PGD

Summary

PGD (phosphogluconate dehydrogenase, HGNC:8891) is a protein-coding gene on chromosome 1p36.22, encoding 6-phosphogluconate dehydrogenase, decarboxylating (P52209). Catalyzes the oxidative decarboxylation of 6-phosphogluconate to ribulose 5-phosphate and CO(2), with concomitant reduction of NADP to NADPH. It is a selective cancer dependency (DepMap: 79.8% of cell lines).

6-phosphogluconate dehydrogenase is the second dehydrogenase in the pentose phosphate shunt. Deficiency of this enzyme is generally asymptomatic, and the inheritance of this disorder is autosomal dominant. Hemolysis results from combined deficiency of 6-phosphogluconate dehydrogenase and 6-phosphogluconolactonase suggesting a synergism of the two enzymopathies. Several transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 5226 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 75 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 79.8% of screened cell lines
• MANE Select transcript: NM_002631

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8891
Approved symbol	PGD
Name	phosphogluconate dehydrogenase
Location	1p36.22
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000142657
Ensembl biotype	protein_coding
OMIM	172200
Entrez	5226

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 15 protein_coding, 3 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000270776, ENST00000460189, ENST00000465632, ENST00000477958, ENST00000483936, ENST00000487775, ENST00000491493, ENST00000493288, ENST00000496718, ENST00000498356, ENST00000863228, ENST00000863229, ENST00000863230, ENST00000922425, ENST00000922426, ENST00000922427, ENST00000922428, ENST00000957131, ENST00000957132, ENST00000957133

RefSeq mRNA: 3 — MANE Select: NM_002631 NM_001304451, NM_001304452, NM_002631

CCDS: CCDS113

Canonical transcript exons

ENST00000270776 — 13 exons

Exon	Start	End
ENSE00001229441	10419630	10420511
ENSE00001916920	10399064	10399125
ENSE00002889830	10400393	10400572
ENSE00002968744	10404161	10404279
ENSE00003506702	10403071	10403136
ENSE00003544484	10419417	10419539
ENSE00003560207	10399629	10399704
ENSE00003623710	10416987	10417117
ENSE00003691826	10418826	10418925
ENSE00003786496	10408071	10408140
ENSE00003787396	10411418	10411552
ENSE00003788764	10413062	10413251
ENSE00003790627	10417376	10417509

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 99.37.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 149.9360 / max 1355.6913, expressed in 1825 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
570	149.5064	1825
571	0.4296	210

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	99.37	gold quality
monocyte	CL:0000576	99.17	gold quality
esophagus mucosa	UBERON:0002469	99.16	gold quality
stromal cell of endometrium	CL:0002255	99.10	gold quality
mononuclear cell	CL:0000842	99.00	gold quality
cortical plate	UBERON:0005343	98.97	gold quality
leukocyte	CL:0000738	98.96	gold quality
esophagus squamous epithelium	UBERON:0006920	98.89	gold quality
bone marrow	UBERON:0002371	98.35	gold quality
granulocyte	CL:0000094	98.27	gold quality
ganglionic eminence	UBERON:0004023	98.26	gold quality
epithelium of esophagus	UBERON:0001976	98.19	gold quality
islet of Langerhans	UBERON:0000006	97.93	gold quality
gall bladder	UBERON:0002110	97.92	gold quality
bone marrow cell	CL:0002092	97.75	gold quality
blood	UBERON:0000178	97.72	gold quality
embryo	UBERON:0000922	97.68	gold quality
oral cavity	UBERON:0000167	97.67	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.54	gold quality
ventricular zone	UBERON:0003053	97.42	gold quality
pharyngeal mucosa	UBERON:0000355	97.41	gold quality
right lung	UBERON:0002167	96.80	gold quality
endometrium epithelium	UBERON:0004811	96.71	gold quality
minor salivary gland	UBERON:0001830	96.67	gold quality
upper lobe of left lung	UBERON:0008952	96.62	gold quality
mouth mucosa	UBERON:0003729	96.51	gold quality
right testis	UBERON:0004534	96.50	gold quality
upper lobe of lung	UBERON:0008948	96.32	gold quality
left testis	UBERON:0004533	96.21	gold quality
jejunal mucosa	UBERON:0000399	96.07	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-HCAD-1	yes	215.80
E-CURD-122	yes	64.26
E-MTAB-6678	yes	23.59
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NFE2L2, SREBF1

miRNA regulators (miRDB)

39 targeting PGD, 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-3613-3P	100.00	76.36	7965
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-516B-5P	99.56	66.33	1495
HSA-MIR-5571-5P	99.49	66.99	1764
HSA-MIR-12131	99.48	68.72	1673
HSA-MIR-548G-3P	99.48	68.67	2159
HSA-MIR-578	99.46	68.36	1787
HSA-MIR-5009-3P	99.45	69.43	1341
HSA-MIR-208A-5P	99.42	70.83	1913
HSA-MIR-208B-5P	99.42	70.83	1952
HSA-MIR-4727-5P	99.23	67.55	1154
HSA-MIR-6738-3P	99.03	67.14	1326
HSA-MIR-622	98.99	66.48	1050
HSA-MIR-4724-5P	98.87	67.75	1324
HSA-MIR-5006-5P	98.79	66.92	1246
HSA-MIR-7114-5P	98.51	67.87	1349
HSA-MIR-581	98.39	67.42	835
HSA-MIR-6804-5P	98.39	65.77	1084
HSA-MIR-4436B-3P	98.25	65.26	1494
HSA-MIR-6735-5P	98.24	65.36	1488

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 79.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 14)

• Hsa-miR-132 and -212 were negatively correlated with PGD in the prefrontal cortex of individuals affected with schizophrenia and bipolar disorders. (PMID:20675101)
• Data suggest that the affinity of Nox2 for NADPH is increased in the presence of 6PGDH on cell stimulation. (PMID:21444627)
• A protein encoded by this locus was found to be differentially expressed in postmortem brains from patients with atypical frontotemporal lobar degeneration. (PMID:22360420)
• Glycolytic cancer cells lacking 6-phosphogluconate dehydrogenase metabolize glucose to induce senescence (PMID:22677172)
• Expression of 6PGD positively correlates with advancing stage of lung carcinoma. Knockdown of 6PGD by shRNA potently inhibits c-Met tyrosine phosphorylation. (PMID:23973484)
• copy number gain of the PGD gene was consistently identified in cervical cancers but not in the normal tissues (PMID:24125036)
• Results show that 6PGD activity is upregulated with increased lysine acetylation in primary leukemia cells from human patients, providing mechanistic insights into 6PGD upregulation in cancer cells. (PMID:25042803)
• Studies indicate link between the 6-phosphogluconate dehydrogenase, oxidative pentose phosphate pathway (PPP) and lipogenesis through Ru-5-P-dependent inhibition of serine/threonine protein kinase LKB1-AMPK signalling. (PMID:26479318)
• identified that 6-phosphogluconate dehydrogenase (6PGD) is critically involved in the development of anaplastic thyroid cancer (ATC) resistance to doxorubicin. 6PGD inhibition disrupts metabolic reprogramming in doxorubicin-resistant ATC cells. (PMID:29534964)
• 6-phosphogluconate dehydrogenase (6PGD) is aberrantly upregulated and activated in cervical cancer cells and patient tissues compared to normal counterparts. 6PGD inhibition decreases growth and migration, and enhances chemosensitivity in cervical cancer. Inhibition of 6PGD activates AMP-activated protein kinase and decreases rhoA GTP-binding protein and rac1 GTP-binding protein activities. (PMID:30182212)
• HIF-1alpha regulates cellular metabolism, and Imatinib resistance by targeting phosphogluconate dehydrogenase in gastrointestinal stromal tumors. (PMID:32719331)
• 6PGD Upregulation is Associated with Chemo- and Immuno-Resistance of Renal Cell Carcinoma via AMPK Signaling-Dependent NADPH-Mediated Metabolic Reprograming. (PMID:32829780)
• Critical Role of 6-Phosphogluconate Dehydrogenase in TAp73-Mediated Cancer Cell Proliferation. (PMID:37071129)
• 6-Phosphogluconate dehydrogenase promotes glycolysis and fatty acid synthesis by inhibiting the AMPK pathway in lung adenocarcinoma cells. (PMID:39179096)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pgd	ENSDARG00000015343
mus_musculus	Pgd	ENSMUSG00000028961
rattus_norvegicus	Pgd	ENSRNOG00000076812
drosophila_melanogaster	Pgd	FBGN0004654
caenorhabditis_elegans		WBGENE00012015

Protein

Protein identifiers

6-phosphogluconate dehydrogenase, decarboxylating — P52209 (reviewed: P52209)

All UniProt accessions (6): P52209, K7EJT3, K7ELN9, K7EM49, K7EMN2, K7EPF6

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the oxidative decarboxylation of 6-phosphogluconate to ribulose 5-phosphate and CO(2), with concomitant reduction of NADP to NADPH.

Subunit / interactions. Homodimer.

Subcellular location. Cytoplasm.

Pathway. Carbohydrate degradation; pentose phosphate pathway; D-ribulose 5-phosphate from D-glucose 6-phosphate (oxidative stage): step 3/3.

Similarity. Belongs to the 6-phosphogluconate dehydrogenase family.

Isoforms (2)

UniProt ID	Names	Canonical?
P52209-1	1	yes
P52209-2	2

RefSeq proteins (3): NP_001291380, NP_001291381, NP_002622* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006113	6PGDH_Gnd/GntZ	Family
IPR006114	6PGDH_C	Domain
IPR006115	6PGDH_NADP-bd	Domain
IPR006183	Pgluconate_DH	Family
IPR006184	6PGdom_BS	Binding_site
IPR008927	6-PGluconate_DH-like_C_sf	Homologous_superfamily
IPR013328	6PGD_dom2	Homologous_superfamily
IPR036291	NAD(P)-bd_dom_sf	Homologous_superfamily

Pfam: PF00393, PF03446

Enzyme classification (BRENDA):

• EC 1.1.1.44 — phosphogluconate dehydrogenase (NADP+-dependent, decarboxylating) (BRENDA: 80 organisms, 86 substrates, 273 inhibitors, 232 Km, 56 kcat entries)

Substrate kinetics (BRENDA)

13 substrates with measured Km, best-characterized 13. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
NADP+	0.0009–100	95
6-PHOSPHOGLUCONATE	0.006–3.13	63
6-PHOSPHO-D-GLUCONATE	0.0001–33.7	27
NAD+	0.0119–114	22
6-PHOSPHONO-D-GLUCONATE	0.0035–0.03	6
2-DEOXY-3-OXO-6-PHOSPHOGLUCONATE	0.0096–1.42	3
2-DEOXY-6-PHOSPHOGLUCONATE	0.55–1.42	3
6,7-DIDEOXY-7-PHOSPHONO-D-GLUCOHEPTONATE	0.0048–0.011	2
CO2	34–50	2
MGCL2	1.7–2.4	2
NADPH	0.0002–0.002	2
RIBULOSE-5-PHOSPHATE	0.02–1	2
MG2+	3.33	1

Catalyzed reactions (Rhea), 1 shown:

• 6-phospho-D-gluconate + NADP(+) = D-ribulose 5-phosphate + CO2 + NADPH (RHEA:10116)

UniProt features (63 total): helix 23, binding site 13, strand 12, modified residue 5, turn 3, active site 2, sequence conflict 2, chain 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
4GWG	X-RAY DIFFRACTION	1.39
4GWK	X-RAY DIFFRACTION	1.53
2JKV	X-RAY DIFFRACTION	2.53
5UQ9	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P52209-F1	96.98	0.96

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 (2): 184 (proton acceptor); 191 (proton donor)

Ligand- & substrate-binding residues (13): 192 (in other chain); 261 (in other chain); 288 (in other chain); 447; 453; 478–481; 10–15 (in other chain); 33–35 (in other chain); 75–77 (in other chain); 103 (in other chain); 103 (in other chain); 129–131 (in other chain) …

Post-translational modifications (5): 38, 57, 59, 129, 309

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-71336	Pentose phosphate pathway
R-HSA-9818028	NFE2L2 regulates pentose phosphate pathway genes
R-HSA-1430728	Metabolism
R-HSA-2262752	Cellular responses to stress
R-HSA-71387	Metabolism of carbohydrates and carbohydrate derivatives
R-HSA-8953897	Cellular responses to stimuli
R-HSA-9711123	Cellular response to chemical stress
R-HSA-9755511	KEAP1-NFE2L2 pathway
R-HSA-9759194	Nuclear events mediated by NFE2L2

MSigDB gene sets: 244 (showing top): GOBP_NADPPLUS_METABOLIC_PROCESS, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, GOBP_GLUCOSE_6_PHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, MARTINEZ_RB1_TARGETS_UP, MARTINEZ_RB1_TARGETS_DN, GOBP_MONOSACCHARIDE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, KEGG_PENTOSE_PHOSPHATE_PATHWAY

GO Biological Process (6): pentose-phosphate shunt (GO:0006098), pentose-phosphate shunt, oxidative branch (GO:0009051), pentose biosynthetic process (GO:0019322), D-gluconate metabolic process (GO:0019521), NADP+ metabolic process (GO:0006739), NADPH regeneration (GO:0006740)

GO Molecular Function (5): phosphogluconate dehydrogenase (decarboxylating) activity (GO:0004616), carbohydrate binding (GO:0030246), carboxylic acid binding (GO:0031406), NADP binding (GO:0050661), oxidoreductase activity (GO:0016491)

GO Cellular Component (4): nucleus (GO:0005634), cytosol (GO:0005829), extracellular exosome (GO:0070062), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Metabolism of carbohydrates and carbohydrate derivatives	1
Nuclear events mediated by NFE2L2	1
Cellular responses to stimuli	1
Metabolism	1
Cellular responses to stress	1
Cellular response to chemical stress	1
KEAP1-NFE2L2 pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
NADPH regeneration	2
cellular anatomical structure	2
pentose-phosphate shunt, oxidative branch	1
pentose-phosphate shunt, non-oxidative branch	1
glucose 6-phosphate metabolic process	1
glucose-6-phosphate dehydrogenase activity	1
phosphogluconate dehydrogenase (decarboxylating) activity	1
pentose-phosphate shunt	1
6-phosphogluconolactonase activity	1
carbohydrate derivative metabolic process	1
pentose metabolic process	1
monosaccharide biosynthetic process	1
carbohydrate metabolic process	1
monocarboxylic acid metabolic process	1
purine nucleotide metabolic process	1
nicotinamide nucleotide metabolic process	1
generation of precursor metabolites and energy	1
NADP+ metabolic process	1
oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor	1
binding	1
anion binding	1
organic acid binding	1
adenyl nucleotide binding	1
catalytic activity	1
intracellular membrane-bounded organelle	1
cytoplasm	1
extracellular vesicle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2738 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PGD	G6PD	P11413	957
PGD	H6PD	O95479	956
PGD	PGM1	P36871	943
PGD	TKT	P29401	847
PGD	TALDO1	P37837	847
PGD	GPI	P06744	846
PGD	PGM2	Q96G03	842
PGD	TKTL1	P51854	833
PGD	TKTL2	Q9H0I9	833
PGD	ME1	P48163	819
PGD	ENO1	P06733	812
PGD	IDNK	Q5T6J7	810
PGD	PGC	P20142	796
PGD	PGLS	O95336	795
PGD	IDH1	O75874	793
PGD	RPIA	P49247	793

IntAct

79 interactions, top by confidence:

A	B	Type	Score
RBM8A	CASC3	psi-mi:“MI:0914”(association)	0.900
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
	PGD	psi-mi:“MI:0945”(oxidoreductase activity electron transfer reaction)	0.440
LTK	PIK3R2	psi-mi:“MI:0914”(association)	0.420
	GNAT3	psi-mi:“MI:0915”(physical association)	0.400
	TK2	psi-mi:“MI:0915”(physical association)	0.400
TERF1	PGD	psi-mi:“MI:0915”(physical association)	0.370
CDK4	PGD	psi-mi:“MI:0915”(physical association)	0.370
Magoh	TRAPPC13	psi-mi:“MI:0914”(association)	0.350
CEP290	SUPT5H	psi-mi:“MI:0914”(association)	0.350
OFD1	SUPT5H	psi-mi:“MI:0914”(association)	0.350
KSR1	FBLL1	psi-mi:“MI:0914”(association)	0.350
BCAR1	PSMD11	psi-mi:“MI:0914”(association)	0.350
BCAR1	MYO1C	psi-mi:“MI:0914”(association)	0.350
STAT1	KPNA6	psi-mi:“MI:0914”(association)	0.350
PLEKHA7	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
NEK4	QSOX1	psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350
	AP3B1	psi-mi:“MI:0914”(association)	0.350
USPL1	ANXA1	psi-mi:“MI:0914”(association)	0.350
RASA1	MYO1C	psi-mi:“MI:0914”(association)	0.350
L3MBTL4	GAPDHS	psi-mi:“MI:0914”(association)	0.350
ZDHHC5	IGKV2D-24	psi-mi:“MI:0914”(association)	0.350
PA	ESYT2	psi-mi:“MI:0914”(association)	0.350
BMI1	HMGB1P1	psi-mi:“MI:0914”(association)	0.350
MAP3K7	ACOT7	psi-mi:“MI:0914”(association)	0.350

BioGRID (224): PGD (Affinity Capture-RNA), PGD (Affinity Capture-RNA), PGD (Two-hybrid), FABP5 (Co-fractionation), GDI1 (Co-fractionation), P4HB (Co-fractionation), PGD (Co-fractionation), PGD (Co-fractionation), PGD (Co-fractionation), PGD (Co-fractionation), PGD (Co-fractionation), PGD (Co-fractionation), PGD (Co-fractionation), PGD (Co-fractionation), PGD (Co-fractionation)

ESM2 similar proteins: C8VP36, O13287, O60037, O84066, P00349, P12013, P14332, P31072, P37754, P38720, P41570, P41572, P41573, P41574, P41575, P41576, P41577, P41578, P41579, P41580, P41581, P41582, P41583, P43774, P52207, P52208, P52209, P53319, P63334, P63335, P70718, P78812, P85968, P96789, Q17761, Q2R480, Q5HFR2, Q6G954, Q6GGI7, Q7VMX4

Diamond homologs: C8VP36, O13287, O60037, O83351, O84066, P00349, P00350, P12013, P14062, P21577, P37754, P37756, P38720, P41570, P41573, P41574, P41575, P41576, P41577, P41578, P41579, P41580, P41581, P41582, P41583, P43774, P52207, P52208, P52209, P53319, P54448, P57208, P63334, P63335, P70718, P78812, P80859, P85968, P96789, Q17761

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
FYN	“up-regulates activity”	PGD	phosphorylation
PGD	“up-regulates quantity”	NADPH(4-)	“chemical modification”
PGD	“down-regulates quantity”	6-phospho-D-gluconate	“chemical modification”
PGD	“up-regulates quantity”	“D-ribulose 5-phosphate”	“chemical modification”
NFE2L2	“up-regulates quantity by expression”	PGD	“transcriptional regulation”
NADPH(4-)	“down-regulates activity”	PGD	binding
PGD	“down-regulates quantity”	NADP(3-)	“chemical modification”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 103 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Downstream signal transduction	5	24.7×	8e-04
Signaling by Receptor Tyrosine Kinases	10	6.7×	8e-04
Cellular responses to stimuli	11	4.5×	3e-03
Infectious disease	12	3.9×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	52
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1941 predictions. Top by Δscore:

Variant	Effect	Δscore
1:10399121:GCCCA:G	donor_gain	1.0000
1:10399126:G:GG	donor_gain	1.0000
1:10399618:T:A	acceptor_gain	1.0000
1:10399624:TCTAG:T	acceptor_gain	1.0000
1:10399626:TA:T	acceptor_loss	1.0000
1:10399626:TAG:T	acceptor_gain	1.0000
1:10399627:A:AG	acceptor_gain	1.0000
1:10399627:AGA:A	acceptor_gain	1.0000
1:10399628:G:GA	acceptor_gain	1.0000
1:10399628:G:GT	acceptor_loss	1.0000
1:10399628:GA:G	acceptor_gain	1.0000
1:10399628:GAG:G	acceptor_gain	1.0000
1:10399628:GAGC:G	acceptor_gain	1.0000
1:10399628:GAGCT:G	acceptor_gain	1.0000
1:10399701:TGTGG:T	donor_loss	1.0000
1:10399702:GTG:G	donor_gain	1.0000
1:10399702:GTGGT:G	donor_loss	1.0000
1:10399703:TG:T	donor_gain	1.0000
1:10399704:GG:G	donor_gain	1.0000
1:10399705:G:GG	donor_gain	1.0000
1:10399705:GTAAG:G	donor_loss	1.0000
1:10399706:T:G	donor_loss	1.0000
1:10400392:GGTCT:G	acceptor_gain	1.0000
1:10400570:TTG:T	donor_gain	1.0000
1:10400570:TTGG:T	donor_loss	1.0000
1:10400571:TGG:T	donor_loss	1.0000
1:10400572:GGTG:G	donor_loss	1.0000
1:10400573:G:GG	donor_gain	1.0000
1:10400573:GTGA:G	donor_loss	1.0000
1:10403068:CA:C	acceptor_loss	1.0000

AlphaMissense

3176 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:10403115:T:A	N103K	1.000
1:10403115:T:G	N103K	1.000
1:10404215:A:C	S129R	1.000
1:10404217:T:A	S129R	1.000
1:10404217:T:G	S129R	1.000
1:10404219:G:A	G130D	1.000
1:10411450:G:C	K184N	1.000
1:10411450:G:T	K184N	1.000
1:10411457:C:G	H187D	1.000
1:10411462:C:A	N188K	1.000
1:10411462:C:G	N188K	1.000
1:10411463:G:T	G189W	1.000
1:10411470:A:T	E191V	1.000
1:10411471:G:C	E191D	1.000
1:10411471:G:T	E191D	1.000
1:10411472:T:C	Y192H	1.000
1:10417484:T:A	W362R	1.000
1:10417484:T:C	W362R	1.000
1:10399649:G:A	G10E	0.999
1:10399662:G:A	M14I	0.999
1:10399662:G:C	M14I	0.999
1:10399662:G:T	M14I	0.999
1:10399663:G:C	G15R	0.999
1:10403113:A:C	N103H	0.999
1:10404210:G:A	G127E	0.999
1:10404216:G:A	S129N	0.999
1:10404216:G:T	S129I	0.999
1:10404218:G:C	G130R	0.999
1:10404218:G:T	G130C	0.999
1:10404219:G:T	G130V	0.999

dbSNP variants (sampled 300 via entrez): RS1000240584 (1:10416525 A>C,T), RS1000284724 (1:10410715 A>G), RS1000292932 (1:10416699 C>T), RS1000521546 (1:10410376 G>T), RS1000530304 (1:10411844 C>G), RS1000843653 (1:10405679 T>C), RS1000943001 (1:10400958 G>A), RS1001086397 (1:10400165 A>C,G), RS1001126704 (1:10411891 A>T), RS1001131443 (1:10406278 A>G), RS1001191384 (1:10409685 T>C), RS1001380399 (1:10400321 A>G), RS1001474530 (1:10411662 A>G), RS1001877069 (1:10416390 T>C,G), RS1001878925 (1:10400004 C>T)

Disease associations

OMIM: gene MIM:172200 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST000752_1	Hepatocellular carcinoma	2.000000e-18
GCST009391_1166	Metabolite levels	6.000000e-06
GCST90002384_524	Hemoglobin	3.000000e-11

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0010460	anthranilic acid measurement
EFO:0004509	hemoglobin measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3404 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 22,804 (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
CHEMBL297453	EPIGALOCATECHIN GALLATE	3	22,804

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

Binding affinities (BindingDB)

10 measured of 10 human assays (10 total across all organisms); most potent 10 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
Sulfonamide derivative, 5	IC50	2530 nM
(Z)-2-butenedioate;10-(1-methyl-4-piperidinylidene)-5H-benzo[1,2]cyclohepta[3,4-b]thiophen-4-one	KI	8300 nM
4-Hydroxy-1,1-dioxo-1,2-dihydro-1lambda6-benzo[e][1,2]thiazine-3-carboxylic acid (5-methyl-thiazol-2-yl)-amide	KI	10100 nM
Sulfonamide derivative, 3	IC50	60100 nM
4-chloro-2-[(furan-2-ylmethyl)amino]-5-sulfamoylbenzoic acid	IC50	125000 nM
2-[(4-{(2,4-diaminopteridin-6-yl)methylamino}phenyl)formamido]pentanedioic acid	KI	137000 nM
Dorzolamide	IC50	1.41e+06 nM
4-amino-5-chloro-N-[2-(diethylamino)ethyl]-2-methoxy-benzamide;hydrochloride	KI	2.11e+06 nM
MLS002153782	IC50	3.66e+06 nM
Gadopentetic acid	KI	7.34e+07 nM

ChEMBL bioactivities

16 potent at pChembl≥5 of 22 total, top 16 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.00	Ki	10	nM	CHEMBL116018
7.46	Ki	35	nM	CHEMBL324609
7.10	Ki	80	nM	CHEMBL114269
6.89	Ki	130	nM	CHEMBL1160945
6.88	Kd	130.8	nM	CHEMBL5653589
6.88	ED50	130.8	nM	CHEMBL5653589
6.68	IC50	210	nM	EPICATECHIN GALLATE
6.44	Ki	360	nM	CHEMBL114269
6.14	IC50	720	nM	EPIGALOCATECHIN GALLATE
5.96	Ki	1100	nM	CHEMBL324609
5.89	IC50	1280	nM	(-)-CATECHINGALLATE
5.84	IC50	1450	nM	GALLOCATECHIN GALLATE
5.82	Ki	1520	nM	CHEMBL323922
5.59	Ki	2540	nM	CHEMBL116018
5.46	Ki	3500	nM	CHEMBL1160944
5.36	Ki	4400	nM	CHEMBL1160943

PubChem BioAssay actives

17 with measured affinity, of 2069 total; 14 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
[(2R,3R)-2,3-dihydroxy-4-(hydroxyamino)-4-oxobutyl] dihydrogen phosphate	7236: Inhibition constant against 6-phosphogluconate dehydrogenase of Trypanosoma brucei expressed in Escherichia coli	ki	0.0100	uM
[(4R,5R)-5-(hydroxycarbamoyl)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl dihydrogen phosphate	7236: Inhibition constant against 6-phosphogluconate dehydrogenase of Trypanosoma brucei expressed in Escherichia coli	ki	0.0350	uM
[(2R,3R)-3-acetyloxy-4-(hydroxyamino)-4-oxo-1-phosphonooxybutan-2-yl] acetate	7236: Inhibition constant against 6-phosphogluconate dehydrogenase of Trypanosoma brucei expressed in Escherichia coli	ki	0.0800	uM
(2R,3R)-2,3-dihydroxy-4-phosphonooxybutanoic acid	7236: Inhibition constant against 6-phosphogluconate dehydrogenase of Trypanosoma brucei expressed in Escherichia coli	ki	0.1300	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148987: Binding affinity to human PGD incubated for 45 mins by Kinobead based pull down assay	kd	0.1308	uM
[(2R,3R)-2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-3,4-dihydro-2H-chromen-3-yl] 3,4,5-trihydroxybenzoate	319370: Inhibition of 6PGD	ic50	0.2100	uM
[(2R,3R)-5,7-dihydroxy-2-(3,4,5-trihydroxyphenyl)-3,4-dihydro-2H-chromen-3-yl] 3,4,5-trihydroxybenzoate	319370: Inhibition of 6PGD	ic50	0.7200	uM
[(2S,3R)-2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-3,4-dihydro-2H-chromen-3-yl] 3,4,5-trihydroxybenzoate	319370: Inhibition of 6PGD	ic50	1.2800	uM
[(2S,3R)-5,7-dihydroxy-2-(3,4,5-trihydroxyphenyl)-3,4-dihydro-2H-chromen-3-yl] 3,4,5-trihydroxybenzoate	319370: Inhibition of 6PGD	ic50	1.4500	uM
[(2R,3R)-4-amino-2,3-dihydroxy-4-oxobutyl] dihydrogen phosphate	7236: Inhibition constant against 6-phosphogluconate dehydrogenase of Trypanosoma brucei expressed in Escherichia coli	ki	1.5200	uM
(5-carboxy-2,3,4,5-tetrahydroxy-3-methylpentoxy)-trihydroxyphosphanium	7236: Inhibition constant against 6-phosphogluconate dehydrogenase of Trypanosoma brucei expressed in Escherichia coli	ki	3.5000	uM
[7,12-diacetyloxy-10,13-dimethyl-17-[5-oxo-5-[(5-sulfamoyl-1,3,4-thiadiazol-2-yl)amino]pentan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl] acetate	1799716: Enzyme Assay from Article 10.1080/14756360701546413: “Investigation of the effects of some sulfonamide derivatives on the activities of glucose-6-phosphate dehydrogenase, 6-phospho gluconate dehydrogenase and glutathione reductase from human erythrocytes.”	ki	4.2000	uM
(5-carboxy-2,3,4-trihydroxy-3-methylpentoxy)-trihydroxyphosphanium	7236: Inhibition constant against 6-phosphogluconate dehydrogenase of Trypanosoma brucei expressed in Escherichia coli	ki	4.4000	uM
Ketotifen	1802944: In Vitro Assay from Article 10.3109/14756360903257900: “Effects of some drugs on human erythrocyte 6-phosphogluconate dehydrogenase: an in vitro study.”	ki	8.3000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression, affects expression, affects cotreatment, increases methylation	5
sodium arsenite	affects cotreatment, increases abundance, increases expression	5
Arsenic Trioxide	affects binding, decreases reaction, increases expression, decreases response to substance, affects cotreatment	5
Tobacco Smoke Pollution	affects expression, increases expression	4
Tretinoin	affects cotreatment, increases expression	4
sulforaphane	increases expression	2
nickel sulfate	increases expression	2
Arsenic	increases abundance, increases expression, affects cotreatment	2
Cadmium	increases expression, decreases reaction, increases abundance, increases palmitoylation	2
Dinitrochlorobenzene	affects binding, increases expression	2
Cadmium Chloride	increases expression, decreases reaction, increases abundance, increases palmitoylation	2
Lactic Acid	increases expression	2
aristolochic acid I	increases expression	1
bisphenol F	increases expression	1
3-(pyridin-3-ylsulfonyl)-5-(trifluoromethyl)-2H-chromen-2-one	increases expression, affects reaction	1
bismuth tripotassium dicitrate	increases expression	1
methylmercuric chloride	increases expression	1
ferulic acid	decreases activity	1
naringenin	decreases activity	1
triphenyl phosphate	affects expression	1
uranyl acetate	affects expression	1
lead acetate	increases expression	1
sodium arsenate	increases abundance, increases expression	1
pyrogallol 1,3-dimethyl ether	increases expression, decreases expression, affects cotreatment, affects localization	1
4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone	decreases expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
cobaltous chloride	decreases expression	1
cinnamyl alcohol	increases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1

ChEMBL screening assays

19 unique, capped per target: 19 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5107671	Binding	Inhibition of 6PGD in human A38-5 cells assessed as increase in intracellular H3K9me3 level at 0.1 to 1000 uM incubated for 45 mins by HTRF assay	Effects of 6-Aminonicotinic Acid Esters on the Reprogrammed Epigenetic State of Distant Metastatic Pancreatic Carcinoma. — ACS Med Chem Lett

Clinical trials (associated diseases)

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