GAPDH

Summary

GAPDH (glyceraldehyde-3-phosphate dehydrogenase, HGNC:4141) is a protein-coding gene on chromosome 12p13.31, encoding Glyceraldehyde-3-phosphate dehydrogenase (P04406). Catalyzes the conversion of D-glyceraldehyde 3-phosphate (G3P) into 3-phospho-D-glyceroyl phosphate in glycolysis and the reverse reaction in gluconeogenesis. It is a common-essential gene (DepMap: required in 99.2% of cancer cell lines).

This gene encodes a member of the glyceraldehyde-3-phosphate dehydrogenase protein family. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. The product of this gene catalyzes an important energy-yielding step in carbohydrate metabolism, the reversible oxidative phosphorylation of glyceraldehyde-3-phosphate in the presence of inorganic phosphate and nicotinamide adenine dinucleotide (NAD). The encoded protein has additionally been identified to have uracil DNA glycosylase activity in the nucleus. Also, this protein contains a peptide that has antimicrobial activity against E. coli, P. aeruginosa, and C. albicans. Studies of a similar protein in mouse have assigned a variety of additional functions including nitrosylation of nuclear proteins, the regulation of mRNA stability, and acting as a transferrin receptor on the cell surface of macrophage. Many pseudogenes similar to this locus are present in the human genome. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 2597 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 41 total — 1 pathogenic
• Druggable target: yes — 4 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 99.2% of screened cell lines (common-essential)
• MANE Select transcript: NM_002046

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4141
Approved symbol	GAPDH
Name	glyceraldehyde-3-phosphate dehydrogenase
Location	12p13.31
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000111640
Ensembl biotype	protein_coding
OMIM	138400
Entrez	2597

Gene structure

Transcript identifiers

Ensembl transcripts: 40 — 35 protein_coding, 5 retained_intron

ENST00000229239, ENST00000396856, ENST00000396858, ENST00000396859, ENST00000396861, ENST00000466525, ENST00000466588, ENST00000474249, ENST00000492719, ENST00000496049, ENST00000619601, ENST00000889642, ENST00000889643, ENST00000889644, ENST00000889645, ENST00000889646, ENST00000889647, ENST00000889648, ENST00000889649, ENST00000889650, ENST00000889651, ENST00000889652, ENST00000920776, ENST00000920777, ENST00000920778, ENST00000920779, ENST00000920780, ENST00000920781, ENST00000920782, ENST00000920783, ENST00000920784, ENST00000920785, ENST00000920786, ENST00000920787, ENST00000920788, ENST00000920789, ENST00000920790, ENST00000920791, ENST00000920792, ENST00000965009

RefSeq mRNA: 5 — MANE Select: NM_002046 NM_001256799, NM_001289745, NM_001289746, NM_001357943, NM_002046

CCDS: CCDS58201, CCDS8549

Canonical transcript exons

ENST00000229239 — 9 exons

Exon	Start	End
ENSE00001902446	6538101	6538371
ENSE00001932108	6534517	6534569
ENSE00003460425	6537584	6537996
ENSE00003562150	6537101	6537216
ENSE00003562276	6534810	6534861
ENSE00003571091	6536494	6536593
ENSE00003663529	6537309	6537390
ENSE00003678358	6536920	6537010
ENSE00003682485	6536684	6536790

Expression profiles

Bgee: expression breadth ubiquitous, 314 present calls, max score 99.99.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3529.9064 / max 23737.5153, expressed in 1828 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
123685	3511.1249	1828
123694	4.9556	1370
123701	4.9138	1436
123695	2.5003	1375
123697	2.0751	1178
123692	1.8780	969
123687	0.7209	319
123693	0.6456	399
206553	0.4000	206
123691	0.3167	140

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pons	UBERON:0000988	99.99	gold quality
frontal pole	UBERON:0002795	99.99	gold quality
paraflocculus	UBERON:0005351	99.99	gold quality
Brodmann (1909) area 10	UBERON:0013541	99.99	gold quality
deltoid	UBERON:0001476	99.98	gold quality
biceps brachii	UBERON:0001507	99.98	gold quality
triceps brachii	UBERON:0001509	99.98	gold quality
postcentral gyrus	UBERON:0002581	99.98	gold quality
middle frontal gyrus	UBERON:0002702	99.98	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.98	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.98	gold quality
Brodmann (1909) area 46	UBERON:0006483	99.98	gold quality
body of tongue	UBERON:0011876	99.98	gold quality
prefrontal cortex	UBERON:0000451	99.97	gold quality
tibialis anterior	UBERON:0001385	99.97	gold quality
parietal lobe	UBERON:0001872	99.97	gold quality
substantia nigra pars compacta	UBERON:0001965	99.97	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.97	gold quality
gluteal muscle	UBERON:0002000	99.97	gold quality
myocardium	UBERON:0002349	99.97	gold quality
lateral globus pallidus	UBERON:0002476	99.97	gold quality
cardiac muscle of right atrium	UBERON:0003379	99.97	gold quality
CA1 field of hippocampus	UBERON:0003881	99.97	gold quality
orbitofrontal cortex	UBERON:0004167	99.97	gold quality
diaphragm	UBERON:0001103	99.96	gold quality
skeletal muscle tissue	UBERON:0001134	99.96	gold quality
heart right ventricle	UBERON:0002080	99.96	gold quality
entorhinal cortex	UBERON:0002728	99.96	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.96	gold quality
cerebellar vermis	UBERON:0004720	99.96	gold quality

Single-cell (SCXA)

Detected in 69 experiment(s), a significant marker in 25.

Experiment	Marker?	Max mean expression
E-MTAB-7249	yes	40877.56
E-GEOD-84465	yes	19781.65
E-MTAB-6308	yes	13654.45
E-ENAD-20	yes	11530.42
E-MTAB-6701	yes	10668.49
E-MTAB-6819	yes	9679.09
E-HCAD-8	yes	9489.75
E-GEOD-137537	yes	9354.89
E-MTAB-9467	yes	7407.26
E-MTAB-7051	yes	7174.51
E-CURD-122	yes	6315.23
E-HCAD-25	yes	5941.65
E-HCAD-4	yes	5371.80
E-CURD-77	yes	5310.29
E-MTAB-10042	yes	5213.66

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, BACH1, CEBPA, CEBPD, EGR1, EPAS1, ESR1, HIF1A, MYC, NFKB, PARP1, PGR, SP1, TBX2, TBXT

miRNA regulators (miRDB)

8 targeting GAPDH, 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-7110-3P	100.00	73.18	2486
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-10395-5P	99.86	67.35	676
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-877-3P	99.09	68.10	1637
HSA-MIR-942-3P	98.81	69.04	876
HSA-MIR-5579-5P	96.32	68.54	730

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.2% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• We identified a nuclear high molecular weight (HMW) GAPDH species in Huntington’s disease cells, suggesting a connection between nuclear GAPDH function and huntingtin localization in this CAG expansion neuronal disease. (PMID:12008025)
• GAPDH is not an ideal internal standard for specific gene expression in testicular tissue specimens (PMID:12121569)
• GAPDH may be involved in the cellular phenotype of age-related neurodegenerative disorders–REVIEW (PMID:12428732)
• dissociation of the GAPDH protein from the HMW species restores its enzymatic activity. (PMID:12503091)
• HIF-2alpha regulates glyceraldehyde-3-phosphate dehydrogenase gene expression in vascular endothelial cells. (PMID:12697324)
• Transcription factors bound to glutamine-responsive element in GAPDH promoter are C/EBPalpha and -delta. (PMID:12842822)
• Glycoaldehyde inactivates GAPD. (PMID:12921788)
• Glyceraldehyde-3-phosphate dehydrogenase might be a novel target for vaccinia anti-apoptotic modulation. (PMID:14515148)
• nuclear GAPDH has a role in the maintenance and/or protection of telomeres (PMID:14630908)
• Thioredoxin regulates the expression of GAPDH. (PMID:14730345)
• GAPDH mRNA expression was correlated with evidence of tumor progression in thymoma. (PMID:15001839)
• data suggest that glyceraldehyde-3-phosphate dehydrogenase (GAPDH) imparts a unique function necessary for membrane trafficking from vesicular tubular clusters (VTCs) that does not require GAPDH glycolytic activity (PMID:15485821)
• significant association between late-onset Alzheimer’s disease and a compound genotype of the three GAPD genes (PMID:15507493)
• Subcellular interactions may mitigate oxidative stress-induced GAPDH modification in human aging. (PMID:15716040)
• results demonstrate that glyceraldehyde-3-phosphate dehydrogenase, a glycolytic and microtubule binding protein, co-localized to neurofibrillary tangles and immunoprecipitated with paired helical filament-tau (PMID:15746184)
• Marked variability of GAPDH expression between tissue types which establish comparative levels of expression and can be used to add value to gene expression data in which GAPDH is used as the internal control. (PMID:15769908)
• GAPDH modified by 4-hydroxy-2-nonenal and 4-hydroxy-2-hexenal is degraded by a giant serine protease, releasing the 23-kDa fragment, not by proteasome or TPP I (PMID:15907785)
• evidence that GAPDH is an epithelial binding receptor for Porphyromonas gingivalis fimbriae (PMID:15985219)
• Conditions associated with elevated intracellular methylglyoxal could modify GAPDH activity in vivo. (PMID:16037232)
• GAPDH is an integral part of the sarcolemmal K(ATP)-channel protein complex, where it couples glycolysis with the K(ATP)-channel activity. (PMID:16082386)
• Data show that the insertion of ferriprotoporphyrin IX (FP) into the red cell membranes exerts two opposite effects on membrane bound G3PD. (PMID:16139273)
• Amyloid-beta induces disulfide bonding and aggregation of GAPDH in Alzheimer’s disease (PMID:16186172)
• GAPDH might be involved in cell cycle regulation by modulating cyclin B-cdk1 activity. (PMID:16474839)
• GAPDH is inaccurate to normalize mRNA levels in studies investigating the effect of bisphosphonates on gene expression; this gene could be considered a potential target to observe the effects of bisphosphonates on cancer cells (PMID:16515701)
• OxLDL downregulated GAPDH via a H2O2-dependent decrease in protein stability. GAPDH protein damage resulted in marked depletion of cellular ATP levels. (PMID:16778134)
• The GAPD gene and its pseudogene may play a role in the development of late-onset Alzheimer disease. However, the effect, if any, is likely to be limited. (PMID:16832079)
• TPI and GAPDH may be candidate Ags for an autoimmune response to neurons and axons in multiple sclerosis. (PMID:17015754)
• identified glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as a new interacting partner of TPPP/p25 within the alpha-synuclein positive Lewy body (PMID:17027006)
• GAPDH interacts with transferrin and the GAPDH-transferrin complex is subsequently internalized into the early endosomes. (PMID:17121833)
• A decrease in the dehydrogenase activity of GAPDH was noted in Alzheimer disease. (PMID:17324518)
• alpha-crystallin B, glyceraldehyde phosphate dehydrogenase (GAPDH), and alpha-enolase identified as significantly S-glutathionylated in Alzheimer’s disease infeior parietal lobule (PMID:17387692)
• Nitric oxide-mediated S-nitrosylation of GAPDH and subsequent nuclear translocation of GAPDH might function as a mediator of TRAIL-induced cell death in thyroid cancer cells. (PMID:17540725)
• Glyceraldehyde-3-phosphate dehydrogenase enhances transcriptional activity of androgen receptor in prostate cancer cells (PMID:17553795)
• Study observed no hypoxia-induced regulation of GAPDH expression in the 3 glioblastoma cell lines; also, GAPDH expression was similar in patient tumor samples of low-grade astrocytoma and glioblastoma, suggesting a lack of hypoxic regulation in vivo. (PMID:17597534)
• These results suggest that the polyQ domain, but not the polyP domain, plays a role in the sequestration of GAPDH to aggregates by mutant htt (PMID:17989880)
• Overexpression of human GAPDH in Escherichia coli did not enhance mutagenesis by diepoxybutane. (PMID:18163542)
• Succination of GAPDH and other thiol proteins may provide the chemical link between glucotoxicity and the pathogenesis of diabetic complications. (PMID:18448829)
• Results show that nuclear GAPDH is acetylated at Lys 160 by the acetyltransferase p300/CREB binding protein (CBP) through direct protein interaction, which in turn stimulates the acetylation and catalytic activity of p300/CBP. (PMID:18552833)
• A redox-modulated direct p38/GAPDH-Oct-1 interaction nucleates the occupancy of the H2B promoter by the OCA-S complex, in which p36/LDH plays a critical role in the hierarchical organization of the complex. (PMID:18682386)
• GAPDH, a multifunctional protein, now adds regulation of mRNA stability to its repertoire. (PMID:18708368)

Cross-species orthologs

16 orthologs

Organism	Symbol	Gene ID
danio_rerio	gapdh	ENSDARG00000043457
mus_musculus	Gapdh	ENSMUSG00000057666
mus_musculus	Gapdhrt	ENSMUSG00000097148
mus_musculus	Gapdhrt2	ENSMUSG00000110469
rattus_norvegicus	Gapdh	ENSRNOG00000018630
rattus_norvegicus	Gapdh-ps17	ENSRNOG00000022174
rattus_norvegicus	Gapdhl10	ENSRNOG00000028958
rattus_norvegicus		ENSRNOG00000030963
rattus_norvegicus	AABR07025010.1	ENSRNOG00000033057
rattus_norvegicus		ENSRNOG00000066746
rattus_norvegicus	Gapdh-ps1	ENSRNOG00000071205
drosophila_melanogaster	CG9010	FBGN0034173
caenorhabditis_elegans		WBGENE00001683
caenorhabditis_elegans		WBGENE00001684
caenorhabditis_elegans		WBGENE00001685
caenorhabditis_elegans		WBGENE00001686

Paralogs (1): GAPDHS (ENSG00000105679)

Protein

Protein identifiers

Glyceraldehyde-3-phosphate dehydrogenase — P04406 (reviewed: P04406)

Alternative names: Peptidyl-cysteine S-nitrosylase GAPDH

All UniProt accessions (3): P04406, E7EUT5, V9HVZ4

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the conversion of D-glyceraldehyde 3-phosphate (G3P) into 3-phospho-D-glyceroyl phosphate in glycolysis and the reverse reaction in gluconeogenesis. Also shows nitrosylase activity, thereby playing a role in nuclear functions. Modulates the organization and assembly of the cytoskeleton. Facilitates the CHP1-dependent microtubule and membrane associations through its ability to stimulate the binding of CHP1 to microtubules. Component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes. Upon interferon-gamma treatment assembles into the GAIT complex which binds to stem loop-containing GAIT elements in the 3’-UTR of diverse inflammatory mRNAs (such as ceruplasmin) and suppresses their translation. Also plays a role in innate immunity by promoting TNF-induced NF-kappa-B activation and type I interferon production, via interaction with TRAF2 and TRAF3, respectively. Participates in nuclear events including transcription, RNA transport, DNA replication and apoptosis. Nuclear functions are probably due to the nitrosylase activity that mediates cysteine S-nitrosylation of nuclear target proteins such as SIRT1, HDAC2 and PRKDC.

Subunit / interactions. Homotetramer. Interacts with TPPP; the interaction is direct. Interacts (when S-nitrosylated) with SIAH1; leading to nuclear translocation. Interacts with RILPL1/GOSPEL, leading to prevent the interaction between GAPDH and SIAH1 and prevent nuclear translocation. Interacts with CHP1; the interaction increases the binding of CHP1 with microtubules. Associates with microtubules. Interacts with EIF1AD, USP25, PRKCI and WARS1. Interacts with phosphorylated RPL13A; inhibited by oxidatively-modified low-densitity lipoprotein (LDL(ox)). Component of the GAIT complex. Interacts with FKBP6; leading to inhibit GAPDH catalytic activity. Interacts with TRAF2, promoting TRAF2 ubiquitination. Interacts with TRAF3, promoting TRAF3 ubiquitination.

Subcellular location. Cytoplasm. Cytosol. Nucleus. Perinuclear region. Membrane. Cytoskeleton.

Post-translational modifications. S-nitrosylation of Cys-152 leads to interaction with SIAH1, followed by translocation to the nucleus. S-nitrosylation of Cys-247 is induced by interferon-gamma and LDL(ox) implicating the iNOS-S100A8/9 transnitrosylase complex and seems to prevent interaction with phosphorylated RPL13A and to interfere with GAIT complex activity. ISGylated. Sulfhydration at Cys-152 increases catalytic activity. Oxidative stress can promote the formation of high molecular weight disulfide-linked GAPDH aggregates, through a process called nucleocytoplasmic coagulation. Such aggregates can be observed in vivo in the affected tissues of patients with Alzheimer disease or alcoholic liver cirrhosis, or in cell cultures during necrosis. Oxidation at Met-46 may play a pivotal role in the formation of these insoluble structures. This modification has been detected in vitro following treatment with free radical donor (+/-)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide. It has been proposed to destabilize nearby residues, increasing the likelihood of secondary oxidative damages, including oxidation of Tyr-45 and Met-105. This cascade of oxidations may augment GAPDH misfolding, leading to intermolecular disulfide cross-linking and aggregation. Succination of Cys-152 and Cys-247 by the Krebs cycle intermediate fumarate, which leads to S-(2-succinyl)cysteine residues, inhibits glyceraldehyde-3-phosphate dehydrogenase activity. Fumarate concentration as well as succination of cysteine residues in GAPDH is significantly increased in muscle of diabetic mammals. It was proposed that the S-(2-succinyl)cysteine chemical modification may be a useful biomarker of mitochondrial and oxidative stress in diabetes and that succination of GAPDH and other thiol proteins by fumarate may contribute to the metabolic changes underlying the development of diabetes complications. (Microbial infection) Glycosylated by C.rodentium protein NleB, enteropathogenic E.coli protein NleB1 and S.typhimurium protein Ssek1: arginine GlcNAcylation prevents the interaction with TRAF2 and TRAF3. This leads to reduced ubiquitination of TRAF2 and TRAF3, and subsequent inhibition of NF-kappa-B signaling and type I interferon production, respectively.

Activity regulation. Glyceraldehyde-3-phosphate dehydrogenase activity is inhibited by fumarate, via the formation of S-(2-succinyl)cysteine residues.

Domain organisation. The [IL]-x-C-x-x-[DE] motif is a proposed target motif for cysteine S-nitrosylation mediated by the iNOS-S100A8/A9 transnitrosylase complex.

Pathway. Carbohydrate degradation; glycolysis; pyruvate from D-glyceraldehyde 3-phosphate: step 1/5.

Similarity. Belongs to the glyceraldehyde-3-phosphate dehydrogenase family.

Isoforms (2)

UniProt ID	Names	Canonical?
P04406-1	1	yes
P04406-2	2

RefSeq proteins (5): NP_001243728, NP_001276674, NP_001276675, NP_001344872, NP_002037* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006424	Glyceraldehyde-3-P_DH_1	Family
IPR020828	GlycerAld_3-P_DH_NAD(P)-bd	Domain
IPR020829	GlycerAld_3-P_DH_cat	Domain
IPR020830	GlycerAld_3-P_DH_AS	Active_site
IPR020831	GlycerAld/Erythrose_P_DH	Family
IPR036291	NAD(P)-bd_dom_sf	Homologous_superfamily

Pfam: PF00044, PF02800

Enzyme classification (BRENDA):

• EC 1.2.1.12 — glyceraldehyde-3-phosphate dehydrogenase (phosphorylating) (BRENDA: 126 organisms, 100 substrates, 290 inhibitors, 310 Km, 60 kcat entries)

Substrate kinetics (BRENDA)

19 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
NAD+	—	114
D-GLYCERALDEHYDE 3-PHOSPHATE	0.0003–15	94
3-PHOSPHO-D-GLYCEROYL PHOSPHATE	0.002–1.78	24
PHOSPHATE	0.2–37	23
NADH	0.0033–0.537	15
ARSENATE	1–8.3	4
1,3-DIPHOSPHOGLYCERIC ACID	0.01–0.018	3
D-GLYCERALDEHYDE-3-PHOSPHATE	0.0734–0.5	3
N6-(2-CARBOXYETHYL)-NAD+	0.0102–0.145	3
3-ACETYL-NAD+	0.158–0.62	2
3-ACETYLPYRIDINE HYPOXANTHINE NUCLEOTIDE	1.43–8.15	2
ERYTHROSE 4-PHOSPHATE	0.119–0.127	2
NADP+	1.7–7.1	2
THIO-NAD+	0.0435–0.235	2
ACETALDEHYDE	0.31	1

Catalyzed reactions (Rhea), 2 shown:

• D-glyceraldehyde 3-phosphate + phosphate + NAD(+) = (2R)-3-phospho-glyceroyl phosphate + NADH + H(+) (RHEA:10300)
• S-nitroso-L-cysteinyl-[GAPDH] + L-cysteinyl-[protein] = L-cysteinyl-[GAPDH] + S-nitroso-L-cysteinyl-[protein] (RHEA:66684)

UniProt features (120 total): modified residue 45, strand 20, helix 14, mutagenesis site 14, binding site 9, turn 5, glycosylation site 2, sequence variant 2, initiator methionine 1, chain 1, site 1, region of interest 1, short sequence motif 1, active site 1, cross-link 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

21 structures.

PDB	Method	Resolution (Å)
6YND	X-RAY DIFFRACTION	1.52
1U8F	X-RAY DIFFRACTION	1.75
9L3E	X-RAY DIFFRACTION	1.77
8P5F	X-RAY DIFFRACTION	1.82
6M61	X-RAY DIFFRACTION	1.82
6YNE	X-RAY DIFFRACTION	1.85
8G17	ELECTRON MICROSCOPY	1.98
4WNC	X-RAY DIFFRACTION	1.99
8G15	ELECTRON MICROSCOPY	2.07
8G16	ELECTRON MICROSCOPY	2.07
8G12	ELECTRON MICROSCOPY	2.17
6IQ6	X-RAY DIFFRACTION	2.29
4WNI	X-RAY DIFFRACTION	2.3
8G13	ELECTRON MICROSCOPY	2.3
8G14	ELECTRON MICROSCOPY	2.3
6YNF	X-RAY DIFFRACTION	2.39
1ZNQ	X-RAY DIFFRACTION	2.5
6YNH	X-RAY DIFFRACTION	2.62
6ADE	X-RAY DIFFRACTION	3.15
8DNS	ELECTRON MICROSCOPY	3.22
3GPD	X-RAY DIFFRACTION	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P04406-F1	98.17	0.99

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): 179 (activates thiol group during catalysis); 152 (nucleophile)

Ligand- & substrate-binding residues (9): 182; 211–212; 234; 316; 13–14; 35; 80; 122; 151–153

Post-translational modifications (46): 5, 9, 42, 46, 61, 64, 66, 70, 75, 83, 122, 148, 149, 151, 152, 152, 152, 152, 153, 155 …

Glycosylation sites (2): 197, 200

Mutagenesis-validated functional residues (14):

Position	Phenotype
46	drastic reduction of the extent and significant prolongation of the lag phase of free radical-induced aggregation.
105	increased resistance to free radical-induced aggregation.
152	markedly reduced glycolytic activity; when associated with s-156 and s-247. forms free radical-induced aggregates, but t
156	markedly reduced glycolytic activity; when associated with s-152 and s-247. forms free radical-induced aggregates, but t
196	increased free radical-induced aggregation.
211	does not affect glycosylation by c.rodentium protein nleb.
229	does not affect glycosylation by c.rodentium protein nleb.
241	does not affect glycosylation by c.rodentium protein nleb.
245	inhibits s-nitrosylation of cys-247; when associated with m-250.
246	does not affect glycosylation by c.rodentium protein nleb.
247	markedly reduced glycolytic activity; when associated with s-152 and s-156. forms free radical-induced aggregates, but t
250	inhibits s-nitrosylation of cys-247; when associated with m-245.
277	does not affect glycosylation by c.rodentium protein nleb.
320	no effect on free radical-induced aggregation.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-70171	Glycolysis
R-HSA-70263	Gluconeogenesis

MSigDB gene sets: 435 (showing top): GOBP_CYTOPLASMIC_TRANSLATION, RNGTGGGC_UNKNOWN, E2F_Q4, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, E2F_Q4_01, GOBP_REGULATION_OF_AUTOPHAGY, HONMA_DOCETAXEL_RESISTANCE, GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_PROTEOLYSIS, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, HARRIS_HYPOXIA, E2F4DP1_01, GOBP_POSITIVE_REGULATION_OF_TYPE_I_INTERFERON_PRODUCTION, GOBP_RESPONSE_TO_PEPTIDE, GCANCTGNY_MYOD_Q6

GO Biological Process (22): microtubule cytoskeleton organization (GO:0000226), positive regulation of cytokine production (GO:0001819), glycolytic process (GO:0006096), negative regulation of endopeptidase activity (GO:0010951), regulation of macroautophagy (GO:0016241), negative regulation of translation (GO:0017148), killing of cells of another organism (GO:0031640), positive regulation of type I interferon production (GO:0032481), peptidyl-cysteine S-trans-nitrosylation (GO:0035606), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), protein stabilization (GO:0050821), defense response to fungus (GO:0050832), neuron apoptotic process (GO:0051402), obsolete killing by host of symbiont cells (GO:0051873), canonical glycolysis (GO:0061621), antimicrobial humoral immune response mediated by antimicrobial peptide (GO:0061844), cellular response to type II interferon (GO:0071346), immune system process (GO:0002376), glucose metabolic process (GO:0006006), regulation of translation (GO:0006417), apoptotic process (GO:0006915), innate immune response (GO:0045087)

GO Molecular Function (13): glyceraldehyde-3-phosphate dehydrogenase (NAD+) (phosphorylating) activity (GO:0004365), microtubule binding (GO:0008017), aspartic-type endopeptidase inhibitor activity (GO:0019828), peptidyl-cysteine S-nitrosylase activity (GO:0035605), identical protein binding (GO:0042802), NADP binding (GO:0050661), NAD binding (GO:0051287), disordered domain specific binding (GO:0097718), nucleotide binding (GO:0000166), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor (GO:0016620), transferase activity (GO:0016740)

GO Cellular Component (14): nucleus (GO:0005634), cytoplasm (GO:0005737), lipid droplet (GO:0005811), cytosol (GO:0005829), plasma membrane (GO:0005886), microtubule cytoskeleton (GO:0015630), membrane (GO:0016020), nuclear membrane (GO:0031965), vesicle (GO:0031982), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), GAIT complex (GO:0097452), ribonucleoprotein complex (GO:1990904), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Glucose metabolism	2

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
glyceraldehyde-3-phosphate dehydrogenase [NAD(P)+] (phosphorylating) activity	2
translation	2
adenyl nucleotide binding	2
catalytic activity	2
intracellular membraneless organelle	2
cytoplasm	2
protein-containing complex	2
cytoskeleton organization	1
microtubule-based process	1
cytokine production	1
regulation of cytokine production	1
positive regulation of gene expression	1
positive regulation of multicellular organismal process	1
phosphoglycerate kinase activity	1
phosphoglycerate mutase activity	1
phosphopyruvate hydratase activity	1
pyruvate kinase activity	1
pyruvate metabolic process	1
generation of precursor metabolites and energy	1
aerobic respiration	1
carbohydrate catabolic process	1
pyridine nucleotide catabolic process	1
ADP catabolic process	1
ATP metabolic process	1
nicotinamide nucleotide metabolic process	1
endopeptidase activity	1
negative regulation of peptidase activity	1
regulation of endopeptidase activity	1
regulation of autophagy	1
macroautophagy	1
regulation of translation	1
negative regulation of gene expression	1
negative regulation of protein metabolic process	1
cell killing	1
disruption of cell in another organism	1
positive regulation of cytokine production	1
regulation of type I interferon production	1
type I interferon production	1
peptidyl-cysteine S-nitrosylation	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

426 interactions, top by confidence:

A	B	Type	Score
EGFR	GAPDH	psi-mi:“MI:0914”(association)	0.790
EGFR	GAPDH	psi-mi:“MI:0915”(physical association)	0.790
NDUFS3	NDUFS8	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
GAPDH	TXN	psi-mi:“MI:0915”(physical association)	0.680
GAPDH	HTT	psi-mi:“MI:0915”(physical association)	0.670
GAPDH	S100A8	psi-mi:“MI:0914”(association)	0.650
S100A8	GAPDH	psi-mi:“MI:0914”(association)	0.650
S100A8	GAPDH	psi-mi:“MI:0407”(direct interaction)	0.650
GAPDH	S100A8	psi-mi:“MI:0407”(direct interaction)	0.650
GAPDH	GAPDHS	psi-mi:“MI:0914”(association)	0.620
GAPDH	CAMK2A	psi-mi:“MI:0915”(physical association)	0.560
GAPDH	CRMP1	psi-mi:“MI:0915”(physical association)	0.560
GAPDH	CTNNB1	psi-mi:“MI:0915”(physical association)	0.560
GAPDH	FYN	psi-mi:“MI:0915”(physical association)	0.560
GAPDH	PRKACA	psi-mi:“MI:0915”(physical association)	0.560
FKBP6	GAPDH	psi-mi:“MI:0915”(physical association)	0.560
DHRS9	GAPDH	psi-mi:“MI:0915”(physical association)	0.560
GAPDH	KAT5	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (1024): GAPDH (Affinity Capture-MS), GAPDH (Affinity Capture-MS), GAPDH (Affinity Capture-MS), GAPDH (Affinity Capture-MS), GAPDH (Affinity Capture-MS), GAPDH (Affinity Capture-MS), GAPDH (Two-hybrid), GAPDH (Affinity Capture-MS), GAPDH (Affinity Capture-MS), GAPDH (Affinity Capture-MS), MAP3K5 (Affinity Capture-Western), SIAH1 (Affinity Capture-Western), GAPDHS (Affinity Capture-MS), ASPSCR1 (Affinity Capture-MS), GAPDH (Affinity Capture-MS)

ESM2 similar proteins: A2YQT7, A3FKF7, O01360, O44104, O57479, P00355, P00356, P04406, P04796, P04797, P07486, P07487, P08735, P0CN74, P0CN75, P10096, P10097, P16858, P17244, P17729, P17878, P25858, P26517, P32636, P32637, P46406, P51469, P53430, P56649, Q01597, Q01982, Q05025, Q09054, Q0J8A4, Q1DTF9, Q28259, Q28554, Q2U0J7, Q39769, Q4KYY3

Diamond homologs: A2YQT7, A3FKF7, O01360, O13507, O43026, O44104, O57479, P00355, P00356, P00357, P00358, P00359, P04406, P04796, P04797, P04970, P07486, P07487, P08477, P08735, P09094, P09317, P0CN74, P0CN75, P10096, P16858, P17244, P17331, P17878, P19089, P25858, P25861, P26517, P26518, P26519, P26520, P26521, P26988, P28844, P29497

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
BACH1	“up-regulates quantity”	GAPDH	“transcriptional regulation”
GAPDH	“up-regulates quantity”	“3-phosphonato-D-glyceroyl phosphate(4-)”	“chemical modification”
GAPDH	“down-regulates quantity”	“D-glyceraldehyde 3-phosphate(2-)”	“chemical modification”
VRK2	“up-regulates activity”	GAPDH	phosphorylation
FBXW10	“up-regulates activity”	GAPDH	polyubiquitination
STK4	“up-regulates activity”	GAPDH	phosphorylation
AKT1	“down-regulates activity”	GAPDH	phosphorylation
PRKAA1	“up-regulates activity”	GAPDH	phosphorylation
AMPK	“up-regulates activity”	GAPDH	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 165 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
Opioid Signalling	5	11.9×	4e-03
GSK3B-mediated proteasomal degradation of PD-L1(CD274)	5	10.6×	5e-03
Degradation of GLI2 by the proteasome	5	10.0×	6e-03
GLI3 is processed to GLI3R by the proteasome	5	10.0×	6e-03
Packaging Of Telomere Ends	5	9.8×	6e-03
Transcriptional and post-translational regulation of MITF-M expression and activity	6	9.6×	3e-03
Recognition and association of DNA glycosylase with site containing an affected purine	5	9.1×	7e-03
Cleavage of the damaged purine	5	9.1×	7e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of telomere maintenance	5	17.6×	3e-03
stem cell population maintenance	6	17.4×	2e-03
mitochondrial electron transport, NADH to ubiquinone	5	12.4×	7e-03
circadian rhythm	6	10.1×	6e-03
negative regulation of gene expression	10	4.8×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	10
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
524202	NM_014865.4(NCAPD2):c.4120+2T>C	Pathogenic

SpliceAI

1341 predictions. Top by Δscore:

Variant	Effect	Δscore
12:6534860:GG:G	donor_gain	1.0000
12:6534861:GG:G	donor_gain	1.0000
12:6536491:TA:T	acceptor_loss	1.0000
12:6536492:A:AG	acceptor_gain	1.0000
12:6536493:G:GA	acceptor_gain	1.0000
12:6536493:GA:G	acceptor_gain	1.0000
12:6536493:GAT:G	acceptor_gain	1.0000
12:6536493:GATT:G	acceptor_gain	1.0000
12:6536493:GATTT:G	acceptor_gain	1.0000
12:6536592:TG:T	donor_gain	1.0000
12:6536593:GG:G	donor_gain	1.0000
12:6536594:G:GG	donor_gain	1.0000
12:6536594:GT:G	donor_loss	1.0000
12:6536678:CCCCA:C	acceptor_loss	1.0000
12:6536679:CCCAG:C	acceptor_loss	1.0000
12:6536680:CCA:C	acceptor_loss	1.0000
12:6536681:CA:C	acceptor_loss	1.0000
12:6536682:AGGT:A	acceptor_loss	1.0000
12:6536683:G:T	acceptor_loss	1.0000
12:6536713:T:TA	acceptor_gain	1.0000
12:6536786:CAGGA:C	donor_gain	1.0000
12:6536787:AGGA:A	donor_gain	1.0000
12:6536788:G:GT	donor_gain	1.0000
12:6536788:GGAG:G	donor_loss	1.0000
12:6536789:GA:G	donor_gain	1.0000
12:6536789:GAG:G	donor_loss	1.0000
12:6536790:AGT:A	donor_loss	1.0000
12:6536792:T:G	donor_loss	1.0000
12:6536798:G:GT	donor_gain	1.0000
12:6536810:G:GT	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000456643 (12:6536400 G>A,C), RS1001147308 (12:6536368 C>T), RS1001428291 (12:6536152 G>A,T), RS1001439727 (12:6538703 A>G), RS1001754507 (12:6538862 G>A,C), RS1003361165 (12:6533443 T>G), RS1003449954 (12:6534531 C>G,T), RS1003996379 (12:6534482 G>A,C), RS1004009478 (12:6533205 G>GGCA), RS1005051174 (12:6534746 G>A,T), RS1005160800 (12:6535567 C>A), RS1005479297 (12:6535452 T>C), RS1005513285 (12:6534592 C>T), RS1005695394 (12:6537541 G>A), RS1005968385 (12:6533457 G>C)

Disease associations

OMIM: gene MIM:138400 | disease phenotypes: MIM:617983

GenCC curated gene-disease

Mondo (1): microcephaly 21, primary, autosomal recessive (MONDO:0054804)

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006585_2473	Blood protein levels	1.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2284 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

4 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 241,859 (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
CHEMBL477	ADENOSINE	4	222,014
CHEMBL1232461	MOLIBRESIB	2	1,538
CHEMBL337702	OXIDOPAMINE	2	9,715
CHEMBL8260	BAICALEIN	2	8,592

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

Binding affinities (BindingDB)

15 measured of 20 human assays (33 total across all organisms); most potent 15 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
(7Z)-3-bromanyl-7-(furan-2-ylmethylidene)-[1,3]thiazolo[4,5]imidazo[1,2-b]pyridin-8-one	IC50	1230 nM
2-[5-[(Z)-(3-bromanyl-8-oxidanylidene-[1,3]thiazolo[4,5]imidazo[1,2-b]pyridin-7-ylidene)methyl]furan-2-yl]benzoic acid	IC50	1250 nM
2-[5-[(Z)-(1-keto-5,7-dimethyl-thiazolo[3,2-a]benzimidazol-2-ylidene)methyl]-2-furyl]benzoic acid	IC50	5820 nM
8-carbethoxy-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinoline-4-carboxylic acid	IC50	15800 nM
(9Z)-9-(3,3-dihydroxyprop-2-enylidene)-5,6-dihydroxy-xanthene-3,4-quinone	IC50	15800 nM
MLS000065807	IC50	27400 nM
5,6-bis(2-furanyl)-3-(methylthio)-1,2,4-triazine	IC50	29500 nM
2-[[4-(2-methylphenyl)-1,2,4-triazol-3-yl]sulfanyl]-1-(4-phenylpiperazin-1-yl)ethanone	IC50	36300 nM
6,7-dimethyl-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinoline-4-carboxylic acid	IC50	40400 nM
6-iodanyl-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinoline-4-carboxylic acid	IC50	47800 nM
MLS-0111921.0001	IC50	50100 nM
8-sulfamoyl-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinoline-4-carboxylic acid	IC50	62200 nM
(E)-N-(5-methyl-1,2-oxazol-3-yl)-3-thiophen-2-yl-prop-2-enamide	IC50	62600 nM
MLS-0111922.0001	IC50	93800 nM
MLS-0111919.0001	IC50	99700 nM

ChEMBL bioactivities

18 potent at pChembl≥5 of 69 total, top 18 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.22	Kd	60.23	nM	CHEMBL5653589
7.22	ED50	60.23	nM	CHEMBL5653589
7.00	IC50	100	nM	CHEMBL3559427
6.23	IC50	590	nM	CHEMBL256155
5.89	IC50	1300	nM	CHEMBL124807
5.87	IC50	1340	nM	CHEMBL3604082
5.85	IC50	1410	nM	CHEMBL3604098
5.64	IC50	2310	nM	CHEMBL1371869
5.62	IC50	2410	nM	CHEMBL3604105
5.30	IC50	5000	nM	CHEMBL307758
5.28	IC50	5300	nM	CHEMBL1452781
5.27	IC50	5350	nM	MOLIBRESIB
5.14	Kd	7200	nM	CHEMBL18879
5.12	Kd	7500	nM	CHEMBL243788
5.10	IC50	8000	nM	OXIDOPAMINE
5.08	Kd	8392	nM	CHEMBL3752910
5.08	ED50	8392	nM	CHEMBL3752910
5.00	IC50	1e+04	nM	CHEMBL1775010

PubChem BioAssay actives

14 with measured affinity, of 188 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148414: Binding affinity to human GAPDH incubated for 45 mins by Kinobead based pull down assay	kd	0.0602	uM
[[(2R,5R)-5-(4-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2R,5R)-3-hydroxy-4-[(3-methoxybenzoyl)amino]-5-[6-(naphthalen-1-ylmethylamino)purin-9-yl]oxolan-2-yl]methyl phosphate	75719: Inhibitory concentration of compound against glyceraldehyde-3-phosphate dehydrogenase was determined	ic50	0.1000	uM
2-phenoxynaphthalene-1,4-dione	1240912: Inhibition of recombinant human GAPDH assessed as oxidative phosphorylation of D-glyceraldehyde-3-phosphate to 1,3-bisphosphoglycerate by spectrophotometric method	ic50	0.5900	uM
(2R,3R,4S,5R)-2-(6-amino-8-thiophen-2-ylpurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol	75727: Tested for the inhibitory activity against Glycosomal glyceraldehyde 3-phosphate dehydrogenase (gGAPDH) of human erythrocyte	ic50	1.3000	uM
2-(4-fluorophenoxy)-8-methoxynaphthalene-1,4-dione	1240912: Inhibition of recombinant human GAPDH assessed as oxidative phosphorylation of D-glyceraldehyde-3-phosphate to 1,3-bisphosphoglycerate by spectrophotometric method	ic50	1.3400	uM
2-(4-methoxyphenoxy)anthracene-1,4-dione	1240912: Inhibition of recombinant human GAPDH assessed as oxidative phosphorylation of D-glyceraldehyde-3-phosphate to 1,3-bisphosphoglycerate by spectrophotometric method	ic50	1.4100	uM
5-hydroxy-2-phenoxynaphthalene-1,4-dione	1240912: Inhibition of recombinant human GAPDH assessed as oxidative phosphorylation of D-glyceraldehyde-3-phosphate to 1,3-bisphosphoglycerate by spectrophotometric method	ic50	2.4100	uM
[(2R,5R)-3-hydroxy-4-[(3-methoxybenzoyl)amino]-5-[6-(naphthalen-1-ylmethylamino)purin-9-yl]oxolan-2-yl]methyl dihydrogen phosphate	75719: Inhibitory concentration of compound against glyceraldehyde-3-phosphate dehydrogenase was determined	ic50	5.0000	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2179054: Inhibition of GAPDH (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	5.3500	uM
2,5-dihydroxy-3-[2-(2-methylbut-3-en-2-yl)-1H-indol-3-yl]-6-[7-(3-methylbut-2-enyl)-1H-indol-3-yl]cyclohexa-2,5-diene-1,4-dione	292161: Binding affinity to GAPDH in human erythrocytes	kd	7.2000	uM
N-[3-[2,5-dihydroxy-4-[7-(3-methylbut-2-enyl)-1H-indol-3-yl]-3,6-dioxocyclohexa-1,4-dien-1-yl]-2-methyl-1H-indol-5-yl]-6-[5-(2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl)pentanoylamino]hexanamide	292161: Binding affinity to GAPDH in human erythrocytes	kd	7.5000	uM
5-(2-aminoethyl)benzene-1,2,4-triol	500286: Inhibition of GAPDH	ic50	8.0000	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148414: Binding affinity to human GAPDH incubated for 45 mins by Kinobead based pull down assay	kd	8.3922	uM
(2R,3R,4S,5R)-2-(6-amino-8-phenylpurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol	75727: Tested for the inhibitory activity against Glycosomal glyceraldehyde 3-phosphate dehydrogenase (gGAPDH) of human erythrocyte	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, increases expression, affects cotreatment	6
sodium arsenite	affects cotreatment, decreases reaction, increases reduction, increases expression	5
Hydrogen Peroxide	increases expression, decreases expression, decreases reaction	4
Oxygen	decreases reaction, increases expression, affects cotreatment, affects binding, increases reaction	4
cobaltous chloride	increases expression, decreases reaction	3
Glucose	increases expression, decreases activity, decreases reaction, increases ADP-ribosylation, increases chemical synthesis	3
Tobacco Smoke Pollution	affects expression, increases expression, increases metabolic processing	3
Cadmium Chloride	decreases activity, increases abundance, increases expression, decreases reaction	3
bisphenol F	increases expression, affects cotreatment, decreases expression	2
nickel chloride	increases expression	2
Decitabine	decreases expression, increases expression	2
Arsenic Trioxide	affects binding, decreases reaction, decreases expression, increases reaction, affects cotreatment	2
Cisplatin	decreases reaction, increases expression, decreases expression, affects cotreatment	2
Copper	affects binding	2
Dactinomycin	affects cotreatment, increases secretion, increases expression	2
Glutathione	decreases reaction, decreases abundance, increases reaction, decreases activity, increases metabolic processing (+4 more)	2
Tretinoin	decreases expression, increases reaction	2
1-Methyl-4-phenylpyridinium	increases expression, decreases reaction	2
Okadaic Acid	decreases expression, affects expression	2
Nanotubes, Carbon	affects expression, increases expression	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
TAK-243	increases sumoylation	1
PF-06840003	decreases expression, decreases reaction	1
syringic acid	decreases reaction, increases secretion	1
triphenyl phosphate	affects expression	1
cumene hydroperoxide	increases expression	1
sodium arsenate	decreases expression	1

ChEMBL screening assays

90 unique, capped per target: 90 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1014658	Binding	Inhibition of GAPDH	Design and synthesis of pyrazole derivatives as potent and selective inhibitors of tissue-nonspecific alkaline phosphatase (TNAP). — Bioorg Med Chem Lett

Cellosaurus cell lines

2 cell lines: 1 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D7QI	Ubigene A-549 GAPDH KO	Cancer cell line	Male
CVCL_YM16	HEK293T GAPDH-KD	Transformed cell line	Female

Clinical trials (associated diseases)

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