LDHA

Summary

LDHA (lactate dehydrogenase A, HGNC:6535) is a protein-coding gene on chromosome 11p15.1, encoding L-lactate dehydrogenase A chain (P00338). Interconverts simultaneously and stereospecifically pyruvate and lactate with concomitant interconversion of NADH and NAD(+).

This gene encodes the A subunit of lactate dehydrogenase enzyme which catalyzes the reversible conversion of pyruvate to lactate with the concomitant oxidation of NADH to NAD in anaerobic glycolysis. The protein is found predominantly in skeletal muscle and belongs to the lactate dehydrogenase family. Mutations in this gene have been linked to exertional myoglobinuria. The human genome contains several non-transcribed pseudogenes of this gene.

Source: NCBI Gene 3939 — RefSeq curated summary.

At a glance

• Gene–disease (curated): glycogen storage disease due to lactate dehydrogenase M-subunit deficiency (Strong, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 261 total — 8 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 36
• Druggable target: yes — 4 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_005566

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6535
Approved symbol	LDHA
Name	lactate dehydrogenase A
Location	11p15.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000134333
Ensembl biotype	protein_coding
OMIM	150000
Entrez	3939

Gene structure

Transcript identifiers

Ensembl transcripts: 48 — 35 protein_coding, 7 nonsense_mediated_decay, 6 retained_intron

ENST00000227157, ENST00000375710, ENST00000379412, ENST00000396222, ENST00000422447, ENST00000430553, ENST00000460405, ENST00000469976, ENST00000478970, ENST00000486690, ENST00000494573, ENST00000495052, ENST00000535451, ENST00000536528, ENST00000537296, ENST00000538451, ENST00000539814, ENST00000541097, ENST00000542179, ENST00000543445, ENST00000543695, ENST00000545215, ENST00000545467, ENST00000859176, ENST00000859177, ENST00000859178, ENST00000859179, ENST00000859180, ENST00000859181, ENST00000859182, ENST00000911977, ENST00000911978, ENST00000911979, ENST00000911980, ENST00000911981, ENST00000911982, ENST00000911983, ENST00000911984, ENST00000911985, ENST00000911986, ENST00000911987, ENST00000911988, ENST00000911989, ENST00000911990, ENST00000969387, ENST00000969388, ENST00000969389, ENST00000969390

RefSeq mRNA: 5 — MANE Select: NM_005566 NM_001135239, NM_001165414, NM_001165415, NM_001165416, NM_005566

CCDS: CCDS44549, CCDS53609, CCDS53610, CCDS53611, CCDS7839

Canonical transcript exons

ENST00000422447 — 8 exons

Exon	Start	End
ENSE00001951553	18394563	18394636
ENSE00002291613	18407117	18408425
ENSE00003595211	18400837	18401010
ENSE00003598935	18396819	18396968
ENSE00003609459	18403694	18403811
ENSE00003627857	18399431	18399548
ENSE00003686114	18402840	18403013
ENSE00003686483	18405449	18405572

Expression profiles

Bgee: expression breadth ubiquitous, 157 present calls, max score 99.75.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 1073.3122 / max 35433.5134, expressed in 1827 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
113323	1019.7337	1826
113324	47.0883	1816
113326	3.7393	864
113328	1.1099	648
113327	0.6720	302
113325	0.5582	311
113329	0.4108	147

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	99.75	gold quality
zone of skin	UBERON:0000014	99.46	gold quality
skin of leg	UBERON:0001511	99.46	gold quality
skin of abdomen	UBERON:0001416	99.45	gold quality
popliteal artery	UBERON:0002250	99.45	gold quality
tibial artery	UBERON:0007610	99.45	gold quality
metanephros cortex	UBERON:0010533	99.45	gold quality
aorta	UBERON:0000947	99.44	gold quality
muscle of leg	UBERON:0001383	99.44	gold quality
artery	UBERON:0001637	99.44	gold quality
calcaneal tendon	UBERON:0003701	99.44	gold quality
colonic epithelium	UBERON:0000397	99.43	gold quality
muscle organ	UBERON:0001630	99.43	gold quality
skeletal muscle organ	UBERON:0014892	99.43	gold quality
vermiform appendix	UBERON:0001154	99.42	gold quality
right adrenal gland	UBERON:0001233	99.42	gold quality
left adrenal gland	UBERON:0001234	99.42	gold quality
gastrocnemius	UBERON:0001388	99.42	gold quality
ascending aorta	UBERON:0001496	99.42	gold quality
thoracic aorta	UBERON:0001515	99.41	gold quality
right adrenal gland cortex	UBERON:0035827	99.41	gold quality
descending thoracic aorta	UBERON:0002345	99.40	gold quality
adrenal gland	UBERON:0002369	99.40	gold quality
left adrenal gland cortex	UBERON:0035825	99.40	gold quality
duodenum	UBERON:0002114	99.39	gold quality
subcutaneous adipose tissue	UBERON:0002190	99.39	gold quality
tonsil	UBERON:0002372	99.39	gold quality
adipose tissue	UBERON:0001013	99.37	gold quality
left coronary artery	UBERON:0001626	99.36	gold quality
mucosa of stomach	UBERON:0001199	99.35	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-MTAB-7051	yes	2906.29
E-GEOD-84465	yes	1713.49
E-MTAB-10287	yes	38.73
E-MTAB-9067	yes	22.00
E-GEOD-81608	yes	17.82
E-MTAB-8498	yes	10.94
E-GEOD-81547	yes	8.12
E-MTAB-9801	yes	6.70
E-MTAB-6819	no	5313.98
E-MTAB-10662	no	2194.26
E-MTAB-10596	no	1737.52
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ARNT, ATF1, CREB1, EPAS1, HIF1A, HSF1, JUN, MLXIP, MYC, SP1

miRNA regulators (miRDB)

50 targeting LDHA, 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-1277-5P	100.00	73.95	5056
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-3913-5P	99.78	67.26	968
HSA-MIR-1208	99.70	68.28	1533
HSA-MIR-646	99.68	67.84	1645
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-6751-5P	99.56	64.99	1145
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-3122	99.50	66.33	821
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-6083	99.47	68.73	2393
HSA-MIR-12132	99.47	68.90	1341
HSA-MIR-889-3P	99.40	69.76	2103
HSA-MIR-3614-5P	99.30	65.25	837
HSA-MIR-410-3P	99.27	69.98	2457
HSA-MIR-6803-5P	99.19	63.90	1026
HSA-MIR-4801	98.96	69.42	2096
HSA-MIR-6074	98.89	69.64	2187

Literature-anchored findings (GeneRIF, showing 40)

• an LDHA exon5 haplotype confers increased risk for paradoxically decreased minute volume respiratory response to CO2 challenge but not to panic disorder (PMID:12555229)
• The study of this protein in a sportsman is significant for assessment of training efficiency. (PMID:12629811)
• The activity of this enzyme was studied in tissues, erythrocytes, and blood plasma of patients with peptic ulcer both in its uncomplicated course and in the development of complications. (PMID:12712614)
• These data indicate that LDH-A is induced through a non-genomic pathway of estrogen action. (PMID:15240094)
• Lactate dehydrogenase 5 content in tumor cells is directly related to an up-regulated hypoxia inducible factor pathway and is linked with an aggressive phenotype in colorectal adenocarcinomas. (PMID:16132575)
• Reduction in LDH-A activity resulted in stimulation of mitochondrial respiration and decrease of mitochondrial membrane potential.The tumorigenicity of the LDH-A-deficient cells was severely diminished. (PMID:16766262)
• LDH1 was decreased in essential thrombocythemia. This isoenzymatic pattern could be expression of a metabolic adaptation. (PMID:17178662)
• LDH5 was reduced in idiopathic myelofibrosis. This isoenzymatic pattern could be expression of a metabolic adaptation [LDH5] (PMID:17178662)
• biophysical study of ligand binding and protein dynamics in lactate dehydrogenase (PMID:17483170)
• The results of the current study show that LDH-5 expression may be a useful prognostic factor for patients with gastric carcinoma. (PMID:18521687)
• LDL-M is released into blood fo patients exposed to myocardial ischemia reperfusion. (PMID:18534967)
• Modulation of LDH expression involves alpha6beta4 integrin-FAK-p38MAPK pathway. (PMID:18814027)
• The expression of LDH and its isoenzymes in pleural effusions reflects the host reaction in pleural space and, in non-small-cell lung cancer, may also feature the anaerobic phenotype of cancer cells. (PMID:18821170)
• LDH5 is highly upregulated in B-cell non-Hodgkin lymphomas and is in direct relation to factor HIF1alpha and HIF2alpha expression. LDH5 expression is linked with activated VEGFR2/KDR expression in both lymphoid lesions. (PMID:19021062)
• LDH-A knockdown in the background of FH knockdown results in significant reduction in tumor growth in a xenograft mouse model. (PMID:19276158)
• ErbB2 promotes glycolysis at least partially through the HSF1-mediated upregulation of LDH-A. (PMID:19668225)
• Correlation of LDH-5 expression with clinicopathological factors and with the expression of Bcl-2, Bcl-XL, Mcl-1 and GRP78 was examined in pigmented lesions, including nevi and melanoma at different stages of progression (PMID:19838163)
• LDH5 is highly expressed in squamous cell head and neck cancer and is linked with local relapse, survival and distant metastasis. (PMID:19923867)
• LDH5 is overexpressed in non-small cell lung cancer and could serve as a marker for malignancy. LDH5 correlates positively with the prognostic marker transketolase like 1 protein. (PMID:20385008)
• High lactate dehydrogenase is associated with acute adult T-cell leukemia/lymphoma. (PMID:20828817)
• Presented are QM/MM calculations that show differences in geometries of active sites of M(4) and H(4) isoforms of human LDH ligated with oxamate, pyruvate or L-lactate. (PMID:20951115)
• High LDH is associated with M1b prostate cancer. (PMID:21249322)
• LDH-A reduction resulted in an inhibited cancer cell proliferation, elevated intracellular oxidative stress, and induction of mitochondrial pathway apoptosis. (PMID:21452021)
• Serum LDH and tissue LDH5 levels are complementary features that help to characterize the activity of LDH in colorectal cancer and have a potent value in predicting response to chemotherapy. (PMID:21632858)
• Results show that S-100B, MIA and LDH levels were significantly higher in patients with advanced melanoma than in disease-free patients or healthy controls. (PMID:21858537)
• LDH-A is tyrosine phosphorylated and activated by FGFR1 in cancer cells. (PMID:21969607)
• Case Report: describe an elderly patient with physical therapy-induced rhabdomyolysis complicated by acute kidney injury associated with reduced skeletal muscle LDH-A activity. (PMID:22127970)
• A protein encoded by this locus was found to be differentially expressed in postmortem brains from patients with atypical frontotemporal lobar degeneration. (PMID:22360420)
• We demonstrate that LDH-A reduction can suppress the tumorigenicity of intestinal-type gastric cancer (ITGC) cells by downregulating Oct4 both in vitro and in vivo. (PMID:22429998)
• Data suggest that serum lactate dehydrogenase (LDH) kinetics might reflect disease behaviour in extracranial metastatic and primary sites without need for comprehensive imaging studies and is a quite inexpensive diagnostic test. (PMID:22593701)
• Studies indicate the mechanisms by which lactate dehydrogenase A (LDHA) promotes tumor growth and metastasis. (PMID:22897481)
• Lactic acid induces myofibroblast differentiation via pH-dependent activation of transforming growth factor beta. (PMID:22923663)
• Cells expressing either PDK1 or LDHA maintained a lower mitochondrial membrane potential and decreased reactive oxygen species production with or without exposure to toxins. (PMID:22948140)
• LDHA plays an important role in the progression of esophageal squamous cell carcinoma by modulating cell growth (PMID:22961700)
• Elevated lactate dehydrogenase level is associated with recurrent or refractory aggressive lymphoma. (PMID:23166385)
• Increased LDH5 expression is associated with lymph node metastasis in oral squamous cell carcinoma. (PMID:23184277)
• Data indicate that serum lactic dehydrogenase (S-LDH) appears to be a significant independent prognostic index in patients with metastatic nasopharyngeal carcinoma (NPC). (PMID:23266049)
• The result suggest that assessment of NGAL in peritoneal fluids, especially in combination with LDH, may be a reliable approach for screening of bacterial peritonitis in patients with new onset nonmalignant ascites. (PMID:23318563)
• Lactate dehydrogenase A is overexpressed in pancreatic cancer. (PMID:23404405)
• Human LDHA was introduced as a transgene to Ldhc-null mice and rescued sperm function. (PMID:23467744)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
danio_rerio	ldha	ENSDARG00000101251
mus_musculus	Ldha	ENSMUSG00000063229

Paralogs (5): LDHB (ENSG00000111716), MDH2 (ENSG00000146701), LDHC (ENSG00000166796), LDHAL6A (ENSG00000166800), LDHAL6B (ENSG00000171989)

Protein

Protein identifiers

L-lactate dehydrogenase A chain — P00338 (reviewed: P00338)

Alternative names: Cell proliferation-inducing gene 19 protein, LDH muscle subunit, Renal carcinoma antigen NY-REN-59

All UniProt accessions (12): P00338, F5GWW2, F5GXC7, F5GXH2, F5GXU1, F5GXY2, F5GYU2, F5GZQ4, F5H5J4, F5H6W8, F5H8H6, V9HWB9

UniProt curated annotations — full annotation on UniProt →

Function. Interconverts simultaneously and stereospecifically pyruvate and lactate with concomitant interconversion of NADH and NAD(+).

Subunit / interactions. Homotetramer. Interacts with PTEN upstream reading frame protein MP31. Interacts with folliculin FLCN; the interaction is direct and inhibits enzymatic activity.

Subcellular location. Cytoplasm.

Tissue specificity. Predominantly expressed in anaerobic tissues such as skeletal muscle and liver.

Post-translational modifications. ISGylated.

Disease relevance. Glycogen storage disease 11 (GSD11) [MIM:612933] A metabolic disorder that results in exertional myoglobinuria, pain, cramps and easy fatigue. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Fermentation of pyruvate to lactate is inhibited when bound to folliculin FLCN, perhaps partly by FLCN preventing binding of cofactor NADH.

Pathway. Fermentation; pyruvate fermentation to lactate; (S)-lactate from pyruvate: step 1/1.

Similarity. Belongs to the LDH/MDH superfamily. LDH family.

Isoforms (5)

UniProt ID	Names	Canonical?
P00338-1	1	yes
P00338-2	2
P00338-3	3
P00338-4	4
P00338-5	5

RefSeq proteins (5): NP_001128711, NP_001158886, NP_001158887, NP_001158888, NP_005557* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001236	Lactate/malate_DH_N	Domain
IPR001557	L-lactate/malate_DH	Family
IPR011304	L-lactate_DH	Family
IPR015955	Lactate_DH/Glyco_Ohase_4_C	Homologous_superfamily
IPR018177	L-lactate_DH_AS	Active_site
IPR022383	Lactate/malate_DH_C	Domain
IPR036291	NAD(P)-bd_dom_sf	Homologous_superfamily

Pfam: PF00056, PF02866

Enzyme classification (BRENDA):

• EC 1.1.1.27 — L-lactate dehydrogenase (BRENDA: 149 organisms, 178 substrates, 252 inhibitors, 294 Km, 98 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
PYRUVATE	0.016–77	118
NADH	0.007–44	55
(S)-LACTATE	0.0018–1100	50
NAD+	0.0081–5	25
PHENYLPYRUVATE	1.76–8.23	6
3-ACETYLPYRIDINE ADENINE DINUCLEOTIDE	0.123–0.408	4
LACTATE	3.3–105.1	4
L-LACTATE	0.047–60	3
2-OXOBUTANOATE	77	1
2-OXOBUTYRATE	0.6	1
2-OXOVALERATE	0.116	1
3,4-DIHYDROXYPHENYLPYRUVATE	11.37	1
APAD+	0.0085	1
APADH	0.0166	1
GLYOXYLATE	25	1

Catalyzed reactions (Rhea), 1 shown:

• (S)-lactate + NAD(+) = pyruvate + NADH + H(+) (RHEA:23444)

UniProt features (73 total): modified residue 20, helix 15, strand 15, binding site 7, splice variant 6, mutagenesis site 3, sequence variant 2, initiator methionine 1, chain 1, active site 1, cross-link 1, turn 1

Structure

Experimental structures (PDB)

46 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
5W8J	X-RAY DIFFRACTION	1.55
5W8K	X-RAY DIFFRACTION	1.6
5W8H	X-RAY DIFFRACTION	1.8
9BK2	X-RAY DIFFRACTION	1.85
4JNK	X-RAY DIFFRACTION	1.9
4RLS	X-RAY DIFFRACTION	1.91
5W8I	X-RAY DIFFRACTION	1.95
5W8L	X-RAY DIFFRACTION	1.95
6BB0	X-RAY DIFFRACTION	1.95
6MV8	X-RAY DIFFRACTION	1.95
6Q13	X-RAY DIFFRACTION	2
4QO8	X-RAY DIFFRACTION	2
6MVA	X-RAY DIFFRACTION	2.02
5IXS	X-RAY DIFFRACTION	2.05
6BAX	X-RAY DIFFRACTION	2.05
6Q0D	X-RAY DIFFRACTION	2.05
4M49	X-RAY DIFFRACTION	2.05
4L4R	X-RAY DIFFRACTION	2.1
4OKN	X-RAY DIFFRACTION	2.1
6BAD	X-RAY DIFFRACTION	2.1
4R68	X-RAY DIFFRACTION	2.11
4QO7	X-RAY DIFFRACTION	2.14
4ZVV	X-RAY DIFFRACTION	2.2
1I10	X-RAY DIFFRACTION	2.3
6BB1	X-RAY DIFFRACTION	2.3
8FW6	X-RAY DIFFRACTION	2.34
4AJP	X-RAY DIFFRACTION	2.38
5ZJD	X-RAY DIFFRACTION	2.39
4OJN	X-RAY DIFFRACTION	2.4
6BAG	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P00338-F1	96.08	0.92

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): 193 (proton acceptor)

Ligand- & substrate-binding residues (7): 29–57; 99; 106; 138; 138; 169; 248

Post-translational modifications (21): 2, 5, 5, 10, 14, 18, 57, 81, 118, 118, 126, 224, 232, 239, 243, 309, 310, 318, 318, 322 …

Mutagenesis-validated functional residues (3):

Position	Phenotype
56	abolishes interaction with mp31.
99	abolishes interaction with mp31.
106	increases binding to flcn.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-70268	Pyruvate metabolism
R-HSA-9861718	Regulation of pyruvate metabolism
R-HSA-1428517	Aerobic respiration and respiratory electron transport
R-HSA-1430728	Metabolism

MSigDB gene sets: 0 (showing top):

GO Biological Process (6): lactate metabolic process (GO:0006089), glycolytic process (GO:0006096), obsolete homolactic fermentation (GO:0019661), substantia nigra development (GO:0021762), pyruvate catabolic process (GO:0042867), carboxylic acid metabolic process (GO:0019752)

GO Molecular Function (8): L-lactate dehydrogenase (NAD+) activity (GO:0004459), identical protein binding (GO:0042802), cadherin binding (GO:0045296), catalytic activity (GO:0003824), lactate dehydrogenase activity (GO:0004457), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor (GO:0016616)

GO Cellular Component (8): nucleus (GO:0005634), mitochondrion (GO:0005739), cytosol (GO:0005829), membrane (GO:0016020), sperm fibrous sheath (GO:0035686), extracellular exosome (GO:0070062), oxidoreductase complex (GO:1990204), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Aerobic respiration and respiratory electron transport	1
Pyruvate metabolism	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
pyruvate metabolic process	2
oxidoreductase activity, acting on CH-OH group of donors	2
intracellular membrane-bounded organelle	2
cytoplasm	2
monocarboxylic acid metabolic process	1
phosphoglycerate kinase activity	1
phosphoglycerate mutase activity	1
phosphopyruvate hydratase activity	1
pyruvate kinase activity	1
generation of precursor metabolites and energy	1
aerobic respiration	1
carbohydrate catabolic process	1
pyridine nucleotide catabolic process	1
glyceraldehyde-3-phosphate dehydrogenase [NAD(P)+] (phosphorylating) activity	1
ADP catabolic process	1
ATP metabolic process	1
nicotinamide nucleotide metabolic process	1
midbrain development	1
neural nucleus development	1
monocarboxylic acid catabolic process	1
oxoacid metabolic process	1
L-2-hydroxycarboxylate dehydrogenase (NAD+) activity	1
L-lactate dehydrogenase activity	1
protein binding	1
cell adhesion molecule binding	1
molecular_function	1
binding	1
catalytic activity	1
sperm flagellum	1
extracellular vesicle	1
catalytic complex	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

5853 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LDHA	LDHC	P07864	895
LDHA	PKM	P14618	891
LDHA	GAPDH	P00354	873
LDHA	SLC2A1	P11166	850
LDHA	PFKFB3	Q16875	837
LDHA	H6PD	O95479	829
LDHA	HK2	P52789	828
LDHA	PDK1	Q15118	828
LDHA	HIF1A	Q16665	815
LDHA	G6PD	P11413	813
LDHA	GPI	P06744	809
LDHA	PGK1	P00558	801
LDHA	ENO1	P06733	801
LDHA	TPI1	P00938	798
LDHA	ALDOA	P04075	798

IntAct

216 interactions, top by confidence:

A	B	Type	Score
LDHA	LDHB	psi-mi:“MI:0914”(association)	0.800
LDHA	LDHB	psi-mi:“MI:0915”(physical association)	0.800
LDHB	LDHA	psi-mi:“MI:0914”(association)	0.800
LDHA	LDHC	psi-mi:“MI:0914”(association)	0.770
LDHA	LDHC	psi-mi:“MI:0915”(physical association)	0.770
LDHC	LDHA	psi-mi:“MI:0914”(association)	0.770
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
LDHA	LDHA	psi-mi:“MI:0915”(physical association)	0.670
HSPA8	LDHA	psi-mi:“MI:0407”(direct interaction)	0.640
HSPA8	LDHA	psi-mi:“MI:0915”(physical association)	0.640
LDHA	HSPA8	psi-mi:“MI:0915”(physical association)	0.640
TUBB3	POTEF	psi-mi:“MI:0914”(association)	0.530

BioGRID (591): LDHA (Affinity Capture-MS), LDHA (Affinity Capture-MS), LDHB (Two-hybrid), MAPK10 (Two-hybrid), LDHA (Affinity Capture-MS), LDHA (Affinity Capture-MS), LDHA (Affinity Capture-MS), LDHA (Affinity Capture-MS), LDHA (Affinity Capture-MS), LDHA (Affinity Capture-RNA), ABAT (Co-fractionation), ACADM (Co-fractionation), ADK (Co-fractionation), ALDH1B1 (Co-fractionation), ALDH2 (Co-fractionation)

ESM2 similar proteins: A0A1F3, A5A6N7, P00336, P00337, P00338, P00339, P00340, P00341, P04642, P06151, P07195, P13491, P13743, P16125, P19858, P33571, P42120, P42123, P69080, P69081, P69082, P79912, P79913, Q4R5B6, Q5E9B1, Q5R1W9, Q5R5F0, Q6DGK2, Q92055, Q98SK9, Q98SL0, Q98SL1, Q98SL2, Q9BE24, Q9PT42, Q9PT43, Q9PVK4, Q9PVK5, Q9PW04, Q9PW05

Diamond homologs: A0A1F3, A5A6N7, A5I1Z6, A7FU32, B1L1N3, C1FMZ1, O13276, O13277, O13278, O93401, O93537, O93538, O93539, O93540, O93541, O93542, O93543, O93544, O93545, O93546, P00336, P00337, P00338, P00339, P00340, P00341, P00342, P04642, P06151, P07195, P07864, P13490, P13491, P13743, P16125, P19629, P19858, P20373, P22988, P22989

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
FGFR1	up-regulates	LDHA	phosphorylation
LDHA	up-regulates	Glycolysis
LDHA	“down-regulates quantity”	pyruvate	“chemical modification”
LDHA	“up-regulates quantity”	(S)-lactate	“chemical modification”
“HIF-1 complex”	“up-regulates quantity by expression”	LDHA	“transcriptional regulation”
“HIF-1 complex”	“up-regulates quantity”	LDHA	“transcriptional regulation”
MYC	“up-regulates quantity”	LDHA	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 177 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
Processive synthesis on the C-strand of the telomere	6	38.1×	2e-06
Telomere C-strand (Lagging Strand) Synthesis	6	38.1×	2e-06
Removal of the Flap Intermediate from the C-strand	6	31.7×	5e-06
Polymerase switching on the C-strand of the telomere	6	21.1×	5e-05
Dengue Virus Genome Translation and Replication	6	15.9×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of telomere maintenance via telomerase	5	24.4×	1e-03
mRNA stabilization	5	12.2×	8e-03
mRNA splicing, via spliceosome	9	5.5×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	5
Uncertain significance	118
Likely benign	74
Benign	33

Top pathogenic / likely-pathogenic (13)

Variant ID	HGVS	Classification
14566	NM_005566.4(LDHA):c.759_778del (p.Leu254fs)	Pathogenic
2137028	NM_005566.4(LDHA):c.505C>T (p.Arg169Ter)	Pathogenic
2848332	NM_005566.4(LDHA):c.631_632dup (p.Leu211_Lys212insTer)	Pathogenic
2903039	NM_005566.4(LDHA):c.410C>A (p.Ser137Ter)	Pathogenic
4709813	NM_005566.4(LDHA):c.640_641del (p.Leu214fs)	Pathogenic
4715484	NM_005566.4(LDHA):c.298C>T (p.Gln100Ter)	Pathogenic
4807073	NM_005566.4(LDHA):c.467dup (p.Asn156fs)	Pathogenic
976711	GRCh37/hg19 11p15.1(chr11:18418095-18422557)	Pathogenic
1925742	NM_005566.4(LDHA):c.126+2T>C	Likely pathogenic
2137026	NM_005566.4(LDHA):c.244G>A (p.Asp82Asn)	Likely pathogenic
3599453	NM_005566.4(LDHA):c.710+1del	Likely pathogenic
4712109	NM_005566.4(LDHA):c.419-1G>C	Likely pathogenic
4773910	NM_005566.4(LDHA):c.593-1del	Likely pathogenic

SpliceAI

1025 predictions. Top by Δscore:

Variant	Effect	Δscore
11:18396814:TATA:T	acceptor_loss	1.0000
11:18396815:ATAG:A	acceptor_loss	1.0000
11:18396816:TA:T	acceptor_loss	1.0000
11:18396817:A:AG	acceptor_gain	1.0000
11:18396817:AGAT:A	acceptor_loss	1.0000
11:18396818:G:GA	acceptor_gain	1.0000
11:18396818:GA:G	acceptor_gain	1.0000
11:18396818:GAT:G	acceptor_gain	1.0000
11:18396818:GATT:G	acceptor_gain	1.0000
11:18396818:GATTC:G	acceptor_gain	1.0000
11:18396964:TGAAG:T	donor_gain	1.0000
11:18396965:GAAG:G	donor_gain	1.0000
11:18396965:GAAGG:G	donor_gain	1.0000
11:18396967:AG:A	donor_gain	1.0000
11:18396967:AGG:A	donor_loss	1.0000
11:18396968:GG:G	donor_gain	1.0000
11:18396969:G:GG	donor_gain	1.0000
11:18399426:TTTA:T	acceptor_loss	1.0000
11:18399428:TA:T	acceptor_loss	1.0000
11:18399430:G:GC	acceptor_loss	1.0000
11:18399430:GGAC:G	acceptor_gain	1.0000
11:18399482:G:GT	donor_gain	1.0000
11:18400835:A:AG	acceptor_gain	1.0000
11:18400836:G:GG	acceptor_gain	1.0000
11:18400836:GACT:G	acceptor_gain	1.0000
11:18402836:A:AG	acceptor_gain	1.0000
11:18402836:ATAGT:A	acceptor_gain	1.0000
11:18402837:T:G	acceptor_gain	1.0000
11:18402837:TAG:T	acceptor_loss	1.0000
11:18402838:A:AG	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000405166 (11:18406190 T>C), RS1000578524 (11:18400115 T>G), RS1000845636 (11:18392721 C>G,T), RS1000859170 (11:18406543 C>T), RS1000891975 (11:18398816 A>G,T), RS1001137031 (11:18393888 TAAAC>T), RS1001614504 (11:18407040 T>C), RS1001719617 (11:18406207 A>C,G,T), RS1001797255 (11:18400479 A>C,G), RS1001892032 (11:18400263 A>T), RS1001964664 (11:18394368 A>G), RS1002056342 (11:18406580 G>T), RS1002678689 (11:18406216 G>A), RS1002898786 (11:18401684 A>G,T), RS1003121149 (11:18401564 G>A,C)

Disease associations

OMIM: gene MIM:150000 | disease phenotypes: MIM:612933

GenCC curated gene-disease

Disease	Classification	Inheritance
glycogen storage disease due to lactate dehydrogenase M-subunit deficiency	Strong	Autosomal recessive

Mondo (1): glycogen storage disease due to lactate dehydrogenase M-subunit deficiency (MONDO:0013047)

Orphanet (1): Glycogen storage disease due to lactate dehydrogenase M-subunit deficiency (Orphanet:284426)

HPO phenotypes

36 total (30 of 36 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000083	Renal insufficiency
HP:0000989	Pruritus
HP:0001036	Parakeratosis
HP:0001787	Abnormal delivery
HP:0001919	Acute kidney injury
HP:0002046	Heat intolerance
HP:0002063	Rigidity
HP:0002151	Increased circulating lactate concentration
HP:0002910	Elevated circulating hepatic transaminase concentration
HP:0002913	Myoglobinuria
HP:0003072	Hypercalcemia
HP:0003201	Rhabdomyolysis
HP:0003236	Elevated circulating creatine kinase concentration
HP:0003326	Myalgia
HP:0003388	Easy fatigability
HP:0003394	Muscle spasm
HP:0003542	Increased circulating pyruvate concentration
HP:0003546	Exercise intolerance
HP:0003552	Muscle stiffness
HP:0003621	Juvenile onset
HP:0003738	Exercise-induced myalgia
HP:0007432	Intermittent generalized erythematous papular rash
HP:0008305	Exercise-induced myoglobinuria
HP:0008331	Elevated creatine kinase after exercise
HP:0009045	Exercise-induced rhabdomyolysis
HP:0011356	Regional abnormality of skin
HP:0012622	Chronic kidney disease
HP:0025474	Erythematous plaque
HP:0025526	Psoriasiform lesion

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST000876_2	Amyloid A serum levels	4.000000e-22
GCST000876_4	Amyloid A serum levels	3.000000e-111
GCST012020_424	Serum metabolite levels	6.000000e-17

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C538133	Lactate dehydrogenase deficiency type A (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4835 (SINGLE PROTEIN), CHEMBL5465226 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

4 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 267,775 (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
CHEMBL190461	CANNABIDIOL	4	26,379
CHEMBL465	DRONABINOL	4	62,107
CHEMBL752	ADENOSINE PHOSPHATE	4	165,316
CHEMBL51483	GOSSYPOL	3	13,973

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

Binding affinities (BindingDB)

2 measured of 23 human assays (23 total across all organisms); most potent 2 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
GNE-140 (6)	IC50	3 nM
US10961200, Compound 375	IC50	550 nM	US-10961200: Small molecule inhibitors of lactate dehydrogenase and methods of use thereof

ChEMBL bioactivities

907 potent at pChembl≥5 of 1132 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.80	Kd	0.016	nM	CHEMBL4859303
10.71	Kd	0.0193	nM	CHEMBL4782843
10.20	Kd	0.0634	nM	CHEMBL4753379
10.18	Kd	0.0667	nM	CHEMBL4748782
10.15	IC50	0.07	nM	CHEMBL4850573
10.00	IC50	0.1	nM	CHEMBL4855986
9.96	Kd	0.11	nM	CHEMBL4081890
9.91	Kd	0.1235	nM	CHEMBL4787852
9.52	IC50	0.3	nM	CHEMBL4861379
9.52	IC50	0.3	nM	CHEMBL4847068
9.48	Kd	0.33	nM	CHEMBL4100845
9.40	IC50	0.4	nM	CHEMBL4873879
9.36	Kd	0.44	nM	CHEMBL4847591
9.30	IC50	0.5	nM	CHEMBL4864519
9.05	IC50	0.9	nM	CHEMBL5181496
9.04	Kd	0.91	nM	CHEMBL4872752
9.00	IC50	1	nM	CHEMBL4792513
8.96	Kd	1.1	nM	CHEMBL4860066
8.82	Kd	1.5	nM	CHEMBL4877797
8.80	IC50	1.6	nM	CHEMBL5183539
8.77	Kd	1.7	nM	CHEMBL3335794
8.74	IC50	1.8	nM	CHEMBL5201115
8.66	IC50	2.2	nM	CHEMBL5181996
8.60	IC50	2.5	nM	CHEMBL5194549
8.60	IC50	2.5	nM	CHEMBL5185237
8.59	IC50	2.6	nM	CHEMBL3335794
8.59	IC50	2.6	nM	CHEMBL5416627
8.57	IC50	2.7	nM	CHEMBL5196929
8.54	IC50	2.9	nM	CHEMBL5176448
8.54	IC50	2.9	nM	CHEMBL5182266
8.52	IC50	3	nM	CHEMBL4576717
8.52	IC50	3	nM	CHEMBL4065858
8.52	IC50	3	nM	CHEMBL4786682
8.52	IC50	3	nM	CHEMBL4753379
8.49	IC50	3.2	nM	CHEMBL5194549
8.43	IC50	3.7	nM	CHEMBL5189879
8.42	IC50	3.8	nM	CHEMBL5188480
8.40	IC50	4	nM	CHEMBL4435570
8.40	IC50	4	nM	CHEMBL5177632
8.36	IC50	4.4	nM	CHEMBL5181496
8.32	Ki	4.8	nM	CHEMBL3335794
8.30	IC50	5	nM	CHEMBL3335792
8.30	IC50	5	nM	CHEMBL4467769
8.30	IC50	5	nM	CHEMBL4797357
8.30	IC50	5	nM	CHEMBL4873611
8.30	IC50	5	nM	CHEMBL4852130
8.30	IC50	5	nM	CHEMBL4849137
8.22	IC50	6	nM	CHEMBL3581197
8.22	IC50	6	nM	CHEMBL4752940
8.22	IC50	6	nM	CHEMBL4861089

PubChem BioAssay actives

902 with measured affinity, of 1640 total; 50 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
2-[5-(cyclopropylmethyl)-4-[(3-fluoro-4-sulfamoylphenyl)methyl]-3-[4-fluoro-3-[[5-(trifluoromethyl)furan-2-yl]methoxy]phenyl]pyrazol-1-yl]-1,3-thiazole-4-carboxylic acid	1759147: Binding affinity to LDHA (unknown origin) by SPR analysis	kd	<0.0001	uM
2-[5-(cyclopropylmethyl)-3-(3-cyclopropyloxy-4-fluorophenyl)-4-[(3-fluoro-4-sulfamoylphenyl)methyl]pyrazol-1-yl]-1,3-thiazole-4-carboxylic acid	1759147: Binding affinity to LDHA (unknown origin) by SPR analysis	kd	<0.0001	uM
2-[3-[3-(2-cyclopentylethynyl)-4-fluorophenyl]-5-(cyclopropylmethyl)-4-[(3-fluoro-4-sulfamoylphenyl)methyl]pyrazol-1-yl]-1,3-thiazole-4-carboxylic acid	1676295: Binding affinity to human His-tagged LDHA by SPR analysis	kd	<0.0001	uM
2-[5-(cyclopropylmethyl)-4-[(3-fluoro-4-sulfamoylphenyl)methyl]-3-(3-phenylmethoxyphenyl)pyrazol-1-yl]-1,3-thiazole-4-carboxylic acid	1759147: Binding affinity to LDHA (unknown origin) by SPR analysis	kd	<0.0001	uM
2-[5-(cyclopropylmethyl)-3-[3-[(2,2-difluorocyclopropyl)methoxy]-4-fluorophenyl]-4-[(3-fluoro-4-sulfamoylphenyl)methyl]pyrazol-1-yl]-1,3-thiazole-4-carboxylic acid	1759147: Binding affinity to LDHA (unknown origin) by SPR analysis	kd	<0.0001	uM
3-(carbamoylamino)-N-(2-methyl-1,3-benzothiazol-6-yl)propanamide	671895: Binding affinity to 6-His-tagged human LDHA (2 to 322 amino acid residue) expressed in Escherichia coli BL21 (DE3) cells by NMR analysis in presence of NADH	kd	<0.0001	uM
3-(carbamoylamino)-N-(2-propylsulfanyl-1,3-benzothiazol-6-yl)propanamide	671895: Binding affinity to 6-His-tagged human LDHA (2 to 322 amino acid residue) expressed in Escherichia coli BL21 (DE3) cells by NMR analysis in presence of NADH	kd	<0.0001	uM
2-[5-(cyclopropylmethyl)-3-(3-phenylphenyl)-4-[(4-sulfamoylphenyl)methyl]pyrazol-1-yl]-1,3-thiazole-4-carboxylic acid	1477142: Binding affinity to human His-tagged LDHA in presence of NADH by SPR assay	kd	0.0001	uM
2-[5-(cyclopropylmethyl)-4-[(3-fluoro-4-sulfamoylphenyl)methyl]-3-[3-[2-(5-methylthiophen-2-yl)ethynyl]phenyl]pyrazol-1-yl]-1,3-thiazole-4-carboxylic acid	1676295: Binding affinity to human His-tagged LDHA by SPR analysis	kd	0.0001	uM
2-[5-(cyclopropylmethyl)-3-[4-fluoro-3-[2-(5-methylthiophen-2-yl)ethynyl]phenyl]-4-[(3-fluoro-4-sulfamoylphenyl)methyl]pyrazol-1-yl]-1,3-thiazole-4-carboxylic acid	1676295: Binding affinity to human His-tagged LDHA by SPR analysis	kd	0.0001	uM
2-[3-[3-[4-[(5-carboxy-1H-triazol-4-yl)oxy]phenyl]-4-fluorophenyl]-5-(cyclopropylmethyl)-4-[(3-fluoro-4-sulfamoylphenyl)methyl]pyrazol-1-yl]-1,3-thiazole-4-carboxylic acid	1768420: Inhibition of recombinant human LDHA expressed in BL21 gold (DE3) using sodium pyruvate as substrate preincubated for 10 mins followed by sodium pyruvate and NADPH addition	ic50	0.0001	uM
2-[3-[3-(3-cyclopentylprop-1-ynyl)-4-fluorophenyl]-5-(cyclopropylmethyl)-4-[(3-fluoro-4-sulfamoylphenyl)methyl]pyrazol-1-yl]-1,3-thiazole-4-carboxylic acid	1676295: Binding affinity to human His-tagged LDHA by SPR analysis	kd	0.0001	uM
2-[3-[3-[3-[(5-carboxy-1H-triazol-4-yl)oxy]phenyl]-4-fluorophenyl]-5-(cyclopropylmethyl)-4-[(3-fluoro-4-sulfamoylphenyl)methyl]pyrazol-1-yl]-1,3-thiazole-4-carboxylic acid	1768420: Inhibition of recombinant human LDHA expressed in BL21 gold (DE3) using sodium pyruvate as substrate preincubated for 10 mins followed by sodium pyruvate and NADPH addition	ic50	0.0001	uM
2-[5-cyclopropyl-3-(3-phenylphenyl)-4-[(4-sulfamoylphenyl)methyl]pyrazol-1-yl]-1,3-thiazole-4-carboxylic acid	1477142: Binding affinity to human His-tagged LDHA in presence of NADH by SPR assay	kd	0.0003	uM
2-[3-[3-[4-(5-carboxy-2H-triazol-4-yl)phenyl]-4-fluorophenyl]-5-(cyclopropylmethyl)-4-[(3-fluoro-4-sulfamoylphenyl)methyl]pyrazol-1-yl]-1,3-thiazole-4-carboxylic acid	1768420: Inhibition of recombinant human LDHA expressed in BL21 gold (DE3) using sodium pyruvate as substrate preincubated for 10 mins followed by sodium pyruvate and NADPH addition	ic50	0.0003	uM
2-[3-[3-[4-[(5-carboxy-2H-triazol-4-yl)sulfanyl]phenyl]-4-fluorophenyl]-5-(cyclopropylmethyl)-4-[(3-fluoro-4-sulfamoylphenyl)methyl]pyrazol-1-yl]-1,3-thiazole-4-carboxylic acid	1768420: Inhibition of recombinant human LDHA expressed in BL21 gold (DE3) using sodium pyruvate as substrate preincubated for 10 mins followed by sodium pyruvate and NADPH addition	ic50	0.0003	uM
2-[5-(cyclopropylmethyl)-4-[(3-fluoro-4-sulfamoylphenyl)methyl]-3-(3-morpholin-4-ylphenyl)pyrazol-1-yl]-1,3-thiazole-4-carboxylic acid	1759147: Binding affinity to LDHA (unknown origin) by SPR analysis	kd	0.0004	uM
2-[3-[3-[(5-carboxy-1H-triazol-4-yl)oxy]-4-fluorophenyl]-5-(cyclopropylmethyl)-4-[(3-fluoro-4-sulfamoylphenyl)methyl]pyrazol-1-yl]-1,3-thiazole-4-carboxylic acid	1768420: Inhibition of recombinant human LDHA expressed in BL21 gold (DE3) using sodium pyruvate as substrate preincubated for 10 mins followed by sodium pyruvate and NADPH addition	ic50	0.0004	uM
2-[3-[3-[(5-carboxy-2H-triazol-4-yl)sulfanyl]phenyl]-5-(cyclopropylmethyl)-4-[(3-fluoro-4-sulfamoylphenyl)methyl]pyrazol-1-yl]-1,3-thiazole-4-carboxylic acid	1768420: Inhibition of recombinant human LDHA expressed in BL21 gold (DE3) using sodium pyruvate as substrate preincubated for 10 mins followed by sodium pyruvate and NADPH addition	ic50	0.0005	uM
2-[5-(cyclopropylmethyl)-3-[4-fluoro-3-[(3-fluorophenyl)methoxy]phenyl]-4-[(3-fluoro-4-sulfamoylphenyl)methyl]pyrazol-1-yl]-1,3-thiazole-4-carboxylic acid	1759147: Binding affinity to LDHA (unknown origin) by SPR analysis	kd	0.0009	uM
5-(2-chlorophenyl)sulfanyl-2-[6-(cyclohexylamino)-2-pyridinyl]-2-[6-(3,4-difluoroanilino)-2-pyridinyl]-4-hydroxy-1,3-dihydropyridin-6-one	1882403: Inhibition of LDHA (unknown origin)	ic50	0.0009	uM
2-[5-(cyclopropylmethyl)-3-[4-fluoro-3-[3-fluoro-3-(oxolan-3-yl)prop-1-ynyl]phenyl]-4-[(3-fluoro-4-sulfamoylphenyl)methyl]pyrazol-1-yl]-1,3-thiazole-4-carboxylic acid	1676289: Inhibition of recombinant human LDHA using sodium pyruvate as substrate preincubated for 5 mins followed by diaphorase/resazurin addition and measured after 20 mins by fluorescence based assay	ic50	0.0010	uM
2-[5-(cyclopropylmethyl)-3-[4-fluoro-3-(4-methylphenoxy)phenyl]-4-[(3-fluoro-4-sulfamoylphenyl)methyl]pyrazol-1-yl]-1,3-thiazole-4-carboxylic acid	1759147: Binding affinity to LDHA (unknown origin) by SPR analysis	kd	0.0011	uM
2-[3-(3-anilinophenyl)-5-(cyclopropylmethyl)-4-[(4-sulfamoylphenyl)methyl]pyrazol-1-yl]-1,3-thiazole-4-carboxylic acid	1759147: Binding affinity to LDHA (unknown origin) by SPR analysis	kd	0.0015	uM
(2R)-5-(2-chlorophenyl)sulfanyl-2-[6-(3,4-difluoroanilino)-2-pyridinyl]-2-[6-(4-fluoroanilino)-2-pyridinyl]-4-hydroxy-1,3-dihydropyridin-6-one	1882403: Inhibition of LDHA (unknown origin)	ic50	0.0016	uM
3-[[3-(cyclopropylsulfamoyl)-7-(2,4-dimethoxypyrimidin-5-yl)quinolin-4-yl]amino]-5-(3,5-difluorophenoxy)benzoic acid	1477143: Binding affinity to human His-tagged LDHA in absence of NADH by SPR assay	kd	0.0017	uM
5-(2-chlorophenyl)sulfanyl-2-[6-(4-fluorophenoxy)-2-pyridinyl]-4-hydroxy-2-(4-morpholin-4-ylphenyl)-1,3-dihydropyridin-6-one	1882403: Inhibition of LDHA (unknown origin)	ic50	0.0018	uM
5-(2-chlorophenyl)sulfanyl-4-hydroxy-2-(2-hydroxyphenyl)-2-thiophen-3-yl-3H-pyran-6-one	1882403: Inhibition of LDHA (unknown origin)	ic50	0.0022	uM
5-(2-chlorophenyl)sulfanyl-2-[6-(4-fluoroanilino)-2-pyridinyl]-4-hydroxy-2-(4-morpholin-4-ylphenyl)-1,3-dihydropyridin-6-one	1882403: Inhibition of LDHA (unknown origin)	ic50	0.0025	uM
5-(2-chlorophenyl)sulfanyl-2-[6-(3,4-difluoroanilino)-2-pyridinyl]-4-hydroxy-2-(6-phenoxy-2-pyridinyl)-1,3-dihydropyridin-6-one	1882403: Inhibition of LDHA (unknown origin)	ic50	0.0025	uM
2-[5-(cyclopropylmethyl)-3-[3-[6-[[13-[[(2S)-3,3-dimethyl-1-[(2S,4R)-2-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methylcarbamoyl]-4-phenylmethoxypyrrolidin-1-yl]-1-oxobutan-2-yl]amino]-13-oxotridecanoyl]amino]hex-1-ynyl]phenyl]-4-[(4-sulfamoylphenyl)methyl]pyrazol-1-yl]-1,3-thiazole-4-carboxylic acid	1964687: Inhibition of recombinant human LDHA	ic50	0.0026	uM
5-(2-chlorophenyl)sulfanyl-2-[6-(3,4-difluoroanilino)-2-pyridinyl]-4-hydroxy-2-[6-(oxan-4-ylamino)-2-pyridinyl]-1,3-dihydropyridin-6-one	1882403: Inhibition of LDHA (unknown origin)	ic50	0.0027	uM
5-(2-chlorophenyl)sulfanyl-2-[3-[(5-fluoro-2-pyridinyl)amino]phenyl]-4-hydroxy-2-thiophen-3-yl-3H-pyran-6-one	1882403: Inhibition of LDHA (unknown origin)	ic50	0.0029	uM
5-(2-chlorophenyl)sulfanyl-2-[6-(4-fluoroanilino)-2-pyridinyl]-4-hydroxy-2-thiophen-3-yl-3H-pyran-6-one	1882403: Inhibition of LDHA (unknown origin)	ic50	0.0029	uM
(2R)-5-(2-chlorophenyl)sulfanyl-4-hydroxy-2-(4-morpholin-4-ylphenyl)-2-thiophen-3-yl-1,3-dihydropyridin-6-one	1631170: Inhibition of human recombinant carboxy-terminal His-tagged LDHA by UV endpoint assay	ic50	0.0030	uM
2-[5-(cyclopropylmethyl)-3-[4-fluoro-3-(4-hydroxybut-1-ynyl)phenyl]-4-[(3-fluoro-4-sulfamoylphenyl)methyl]pyrazol-1-yl]-1,3-thiazole-4-carboxylic acid	1676289: Inhibition of recombinant human LDHA using sodium pyruvate as substrate preincubated for 5 mins followed by diaphorase/resazurin addition and measured after 20 mins by fluorescence based assay	ic50	0.0030	uM
5-(2-chlorophenyl)sulfanyl-2-[3-(4-fluoroanilino)phenyl]-4-hydroxy-2-thiophen-3-yl-1,3-dihydropyridin-6-one	1631170: Inhibition of human recombinant carboxy-terminal His-tagged LDHA by UV endpoint assay	ic50	0.0030	uM
(2S)-5-(2-chlorophenyl)sulfanyl-2-[6-(3,4-difluoroanilino)-2-pyridinyl]-2-[6-(4-fluoroanilino)-2-pyridinyl]-4-hydroxy-1,3-dihydropyridin-6-one	1882403: Inhibition of LDHA (unknown origin)	ic50	0.0037	uM
5-(2-chlorophenyl)sulfanyl-2-[6-(3,4-difluoroanilino)-2-pyridinyl]-4-hydroxy-2-(6-quinolin-5-yloxy-2-pyridinyl)-1,3-dihydropyridin-6-one	1882403: Inhibition of LDHA (unknown origin)	ic50	0.0038	uM
(2R)-5-(2-chlorophenyl)sulfanyl-2-[3-(4-fluoroanilino)phenyl]-4-hydroxy-2-thiophen-3-yl-3H-pyran-6-one	1882403: Inhibition of LDHA (unknown origin)	ic50	0.0040	uM
5-(2-chlorophenyl)sulfanyl-2-[3-(cyclohexylamino)phenyl]-4-hydroxy-2-thiophen-3-yl-1,3-dihydropyridin-6-one	1631170: Inhibition of human recombinant carboxy-terminal His-tagged LDHA by UV endpoint assay	ic50	0.0040	uM
3-(2-chlorophenyl)sulfanyl-6-(4-morpholin-4-ylphenyl)-6-thiophen-3-ylpiperidine-2,4-dione	1167915: Inhibition of LDHA (unknown origin)	ic50	0.0050	uM
2-[5-(cyclopropylmethyl)-3-[4-fluoro-3-(oxolan-2-ylmethoxy)phenyl]-4-[(3-fluoro-4-sulfamoylphenyl)methyl]pyrazol-1-yl]-1,3-thiazole-4-carboxylic acid	1759142: Inhibition of recombinant human LDHA using sodium pyruvate as substrate preincubated for 5 mins followed by diaphorase/resazurin addition and measured after 20 mins by fluorescence based assay	ic50	0.0050	uM
2-[5-(cyclopropylmethyl)-3-[4-fluoro-3-(oxolan-3-ylmethoxy)phenyl]-4-[(3-fluoro-4-sulfamoylphenyl)methyl]pyrazol-1-yl]-1,3-thiazole-4-carboxylic acid	1759142: Inhibition of recombinant human LDHA using sodium pyruvate as substrate preincubated for 5 mins followed by diaphorase/resazurin addition and measured after 20 mins by fluorescence based assay	ic50	0.0050	uM
2-[4-(4-acetylpiperazin-1-yl)phenyl]-5-(2-chlorophenyl)sulfanyl-4-hydroxy-2-thiophen-3-yl-1,3-dihydropyridin-6-one	1631170: Inhibition of human recombinant carboxy-terminal His-tagged LDHA by UV endpoint assay	ic50	0.0050	uM
2-[5-(cyclopropylmethyl)-3-[4-fluoro-3-[3-hydroxy-3-(oxolan-3-yl)prop-1-ynyl]phenyl]-4-[(3-fluoro-4-sulfamoylphenyl)methyl]pyrazol-1-yl]-1,3-thiazole-4-carboxylic acid	1676289: Inhibition of recombinant human LDHA using sodium pyruvate as substrate preincubated for 5 mins followed by diaphorase/resazurin addition and measured after 20 mins by fluorescence based assay	ic50	0.0050	uM
2-[3-[3-(tert-butylcarbamoyl)-4-fluorophenyl]-5-(cyclopropylmethyl)-4-[(3-fluoro-4-sulfamoylphenyl)methyl]pyrazol-1-yl]-1,3-thiazole-4-carboxylic acid	1759142: Inhibition of recombinant human LDHA using sodium pyruvate as substrate preincubated for 5 mins followed by diaphorase/resazurin addition and measured after 20 mins by fluorescence based assay	ic50	0.0060	uM
2-[5-(cyclopropylmethyl)-3-[4-fluoro-3-[3-hydroxy-3-(oxetan-3-yl)prop-1-ynyl]phenyl]-4-[(3-fluoro-4-sulfamoylphenyl)methyl]pyrazol-1-yl]-1,3-thiazole-4-carboxylic acid	1676289: Inhibition of recombinant human LDHA using sodium pyruvate as substrate preincubated for 5 mins followed by diaphorase/resazurin addition and measured after 20 mins by fluorescence based assay	ic50	0.0060	uM
[(1R)-1-phenylethyl] 2-[4-chloro-3-[4-(2,6-dichlorophenyl)-2-hydroxy-6-oxocyclohexen-1-yl]sulfanylphenyl]acetate	1227835: Inhibition of human LDH-A by biochemical assay	ic50	0.0060	uM
2-[3-(3-benzamido-4-fluorophenyl)-5-(cyclopropylmethyl)-4-[(3-fluoro-4-sulfamoylphenyl)methyl]pyrazol-1-yl]-1,3-thiazole-4-carboxylic acid	1759142: Inhibition of recombinant human LDHA using sodium pyruvate as substrate preincubated for 5 mins followed by diaphorase/resazurin addition and measured after 20 mins by fluorescence based assay	ic50	0.0070	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Oxygen	increases expression, increases secretion, affects expression, decreases reaction, increases activity (+4 more)	11
Cadmium	increases abundance, increases expression, affects cotreatment, increases secretion, increases reaction (+3 more)	7
bisphenol A	decreases expression, affects binding, increases reaction, increases expression, affects expression (+1 more)	6
sodium arsenite	increases reaction, increases secretion, decreases reaction, affects expression, decreases expression (+2 more)	6
Acetylcysteine	affects reaction, increases abundance, decreases reaction, increases expression, increases secretion (+1 more)	6
Cadmium Chloride	increases secretion, decreases expression, affects reaction, decreases reaction, increases abundance (+3 more)	6
Valproic Acid	affects cotreatment, increases expression, decreases expression	5
3-methyladenine	increases expression, increases activity, decreases expression, decreases reaction, increases abundance	4
trichostatin A	affects cotreatment, increases expression	3
arsenite	increases expression, affects reaction, affects binding, increases reaction	3
cobaltous chloride	increases expression	3
(+)-JQ1 compound	decreases expression, decreases phosphorylation, increases expression, decreases reaction	3
Acetaminophen	decreases reaction, decreases activity, decreases expression	3
Air Pollutants	increases abundance, increases secretion, decreases expression	3
Benzo(a)pyrene	decreases expression, increases methylation, increases mutagenesis	3
Estradiol	affects cotreatment, increases expression, decreases expression	3
Formaldehyde	increases expression, decreases expression, affects reaction, increases activity, increases abundance (+2 more)	3
Glucose	decreases reaction, affects reaction, increases expression, increases activity	3
Potassium Dichromate	decreases reaction, increases expression, increases reaction, increases secretion	3
Silicon Dioxide	decreases expression, increases secretion, increases expression	3
Tobacco Smoke Pollution	affects expression, decreases expression, increases expression	3
Tunicamycin	increases expression, decreases expression, affects reaction	3
Particulate Matter	decreases expression, increases abundance, increases expression	3
methylmercuric chloride	decreases expression	2
nickel chloride	decreases reaction, increases expression, affects reaction, increases abundance, increases phosphorylation	2
diallyl trisulfide	decreases response to substance, decreases expression, decreases reaction, increases cleavage	2
2,3’,4,4’,5-pentachlorobiphenyl	increases expression, decreases reaction, affects reaction	2
chromium hexavalent ion	increases expression, decreases reaction	2
4-phenylbutyric acid	decreases reaction, increases expression	2
4,6-dimorpholino-N-(4-nitrophenyl)-1,3,5-triazin-2-amine	decreases reaction, increases expression, decreases expression	2

ChEMBL screening assays

199 unique, capped per target: 197 binding, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1692976	Binding	Inhibition of human LDH-A using pyruvate as substrate and NADH as cofactor at 125 uM after 5 mins by calorimetric assay relative to control	Discovery of N-hydroxyindole-based inhibitors of human lactate dehydrogenase isoform A (LDH-A) as starvation agents against cancer cells. — J Med Chem
CHEMBL760024	Functional	In vitro relative activity against the D6 clone of Plasmodium falciparum parasite LDH was evaluated by using artemisinin as a control	Structure-activity relationships of the antimalarial agent artemisinin. 3. Total synthesis of (+)-13-carbaartemisinin and related tetra- and tricyclic structures. — J Med Chem

Cellosaurus cell lines

9 cell lines: 8 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B7XZ	Abcam Raji LDHA KO	Cancer cell line	Male
CVCL_B9YP	Abcam THP-1 LDHA KO	Cancer cell line	Male
CVCL_C7AG	Abcam PC-3 LDHA KO	Cancer cell line	Male
CVCL_D9IG	Ubigene HEK293 LDHA KO	Transformed cell line	Female
CVCL_E0VQ	Ubigene Huh-7 LDHA KO	Cancer cell line	Male
CVCL_E0ZC	Ubigene MSTO-211H LDHA KO	Cancer cell line	Male
CVCL_E1FA	Ubigene ZR-75-1 LDHA KO	Cancer cell line	Female
CVCL_SV40	HAP1 LDHA (-) 1	Cancer cell line	Male
CVCL_SV41	HAP1 LDHA (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT07459582	Not specified	RECRUITING	Accuracy of Home Lactate Meter and Accu-chek Glucometer in Patients With Glycogen Storage Disease