
Location	Xq28
Locus type	gene with protein product
Status	Approved
Aliases	G6PD1
Ensembl gene	ENSG00000160211
Ensembl biotype	protein_coding
OMIM	305900
Entrez	2539

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 22 protein_coding, 6 retained_intron, 5 nonsense_mediated_decay

ENST00000369620, ENST00000393562, ENST00000393564, ENST00000433845, ENST00000439227, ENST00000440967, ENST00000488434, ENST00000489497, ENST00000490651, ENST00000497281, ENST00000567614, ENST00000647501, ENST00000696420, ENST00000696421, ENST00000696422, ENST00000696423, ENST00000696424, ENST00000696425, ENST00000696426, ENST00000696427, ENST00000696428, ENST00000696429, ENST00000696430, ENST00000696431, ENST00000907454, ENST00000907455, ENST00000907456, ENST00000907457, ENST00000915894, ENST00000915895, ENST00000915896, ENST00000915897, ENST00000968237

RefSeq mRNA: 3 — MANE Select: NM_001360016 NM_000402, NM_001042351, NM_001360016

CCDS: CCDS44023

Canonical transcript exons

ENST00000393562 — 13 exons

Exon	Start	End
ENSE00001050595	154534338	154534496
ENSE00001050598	154534035	154534160
ENSE00001050600	154532188	154532280
ENSE00001050601	154533576	154533669
ENSE00001050602	154532567	154532802
ENSE00001050603	154535168	154535385
ENSE00001050607	154531391	154532090
ENSE00003519724	154532386	154532462
ENSE00003546872	154535937	154536045
ENSE00003590122	154536141	154536178
ENSE00003657354	154546036	154546163
ENSE00003815113	154546789	154546846
ENSE00003967332	154532942	154533128

Expression profiles

Bgee: expression breadth ubiquitous, 218 present calls, max score 98.26.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 125.2225 / max 1027.8786, expressed in 1826 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
201049	116.2509	1826
66090	10.8152	1389
201052	5.8760	1739
201050	1.3612	734
201048	0.5259	265
66091	0.4501	223
201042	0.3966	207
201051	0.3617	163

Top tissues by expression

271 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	98.26	gold quality
granulocyte	CL:0000094	97.57	gold quality
right testis	UBERON:0004534	97.26	gold quality
left testis	UBERON:0004533	97.08	gold quality
monocyte	CL:0000576	96.81	gold quality
leukocyte	CL:0000738	96.67	gold quality
mononuclear cell	CL:0000842	96.65	gold quality
right adrenal gland cortex	UBERON:0035827	96.30	gold quality
right adrenal gland	UBERON:0001233	96.27	gold quality
left adrenal gland	UBERON:0001234	96.04	gold quality
left adrenal gland cortex	UBERON:0035825	95.86	gold quality
gall bladder	UBERON:0002110	95.80	gold quality
right lobe of thyroid gland	UBERON:0001119	95.78	gold quality
left lobe of thyroid gland	UBERON:0001120	95.35	gold quality
left coronary artery	UBERON:0001626	95.26	gold quality
adenohypophysis	UBERON:0002196	95.07	gold quality
testis	UBERON:0000473	94.86	gold quality
descending thoracic aorta	UBERON:0002345	94.75	gold quality
lower esophagus mucosa	UBERON:0035834	94.61	gold quality
adrenal cortex	UBERON:0001235	94.56	gold quality
coronary artery	UBERON:0001621	94.53	gold quality
islet of Langerhans	UBERON:0000006	94.48	gold quality
esophagus mucosa	UBERON:0002469	94.38	gold quality
thoracic aorta	UBERON:0001515	94.35	gold quality
ascending aorta	UBERON:0001496	94.31	gold quality
pituitary gland	UBERON:0000007	94.24	gold quality
right ovary	UBERON:0002118	94.14	gold quality
right coronary artery	UBERON:0001625	93.98	gold quality
adrenal gland	UBERON:0002369	93.86	gold quality
blood	UBERON:0000178	93.64	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	37.85
E-ANND-3	yes	7.70
E-CURD-112	no	2.98

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB1, CREM, NFE2L2, SREBF1, SREBF2, VDR

miRNA regulators (miRDB)

33 targeting G6PD, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-377-5P	99.70	65.28	712
HSA-MIR-6086	99.70	65.38	699
HSA-MIR-5197-5P	99.64	69.08	1494
HSA-MIR-7150	99.62	66.80	1322
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-504-3P	99.30	67.18	1745
HSA-MIR-7160-5P	99.11	67.17	2207
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-485-5P	99.10	64.78	1889
HSA-MIR-6884-5P	99.10	64.50	1987
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-12125	98.59	67.54	1044
HSA-MIR-1237-3P	98.55	67.65	1423
HSA-MIR-3944-5P	98.50	67.55	997
HSA-MIR-138-5P	98.43	70.49	1292
HSA-MIR-891A-3P	98.05	67.99	970
HSA-MIR-4736	97.96	65.89	1287
HSA-MIR-6787-5P	97.54	63.85	457
HSA-MIR-4640-5P	97.42	66.33	1543
HSA-MIR-4726-5P	97.24	65.67	1299
HSA-MIR-122-5P	97.23	64.92	1024
HSA-MIR-885-3P	95.14	63.08	448

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 10.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• DNA mutational analysis in Thailand: G6PD Viangchan (871G>A) is the most common deficiency variant in the Thai population (PMID:11793482)
• A single mutation 202G>A in the human glucose-6-phosphate dehydrogenase gene (G6PD) can cause acute hemolysis by itself. (PMID:11852882)
• a candidate gene for diabetes (PMID:11874436)
• 31 alleles carrying the betaS mutation, 6 beta-thalassaemic alleles & 17 G6PD alleles, were studied from a group of carriers or affected subjects. Allele frequencies were 3% for haemoglobin S, 1% for beta-thalassaemia trait and 9.5% for G6PD deficiency. (PMID:11920200)
• Deletion of leucine 61 in glucose-6-phosphate dehydrogenase leads to chronic nonspherocytic anemia, granulocyte dysfunction, and increased susceptibility to infections. (PMID:12130518)
• Recombinant human glucose-6-phosphate dehydrogenase uses a rapid-equilibrium random-order mechanism for substrate binding. (PMID:12135480)
• nucleotide diversity across a 5.2-kb region of G6PD in a sample of 160 Africans and 56 non-Africans, to determine how selection has shaped patterns of DNA variation at this gene (PMID:12378426)
• Mutational analysis of G6PD variants in Malaysian Malays with G6PD deficiency. (PMID:12497642)
• Nucleotide variability at G6pd and the signature of malarial selection in humans. (PMID:12524354)
• Significant difference in distribution of G6PD activities as grouped by an increment of 100 U/10(12) red blood cells (RBCs) was observed between diabetic patients and healthy subjects. (PMID:12588050)
• HPRT and G6PD origins of replication that are functional in the active X chromosome are utilized even when the two genes are transcriptionally silent in the inactive X chromosome. (PMID:12616531)
• the association of G6PD Sumare and G6PD A- in a compound heterozygote gave rise to a very mild chronic hemolysis, and the red cell population containing G6PD A- is probably enough to protect against severe chronic hemolysis (PMID:12737938)
• Molecular characterization of G6PD Insuli–a novel 989 CGC –> CAC (330 Arg –> His) mutation in exon 9 in the Indian population with normal enzyme activity (PMID:12737940)
• This study suggests that the metabolic consequences of a combined deficiency of GPI and G6PD might be responsible for a different clinical outcome, severe congenital hemolytic anemia, than predicted for either defect in isolation. (PMID:12737943)
• G6PD deficiency was studied in Nepalese males. (PMID:12768444)
• screening a Mexican population identified new mutations located at cDNA nt 376 A –> T (126 Asn –> Tyr), nt 770 G –> T (257 Arg –> Leu), nt 1094 G –> A (365 Arg –> His), and nt 1285 A –> G (429 Lys –> Glu) (PMID:12850494)
• glycolaldehyde inactivates glucose-6-phosphate dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase, and Cu,Zn superoxide dismutase, suppresses cell growth, and induces apoptosis. (PMID:12921788)
• 4% of males in the Kuwaiti population have G6PD deficiency coexisting with low activity of the UDPGT1 promoter (PMID:12972027)
• distribution of erythrocyte G6PD activity in human populations reveals a selective pressure for maintaining high activity (PMID:14614139)
• identified two de novo missense mutations in patients with severe G6PD deficiency as sites Pro409 and Val431, located on different subunits, that interact directly across the subunit interface and perturb formation of the G6PD dimer upon mutation (PMID:14757424)
• gene 1226 C–>G mutation in a chronic nonspherocytic hemolytic anemia patient causes significant differences in Km values and enzyme stability, by changing tetramer interactions and disturbing the binding of structural NADP+ (PMID:14757426)
• determined the frequency of glucose-6-phosphate dehydrogenase (G6PD) deficiency in Cyprus; one previously undescribed mutation in exon 3, 148C–>T (Pro50Ser), was found (PMID:15223006)
• genetic diversity of enzyme forms in GPD deficiency in India. (PMID:15315792)
• uncommon splice site mutation causes enzyme deficiency (PMID:15466166)
• G6PD cDNA 1388 (G–>A), 1376 (G–>T), 95(A–> G), 392 (G–>T), 1024 (C–>T) and 1311 (C–>T) accompanied with intron 11 (93 T–>C) are the common mutations in Chinese population. (PMID:15476167)
• Review. Nearly 150 different G6PD variants have been described. The recent determination of its 3-dimensional structure explains the mechanisms of G6PD deficiency in terms of structure-function relationship. (PMID:15506519)
• Based on the increased susceptibility of G6PD-deficient patients to oxidative stress, an increase in Se-GSH-Px activity can facilitate the detoxification of reactive oxygen species. (PMID:15598086)
• G6PD mutation from G6PD deficient patients were analyzed. (PMID:15622766)
• We have shown two distinct CREB-responsive sites in the glucose-6-phosphatase gene promoter that are responding to a constitutively active CREB or elevated concentrations of the catalytic subunit of cAMP-dependent protein kinase in the nucleus. (PMID:15659240)
• G6PD Viangchan and Mahidol are common Southeast Asian variants and support the theory of genetic drifts throughout Southeast Asia. (PMID:15727905)
• UGT1A1, OATP2 and G6PD genes have roles in genetic predisposition to unconjugated hyperbilirubinemia (PMID:15864125)
• G6PD Viangchan and G6PD Mediterranean account for the main variants in G6PD deficiency among the Malay population in Malaysia. (PMID:15906717)
• G6PD deficiency alone is not causative of diabetic ketosis and alterations in genes controlling both insulin secretion and G6PD-mediated antioxidant defenses may contribute to the predisposition in West Africans (PMID:15914531)
• Mediterranean mutation at nt 563(C–>T) is predominant in the Iran’s Golestan province (69%) and 26.7% of patients have Chatham mutation at nt 1003(G–>A) (PMID:15957246)
• analysis of disease phenotype in two human glucose 6-phosphate dehydrogenase mutants, G6PD(Union) and G6PD(Andalus) (PMID:16088936)
• A novel variant, named G6PD Split, is caused by a nucleotide change 1442 C–>G leading to the amino acid substitution 481 Pro–>Arg and is characterized by moderate enzyme deficiency (class III variant). (PMID:16143877)
• G6PD Viangchan (871G>A) is the most common G6PD-deficient variant in the Cambodian population. (PMID:16155737)
• G-6-PD deficiency coexists with G71R or A388G mutation in some individuals with neonatal jaundice in Guangxi region. (PMID:16255851)
• Data show that 34 heterozygous females with from patients with G6PD deficiency variants was identified by denaturing high-performance liquid chromatography. (PMID:16331553)
• Microtubule motor proteins colocalize with G6PDase; microtubule motor proteins participate in hexose monophosphate shunt enzyme transport within leukocytes. (PMID:16483869)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	g6pd	ENSDARG00000071065
mus_musculus	G6pdx	ENSMUSG00000031400
mus_musculus	G6pd2	ENSMUSG00000089992
rattus_norvegicus	G6pd	ENSRNOG00000056728
drosophila_melanogaster	Zw	FBGN0004057
caenorhabditis_elegans		WBGENE00007108

Paralogs (1): H6PD (ENSG00000049239)

Protein

Protein identifiers

Glucose-6-phosphate 1-dehydrogenase — P11413 (reviewed: P11413)

All UniProt accessions (15): P11413, A0A384NL00, A0A8Q3SIN6, A0A8Q3SIS5, A0A8Q3SJB9, A0A8Q3WL80, A0A8Q3WL83, A0A8Q3WL90, A0A8Q3WL93, A0A8Q3WL95, A0A8Q3WLB9, A0A8Q3WLT0, E7EM57, E7EUI8, E9PD92

UniProt curated annotations — full annotation on UniProt →

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. Also catalyzes the conversion of NAADPH, which is produced by enzymes such as DUOX1, DUOX2 and NOX5 from NAADP and promotes Ca(2+) signaling during T cell activation, back to NAADP.

Subunit / interactions. Homotetramer; dimer of dimers. Interacts with SIRT2; the interaction is enhanced by H(2)O(2) treatment. Forms a ternary complex with ALDOB and TP53; this interaction is direct. ALDOB stabilizes the complex inhibiting G6PD activity and keeping oxidative pentose phosphate metabolism in check.

Subcellular location. Cytoplasm. Cytosol. Membrane.

Tissue specificity. Isoform Long is found in lymphoblasts, granulocytes and sperm.

Post-translational modifications. Acetylated by ELP3 at Lys-403; acetylation inhibits its homodimerization and enzyme activity. Deacetylated by SIRT2 at Lys-403; deacetylation stimulates its enzyme activity.

Disease relevance. Anemia, congenital, non-spherocytic hemolytic, 1 (CNSHA1) [MIM:300908] An X-linked 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. The disease is caused by variants 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 CNSHA1 are recognized. Class-I variants are associated with severe CNSHA1; 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. Carbohydrate degradation; pentose phosphate pathway; D-ribulose 5-phosphate from D-glucose 6-phosphate (oxidative stage): step 1/3.

Polymorphism. The sequence shown is that of variant B, the most common variant.

Miscellaneous. Binds two molecules of NADP. The first one is a cosubstrate (bound to the N-terminal domain), the second is bound to the C-terminal domain and functions as a structural element.

Similarity. Belongs to the glucose-6-phosphate dehydrogenase family.

Isoforms (3)

UniProt ID	Names	Canonical?
P11413-1	Short	yes
P11413-2	Long
P11413-3	3

RefSeq proteins (3): NP_000393, NP_001035810, NP_001346945* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001282	G6P_DH	Family
IPR019796	G6P_DH_AS	Active_site
IPR022674	G6P_DH_NAD-bd	Domain
IPR022675	G6P_DH_C	Domain
IPR036291	NAD(P)-bd_dom_sf	Homologous_superfamily

Pfam: PF00479, PF02781

Enzyme classification (BRENDA):

• EC 1.1.1.49 — glucose-6-phosphate dehydrogenase (NADP+) (BRENDA: 69 organisms, 77 substrates, 226 inhibitors, 195 Km, 69 kcat entries)

Substrate kinetics (BRENDA)

11 substrates with measured Km, best-characterized 11. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
D-GLUCOSE 6-PHOSPHATE	0.0021–50.7	81
NADP+	—	79
NAD+	0.047–14.66	8
NADPH	0.014–0.023	4
2-DEOXY-D-GLUCOSE 6-PHOSPHATE	0.374–35	3
6-PHOSPHONOGLUCONATE	0.279–0.864	2
D-GALACTOSE 6-PHOSPHATE	0.031–0.051	2
DEAMINO-NADP+	0.0156	1
THIO-NAD+	1.5	1
THIO-NADP+	0.06	1
2-DEOXYGLUCOSE 6-PHOSPHATE	—	0

Catalyzed reactions (Rhea), 2 shown:

• D-glucose 6-phosphate + NADP(+) = 6-phospho-D-glucono-1,5-lactone + NADPH + H(+) (RHEA:15841)
• NAADP(+) + D-glucose 6-phosphate = NAADPH + 6-phospho-D-glucono-1,5-lactone + H(+) (RHEA:86243)

UniProt features (172 total): sequence variant 72, helix 26, strand 23, binding site 20, modified residue 11, turn 7, mutagenesis site 6, sequence conflict 2, splice variant 2, initiator methionine 1, chain 1, active site 1

Structure

Experimental structures (PDB)

25 structures.

PDB	Method	Resolution (Å)
6JYU	X-RAY DIFFRACTION	1.89
6E08	X-RAY DIFFRACTION	1.9
7SNH	ELECTRON MICROSCOPY	2.2
7ZVE	X-RAY DIFFRACTION	2.28
7ZVD	X-RAY DIFFRACTION	2.46
2BH9	X-RAY DIFFRACTION	2.5
7SNI	ELECTRON MICROSCOPY	2.5
7UC2	ELECTRON MICROSCOPY	2.5
6E07	X-RAY DIFFRACTION	2.6
5UKW	X-RAY DIFFRACTION	2.65
7SNG	ELECTRON MICROSCOPY	2.8
2BHL	X-RAY DIFFRACTION	2.9
7SEH	X-RAY DIFFRACTION	2.9
7UAL	ELECTRON MICROSCOPY	2.9
6VAQ	X-RAY DIFFRACTION	2.95
1QKI	X-RAY DIFFRACTION	3
7TOE	ELECTRON MICROSCOPY	3
6VA7	X-RAY DIFFRACTION	3.07
6VA0	X-RAY DIFFRACTION	3.1
7SNF	ELECTRON MICROSCOPY	3.5
7UAG	ELECTRON MICROSCOPY	3.5
7SEI	X-RAY DIFFRACTION	3.65
7TOF	ELECTRON MICROSCOPY	3.7
6VA8	X-RAY DIFFRACTION	3.95
6VA9	X-RAY DIFFRACTION	3.95

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P11413-F1	94.54	0.91

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 263 (proton acceptor)

Ligand- & substrate-binding residues (20): 258; 357; 360; 365; 366; 370; 393; 395; 401–403; 421–423; 487; 503 …

Post-translational modifications (11): 26, 2, 8, 10, 89, 171, 171, 403, 432, 497, 503

Mutagenesis-validated functional residues (6):

Position	Phenotype
171	inhibits catalytic activity. does not impair dimerization.
386	impairs dimerization and reduces catalytic activity.
386	does not impair dimerization and catalytic activity.
403	impairs dimerization and reduces catalytic activity in cells under oxidative stress.
403	does not impair dimerization and catalytic activity.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-5628897	TP53 Regulates Metabolic Genes
R-HSA-71336	Pentose phosphate pathway
R-HSA-9818028	NFE2L2 regulates pentose phosphate pathway genes

MSigDB gene sets: 419 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_POSITIVE_REGULATION_OF_CALCIUM_ION_TRANSPORT, GOBP_RESPONSE_TO_ETHANOL, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_MYELOID_CELL_HOMEOSTASIS, GOBP_NEGATIVE_REGULATION_OF_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_MYELOID_CELL_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_MUSCLE_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_NADPPLUS_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_CELL_GROWTH, GOBP_NEGATIVE_REGULATION_OF_REACTIVE_OXYGEN_SPECIES_METABOLIC_PROCESS, GOBP_ERYTHROCYTE_HOMEOSTASIS, GOBP_GROWTH, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION

GO Biological Process (21): glucose metabolic process (GO:0006006), pentose-phosphate shunt (GO:0006098), lipid metabolic process (GO:0006629), cholesterol biosynthetic process (GO:0006695), NADP+ metabolic process (GO:0006739), glutathione metabolic process (GO:0006749), pentose-phosphate shunt, oxidative branch (GO:0009051), response to iron(III) ion (GO:0010041), pentose biosynthetic process (GO:0019322), substantia nigra development (GO:0021762), response to food (GO:0032094), cellular response to oxidative stress (GO:0034599), erythrocyte maturation (GO:0043249), regulation of neuron apoptotic process (GO:0043523), response to ethanol (GO:0045471), ribose phosphate biosynthetic process (GO:0046390), glucose 6-phosphate metabolic process (GO:0051156), negative regulation of cell growth involved in cardiac muscle cell development (GO:0061052), positive regulation of calcium ion transmembrane transport via high voltage-gated calcium channel (GO:1904879), negative regulation of reactive oxygen species metabolic process (GO:2000378), NADPH regeneration (GO:0006740)

GO Molecular Function (9): glucose-6-phosphate dehydrogenase activity (GO:0004345), D-glucose binding (GO:0005536), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), NADP binding (GO:0050661), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on CH-OH group of donors (GO:0016614), carbohydrate binding (GO:0030246)

GO Cellular Component (6): cytoplasm (GO:0005737), cytosol (GO:0005829), cytoplasmic side of plasma membrane (GO:0009898), membrane (GO:0016020), centriolar satellite (GO:0034451), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Transcriptional Regulation by TP53	1
Metabolism of carbohydrates and carbohydrate derivatives	1
Nuclear events mediated by NFE2L2	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
NADPH regeneration	2
carbohydrate derivative metabolic process	2
binding	2
hexose metabolic process	1
pentose-phosphate shunt, oxidative branch	1
pentose-phosphate shunt, non-oxidative branch	1
glucose 6-phosphate metabolic process	1
primary metabolic process	1
cholesterol metabolic process	1
sterol biosynthetic process	1
secondary alcohol biosynthetic process	1
purine nucleotide metabolic process	1
nicotinamide nucleotide metabolic process	1
modified amino acid metabolic process	1
sulfur compound metabolic process	1
glucose-6-phosphate dehydrogenase activity	1
phosphogluconate dehydrogenase (decarboxylating) activity	1
pentose-phosphate shunt	1
6-phosphogluconolactonase activity	1
response to iron ion	1
pentose metabolic process	1
monosaccharide biosynthetic process	1
midbrain development	1
neural nucleus development	1
response to nutrient levels	1
response to chemical	1
response to oxidative stress	1
cellular response to chemical stress	1
cell maturation	1
erythrocyte development	1
regulation of apoptotic process	1
neuron apoptotic process	1
response to alcohol	1
ribose phosphate metabolic process	1
organophosphate biosynthetic process	1
carbohydrate derivative biosynthetic process	1
organophosphate metabolic process	1
negative regulation of cardiac muscle hypertrophy	1
negative regulation of cell growth	1

Protein interactions and networks

STRING

3924 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
G6PD	GPI	P06744	971
G6PD	PGD	P52209	957
G6PD	GSR	P00390	917
G6PD	TP53	P04637	868
G6PD	TKT	P29401	819
G6PD	TKTL1	P51854	814
G6PD	LDHA	P00338	813
G6PD	TKTL2	Q9H0I9	811
G6PD	TALDO1	P37837	809
G6PD	GCK	P35557	806
G6PD	GPX6	P59796	804
G6PD	GPX5	O75715	804
G6PD	GPX8	Q8TED1	804
G6PD	GPX2	P18283	803
G6PD	GPX7	Q96SL4	802

IntAct

58 interactions, top by confidence:

A	B	Type	Score
MED18	MED19	psi-mi:“MI:0914”(association)	0.840
G6PD	G6PD	psi-mi:“MI:0915”(physical association)	0.570
GRB2	ARHGEF35	psi-mi:“MI:0914”(association)	0.530
ATP6V1B2	ATP6V1G1	psi-mi:“MI:0914”(association)	0.530
SIRT2	G6PD	psi-mi:“MI:0915”(physical association)	0.520
G6PD	SIRT2	psi-mi:“MI:0915”(physical association)	0.520
CPSF6	DDX39A	psi-mi:“MI:0914”(association)	0.480
G6PD	H1-2	psi-mi:“MI:0915”(physical association)	0.400
	TK2	psi-mi:“MI:0915”(physical association)	0.400
SDC1	ILVBL	psi-mi:“MI:0915”(physical association)	0.400
HSPB1	G6PD	psi-mi:“MI:0915”(physical association)	0.400
G6PD	HSPB1	psi-mi:“MI:0915”(physical association)	0.400
Snw1	AKR7A2	psi-mi:“MI:0914”(association)	0.350
CTR9	POLR2B	psi-mi:“MI:0914”(association)	0.350
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
GRN	OPA1	psi-mi:“MI:0914”(association)	0.350
SH3GL3	HMGB1P1	psi-mi:“MI:0914”(association)	0.350
SH2D3C	ANXA2P2	psi-mi:“MI:0914”(association)	0.350
PRKAR1A	ADAM10	psi-mi:“MI:0914”(association)	0.350
SHOC2	IDH1	psi-mi:“MI:0914”(association)	0.350
PRKCE	PAPSS1	psi-mi:“MI:0914”(association)	0.350
CAV1	ACOT7	psi-mi:“MI:0914”(association)	0.350
PRKCG	HSPB1	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
CSAG2	CAMK2D	psi-mi:“MI:0914”(association)	0.350
TIFAB	DDX3X	psi-mi:“MI:0914”(association)	0.350
	CLIC1	psi-mi:“MI:0914”(association)	0.350

BioGRID (244): G6PD (Two-hybrid), G6PD (Affinity Capture-MS), G6PD (Affinity Capture-MS), ARFIP1 (Co-fractionation), C6orf211 (Co-fractionation), CDA (Co-fractionation), DUT (Co-fractionation), FDPS (Co-fractionation), G6PD (Co-fractionation), G6PD (Co-fractionation), G6PD (Co-fractionation), G6PD (Co-fractionation), G6PD (Co-fractionation), HARS (Co-fractionation), HSPA9 (Co-fractionation)

ESM2 similar proteins: A0A1E5S1A9, A0M3I8, O00091, O14137, O54537, O55044, O59812, O84188, P04807, P05370, P0AC53, P0AC54, P11410, P11411, P11412, P11413, P12646, P21907, P33284, P37830, P37986, P41571, P44311, P48828, P48848, P48992, P54547, P54996, P73411, P77809, P97324, Q00612, Q27464, Q27638, Q29492, Q42919, Q43793, Q54NG9, Q557D2, Q55C16

Diamond homologs: A0A1E5S1A9, A0QP90, O00091, O14137, O24357, O51581, O54537, O55044, O59812, O68282, O83491, O84188, O95479, P05370, P0A585, P0A587, P0AC53, P0AC54, P11410, P11411, P11412, P11413, P12646, P15588, P21907, P29686, P37830, P37986, P41571, P41764, P44311, P48826, P48828, P48848, P48992, P54547, P54996, P57405, P73411, P77809

SIGNOR signaling

16 interactions.

A	Effect	B	Mechanism
PRKCD	up-regulates	G6PD	phosphorylation
SIRT5	“up-regulates activity”	G6PD	“catalytic activity”
G6PD	“down-regulates quantity”	“alpha-D-glucose 6-phosphate(2-)”	“chemical modification”
G6PD	“up-regulates quantity”	6-O-phosphono-D-glucono-1,5-lactone	“chemical modification”
G6PD	“up-regulates quantity”	NADPH(4-)	“chemical modification”
NFE2L2	“up-regulates quantity by expression”	G6PD	“transcriptional regulation”
TP53	“down-regulates activity”	G6PD	binding
PLK1	“up-regulates activity”	G6PD	phosphorylation
OGT	“up-regulates activity”	G6PD	glycosylation
OGA	“down-regulates activity”	G6PD	deglycosylation
G6PD	“down-regulates quantity”	NADP(3-)	“chemical modification”
MAP3K14	“up-regulates activity”	G6PD	phosphorylation
CSNK2A1	“up-regulates activity”	G6PD	phosphorylation
SRC	“up-regulates activity”	G6PD	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

883 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	67
Likely pathogenic	122
Uncertain significance	194
Likely benign	293
Benign	24

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
100058	NM_000402.4(G6PD):c.1466G>T (p.Arg489Leu)	Pathogenic
100059	NM_000402.4(G6PD):c.1478G>A (p.Arg493His)	Pathogenic
10363	NM_000402.4(G6PD):c.1093G>A (p.Ala365Thr)	Pathogenic
10370	NM_000402.4(G6PD):c.1268G>A (p.Arg423His)	Pathogenic
10376	NM_000402.4(G6PD):c.1250G>A (p.Arg417His)	Pathogenic
10377	NM_000402.4(G6PD):c.1243T>C (p.Cys415Arg)	Pathogenic
10385	NM_000402.4(G6PD):c.1147C>T (p.Pro383Ser)	Pathogenic
10387	NM_001360016.2(G6PD):c.680G>T (p.Arg227Leu)	Pathogenic
10391	NM_000402.4(G6PD):c.682C>T (p.Arg228Cys)	Pathogenic
10396	NM_000402.4(G6PD):c.1249C>T (p.Arg417Cys)	Pathogenic
10398	NM_000402.4(G6PD):c.1319G>A (p.Gly440Asp)	Pathogenic
10407	NM_000402.4(G6PD):c.607T>C (p.Phe203Leu)	Pathogenic
10419	G6PD Amsterdam	Pathogenic
10420	G6PD ZURICH	Pathogenic
10421	G6PD VARNSDORF	Pathogenic
10422	NM_000402.4(G6PD):c.1466G>C (p.Arg489Pro)	Pathogenic
1198343	NM_001360016.2(G6PD):c.1361G>C (p.Arg454Pro)	Pathogenic
1330149	NM_001360016.2(G6PD):c.551C>T (p.Ser184Phe)	Pathogenic
1685831	NM_001360016.2(G6PD):c.1143C>G (p.Phe381Leu)	Pathogenic
1685833	NM_001360016.2(G6PD):c.323T>A (p.Val108Glu)	Pathogenic
1722643	NM_001042351.3(G6PD):c.-9+2T>G	Pathogenic
1722644	NM_001360016.2(G6PD):c.882del (p.Lys293_Cys294insTer)	Pathogenic
1722645	NM_001360016.2(G6PD):c.1478_1479insAGGAGGCAGA (p.Asp493fs)	Pathogenic
1722646	NM_001042351.1(G6PD):c.1054_1055insG	Pathogenic
1722647	NM_001360016.2(G6PD):c.916G>A (p.Gly306Ser)	Pathogenic
1722648	NM_001360016.2(G6PD):c.1283dup (p.Tyr428Ter)	Pathogenic
1722649	NM_001360016.2(G6PD):c.31C>T (p.Gln11Ter)	Pathogenic
1722650	NM_001360016.2(G6PD):c.130G>A (p.Ala44Thr)	Pathogenic
1722653	NM_001360016.2(G6PD):c.283_285del (p.Lys95del)	Pathogenic
1722656	NM_001360016.2(G6PD):c.519C>G (p.Phe173Leu)	Pathogenic

SpliceAI

2052 predictions. Top by Δscore:

Variant	Effect	Δscore
X:154532281:C:CC	acceptor_gain	1.0000
X:154532380:CCTCA:C	donor_loss	1.0000
X:154532381:CTCAC:C	donor_loss	1.0000
X:154532382:TCAC:T	donor_loss	1.0000
X:154532383:CAC:C	donor_loss	1.0000
X:154532458:ACGTT:A	acceptor_gain	1.0000
X:154532459:CGTT:C	acceptor_gain	1.0000
X:154532459:CGTTC:C	acceptor_gain	1.0000
X:154532460:GTT:G	acceptor_gain	1.0000
X:154532461:TT:T	acceptor_gain	1.0000
X:154532463:C:CC	acceptor_gain	1.0000
X:154532463:C:CG	acceptor_loss	1.0000
X:154532465:G:C	acceptor_gain	1.0000
X:154532562:GGCAC:G	donor_loss	1.0000
X:154532565:ACCT:A	donor_loss	1.0000
X:154532573:T:C	donor_gain	1.0000
X:154532798:CACCC:C	acceptor_gain	1.0000
X:154532799:ACCC:A	acceptor_gain	1.0000
X:154532800:CCC:C	acceptor_gain	1.0000
X:154532800:CCCC:C	acceptor_gain	1.0000
X:154532801:CC:C	acceptor_gain	1.0000
X:154532801:CCC:C	acceptor_gain	1.0000
X:154532802:CC:C	acceptor_gain	1.0000
X:154532803:C:CC	acceptor_gain	1.0000
X:154532803:C:G	acceptor_loss	1.0000
X:154532804:T:G	acceptor_loss	1.0000
X:154532806:C:CT	acceptor_gain	1.0000
X:154532807:G:C	acceptor_gain	1.0000
X:154533129:CTGA:C	acceptor_loss	1.0000
X:154533571:CCTAC:C	donor_loss	1.0000

AlphaMissense

3420 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:154532948:A:G	W349R	1.000
X:154532948:A:T	W349R	1.000
X:154534379:G:C	H201Q	1.000
X:154534379:G:T	H201Q	1.000
X:154534381:G:C	H201D	1.000
X:154534383:T:A	D200V	1.000
X:154534472:C:A	E170D	1.000
X:154534472:C:G	E170D	1.000
X:154534473:T:A	E170V	1.000
X:154532261:A:G	W462R	0.999
X:154532261:A:T	W462R	0.999
X:154532264:C:G	A461P	0.999
X:154532394:G:C	F452L	0.999
X:154532394:G:T	F452L	0.999
X:154532396:A:G	F452L	0.999
X:154532431:A:G	L440P	0.999
X:154532441:A:G	Y437H	0.999
X:154532589:A:G	L422P	0.999
X:154532633:C:A	K407N	0.999
X:154532633:C:G	K407N	0.999
X:154532659:C:G	A399P	0.999
X:154532676:C:G	R393P	0.999
X:154532685:A:G	L390P	0.999
X:154532946:C:A	W349C	0.999
X:154532946:C:G	W349C	0.999
X:154533651:G:C	H263Q	0.999
X:154533651:G:T	H263Q	0.999
X:154533652:T:C	H263R	0.999
X:154533653:G:C	H263D	0.999
X:154533654:G:C	N262K	0.999

dbSNP variants (sampled 300 via entrez): RS1000300912 (X:154542862 G>A), RS1000781286 (X:154544389 T>A), RS1000907549 (X:154544711 A>G), RS1000937138 (X:154536034 C>T), RS1001076759 (X:154536489 A>C,G), RS1001296301 (X:154533354 T>C), RS1001576945 (X:154541190 G>C), RS1001700933 (X:154548452 C>T), RS1001726961 (X:154548896 A>G), RS1002298657 (X:154534686 T>A), RS1002971500 (X:154531616 G>A,C), RS1003376621 (X:154546505 G>A,T), RS1003923823 (X:154531677 T>A,C,G), RS1004113189 (X:154539443 A>G), RS1004313219 (X:154547203 G>A)

Disease associations

OMIM: gene MIM:305900 | disease phenotypes: MIM:300908, MIM:601894, MIM:611162, MIM:138990, MIM:306400, MIM:143890, MIM:300291, MIM:182230, MIM:308300, MIM:300301, MIM:300584, MIM:300636, MIM:301081

GenCC curated gene-disease

Disease	Classification	Inheritance
anemia, nonspherocytic hemolytic, due to G6PD deficiency	Definitive	X-linked
class I glucose-6-phosphate dehydrogenase deficiency	Supportive	X-linked

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
G6PD deficiency	Definitive	XL
anemia, nonspherocytic hemolytic, due to G6PD deficiency	Definitive	XL

Mondo (16): G6PD deficiency (MONDO:0005775), anemia, nonspherocytic hemolytic, due to G6PD deficiency (MONDO:0010480), glomerulopathy with fibronectin deposits 2 (MONDO:0011165), malaria, susceptibility to (MONDO:0021024), granulomatous disease, chronic, X-linked (MONDO:0010600), congenital nonspherocytic hemolytic anemia (MONDO:0006506), hypercholesterolemia, familial, 1 (MONDO:0007750), ectodermal dysplasia and immunodeficiency 1 (MONDO:0020740), septooptic dysplasia (MONDO:0008428), incontinentia pigmenti (MONDO:0010631), hemolytic anemia (MONDO:0003664), familial hemolytic anemia (MONDO:0003689), anhidrotic ectodermal dysplasia-immunodeficiency-osteopetrosis-lymphedema syndrome (MONDO:0010295), immunodeficiency 33 (MONDO:0010386), autoinflammatory disease, X-linked (MONDO:0800129)

Orphanet (13): Class I glucose-6-phosphate dehydrogenase deficiency (Orphanet:466026), Malaria (Orphanet:673), Fibronectin glomerulopathy (Orphanet:84090), Chronic granulomatous disease (Orphanet:379), Homozygous familial hypercholesterolemia (Orphanet:391665), Hypohidrotic ectodermal dysplasia (Orphanet:238468), Hypohidrotic ectodermal dysplasia with immunodeficiency (Orphanet:98813), Septo-optic dysplasia spectrum (Orphanet:3157), Incontinentia pigmenti (Orphanet:464), X-linked mendelian susceptibility to mycobacterial diseases (Orphanet:319605), OBSOLETE: X-linked mendelian susceptibility to mycobacterial diseases due to IKBKG deficiency (Orphanet:319612), Hypohidrotic ectodermal dysplasia-immunodeficiency-osteopetrosis-lymphedema syndrome (Orphanet:69088), NEMO deleted exon 5 autoinflammatory syndrome (Orphanet:699605)

HPO phenotypes

22 total (22 of 22 shown, HPO-id order):

HPO	Term
HP:0000952	Jaundice
HP:0000980	Pallor
HP:0001423	X-linked dominant inheritance
HP:0001744	Splenomegaly
HP:0001923	Reticulocytosis
HP:0001945	Fever
HP:0001974	Increased total leukocyte count
HP:0002027	Abdominal pain
HP:0003577	Congenital onset
HP:0003593	Infantile onset
HP:0003596	Middle age onset
HP:0003621	Juvenile onset
HP:0003641	Hemoglobinuria
HP:0004447	Poikilocytosis
HP:0004814	Fava bean-induced hemolytic anemia
HP:0006579	Prolonged neonatal jaundice
HP:0008282	Unconjugated hyperbilirubinemia
HP:0011273	Anisocytosis
HP:0011462	Young adult onset
HP:0011463	Childhood onset
HP:0020082	Heinz bodies
HP:0410179	Decreased glucose-6-phosphate dehydrogenase level in blood

GWAS associations

19 associations (top):

Study	Trait	p-value
GCST000388_1	Bilirubin levels	9.000000e-09
GCST001873_1	Red blood cell traits	2.000000e-16
GCST001873_11	Red blood cell traits	4.000000e-19
GCST001873_12	Red blood cell traits	2.000000e-11
GCST001873_4	Red blood cell traits	4.000000e-18
GCST001873_9	Red blood cell traits	4.000000e-14
GCST002027_2	Red blood cell traits	9.000000e-09
GCST002027_6	Red blood cell traits	4.000000e-13
GCST002027_7	Red blood cell traits	1.000000e-14
GCST003122_2	Hemoglobin levels	3.000000e-11
GCST004332_2	Red blood cell count	2.000000e-18
GCST004333_1	Red cell distribution width	4.000000e-29
GCST004334_4	Mean corpuscular hemoglobin	5.000000e-11
GCST004335_10	Mean corpuscular volume	1.000000e-17
GCST004335_14	Mean corpuscular volume	1.000000e-17
GCST007952_1	Glycated hemoglobin levels	8.000000e-135
GCST008398_16	Glycated hemoglobin levels	1.000000e-133
GCST012129_1	hemolysis of donated blood (oxidative)	5.000000e-08
GCST012134_4	hemolysis of donated blood (oxidative)	3.000000e-17

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004570	bilirubin measurement
EFO:0004348	hematocrit
EFO:0004305	erythrocyte count
EFO:0009188	Red cell distribution width
EFO:0004509	hemoglobin measurement
EFO:0004527	mean corpuscular hemoglobin
EFO:0007629	hemoglobin A1 measurement
EFO:0004541	HbA1c measurement
EFO:0009473	hemolysis

MeSH disease descriptors (10)

Descriptor	Name	Tree numbers
D000743	Anemia, Hemolytic	C15.378.050.141
D000745	Anemia, Hemolytic, Congenital	C15.378.050.141.150; C16.320.070
D000746	Anemia, Hemolytic, Congenital Nonspherocytic	C15.378.050.141.150.100; C16.320.070.100
D005955	Glucosephosphate Dehydrogenase Deficiency	C15.378.050.141.150.480; C16.320.070.480; C16.320.565.202.402; C18.452.648.202.402
D007184	Incontinentia Pigmenti	C16.131.077.445; C16.131.831.580; C16.320.850.420; C17.800.621.497; C17.800.804.580; C17.800.827.420
D025962	Septo-Optic Dysplasia	C10.292.562.700.375.875; C10.500.034.937; C10.500.760.500; C11.590.436.400.875; C16.131.666.034.937; C16.131.666.763.500
C567533	Anemia, Nonspherocytic Hemolytic, Due To G6pd Deficiency (supp.)
C564538	Ectodermal Dysplasia, Anhidrotic, with Immunodeficiency, Osteopetrosis, and Lymphedema (supp.)
C564210	Granulomatous Disease, Chronic, Autosomal Dominant Type (supp.)
C536289	Immunodeficiency without anhidrotic ectodermal dysplasia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5347 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

8 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 56,412 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL207538	BREXANOLONE	4	1,585
CHEMBL3187985	APOMORPHINE HYDROCHLORIDE	4	5,278
CHEMBL90593	PRASTERONE	4	23,422
CHEMBL51085	EBSELEN	3	13,237
CHEMBL142652	PICEID	2	3,167
CHEMBL2057301	SEPRANOLONE	2	452
CHEMBL253363	PREGNENOLONE	1	9,009
CHEMBL445472	16.ALPHA.-BROMOEPIANDROSTERONE	1	262

PharmGKB: 1 entry (VIP=true, CPIC=true)

PharmGKB clinical annotations

21 annotations.

Variant	Type	Level	Drugs	Phenotypes
G6PD A- 202A_376G	Toxicity	3	pegloticase	Hemolysis;Methemoglobinemia
G6PD A- 202A_376G, G6PD B (reference)	Toxicity	3	glyburide	Hemolytic Anemia
G6PD A- 202A_376G, G6PD B (reference)	Toxicity	3	chloramphenicol	Hemolysis;Hemolytic Anemia
G6PD A- 202A_376G, G6PD B (reference)	Toxicity	3	nitrofurantoin	Hemolysis;Hemolytic Anemia
G6PD A- 202A_376G, G6PD B (reference)	Toxicity	3	dimercaprol	Hemolysis;Lead Poisoning
G6PD A- 202A_376G, G6PD B (reference)	Toxicity	3	sulfasalazine	Hemolysis
G6PD A- 202A_376G, G6PD B (reference)	Efficacy,Toxicity	3	methylene blue	Hemolysis;Hemolytic Anemia;Protein Deficiency
G6PD A- 202A_376G, G6PD B (reference)	Toxicity	4	mefloquine	Malaria
G6PD A- 202A_376G, G6PD B (reference), G6PD Mediterranean Haplotype, G6PD Mediterranean, Dallas, Panama, Sassari, Cagliari, Birmingham	Toxicity	4	chloroquine	Hemolytic Anemia
G6PD A- 202A_376G, G6PD B (reference), G6PD Mediterranean, Dallas, Panama, Sassari, Cagliari, Birmingham	Toxicity	1A	rasburicase	Hemolysis;Methemoglobinemia
G6PD B (reference), G6PD Canton, Taiwan-Hakka, Gifu-like, Agrigento-like	Toxicity	3	sulfamethoxazole	Hemolysis
G6PD B (reference), G6PD Canton, Taiwan-Hakka, Gifu-like, Agrigento-like	Toxicity	4	sulfamethoxazole / trimethoprim	Hemolysis;Hemolytic Anemia
G6PD B (reference), G6PD Mediterranean Haplotype	Toxicity	3	phenazopyridine	Hemolysis;Hemolytic Anemia
G6PD B (reference), G6PD Mediterranean Haplotype, G6PD Mediterranean, Dallas, Panama, Sassari, Cagliari, Birmingham	Toxicity	3	ciprofloxacin	Hemolytic Anemia
G6PD B (reference), G6PD Mediterranean, Dallas, Panama, Sassari, Cagliari, Birmingham	Toxicity	3	aspirin	Hemolysis
G6PD B (reference), G6PD Mediterranean, Dallas, Panama, Sassari, Cagliari, Birmingham	Toxicity	3	sulfadoxine	Hemolysis
G6PD B (reference), G6PD Mediterranean, Dallas, Panama, Sassari, Cagliari, Birmingham	Toxicity	4	sulfametopyrazine	Hemolysis
rs1050828	Toxicity	3	amodiaquine;pyrimethamine;sulfadoxine	Malaria;Malaria;Falciparum
rs1050828	Toxicity	4	artesunate;chlorproguanil;dapsone	Malaria
rs1050828	Toxicity	3	artesunate;primaquine;pyrimethamine;sulfadoxine
rs5030868	Toxicity	3	glyburide	Diabetes Mellitus;Type 2

PharmGKB variants

13 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1050828	G6PD, IKBKG	3	5.50	13	amodiaquine;pyrimethamine;sulfadoxine;artesunate;primaquine;pyrimethamine;sulfadoxine;artesunate;chlorproguanil;dapsone
rs1050829	G6PD		0.00	10
rs2230037	G6PD		0.00	3
rs5030868	G6PD, IKBKG	3	0.25	8	glyburide
rs72554665	G6PD		0.00	2
rs137852342	G6PD		0.00	0
rs137852314	G6PD		0.00	0
rs137852340	G6PD, IKBKG		0.00	0
rs137852330	G6PD		0.00	0
rs137852327	G6PD		0.00	0
rs398123546	G6PD		0.00	0
rs72554664	G6PD		0.00	0
rs137852325	G6PD		0.00	0

PharmGKB dosing guidelines

6 guidelines.

Source	Drug	Guideline	Dosing?	Recommendation?
CPIC	aminosalicylic acid;chloramphenicol;chloroquine;ciprofloxacin;dimercaprol;doxorubicin;furazolidone;glyburide;hydroxychloroquine;mafenide;nalidixic acid;norfloxacin;ofloxacin;phenazopyridine;quinine;sulfadiazine;sulfamethazine;sulfamethoxazole;sulfamethoxazole / trimethoprim;sulfanilamide;sulfasalazine;sulfisoxazole;tolbutamide;vitamin c;Vitamin K and analogues	Annotation of CPIC Guideline for aminosalicylic acid, chloramphenicol, chloroquine, ciprofloxacin, dimercaprol, doxorubicin, furazolidone, glyburide, hydroxychloroquine, mafenide, nalidixic acid, norfloxacin, ofloxacin, phenazopyridine, quinine, sulfadiazine, sulfamethazine, sulfamethoxazole, sulfamethoxazole / trimethoprim, sulfanilamide, sulfasalazine, sulfisoxazole, tolbutamide, vitamin c, Vitamin K and analogues and G6PD
CPIC	aspirin	Annotation of CPIC Guideline for aspirin and G6PD
CPIC	chlorpropamide;dabrafenib;gliclazide;glimepiride;glipizide;mesalazine;moxifloxacin;nicorandil;nitrofurazone;probenecid;quinacrine;sodium nitrate;sulfacetamide;tolazamide;trametinib	Annotation of CPIC Guideline for chlorpropamide, dabrafenib, gliclazide, glimepiride, glipizide, mesalazine, moxifloxacin, nicorandil, nitrofurazone, probenecid, quinacrine, sodium nitrate, sulfacetamide, tolazamide, trametinib and G6PD
CPIC	dapsone;methylene blue;pegloticase;rasburicase;tafenoquine;toluidine blue	Annotation of CPIC Guideline for dapsone, methylene blue, pegloticase, rasburicase, tafenoquine, toluidine blue and G6PD		yes
CPIC	nitrofurantoin	Annotation of CPIC Guideline for nitrofurantoin and G6PD		yes
CPIC	primaquine	Annotation of CPIC Guideline for primaquine and G6PD		yes

Binding affinities (BindingDB)

142 measured of 269 human assays (315 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
2,5-bis(chloranyl)-3-[2-(dimethylamino)-1,3-thiazol-5-yl]-6-pyrrolidin-1-yl-cyclohexa-2,5-diene-1,4-dione	EC50	210 nM
4-amino-3-(4-methylphenyl)-5-[(4-methyl-1-piperazinyl)carbonyl]-1,3-thiazole-2(3H)-thione	IC50	250 nM
2-(3-bromanyl-4-methoxy-phenyl)-6-methyl-imidazo[1,2-a]pyridine	EC50	327 nM
cid_3578672	IC50	342 nM
1-[[1-(1-phenylethyl)-3-pyrrolidinyl]methyl]-3-(2,4,6-trimethylphenyl)thiourea	IC50	343 nM
2,6-dimethylbenzo-1,4-quinone 4-[O-(3,4,5-trimethoxybenzoyl)oxime]	IC50	533 nM
4-(4-methoxybenzoyloxyimino)-2,6-dimethylcyclohexa-2,5-dienone	IC50	574 nM
MLS000621546	IC50	740 nM
SMR000143195	IC50	810 nM
MLS000689390	EC50	880 nM
2-ethoxy-5-hydroxy-1H-benz[g]indole-3-carboxylic acid ethyl ester	IC50	935 nM
1-(3,4-Dimethoxy-benzyl)-2-[(E)-2-(4-methoxy-phenyl)-vinyl]-1H-benzoimidazole	EC50	943 nM
3-chloranyl-N-(3-morpholin-4-ylpropyl)-6-nitro-1-benzothiophene-2-carboxamide	EC50	950 nM
MLS000708819	EC50	970 nM
1-[(4-bromophenyl)carbonothioyl]-4-methylpiperazine	IC50	1140 nM
(2E)-2-(3-methyl-1,3-benzothiazol-2-ylidene)-1-(2-thienyl)ethanone	EC50	1280 nM
MLS000392355	IC50	1490 nM
2-(4,6-dimethyl-3-oxidanylidene-[1,2]thiazolo[5,4-b]pyridin-2-yl)-N-(3-fluorophenyl)ethanamide	EC50	1720 nM
(2Z)-1-(4-methoxyphenyl)-2-(3-methyl-1,3-benzothiazol-2-ylidene)ethanone	EC50	1750 nM
2-(3-keto-4,6-dimethyl-isothiazolo[5,4-b]pyridin-2-yl)-N-propyl-acetamide	EC50	1750 nM
MLS000689393	EC50	1750 nM
3-(4-methylphenyl)-5-(4-morpholinyl)-2-phenyl-1,2,4-thiadiazol-2-ium	EC50	2040 nM
(E)-3-(5-methyl-2-furanyl)-N-[3-[[(E)-3-(5-methyl-2-furanyl)-1-oxoprop-2-enyl]amino]-4-nitrophenyl]-2-propenamide	IC50	2120 nM
MLS000523422	IC50	2130 nM
(5Z)-5-[(4-hydroxy-3,5-dimethoxyphenyl)methylidene]-2-(4-methylphenyl)-4-thiazolone	IC50	2180 nM
1,2,3-trimethyl-2,3-dihydro-1H-perimidine	EC50	2260 nM
3-chloranyl-N-(3,3-dimethylbutan-2-yl)-6-nitro-1-benzothiophene-2-carboxamide	EC50	2470 nM
(4E)-2,3-dihydroxy-4-[[(4-methyl-2-methylimino-1,3-thiazol-3-yl)amino]methylidene]cyclohexa-2,5-dien-1-one	IC50	2720 nM
MLS000392330	IC50	2860 nM
4-[(2-benzoxybenzyl)amino]phenol	EC50	2980 nM
(+)-haematoxylin	IC50	3440 nM
(4-amino-3-phenyl-2-sulfanylidene-1,3-thiazol-5-yl)-(4-methylpiperazin-1-yl)methanone	IC50	3530 nM
4-[(2-ethoxybenzyl)amino]phenol	EC50	3630 nM
(3-chloro-4,5-dimethoxy-benzyl)-(4-pyrrolidinophenyl)amine	EC50	3720 nM
cid_5455628	EC50	3860 nM
2-(4,5-dihydroxy-2-methyl-phenyl)-6-hydroxy-4-methoxy-benzoic acid	IC50	4150 nM
2-(4-chlorophenyl)sulfonyl-4,5-dimethyl-3,6-dihydro-1,2-thiazine 1-oxide	IC50	4170 nM
MLS000392290	EC50	4380 nM
MLS000530834	EC50	4650 nM
(4E)-2,3-dihydroxy-4-[[2-(2-morpholin-4-ylsulfonyl-4-nitrophenyl)hydrazinyl]methylidene]cyclohexa-2,5-dien-1-one	EC50	4660 nM
3,4,5-trimethoxybenzoic acid [(2,5-dimethyl-4-oxo-1-cyclohexa-2,5-dienylidene)amino] ester	IC50	4750 nM
(2-methyl-1,3-thiazol-4-yl)methyl 1,4-bis(oxidanyl)naphthalene-2-carboxylate	IC50	4840 nM
(5E)-1-(2-fluorophenyl)-5-[(5-methyl-2-thienyl)methylene]-2-thioxo-hexahydropyrimidine-4,6-quinone	IC50	4910 nM
3-(4-methylphenyl)-2-phenyl-1,2,4-thiadiazol-2-ium-5-amine;bromide	IC50	4910 nM
2-(1-hydroxy-3-keto-inden-2-yl)-4-quinolone	EC50	4980 nM
MLS000520994	IC50	5120 nM
(2E,5E)-2,5-bis(4-hydroxy-3,5-dimethoxy-benzylidene)cyclopentanone	EC50	5130 nM
MLS000685531	IC50	5150 nM
2-chloro-N-(3,4-dimethylphenyl)-5-(2,5-dioxo-1-pyrrolyl)benzamide	IC50	5400 nM
2-({7-[(5-methyl-1,3,4-thiadiazol-2-yl)thio]-4-nitro-2,1,3-benzoxadiazol-5-yl}amino)ethanol	IC50	6120 nM

ChEMBL bioactivities

54 potent at pChembl≥5 of 286 total, top 48 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.16	IC50	70	nM	CHEMBL5177201
6.97	Kd	106.6	nM	CHEMBL5653589
6.97	ED50	106.6	nM	CHEMBL5653589
6.70	IC50	200	nM	CHEMBL1521758
6.22	IC50	600	nM	CHEMBL5207151
6.10	EC50	800	nM	CHEMBL5172312
6.05	IC50	900	nM	CHEMBL2057971
6.00	IC50	1000	nM	CHEMBL2057293
5.92	IC50	1200	nM	CHEMBL2057300
5.92	IC50	1200	nM	CHEMBL2057640
5.92	Ki	1191	nM	WEDELOLACTONE
5.82	IC50	1500	nM	CHEMBL2057296
5.77	IC50	1700	nM	CHEMBL2057294
5.70	IC50	2000	nM	CHEMBL2057310
5.60	IC50	2500	nM	CHEMBL2057974
5.60	Ki	2537	nM	WEDELOLACTONE
5.58	IC50	2600	nM	CHEMBL3359046
5.52	IC50	3000	nM	CHEMBL5197333
5.52	Ki	3000	nM	EPIANDROSTERONE
5.51	IC50	3100	nM	CHEMBL5199703
5.47	IC50	3400	nM	CHEMBL2057307
5.47	Ki	3400	nM	EPIANDROSTERONE
5.44	Kd	3640	nM	WEDELOLACTONE
5.42	IC50	3800	nM	CHEMBL2057318
5.37	IC50	4300	nM	SEPRANOLONE
5.32	IC50	4800	nM	CHEMBL2057307
5.30	IC50	5000	nM	CHEMBL2057291
5.29	IC50	5180	nM	WEDELOLACTONE
5.28	IC50	5300	nM	CHEMBL1908012
5.28	IC50	5200	nM	CHEMBL2057979
5.24	Ki	5793	nM	WEDELOLACTONE
5.21	Ki	6200	nM	PRASTERONE
5.20	IC50	6300	nM	CHEMBL2057978
5.18	IC50	6600	nM	CHEMBL2057297
5.15	IC50	7110	nM	CHEMBL1703503
5.11	IC50	7800	nM	CHEMBL2057296
5.06	IC50	8730	nM	CHEMBL1342337
5.05	Ki	8900	nM	PRASTERONE
5.05	IC50	8870	nM	CHEMBL45152
5.04	IC50	9200	nM	CHEMBL2057310
5.04	IC50	9170	nM	CHEMBL1717420
5.03	IC50	9400	nM	EPIANDROSTERONE
5.03	IC50	9300	nM	CHEMBL2057973
5.02	IC50	9500	nM	CHEMBL2057293
5.02	IC50	9600	nM	CHEMBL327502
5.00	IC50	9900	nM	CHEMBL2057299
5.00	Ki	9941	nM	WEDELOLACTONE
5.00	IC50	1.01e+04	nM	CHEMBL536950

PubChem BioAssay actives

48 with measured affinity, of 218 total; 30 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-[(5-oxo-6,7,8,9-tetrahydrocyclohepta[d]pyrimidin-2-yl)amino]thiophene-2-carbonitrile	1866594: Inhibition of human G6PD	ic50	0.0700	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148409: Binding affinity to human G6PD incubated for 45 mins by Kinobead based pull down assay	kd	0.1066	uM
N-(4-hydroxynaphthalen-1-yl)-2,5-dimethylbenzenesulfonamide	1866593: Inhibition of human C-terminal His tagged G6PD overexpressed in Escherichia coli BL21	ic50	0.2000	uM
(4Z)-2-[4-(4-chlorophenyl)-1,3-thiazol-2-yl]-5-methyl-4-[(3,4,5-trimethoxyphenyl)methylidene]pyrazol-3-one	1866593: Inhibition of human C-terminal His tagged G6PD overexpressed in Escherichia coli BL21	ic50	0.6000	uM
2-(1H-indol-3-yl)-N-[2-[2-[2-(1H-indol-3-yl)ethylamino]ethyldisulfanyl]ethyl]ethanamine	2022468: Activation of G6PD (unknown origin) expressed in Escherichia coli C43(DE3) cells using G6P as substrate in presence of NADP+ by resazurin dye-based assay	ec50	0.8000	uM
2-hydroxy-1-[(3S,5S,8R,9S,10S,13S,14S,17S)-3-hydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]ethanone	672987: Inhibition of human recombinant N-terminal His tagged G6PD expressed in Escherichia coli JM109 (DE3) cells assessed as production of NADPH after 30 mins by Amplite fluorimetric assay	ic50	0.9000	uM
1-[(3S,5S,8R,9S,10S,13S,14S)-10,13-dimethyl-17-oxo-1,2,3,4,5,6,7,8,9,11,12,14,15,16-tetradecahydrocyclopenta[a]phenanthren-3-yl]-3-ethylurea	1866581: Inhibition of G6PD (unknown origin)	ic50	1.0000	uM
1,8,9-trihydroxy-3-methoxy-[1]benzofuro[3,2-c]chromen-6-one	1757378: Competitive inhibition of G6PD (unknown origin) using glucose-6-phosphate and varying concentrations of NADP+ as substrate by Michaelis-Menten analysis	ki	1.1910	uM
(3S,5S,8R,9S,10S,13S,14S)-10,13-dimethyl-17-oxo-3-(sulfamoylamino)-1,2,3,4,5,6,7,8,9,11,12,14,15,16-tetradecahydrocyclopenta[a]phenanthrene	1866581: Inhibition of G6PD (unknown origin)	ic50	1.2000	uM
(3S,5S,8R,9S,10S,13S,14S,17S)-17-(2-hydroxyacetyl)-10,13-dimethyl-3-(sulfamoylamino)-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene	1866581: Inhibition of G6PD (unknown origin)	ic50	1.2000	uM
methyl N-[(3S,5S,8R,9S,10S,13S,14S)-10,13-dimethyl-17-oxo-1,2,3,4,5,6,7,8,9,11,12,14,15,16-tetradecahydrocyclopenta[a]phenanthren-3-yl]carbamate	672987: Inhibition of human recombinant N-terminal His tagged G6PD expressed in Escherichia coli JM109 (DE3) cells assessed as production of NADPH after 30 mins by Amplite fluorimetric assay	ic50	1.5000	uM
1-butyl-3-[(3S,5S,8R,9S,10S,13S,14S)-10,13-dimethyl-17-oxo-1,2,3,4,5,6,7,8,9,11,12,14,15,16-tetradecahydrocyclopenta[a]phenanthren-3-yl]urea	672987: Inhibition of human recombinant N-terminal His tagged G6PD expressed in Escherichia coli JM109 (DE3) cells assessed as production of NADPH after 30 mins by Amplite fluorimetric assay	ic50	1.7000	uM
(3S,5S,8R,9S,10S,13S,14S,17S)-17-acetyl-10,13-dimethyl-3-(sulfamoylamino)-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene	672987: Inhibition of human recombinant N-terminal His tagged G6PD expressed in Escherichia coli JM109 (DE3) cells assessed as production of NADPH after 30 mins by Amplite fluorimetric assay	ic50	2.0000	uM
2-bromo-1-[(3S,5S,8R,9S,10S,13S,14S,17S)-3-hydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]ethanone	672987: Inhibition of human recombinant N-terminal His tagged G6PD expressed in Escherichia coli JM109 (DE3) cells assessed as production of NADPH after 30 mins by Amplite fluorimetric assay	ic50	2.5000	uM
3-(5-bromo-2-pyridinyl)-2-pyridin-3-ylquinazolin-4-one	1866593: Inhibition of human C-terminal His tagged G6PD overexpressed in Escherichia coli BL21	ic50	2.6000	uM
(3S,5S,8R,9S,10S,13S,14S)-3-hydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,14,15,16-tetradecahydrocyclopenta[a]phenanthren-17-one	394403: Inhibition of human G6PDH using NADP as substrate by Lineweaver-Burke plot	ki	3.0000	uM
3-(4-methoxyphenyl)-2-pyridin-3-ylquinazolin-4-one	1866593: Inhibition of human C-terminal His tagged G6PD overexpressed in Escherichia coli BL21	ic50	3.0000	uM
2-[5-(5-bromo-2-oxoindol-3-yl)-4-hydroxy-2-sulfanylidene-1,3-thiazol-3-yl]-3-phenylpropanoic acid	1866593: Inhibition of human C-terminal His tagged G6PD overexpressed in Escherichia coli BL21	ic50	3.1000	uM
N-[(3S,5S,8R,9S,10S,13S,14S,17S)-17-acetyl-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl]methanesulfonamide	672987: Inhibition of human recombinant N-terminal His tagged G6PD expressed in Escherichia coli JM109 (DE3) cells assessed as production of NADPH after 30 mins by Amplite fluorimetric assay	ic50	3.4000	uM
N-[(3S,5S,8R,9S,10S,13S,14S,17S)-17-(2-hydroxyacetyl)-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl]methanesulfonamide	672987: Inhibition of human recombinant N-terminal His tagged G6PD expressed in Escherichia coli JM109 (DE3) cells assessed as production of NADPH after 30 mins by Amplite fluorimetric assay	ic50	3.8000	uM
1-[(3S,5S,8R,9S,10S,13S,14S,17S)-3-hydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]ethanone	672987: Inhibition of human recombinant N-terminal His tagged G6PD expressed in Escherichia coli JM109 (DE3) cells assessed as production of NADPH after 30 mins by Amplite fluorimetric assay	ic50	4.3000	uM
[(3S,5S,8R,9S,10S,13S,14S)-10,13-dimethyl-17-oxo-1,2,3,4,5,6,7,8,9,11,12,14,15,16-tetradecahydrocyclopenta[a]phenanthren-3-yl]urea	672987: Inhibition of human recombinant N-terminal His tagged G6PD expressed in Escherichia coli JM109 (DE3) cells assessed as production of NADPH after 30 mins by Amplite fluorimetric assay	ic50	5.0000	uM
1-[(3S,5S,8R,9S,10S,13S,14S,17R)-3,17-dihydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,14,15,16-tetradecahydrocyclopenta[a]phenanthren-17-yl]-2-hydroxyethanone	672987: Inhibition of human recombinant N-terminal His tagged G6PD expressed in Escherichia coli JM109 (DE3) cells assessed as production of NADPH after 30 mins by Amplite fluorimetric assay	ic50	5.2000	uM
Ketotifen	1802951: In Vitro Inhibition Assay from Article 10.3109/14756360903489581: “Effects of some drugs on human erythrocyte glucose 6-phosphate dehydrogenase: an in vitro study.”	ki	5.2000	uM
2-hydroxy-1-[(3S,8S,9S,10R,13S,14S,17S)-3-hydroxy-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl]ethanone	672987: Inhibition of human recombinant N-terminal His tagged G6PD expressed in Escherichia coli JM109 (DE3) cells assessed as production of NADPH after 30 mins by Amplite fluorimetric assay	ic50	5.3000	uM
prasterone	394403: Inhibition of human G6PDH using NADP as substrate by Lineweaver-Burke plot	ki	6.2000	uM
(3S,5S,8S,9S,10S,13S,14S,17S)-3-hydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-1,2,3,4,5,6,7,8,9,12,14,15,16,17-tetradecahydrocyclopenta[a]phenanthren-11-one	672987: Inhibition of human recombinant N-terminal His tagged G6PD expressed in Escherichia coli JM109 (DE3) cells assessed as production of NADPH after 30 mins by Amplite fluorimetric assay	ic50	6.3000	uM
N-[(3S,5S,8R,9S,10S,13S,14S)-10,13-dimethyl-17-oxo-1,2,3,4,5,6,7,8,9,11,12,14,15,16-tetradecahydrocyclopenta[a]phenanthren-3-yl]methanesulfonamide	672987: Inhibition of human recombinant N-terminal His tagged G6PD expressed in Escherichia coli JM109 (DE3) cells assessed as production of NADPH after 30 mins by Amplite fluorimetric assay	ic50	6.6000	uM
2-chloro-1-[(3S,5S,8R,9S,10S,13S,14S,17S)-3-hydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]ethanone	672987: Inhibition of human recombinant N-terminal His tagged G6PD expressed in Escherichia coli JM109 (DE3) cells assessed as production of NADPH after 30 mins by Amplite fluorimetric assay	ic50	9.3000	uM
N-[(3S,5S,8R,9S,10S,13S,14S)-10,13-dimethyl-17-oxo-1,2,3,4,5,6,7,8,9,11,12,14,15,16-tetradecahydrocyclopenta[a]phenanthren-3-yl]benzenesulfonamide	672987: Inhibition of human recombinant N-terminal His tagged G6PD expressed in Escherichia coli JM109 (DE3) cells assessed as production of NADPH after 30 mins by Amplite fluorimetric assay	ic50	9.9000	uM

CTD chemical–gene interactions

189 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, decreases activity, decreases reaction, affects methylation, decreases expression (+2 more)	13
Calcitriol	increases activity, increases expression, affects cotreatment	5
Tobacco Smoke Pollution	affects expression, decreases expression, increases expression	5
bisphenol A	increases expression, decreases expression	4
bisphenol S	affects expression, increases expression	3
Arsenic Trioxide	decreases expression, decreases response to substance, affects binding, decreases reaction	3
Benzo(a)pyrene	affects expression, increases expression, affects methylation, affects cotreatment	3
Estradiol	affects cotreatment, decreases expression, increases expression	3
Valproic Acid	affects expression, increases expression, increases methylation	3
protocatechualdehyde	decreases activity, decreases reaction	2
lead acetate	increases expression	2
titanium dioxide	decreases methylation, affects binding, increases expression	2
diethyl maleate	increases expression	2
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	decreases expression	2
(+)-JQ1 compound	increases expression	2
Acetaminophen	increases expression	2
Arsenic	increases abundance, increases expression, affects cotreatment	2
Cisplatin	affects cotreatment, increases expression	2
Doxorubicin	affects expression, increases expression	2
Isoniazid	increases expression, affects expression, decreases activity	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Potassium Dichromate	decreases activity, decreases reaction	2
Primaquine	affects response to substance, decreases response to substance	2
Rotenone	increases expression, decreases expression	2
Tretinoin	increases expression	2
Isotretinoin	decreases expression, increases expression	2
Cyclosporine	decreases expression, increases expression	2
Asbestos, Serpentine	decreases activity	2
Asbestos, Crocidolite	affects binding, decreases activity	2
Asbestos, Amosite	decreases activity, decreases reaction	2

ChEMBL screening assays

49 unique, capped per target: 46 binding, 2 admet, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1011499	Binding	Inhibition of human G6PDH using glucose-6-phosphate as substrate by Lineweaver-Burke plot	Inhibition of Trypanosoma brucei glucose-6-phosphate dehydrogenase by human steroids and their effects on the viability of cultured parasites. — Bioorg Med Chem
CHEMBL1737961	Functional	PUBCHEM_BIOASSAY: Human Glucose-6-Phosphate Dehydrogenase Dose Response Selectivity Assay for Inhibitors of Plasmodium falciparum Glucose-6-Phosphate Dehydrogenase. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):	PubChem BioAssay data set
CHEMBL4630207	ADMET	Inhibition of recombinant human G6PDH expressed in Escherichia coli by fluorescence assay	Development of Selective Steroid Inhibitors for the Glucose-6-phosphate Dehydrogenase from Trypanosoma cruzi. — ACS Med Chem Lett

Cellosaurus cell lines

29 cell lines: 22 finite cell line, 3 cancer cell line, 2 transformed cell line, 1 embryonic stem cell, 1 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_4J08	GM00120	Finite cell line	Female
CVCL_4J09	GM00324	Finite cell line	Male
CVCL_4J10	GM00325	Finite cell line	Male
CVCL_4J11	GM00412	Finite cell line	Male
CVCL_4J21	GM01151	Finite cell line	Male
CVCL_4J22	GM01152	Finite cell line	Male
CVCL_4J24	GM01154	Finite cell line	Female
CVCL_4J26	GM01163	Finite cell line	Male
CVCL_4J27	GM01165	Finite cell line	Female
CVCL_4J29	GM01188	Finite cell line	Male

Clinical trials (associated diseases)

93 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
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)
NCT07468513	PHASE4	RECRUITING	Primaquine for Vivax Malaria in G6PD Intermediate and Deficient Cases.
NCT06231459	PHASE4	COMPLETED	Expression of Pro- and Anti-inflammatory Cytokines During Anti-PCSK9 in Familial Hypercholesterolemia
NCT00140413	PHASE4	COMPLETED	Endocrine Dysfunction and Growth Hormone Deficiency in Children With Optic Nerve Hypoplasia
NCT05777993	PHASE4	ENROLLING_BY_INVITATION	A Study to Provide Continued Access to Mitapivat for Participants Who Previously Completed an Agios-Sponsored Mitapivat Study
NCT00000594	PHASE3	COMPLETED	NHLBI Type II Coronary Intervention Study
NCT00092833	PHASE3	TERMINATED	Investigational Drug in Patients With Hypercholesterolemia or in Patients With Sitosterolemia (0653-026)(COMPLETED)
NCT00134485	PHASE3	COMPLETED	Study To Evaluate The Safety And Efficacy Of Torcetrapib/Atorvastatin In Subjects With Familial Hypercholerolemia
NCT00134511	PHASE3	COMPLETED	Study To Evaluate The Effect Of Torcetrapib/Atorvastatin In Patients With Genetic High Cholesterol Disorder
NCT00136981	PHASE3	COMPLETED	Carotid B-Mode Ultrasound Study to Compare Anti-Atherosclerotic Effect of Torcetrpib/Atorvastatin to Atorvastatin Alone.
NCT00384293	PHASE3	TERMINATED	Carotid IMT (Intima Media Thickening) Study (0524A-041)(TERMINATED)
NCT01524289	PHASE3	COMPLETED	Study to Assess the Tolerability and Efficacy of Anacetrapib (MK-0859) Co-Administered With Statin in Participants With Heterozygous Familial Hypercholesterolemia (MK-0859-020)
NCT06760546	PHASE3	RECRUITING	A Trial of Setmelanotide in Patients With Congenital Hypothalamic Obesity (Sub-study of NCT05774756)
NCT00001729	PHASE3	COMPLETED	Combination Drug Therapy for Patients With Hepatitis C
NCT03548220	PHASE3	COMPLETED	A Study to Evaluate Efficacy and Safety of AG-348 in Not Regularly Transfused Adult Participants With Pyruvate Kinase Deficiency (PKD)
NCT03559699	PHASE3	COMPLETED	A Study Evaluating the Efficacy and Safety of AG-348 in Regularly Transfused Adult Participants With Pyruvate Kinase Deficiency (PKD)
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
NCT00280995	PHASE2	COMPLETED	Dose-escalating Safety Study of ISIS 301012 in Homozygous Familial Hypercholesterolemia Subjects on Lipid Lowering Therapy
NCT00281008	PHASE2	COMPLETED	Study of ISIS 301012 (Mipomersen) in Heterozygous Familial Hypercholesterolemia Subjects on Lipid Lowering Therapy
NCT01375751	PHASE2	COMPLETED	Reduction of Low-Density Lipoprotein Cholesterol (LDL-C) With PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder Study
NCT00110617	PHASE2	COMPLETED	Study of Deferasirox Relative to Subcutaneous Deferoxamine in Sickle Cell Disease Patients
NCT01579110	PHASE2	UNKNOWN	Efficacy and Safety of Levamisole Combined With Standard Prednisolone in Warm Antibody Autoimmune Hemolytic Anemia.
NCT01642979	PHASE2	UNKNOWN	Safety and Efficacy of Levamisole Combined With Cyclosporine A in Patients With Classic Paroxysmal Nocturnal Hemoglobinuria
NCT01760096	PHASE2	UNKNOWN	Safety and Efficacy of Levamisole Combined With Cyclosporine A in Patients With Subclinical Paroxysmal Nocturnal Hemoglobinuria and PNH in the Setting of Another Bone Marrow Failure Syndromes(PNH-2013)
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
NCT07612345	PHASE1	NOT_YET_RECRUITING	High-Dose Vitamin C in G6PDA and Pyruvate Kinase Deficiency: A Safety Study
NCT00515307	PHASE1	COMPLETED	Bone Marrow Stem Cells as a Source of Allogenic Hepatocyte Transplantation in Homozygous Familial Hypercholesterolemia
NCT01583647	PHASE1	TERMINATED	A Study of Extended-release (ER) Niacin/Laropiprant in Adolescents With Heterozygous Familial Hypercholesterolemia (MK-0524A-158)
NCT05004259	PHASE1	COMPLETED	The Safety of Repurposing Daratumumab for Relapsed or Refractory Autoimmune Antibody Mediated Hemolytic Anemia
NCT06684041	PHASE1	COMPLETED	A Safety, Tolerability, Pharmacokinetic/Pharmacodynamic Study, and QT Interval Study of HRS-5965 Capsules in Healthy Subjects
NCT07040787	PHASE1	COMPLETED	Investigation of Drug-drug Interaction of HRS-5965 With Clopidogrel and Clarithromycin in Healthy Subjects
NCT02498340	PHASE2/PHASE3	UNKNOWN	Diet Challenge in G6PD Deficient Egyptian Children: A One- Year Prospective Single Center Study With Genotype - Phenotype Correlation
NCT02937376	EARLY_PHASE1	UNKNOWN	Effects of N-acetyl Cystein (NAC) Supplementation in G6PD Deficient Individuals After Acute Exercise
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