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): 264 total — 7 pathogenic, 5 likely-pathogenic
• GTEx eGene: eQTL in 25 tissues, sQTL in 14 (q < 0.05)
• Phenotypes (HPO): 36
• ChEMBL bioactivity: 4 clinical-phase molecules tested; no curated mechanism-of-action drug
• Constraint (gnomAD): pLI 0.77 (intermediate), LOEUF 0.61 (unconstrained)
• MANE Select transcript: NM_005566
• Interaction hub: 4,568 STRING partners (top 1% of genes corpus-wide)

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: 57 — 38 protein_coding, 13 nonsense_mediated_decay, 6 retained_intron

MANE Select: ENST00000422447

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 2: 10, TSL 3: 5, TSL 4: 2, TSL 5: 3

ENST00000422447, ENST00000227157, ENST00000375710, ENST00000379412, ENST00000396222, 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, ENST00001056684, ENST00001072648, ENST00001072650, ENST00001072652, ENST00001072654, ENST00001072659, ENST00001072662, ENST00001072669, ENST00001128471

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.

Highest expression (Bgee): ventricular zone, zone of skin, skin of leg, skin of abdomen, popliteal artery.

Genetic regulation across tissues (GTEx eQTL / sQTL)

LDHA is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 25 tissues and its splicing (sQTL) in 14 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 39 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Muscle Skeletal	eqtl	1.1e-48	-0.31	11:18369690:G:C
Brain Cerebellum	sqtl	9.4e-20	-0.90	11:18407920:T:C
Brain Frontal Cortex BA9	sqtl	1.4e-18	-0.80	11:18401563:C:T
Testis	sqtl	4.8e-16	+0.46	11:18393073:G:C
Brain Cerebellar Hemisphere	sqtl	1.1e-14	-0.55	11:18393073:G:C
Thyroid	eqtl	7.8e-14	-0.14	11:18385773:G:A
Brain Cortex	sqtl	9.6e-13	-0.77	11:18407920:T:C
Whole Blood	eqtl	5.5e-12	-0.11	11:18379984:G:A
Lung	eqtl	1.7e-10	-0.13	11:18395321:A:G
Adipose Subcutaneous	eqtl	1.2e-09	-0.18	11:18377191:A:C
Artery Aorta	eqtl	2.5e-08	-0.20	11:18377191:A:C
Nerve Tibial	eqtl	2.6e-08	-0.14	11:18383963:G:T
Lung	sqtl	3.5e-08	-0.24	11:18407920:T:C
Artery Tibial	eqtl	4.0e-08	-0.16	11:18390870:C:T
Brain Anterior cingulate cortex BA24	sqtl	1.9e-07	-0.81	11:18393073:G:C
Heart Atrial Appendage	sqtl	2.7e-07	-0.30	11:18393073:G:C
Cells Cultured fibroblasts	eqtl	1.6e-06	-0.09	11:18411103:C:T
Brain Nucleus accumbens basal ganglia	sqtl	2.0e-06	-0.52	11:18401563:C:T
Adipose Visceral Omentum	eqtl	2.8e-06	-0.11	11:18383963:G:T
Breast Mammary Tissue	eqtl	6.8e-06	-0.10	11:18388522:A:T

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

showing 100 of 157 tissues 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
esophagus mucosa	UBERON:0002469	99.34	gold quality
omental fat pad	UBERON:0010414	99.34	gold quality
islet of Langerhans	UBERON:0000006	99.32	gold quality
cortex of kidney	UBERON:0001225	99.32	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.32	gold quality
esophagus	UBERON:0001043	99.30	gold quality
endometrium	UBERON:0001295	99.30	gold quality
right coronary artery	UBERON:0001625	99.30	gold quality
lower esophagus	UBERON:0013473	99.26	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.26	gold quality
mammary gland	UBERON:0001911	99.25	gold quality
small intestine	UBERON:0002108	99.25	gold quality
small intestine Peyer’s patch	UBERON:0003454	99.25	gold quality
thoracic mammary gland	UBERON:0005200	99.25	gold quality
stromal cell of endometrium	CL:0002255	99.23	gold quality
skeletal muscle tissue	UBERON:0001134	99.23	gold quality
superior frontal gyrus	UBERON:0002661	99.22	gold quality
vagina	UBERON:0000996	99.20	gold quality
adult mammalian kidney	UBERON:0000082	99.19	gold quality
intestine	UBERON:0000160	99.19	gold quality
colon	UBERON:0001155	99.19	gold quality
placenta	UBERON:0001987	99.19	gold quality
right atrium auricular region	UBERON:0006631	99.18	gold quality
rectum	UBERON:0001052	99.17	gold quality
ganglionic eminence	UBERON:0004023	99.17	gold quality
embryo	UBERON:0000922	99.16	gold quality
transverse colon	UBERON:0001157	99.16	gold quality
left uterine tube	UBERON:0001303	99.16	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.16	gold quality
adrenal tissue	UBERON:0018303	99.15	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.15	gold quality
smooth muscle tissue	UBERON:0001135	99.14	gold quality
liver	UBERON:0002107	99.13	gold quality
urinary bladder	UBERON:0001255	99.12	gold quality
minor salivary gland	UBERON:0001830	99.11	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.11	gold quality
bone element	UBERON:0001474	99.10	gold quality
bone marrow	UBERON:0002371	99.10	gold quality
right lobe of liver	UBERON:0001114	99.07	gold quality
heart	UBERON:0000948	99.06	gold quality
saliva-secreting gland	UBERON:0001044	99.06	gold quality
cortical plate	UBERON:0005343	99.06	gold quality
kidney	UBERON:0002113	99.05	gold quality
upper lobe of left lung	UBERON:0008952	99.05	gold quality
lymph node	UBERON:0000029	99.03	gold quality
right lobe of thyroid gland	UBERON:0001119	99.01	gold quality
gall bladder	UBERON:0002110	98.99	gold quality
lower esophagus mucosa	UBERON:0035834	98.99	gold quality
bone marrow cell	CL:0002092	98.95	gold quality
prefrontal cortex	UBERON:0000451	98.95	gold quality
heart left ventricle	UBERON:0002084	98.95	gold quality
nerve	UBERON:0001021	98.94	gold quality
tibial nerve	UBERON:0001323	98.94	gold quality
left lobe of thyroid gland	UBERON:0001120	98.93	gold quality
lung	UBERON:0002048	98.93	gold quality
muscle tissue	UBERON:0002385	98.93	gold quality
ectocervix	UBERON:0012249	98.90	gold quality
frontal cortex	UBERON:0001870	98.89	gold quality
thyroid gland	UBERON:0002046	98.89	gold quality
frontal lobe	UBERON:0016525	98.89	gold quality
material anatomical entity	UBERON:0000465	98.85	gold quality
anatomical system	UBERON:0000467	98.85	gold quality
multicellular organism	UBERON:0000468	98.85	gold quality
uterine cervix	UBERON:0000002	98.84	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	98.84	gold quality
anterior cingulate cortex	UBERON:0009835	98.84	gold quality
uterus	UBERON:0000995	98.80	gold quality
hypothalamus	UBERON:0001898	98.80	gold quality
right frontal lobe	UBERON:0002810	98.75	gold quality
cerebral cortex	UBERON:0000956	98.74	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

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Skeletal muscle	tissue	543.8	medium
Frontal cortex	tissue	521.6
Tongue	tissue	466.6
Retina	tissue	411.4
Caudate putamen	tissue	398.0
Vagina	tissue	306.6	low
Liver	tissue	271.8	medium
Adipose tissue	tissue	196.1	medium
Bone marrow	tissue	173.9	medium
Small intestine	tissue	173.3	medium
Urinary bladder	tissue	167.4	medium
Locus coeruleus	tissue	152.5
Duodenum	tissue	148.7	medium
Tonsil	tissue	137.1	medium
Appendix	tissue	131.7	medium
Esophagus	tissue	126.7	medium
Colon	tissue	121.7	low
Smooth muscle	tissue	116.0	not detected
Skin 1	tissue	112.5	low
Rectum	tissue	110.3	medium
Adrenal gland	tissue	108.8	medium
Thymus	tissue	107.4
Placenta	tissue	106.9	not detected
Postcentral gyrus	tissue	102.6
Breast	tissue	98.1	medium
Prefrontal cortex	tissue	98.1
Cerebral cortex	tissue	98.1	medium
Motor cortex	tissue	97.6
Hippocampal formation	tissue	97.4
Kidney	tissue	92.7	medium
Retrosplenial and cingulate cortex	tissue	92.2
Pituitary gland	tissue	91.0
Lymph node	tissue	90.8	medium
Retrosplenial cortex	tissue	82.2
Entorhinal cortex	tissue	78.6
Somatosensory cortex	tissue	77.9
Seminal vesicle	tissue	77.1	medium
Cervix	tissue	76.0	medium
Insular cortex	tissue	73.6
Choroid plexus	tissue	72.6
Gallbladder	tissue	70.9	medium
Heart muscle	tissue	70.8	not detected
Occipital cortex	tissue	69.4
Lung	tissue	68.7	medium
Temporal cortex	tissue	68.5
Nucleus accumbens	tissue	64.3
Hippocampus	tissue	59.8	medium
Thyroid gland	tissue	56.9	medium
Amygdala	tissue	54.0
Salivary gland	tissue	51.8	medium
Testis	tissue	49.4	medium
Prostate	tissue	48.4	medium
Stomach 1	tissue	48.0	medium
Spleen	tissue	47.3	medium
Ovary	tissue	46.5	medium
Endometrium 1	tissue	44.5	medium
Epididymis	tissue	41.1	medium
Cerebellum	tissue	40.9	low
Pancreas	tissue	40.2	low
Fallopian tube	tissue	33.6	medium

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Blood vessel (510.2), Median raphe nucleus (108.6), Nucleus raphe pallidus (107.6), Lateral hypothalamic area (106.6), Ventral hippocampus (97.4).

Regulation

Is transcription factor: no

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

miRNA regulators (miRDB)

Targeting LDHA by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 50 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 0.774, LOEUF 0.613, missense Z 2.23 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000422447 — one region, missense o/e 0.66.

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

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ldha	ENSDARG00000101251
mus_musculus	Ldha	ENSMUSG00000063229
rattus_norvegicus		ENSRNOG00000068651

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

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:96759) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 29 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased hemoglobin content	3
decreased hematocrit	2
hemolytic anemia	2
reticulocytosis	2
decreased erythrocyte cell number	2
postnatal lethality, complete penetrance	2
decreased circulating HDL cholesterol level	1
increased neutrophil cell number	1
spleen hyperplasia	1
decreased body size	1
abnormal erythrocyte morphology	1
increased mean corpuscular volume	1
increased heart weight	1
decreased circulating alanine transaminase level	1
decreased circulating alkaline phosphatase level	1
increased liver weight	1
increased spleen weight	1
increased circulating bilirubin level	1
decreased lactate dehydrogenase level	1
abnormal enzyme/coenzyme activity	1
increased lung weight	1
abnormal common myeloid progenitor cell morphology	1
abnormal leukocyte morphology	1
decreased total body fat amount	1
embryonic lethality during organogenesis, complete penetrance	1

+4 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bifidobacterium longum subsp. longum JCM 1217	E8ME30	100.0%	Diamond
Bifidobacterium longum NCC2705	P0CW93	100.0%	Diamond
Chaenocephalus aceratus	P69080	100.0%	Diamond
Chionodraco rastrospinosus	P69081	100.0%	Diamond
Trematomus bernacchii	P69082	100.0%	Diamond
Gillichthys mirabilis	P69083	100.0%	Diamond
Gillichthys seta	P69084	100.0%	Diamond
Notothenia angustata	P69085	100.0%	Diamond
Pagothenia borchgrevinki	P69086	100.0%	Diamond
Macaca fascicularis	Q4R5B6	100.0%	Diamond
Pan troglodytes	A5A6N7	99.7%	Diamond
Sphyraena idiastes	O13277	99.7%	Diamond
Sphyraena lucasana	O13278	99.7%	Diamond
Rhinogobiops nicholsii	O93401	99.7%	Diamond
Champsocephalus gunnari	O93541	99.7%	Diamond
Dissostichus mawsoni	O93544	99.7%	Diamond
Lindbergichthys nudifrons	O93545	99.7%	Diamond
Patagonotothen tessellata	O93546	99.7%	Diamond
Pongo abelii	Q5R5F0	99.7%	Diamond
Dissostichus eleginoides	Q9PW61	99.7%	Diamond
Bos grunniens	A0A1F3	99.4%	Diamond
Parachaenichthys charcoti	O93538	99.4%	Diamond
Notothenia neglecta	O93539	99.4%	Diamond
Gobionotothen gibberifrons	O93540	99.4%	Diamond
Bos taurus	P19858	99.4%	Diamond
Harpagifer antarcticus	O93537	98.8%	Diamond
Paranotothenia magellanica	O93543	98.8%	Diamond
Caiman crocodilus apaporiensis	Q98SL2	98.8%	Diamond
Alligator mississippiensis	Q9PW06	98.8%	Diamond
Sus scrofa	P00336	98.2%	Diamond
Oryctolagus cuniculus	P13490	97.7%	Diamond
Xenopus laevis	P42119	97.6%	Diamond
Fundulus heteroclitus	P20373	97.5%	Diamond
Fundulus parvipinnis	P42122	97.5%	Diamond
Gallus gallus	P00337	97.3%	Diamond
Anas platyrhynchos	P13743	97.3%	Diamond
Pelodiscus sinensis japonicus	Q98SL0	97.3%	Diamond
Trachemys scripta elegans	Q9PT43	97.3%	Diamond
Monodelphis domestica	Q9XT86	97.3%	Diamond
Eleginops maclovinus	O93542	96.7%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
HPS5	protein-coding	11234
GTF2H1	protein-coding	2965
LDHC	protein-coding	3948
MIR3159	ncRNA	100423016
SAA1	protein-coding	6288
LDHAL6A	protein-coding	160287
UEVLD	protein-coding	55293
TSG101	protein-coding	7251

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): F5GWW2, F5GXC7, F5GXH2, F5GXU1, F5GXY2, F5GYU2, F5GZQ4, F5H5J4, F5H6W8, F5H8H6, P00338, 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)

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

UniProt features (75 total): modified residue 20, helix 18, strand 14, 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)

showing 30 of 46 structures by resolution:

PDB	Title	Method	Resolution (Å)
5W8J	Crystal Structure of Lactate Dehydrogenase A in complex with inhibitor compound 29	X-RAY DIFFRACTION	1.55
5W8K	Crystal Structure of Lactate Dehydrogenase A in complex with inhibitor compound 29 and …	X-RAY DIFFRACTION	1.6
5W8H	Crystal Structure of Lactate Dehydrogenase A in complex with inhibitor compound 11	X-RAY DIFFRACTION	1.8
9BK2	Crystal structure of Lactate dehydrogenase in complex with …	X-RAY DIFFRACTION	1.85
4JNK	Lactate Dehydrogenase A in complex with inhibitor compound 22	X-RAY DIFFRACTION	1.9
4RLS	Lactate Dehydrogenase in complex with inhibitor compound 47	X-RAY DIFFRACTION	1.91
5W8I	Crystal Structure of Lactate Dehydrogenase A in complex with inhibitor compound 23 and …	X-RAY DIFFRACTION	1.95
5W8L	Crystal Structure of Lactate Dehydrogenase A in complex with inhibitor compound 59 and …	X-RAY DIFFRACTION	1.95
6BB0	Lactate Dehydrogenase in complex with inhibitor …	X-RAY DIFFRACTION	1.95
6MV8	LDHA structure in complex with inhibitor 14	X-RAY DIFFRACTION	1.95
6Q13	CRYSTAL STRUCTURE OF LDHA IN COMPLEX WITH COMPOUND NCGC00420737-09 AT 2.00 A RESOLUTION	X-RAY DIFFRACTION	2
4QO8	Lactate Dehydrogenase A in complex with substituted 3-Hydroxy-2-mercaptocyclohex-2-enone …	X-RAY DIFFRACTION	2
6MVA	LDHA structure in complex with inhibitor 14	X-RAY DIFFRACTION	2.02
5IXS	Lactate Dehydrogenase in complex with hydroxylactam inhibitor compound 9: …	X-RAY DIFFRACTION	2.05
6BAX	Lactate Dehydrogenase in complex with inhibitor …	X-RAY DIFFRACTION	2.05
6Q0D	CRYSTAL STRUCTURE OF LDHA IN COMPLEX WITH COMPOUND NCGC00384414-01 AT 2.05 A RESOLUTION	X-RAY DIFFRACTION	2.05
4M49	Lactate Dehydrogenase A in complex with a substituted pyrazine inhibitor compound 18	X-RAY DIFFRACTION	2.05
4L4R	Structural Characterisation of the Apo-form of Human Lactate Dehydrogenase M Isozyme	X-RAY DIFFRACTION	2.1
4OKN	Crystal structure of human muscle L-lactate dehydrogenase, ternary complex with NADH and …	X-RAY DIFFRACTION	2.1
6BAD	Lactate Dehydrogenase in complex with inhibitor …	X-RAY DIFFRACTION	2.1
4R68	Lactate Dehydrogenase in complex with inhibitor compound 31	X-RAY DIFFRACTION	2.11
4QO7	Lactate Dehydrogenase A in complex with substituted 3-Hydroxy-2-mercaptocyclohex-2-enone …	X-RAY DIFFRACTION	2.14
4ZVV	Lactate dehydrogenase A in complex with a trisubstituted piperidine-2,4-dione inhibitor …	X-RAY DIFFRACTION	2.2
1I10	HUMAN MUSCLE L-LACTATE DEHYDROGENASE M CHAIN, TERNARY COMPLEX WITH NADH AND OXAMATE	X-RAY DIFFRACTION	2.3
6BB1	Lactate Dehydrogenase in complex with inhibitor …	X-RAY DIFFRACTION	2.3
8FW6	Human Lactate Dehydrogenase A in Complex with Inhibitor CHK-336	X-RAY DIFFRACTION	2.34
4AJP	Human LDHA in complex with 2-((4-(4-((3-((2-methyl-1,3-benzothiazol- …	X-RAY DIFFRACTION	2.38
5ZJD	Lactate dehydrogenase with NADH and MLA	X-RAY DIFFRACTION	2.39
4OJN	Crystal structure of human muscle L-lactate dehydrogenase	X-RAY DIFFRACTION	2.4
6BAG	Lactate Dehydrogenase in complex with inhibitor …	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Oxidoreductases, Metabolic proteins, Predicted intracellular proteins, Plasma proteins, Cancer-related genes, Candidate cancer biomarkers, Disease related genes, FDA approved drug targets, Small molecule drugs, Human disease related genes, Congenital disorders of metabolism, Congenital disorders of carbohydrate metabolism, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol

Antibody reliability (HPA): IH uncertain · IF enhanced

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)

Position	Role
193	proton acceptor

Ligand- & substrate-binding residues (7)

Position	Role
29–57	NAD(+)
99	NAD(+)
106	substrate
138	NAD(+)
138	substrate
169	substrate
248	substrate

Post-translational modifications (21)

Type	Positions
N-acetylalanine	2
N6-acetyllysine	5, 14, 57, 81, 118, 126, 224, 232, 243, 318
N6-succinyllysine	5, 118, 318
Phosphotyrosine	10, 239
Phosphothreonine	18, 309, 322
Phosphoserine	310
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo2)	57

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

2 curated (TAS) of 4; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

4 pathways:

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

MSigDB gene sets: 0 (showing top):

GO Biological Process (5): lactate metabolic process (GO:0006089), glycolytic process (GO:0006096), 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 (7): nucleus (GO:0005634), mitochondrion (GO:0005739), cytosol (GO:0005829), membrane (GO:0016020), sperm fibrous sheath (GO:0035686), extracellular exosome (GO:0070062), cytoplasm (GO:0005737)

Reactome top-level categories

3 top-level categories:

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

GO top-level categories

32 GO namespaces:

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 (phosphorylating, [NAD(P)+] ) 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
intracellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 9 of 20 annotations. The rest are phylogenetic / computational / electronic (IEA).

9 experimentally-supported GO terms:

GO term	NS	Evidence
lactate metabolic process	BP	direct assay
substantia nigra development	BP	high-throughput mutant
cytosol	CC	direct assay
extracellular exosome	CC	high-throughput assay
membrane	CC	high-throughput assay
nucleus	CC	high-throughput assay
L-lactate dehydrogenase (NAD+) activity	MF	mutant phenotype
cadherin binding	MF	high-throughput assay
identical protein binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 4,568 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LDHA	PKM	P14618	893
LDHA	SLC2A1	P11166	859
LDHA	HIF1A	Q16665	851
LDHA	MYC	P01106	821
LDHA	HK2	P52789	811
LDHA	GAPDH	P00354	806
LDHA	GPI	P06744	803
LDHA	PGK1	P00558	789
LDHA	G6PD	P11413	786
LDHA	ENO1	P06733	786
LDHA	PDK1	Q15118	784
LDHA	H6PD	O95479	783
LDHA	ALDOA	P04075	772
LDHA	SLC16A3	O15427	767
LDHA	PFKM	P08237	766

IntAct

Human interaction partners of LDHA in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

23 partners by confidence:

Partner	Interaction type	MIscore	Records
LDHB	association	0.800	5
LDHC	association	0.770	6
HSPA8	direct interaction	0.640	4
APOL3	physical association	0.400	1
PPM1K	physical association	0.400	1
YWHAZ	physical association	0.400	1
ACD	physical association	0.370	1
E6	physical association	0.370	1
GSK3A	physical association	0.370	1
MAPK10	physical association	0.370	1
PCNA	physical association	0.370	1
POT1	physical association	0.370	1
SPG11	physical association	0.370	1
TERF1	physical association	0.370	1
TFAP2A	physical association	0.370	1
TINF2	physical association	0.370	1
UBE2E2	physical association	0.370	1
ALG2	association	0.350	1
ARHGAP24	association	0.350	1
ELOVL1	association	0.350	1
ERCC6L	association	0.350	1
LDHAL6A	association	0.350	1
XRN1	physical association	0.000	1

BioGRID (607 interactions; top human partners by supporting records in a sample of 600 records): LDHB (Two-hybrid; 29 records), LDHAL6A (Affinity Capture-MS; 8 records), LDHC (Affinity Capture-MS; 5 records), HULC (Affinity Capture-MS; 4 records), PARK2 (Affinity Capture-MS; 4 records), FBXW7 (Affinity Capture-MS; 3 records), MARCKSL1 (Cross-Linking-MS (XL-MS); 3 records), SQSTM1 (Affinity Capture-MS; 3 records), AGR2 (Affinity Capture-MS; 2 records), ARF4 (Co-fractionation; 2 records), C9orf72 (Affinity Capture-MS; 2 records), CCNF (Proximity Label-MS; 2 records), CFTR (Affinity Capture-MS; 2 records), CUL3 (Affinity Capture-MS; 2 records), DLD (Affinity Capture-MS; 2 records)

SIGNOR signaling

showing 7 of 8 signaling 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”

Protein complexes (CORUM) (2)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

2 complexes by size:

Complex	Subunits	Members
★ ABCC9-KCNJ11-LDHA (muscle form) complex	3	ABCC9, KCNJ11, LDHA
★ LDHA homotetramer	1	LDHA

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 23 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	5	190.3×	3e-09
Telomere C-strand (Lagging Strand) Synthesis	5	190.3×	3e-09
Removal of the Flap Intermediate from the C-strand	5	158.6×	5e-09
Polymerase switching on the C-strand of the telomere	5	105.7×	4e-08

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of telomere maintenance via telomerase	5	166.5×	2e-08

Disease & clinical

Genetic variants

Variant evidence for LDHA: 264 ClinVar records (12 pathogenic / likely pathogenic); 3 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	5
Uncertain significance	119
Likely benign	75
Benign	33

Top pathogenic / likely-pathogenic (12)

Showing all 12 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
2903039	NM_005566.4(LDHA):c.410C>A (p.Ser137Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
2137028	NM_005566.4(LDHA):c.505C>T (p.Arg169Ter)	Pathogenic	criteria provided, single submitter	1
2848332	NM_005566.4(LDHA):c.631_632dup (p.Leu211_Lys212insTer)	Pathogenic	criteria provided, single submitter	1
4715484	NM_005566.4(LDHA):c.298C>T (p.Gln100Ter)	Pathogenic	criteria provided, single submitter	1
4807073	NM_005566.4(LDHA):c.467dup (p.Asn156fs)	Pathogenic	criteria provided, single submitter	1
1925742	NM_005566.4(LDHA):c.126+2T>C	Likely pathogenic	criteria provided, single submitter	1
2137026	NM_005566.4(LDHA):c.244G>A (p.Asp82Asn)	Likely pathogenic	criteria provided, single submitter	1
3599453	NM_005566.4(LDHA):c.710+1del	Likely pathogenic	criteria provided, single submitter	1
4712109	NM_005566.4(LDHA):c.419-1G>C	Likely pathogenic	criteria provided, single submitter	1
4773910	NM_005566.4(LDHA):c.593-1del	Likely pathogenic	criteria provided, single submitter	1
976711	GRCh37/hg19 11p15.1(chr11:18418095-18422557)	Pathogenic	criteria provided, single submitter	1
14566	NM_005566.4(LDHA):c.759_778del (p.Leu254fs)	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore LDHA’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 29 predictions of 497):

Position(s)	Effect	Δscore	Sites
11:18396817–18396818	acceptor_loss	1.0000	4
11:18396969	donor_loss	1.0000	2
11:18399429–18399430	acceptor_loss	1.0000	5
11:18402837	acceptor_gain	1.0000
11:18402838–18402839	acceptor_loss	1.0000	5
11:18402948	donor_gain	1.0000
11:18403692–18403693	acceptor_loss	1.0000	4
11:18403769	donor_gain	1.0000
11:18403812–18403813	donor_loss	1.0000	5
11:18405407	acceptor_gain	1.0000

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

10 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	6.75e-09
Lung Adenocarcinoma (TCGA)	unfavorable	2.07e-07
Kidney Chromophobe (TCGA)	unfavorable	8.71e-07
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	1.22e-06
Pancreatic Adenocarcinoma (TCGA)	unfavorable	4.52e-06
Liver Hepatocellular Carcinoma (validation)	unfavorable	4.81e-06
Lung Adenocarcinoma (validation)	unfavorable	7.09e-05
Glioblastoma Multiforme (TCGA)	unfavorable	0.000184
Pancreatic Adenocarcinoma (validation)	unfavorable	0.000722
Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (TCGA)	unfavorable	0.000933

Disease associations

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

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
glycogen storage disease due to lactate dehydrogenase M-subunit deficiency	Strong	Autosomal recessive	4

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (11 panels, 11 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

11 panels:

Panel	Rating
Acute rhabdomyolysis	green
Glycogen storage disease	green
Hypotonic infant	green
Ketotic hypoglycaemia	green
Leukodystrophy, childhood onset	green
Likely inborn error of metabolism	green
Other rare neuromuscular disorders	green
Paediatric disorders	green
Rhabdomyolysis and metabolic muscle disorders	green
Undiagnosed metabolic disorders	green
Unexplained death in infancy and sudden unexplained death in childhood	green

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 phenotypes (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 activity
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
HP:0025528	Annular cutaneous lesion
HP:0031190	Superficial dermal perivascular inflammatory infiltrate
HP:0031236	Predominantly dermal neutrophilic infiltrate
HP:0040189	Scaling skin
HP:0045040	Abnormal circulating lactate dehydrogenase concentration
HP:0200039	Pustule

GWAS associations

3 associations:

Study	Trait	p-value
GCST000876_4	Amyloid A serum levels	3e-111
GCST000876_2	Amyloid A serum levels	4e-22
GCST012020_378	Serum metabolite levels	6e-17

MeSH disease descriptors

1 disease descriptors:

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

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 270,593 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

4 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL752	ADENOSINE PHOSPHATE	4	166,120
CHEMBL190461	CANNABIDIOL	4	27,105
CHEMBL465	DRONABINOL	4	63,201
CHEMBL51483	GOSSYPOL	3	14,167

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

800 measured of 1454 human assays (1455 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CHEMBL4476621	IC50	0.6 nM
CHEMBL4855986	IC50	0.9 nM
CHEMBL5181496	IC50	0.9 nM
CHEMBL4792513	IC50	1 nM
CHEMBL4861379	IC50	1.1 nM
CHEMBL4850573	IC50	1.2 nM
CHEMBL5183539	IC50	1.6 nM
CHEMBL5201115	IC50	1.8 nM
CHEMBL610377	KD	2 nM
CHEMBL5181996	IC50	2.2 nM
CHEMBL5194549	IC50	2.5 nM
CHEMBL5185237	IC50	2.5 nM
CHEMBL5416627	IC50	2.6 nM
CHEMBL5196929	IC50	2.7 nM
CHEMBL5176448	IC50	2.9 nM
CHEMBL5182266	IC50	2.9 nM
CHEMBL4576717	IC50	3 nM
CHEMBL4847068	IC50	3.6 nM
CHEMBL5189879	IC50	3.7 nM
CHEMBL5188480	IC50	3.8 nM
CHEMBL4435570	IC50	4 nM
CHEMBL5177632	IC50	4 nM
CHEMBL4864519	IC50	4.7 nM
CHEMBL3335792	IC50	5 nM
CHEMBL4467769	IC50	5 nM
2-[5-(cyclopropylmethyl)-3-[4-fluoro-3-[2-(3-hydroxyoxetan-3-yl)ethynyl]phenyl]-4-[(3-fluoro-4-sulfamoylphenyl)methyl]pyrazol-1-yl]-1,3-thiazole-4-carboxylic acid	IC50	5.5 nM	US-20250205203: SUBSTITUTED PYRAZOLYL COMPOUNDS AND METHODS OF USE THEREOF
2-[5-(cyclopropylmethyl)-3-[4-fluoro-3-[2-(3-methyloxetan-3-yl)ethynyl]phenyl]-4-[(3-fluoro-4-sulfamoylphenyl)methyl]pyrazol-1-yl]-1,3-thiazole-4-carboxylic acid	IC50	5.5 nM	US-20250205203: SUBSTITUTED PYRAZOLYL COMPOUNDS AND METHODS OF USE THEREOF
2-[5-(cyclopropylmethyl)-3-[4-fluoro-3-[2-(1-hydroxycyclobutyl)ethynyl]phenyl]-4-[(3-fluoro-4-sulfamoylphenyl)methyl]pyrazol-1-yl]-1,3-thiazole-4-carboxylic acid	IC50	5.5 nM	US-20250205203: SUBSTITUTED PYRAZOLYL COMPOUNDS AND METHODS OF USE THEREOF
2-[5-(cyclopropylmethyl)-4-[(3-fluoro-4-sulfamoylphenyl)methyl]-3-[3-(3-hydroxy-3-methylbut-1-ynyl)phenyl]pyrazol-1-yl]-1,3-thiazole-4-carboxylic acid	IC50	5.5 nM	US-20250205203: SUBSTITUTED PYRAZOLYL COMPOUNDS AND METHODS OF USE THEREOF
2-[5-(cyclopropylmethyl)-4-[(3-fluoro-4-sulfamoylphenyl)methyl]-3-[3-[2-(oxetan-3-yl)ethynyl]phenyl]pyrazol-1-yl]-1,3-thiazole-4-carboxylic acid	IC50	5.5 nM	US-20250205203: SUBSTITUTED PYRAZOLYL COMPOUNDS AND METHODS OF USE THEREOF
2-[5-(cyclopropylmethyl)-4-[(3-fluoro-4-sulfamoylphenyl)methyl]-3-[3-[2-(3-methyloxetan-3-yl)ethynyl]phenyl]pyrazol-1-yl]-1,3-thiazole-4-carboxylic acid	IC50	5.5 nM	US-20250205203: SUBSTITUTED PYRAZOLYL COMPOUNDS AND METHODS OF USE THEREOF
2-[5-(cyclopropylmethyl)-4-[(3-fluoro-4-sulfamoylphenyl)methyl]-3-[3-[2-(3-hydroxyoxetan-3-yl)ethynyl]phenyl]pyrazol-1-yl]-1,3-thiazole-4-carboxylic acid	IC50	5.5 nM	US-20250205203: SUBSTITUTED PYRAZOLYL COMPOUNDS AND METHODS OF USE THEREOF
CHEMBL3581197	IC50	6 nM
CHEMBL4444963	IC50	7 nM
CHEMBL5196259	IC50	8.6 nM
CHEMBL4545064	IC50	9 nM
CHEMBL4436150	IC50	9 nM
CHEMBL4475593	IC50	10 nM
CHEMBL4751495	IC50	10 nM
CHEMBL5202219	IC50	10 nM
2-[5-(cyclopropylmethyl)-3-(4-fluoro-3-prop-1-ynylphenyl)-4-[(3-fluoro-4-sulfamoylphenyl)methyl]pyrazol-1-yl]-1,3-thiazole-4-carboxylic acid	IC50	11 nM	US-11247971: Small molecule inhibitors of lactate dehydrogenase and methods of use thereof
2-[5-(cyclopropylmethyl)-3-[4-fluoro-3-[(E)-prop-1-enyl]phenyl]-4-[(3-fluoro-4-sulfamoylphenyl)methyl]pyrazol-1-yl]-1,3-thiazole-4-carboxylic acid	IC50	11 nM	US-11247971: Small molecule inhibitors of lactate dehydrogenase and methods of use thereof
CHEMBL4873879	IC50	11 nM
CHEMBL5206296	IC50	12 nM
CHEMBL4536094	IC50	13 nM
CHEMBL5172378	IC50	13 nM
CHEMBL5171701	IC50	13 nM
2-[3-(3-cyclopentyloxyphenyl)-5-(cyclopropylmethyl)-4-[(3-fluoro-4-sulfamoylphenyl)methyl]pyrazol-1-yl]-1,3-thiazole-4-carboxylic acid	IC50	13 nM	US-11247971: Small molecule inhibitors of lactate dehydrogenase and methods of use thereof
CHEMBL4521960	IC50	14 nM
CHEMBL3581201	IC50	15 nM

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

905 with measured affinity, of 1716 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

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

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

10 cell lines: 8 cancer cell line, 2 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_F4QV	HyCyte HK-2 [Human kidney] stable cell line for hLDHA overexpression	Transformed cell line	Male
CVCL_SV40	HAP1 LDHA (-) 1	Cancer cell line	Male
CVCL_SV41	HAP1 LDHA (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

1 trials:

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

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for LDHA across ~30M SureChEMBL compounds — explore on Sugi Predict.