LDHC

Summary

LDHC (lactate dehydrogenase C, HGNC:6544) is a protein-coding gene on chromosome 11p15.1, encoding L-lactate dehydrogenase C chain (P07864). Possible role in sperm motility.

Lactate dehydrogenase C catalyzes the conversion of L-lactate and NAD to pyruvate and NADH in the final step of anaerobic glycolysis. LDHC is testis-specific and belongs to the lactate dehydrogenase family. Two transcript variants have been detected which differ in the 5’ untranslated region.

Source: NCBI Gene 3948 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 48 total
• GTEx eGene: eQTL in 50 tissues, sQTL in 1 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.87 (unconstrained)
• MANE Select transcript: NM_017448
• Interaction hub: 1,746 STRING partners (top 10% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6544
Approved symbol	LDHC
Name	lactate dehydrogenase C
Location	11p15.1
Locus type	gene with protein product
Status	Approved
Aliases	CT32
Ensembl gene	ENSG00000166796
Ensembl biotype	protein_coding
OMIM	150150
Entrez	3948

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 11 protein_coding, 7 nonsense_mediated_decay

MANE Select: ENST00000541669

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

ENST00000541669, ENST00000280704, ENST00000396215, ENST00000535809, ENST00000536880, ENST00000537486, ENST00000539369, ENST00000544105, ENST00000545848, ENST00000546146, ENST00000940409, ENST00000982625, ENST00000982626, ENST00001094539, ENST00001094540, ENST00001094541, ENST00001128938, ENST00001144465

RefSeq mRNA: 2 — MANE Select: NM_017448 NM_002301, NM_017448

CCDS: CCDS7840

Canonical transcript exons

ENST00000541669 — 8 exons

Exon	Start	End
ENSE00001106737	18415184	18415301
ENSE00001225733	18412709	18412843
ENSE00001524255	18412318	18412408
ENSE00002269651	18450963	18452063
ENSE00003578471	18434740	18434913
ENSE00003591075	18446210	18446333
ENSE00003598238	18438528	18438645
ENSE00003690421	18429737	18429910

Expression profiles

Bgee: expression breadth ubiquitous, 160 present calls, max score 98.88.

FANTOM5 (CAGE): breadth broad, TPM avg 1.4050 / max 903.0721, expressed in 189 samples.

Highest expression (Bgee): testis, adult organism, sperm, male germ cell, male germ line stem cell (sensu Vertebrata) in testis.

Genetic regulation across tissues (GTEx eQTL / sQTL)

LDHC is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 50 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 51 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Muscle Skeletal	eqtl	2.6e-122	+1.43	11:18411912:A:C
Skin Sun Exposed Lower leg	eqtl	2.8e-106	+1.43	11:18411912:A:C
Adipose Subcutaneous	eqtl	1.9e-104	+1.47	11:18411912:A:C
Lung	eqtl	1.4e-94	+1.44	11:18412342:A:C
Thyroid	eqtl	1.8e-92	+1.38	11:18411912:A:C
Cells Cultured fibroblasts	eqtl	7.8e-92	+1.43	11:18412342:A:C
Artery Tibial	eqtl	2.7e-88	-1.43	11:18448758:G:T
Esophagus Muscularis	eqtl	1.5e-85	+1.43	11:18411912:A:C
Nerve Tibial	eqtl	1.5e-85	+1.41	11:18411912:A:C
Adipose Visceral Omentum	eqtl	4.2e-85	+1.40	11:18412342:A:C
Whole Blood	eqtl	2.6e-84	+1.24	11:18412342:A:C
Skin Not Sun Exposed Suprapubic	eqtl	6.0e-81	+1.37	11:18413911:A:T
Heart Atrial Appendage	eqtl	4.0e-73	+1.48	11:18412342:A:C
Colon Transverse	eqtl	1.8e-66	+1.44	11:18411912:A:C
Breast Mammary Tissue	eqtl	8.3e-66	+1.33	11:18413911:A:T
Heart Left Ventricle	eqtl	5.8e-65	+1.33	11:18411912:A:C
Esophagus Mucosa	eqtl	5.9e-63	+1.36	11:18412342:A:C
Colon Sigmoid	eqtl	5.2e-54	+1.36	11:18411912:A:C
Artery Aorta	eqtl	2.4e-53	+1.38	11:18411912:A:C
Brain Caudate basal ganglia	eqtl	7.3e-51	+1.43	11:18412342:A:C

FANTOM5 promoters

3 alternative TSS:

Promoter ID	TPM avg	Samples expressed
113339	1.3130	179
113340	0.0741	11
206218	0.0180	7

Top tissues by expression

showing 100 of 279 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	98.88	gold quality
right testis	UBERON:0004534	98.80	gold quality
adult organism	UBERON:0007023	98.58	gold quality
sperm	CL:0000019	98.22	gold quality
male germ cell	CL:0000015	97.74	gold quality
testis	UBERON:0000473	96.43	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.87	gold quality
oocyte	CL:0000023	90.38	gold quality
secondary oocyte	CL:0000655	86.95	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.32	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	76.46	gold quality
buccal mucosa cell	CL:0002336	73.40	silver quality
upper arm skin	UBERON:0004263	69.18	gold quality
diaphragm	UBERON:0001103	68.76	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	68.08	gold quality
vastus lateralis	UBERON:0001379	67.88	gold quality
apex of heart	UBERON:0002098	67.49	gold quality
quadriceps femoris	UBERON:0001377	66.87	gold quality
cervix squamous epithelium	UBERON:0006922	66.77	gold quality
decidua	UBERON:0002450	66.74	gold quality
hair follicle	UBERON:0002073	66.67	gold quality
epithelial cell of pancreas	CL:0000083	66.47	gold quality
vena cava	UBERON:0004087	65.93	gold quality
cervix epithelium	UBERON:0004801	64.44	gold quality
triceps brachii	UBERON:0001509	64.09	gold quality
right uterine tube	UBERON:0001302	63.85	gold quality
type B pancreatic cell	CL:0000169	63.10	gold quality
cartilage tissue	UBERON:0002418	63.09	gold quality
jejunal mucosa	UBERON:0000399	62.55	silver quality
pericardium	UBERON:0002407	62.53	gold quality
palpebral conjunctiva	UBERON:0001812	62.45	silver quality
gluteal muscle	UBERON:0002000	62.30	gold quality
olfactory bulb	UBERON:0002264	62.21	gold quality
squamous epithelium	UBERON:0006914	61.78	gold quality
esophagus squamous epithelium	UBERON:0006920	61.35	gold quality
amniotic fluid	UBERON:0000173	60.87	gold quality
pharyngeal mucosa	UBERON:0000355	60.77	gold quality
muscle tissue	UBERON:0002385	60.69	silver quality
mucosa of urinary bladder	UBERON:0001259	60.64	gold quality
epithelium of esophagus	UBERON:0001976	60.40	gold quality
pons	UBERON:0000988	60.24	gold quality
deltoid	UBERON:0001476	60.15	gold quality
jejunum	UBERON:0002115	60.13	silver quality
blood vessel layer	UBERON:0004797	59.92	gold quality
tongue squamous epithelium	UBERON:0006919	59.86	gold quality
body of tongue	UBERON:0011876	59.86	gold quality
myocardium	UBERON:0002349	59.69	gold quality
trachea	UBERON:0003126	59.61	gold quality
upper leg skin	UBERON:0004262	59.57	silver quality
thymus	UBERON:0002370	59.33	gold quality
cerebellar vermis	UBERON:0004720	58.71	gold quality
saphenous vein	UBERON:0007318	58.55	gold quality
oviduct epithelium	UBERON:0004804	58.41	gold quality
epithelium of nasopharynx	UBERON:0001951	58.29	gold quality
nasal cavity epithelium	UBERON:0005384	57.79	gold quality
mammary duct	UBERON:0001765	57.43	gold quality
tendon of biceps brachii	UBERON:0008188	57.41	gold quality
tongue	UBERON:0001723	57.36	gold quality
muscle organ	UBERON:0001630	57.33	gold quality
mucosa of sigmoid colon	UBERON:0004993	56.70	gold quality
synovial joint	UBERON:0002217	56.66	gold quality
endometrium epithelium	UBERON:0004811	56.60	gold quality
duodenum	UBERON:0002114	56.36	gold quality
oral cavity	UBERON:0000167	56.06	gold quality
dorsal root ganglion	UBERON:0000044	56.03	gold quality
cauda epididymis	UBERON:0004360	56.02	gold quality
right lobe of liver	UBERON:0001114	56.00	gold quality
dorsal plus ventral thalamus	UBERON:0001897	55.85	gold quality
subthalamic nucleus	UBERON:0001906	55.80	gold quality
trigeminal ganglion	UBERON:0001675	55.79	gold quality
gingiva	UBERON:0001828	55.70	gold quality
gingival epithelium	UBERON:0001949	55.51	gold quality
substantia nigra pars compacta	UBERON:0001965	55.47	gold quality
pylorus	UBERON:0001166	55.03	gold quality
liver	UBERON:0002107	55.01	gold quality
mammalian vulva	UBERON:0000997	54.80	gold quality
gastrocnemius	UBERON:0001388	54.80	gold quality
metanephros	UBERON:0000081	54.77	gold quality
superficial temporal artery	UBERON:0001614	54.67	gold quality
urethra	UBERON:0000057	54.57	gold quality
medial globus pallidus	UBERON:0002477	54.53	gold quality
cortex of kidney	UBERON:0001225	54.51	gold quality
nipple	UBERON:0002030	54.51	gold quality
substantia nigra pars reticulata	UBERON:0001966	54.43	gold quality
mucosa of paranasal sinus	UBERON:0005030	54.42	gold quality
globus pallidus	UBERON:0001875	54.39	gold quality
adult mammalian kidney	UBERON:0000082	54.33	gold quality
kidney	UBERON:0002113	54.28	gold quality
germinal epithelium of ovary	UBERON:0001304	54.17	gold quality
renal medulla	UBERON:0000362	54.15	gold quality
fallopian tube	UBERON:0003889	54.11	gold quality
muscle of leg	UBERON:0001383	54.09	gold quality
nephron tubule	UBERON:0001231	54.08	silver quality
penis	UBERON:0000989	54.02	gold quality
Brodmann (1909) area 46	UBERON:0006483	53.87	gold quality
inferior vagus X ganglion	UBERON:0005363	53.69	gold quality
superior surface of tongue	UBERON:0007371	53.65	gold quality
ventral tegmental area	UBERON:0002691	53.53	gold quality
trabecular bone tissue	UBERON:0002483	53.52	gold quality
lateral globus pallidus	UBERON:0002476	53.50	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	4370.37
E-GEOD-124263	yes	1284.43
E-ANND-3	yes	3.76

HPA expression

RNA tissue specificity: Tissue enriched

showing 60 of 64 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Testis	tissue	247.8	high
Choroid plexus	tissue	3.1
Nucleus accumbens	tissue	3.0
Hippocampus	tissue	2.8	not detected
Postcentral gyrus	tissue	2.7
Locus coeruleus	tissue	2.2
Cerebellum	tissue	2.0	not detected
Cerebral cortex	tissue	1.3	not detected
Hypothalamus	tissue	1.3
Liver	tissue	1.3	not detected
Retrosplenial cortex	tissue	1.3
Pancreas	tissue	1.2	not detected
Retrosplenial and cingulate cortex	tissue	1.2
Olfactory bulb	tissue	1.2
Basal ganglia	tissue	1.1	not detected
Hippocampal formation	tissue	1.1
Medulla oblongata	tissue	0.9
Ventral forebrain	tissue	0.9
Pons	tissue	0.8
Motor cortex	tissue	0.8
Occipital cortex	tissue	0.8
Insular cortex	tissue	0.8
Putamen	tissue	0.7
Amygdala	tissue	0.7
Thalamus	tissue	0.7
Small intestine	tissue	0.7	not detected
Corpus callosum	tissue	0.7
Periaqueductal gray	tissue	0.7
Septum	tissue	0.7
Prefrontal cortex	tissue	0.6
Tonsil	tissue	0.6	not detected
Epididymis	tissue	0.5	not detected
Midbrain	tissue	0.5
Thyroid gland	tissue	0.5	not detected
Kidney	tissue	0.5	not detected
Entorhinal cortex	tissue	0.5
Fallopian tube	tissue	0.5	not detected
Temporal cortex	tissue	0.5
Salivary gland	tissue	0.4	not detected
Spinal cord	tissue	0.4
Somatosensory cortex	tissue	0.4
Skin 1	tissue	0.3	not detected
Lymph node	tissue	0.3	not detected
Breast	tissue	0.3	not detected
Heart muscle	tissue	0.3	not detected
Retina	tissue	0.3
Esophagus	tissue	0.3	not detected
Colon	tissue	0.3	not detected
Pituitary gland	tissue	0.2
Ovary	tissue	0.2	not detected
Urinary bladder	tissue	0.2	not detected
Superior colliculi	tissue	0.2
Lung	tissue	0.2	not detected
Duodenum	tissue	0.2	not detected
Thymus	tissue	0.2
Bone marrow	tissue	0.2	not detected
Cervix	tissue	0.1	not detected
Adipose tissue	tissue	0.1	not detected
Smooth muscle	tissue	0.1	not detected
Tongue	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 188; highest nTPM — Flocculonodular lobe (4.1), Vermis (4.1), Inferior parietal lobule (3.9), Parietal operculum (3.9), Anterior insular cortex, dorsal (3.7).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB1, CREM, MYBL1, SP1

miRNA regulators (miRDB)

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

6 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-519D-5P	99.41	69.30	2057
HSA-MIR-5695	99.41	67.48	1047
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-596	97.48	63.13	469

Functional genomics

gnomAD constraint: pLI 0.00279, LOEUF 1.87, missense Z -0.101 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000541669 — one region, missense o/e 0.92.

Literature-anchored findings (GeneRIF, showing 13)

• LDH3 was increased in essential thrombocythemia. This isoenzymatic pattern could be expression of a metabolic adaptation. (PMID:17178662)
• LDH3 is a supporting diagnostic marker in cases of chronic tuberculosis. (PMID:17935709)
• hLdhc expression in cancer cells was regulated by transcription factor Sp1 and CREB and promoter CGI methylation (PMID:18930904)
• Elevated serum LDH isoenzymes and AST indicate a disturbance (of uncertain clinical significance) within multiple extraosseous tissues when there is CLCN7 deficiency. (PMID:20499337)
• 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)
• Down-regulated LDH-C4 expression is significantly correlated with lowered enzyme activity in human spermatozoa. (PMID:25795631)
• This is the first report to show a positive correlation between LDH-3 and hemolytic parameters in sickle cell anemia. (PMID:26069337)
• three uniquely identified proteins (CDK6 , galectin-3-binding protein and LDH C) were found, which show tight connection with prostate cancer and presence of all of them was previously linked to certain aspects of prostate cancer (PMID:26503549)
• Lactate dehydrogenase C may act as a novel biomarker for renal cell carcinoma progression and a potential therapeutic target for the treatment of renal cell carcinoma. (PMID:28351304)
• a novel association between the methylation status of CpG sites within LDHC and the development of insulin autoantibodies in the first years of life (PMID:29224923)
• Diagnostic and prognostic value of the cancer-testis antigen lactate dehydrogenase C4 in breast cancer. (PMID:31794764)
• Targeting of lactate dehydrogenase C dysregulates the cell cycle and sensitizes breast cancer cells to DNA damage response targeted therapy. (PMID:34050611)
• Association between serum lactate dehydrogenase and 60-day mortality in Chinese Hakka patients with acute myeloid leukemia: A cohort study. (PMID:34708888)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ldhc	ENSMUSG00000030851
rattus_norvegicus	Ldhc	ENSRNOG00000013103

Paralogs (5): LDHB (ENSG00000111716), LDHA (ENSG00000134333), MDH2 (ENSG00000146701), LDHAL6A (ENSG00000166800), LDHAL6B (ENSG00000171989)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:96764) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 6 distinct phenotype terms.

Mouse phenotype (MP)	Records
impaired fertilization	1
reduced male fertility	1
male infertility	1
asthenozoospermia	1
abnormal sperm physiology	1
abnormal testis physiology	1

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
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
Columba livia	Q9PW07	96.4%	Diamond
Sphyraena argentea	O13276	95.2%	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
LDHAL6A	protein-coding	160287
UEVLD	protein-coding	55293
TSG101	protein-coding	7251
HPS5	protein-coding	11234
GTF2H1	protein-coding	2965
LDHA	protein-coding	3939
MIR3159	ncRNA	100423016

Protein

Protein identifiers

L-lactate dehydrogenase C chain — P07864 (reviewed: P07864)

Alternative names: Cancer/testis antigen 32, LDH testis subunit, LDH-X

All UniProt accessions (9): P07864, A0A140VKA7, F5GWS6, F5GZ11, F5H155, F5H245, F5H326, F5H5G7, G3XAP5

UniProt curated annotations — full annotation on UniProt →

Function. Possible role in sperm motility.

Subunit / interactions. Homotetramer. Interacts with RABL2/RABL2A; binds preferentially to GTP-bound RABL2.

Subcellular location. Cytoplasm.

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

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

RefSeq proteins (2): NP_002292, NP_059144* (*=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 (46 total): helix 17, strand 14, binding site 7, sequence conflict 3, chain 1, active site 1, sequence variant 1, turn 1, modified residue 1

Structure

Experimental structures (PDB)

2 structures by resolution:

PDB	Title	Method	Resolution (Å)
8ZKJ	The crystal structure of apo-LDHC	X-RAY DIFFRACTION	2.38
7EPM	human LDHC complexed with NAD+ and ethylamino acetic acid	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P07864-F1	96.27	0.93

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Oxidoreductases, Metabolic proteins, Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol; end piece; mid piece; principal piece

Antibody reliability (HPA): IH enhanced · IF supported

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 (1)

Type	Positions
Phosphoserine	301

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 3; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

3 pathways:

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

MSigDB gene sets: 125 (showing top): KEGG_CYSTEINE_AND_METHIONINE_METABOLISM, KYNG_DNA_DAMAGE_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, KEGG_GLYCOLYSIS_GLUCONEOGENESIS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, MARTINEZ_RB1_TARGETS_UP, GOBP_ATP_BIOSYNTHETIC_PROCESS, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM5, KYNG_DNA_DAMAGE_BY_GAMMA_RADIATION

GO Biological Process (3): lactate metabolic process (GO:0006089), pyruvate catabolic process (GO:0042867), carboxylic acid metabolic process (GO:0019752)

GO Molecular Function (5): L-lactate dehydrogenase (NAD+) activity (GO:0004459), catalytic activity (GO:0003824), 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), motile cilium (GO:0031514), extracellular exosome (GO:0070062), cytoplasm (GO:0005737), cilium (GO:0005929)

Reactome top-level categories

2 top-level categories:

Category	Pathways
Aerobic respiration and respiratory electron transport	1
Metabolism	1

GO top-level categories

19 GO namespaces:

Category	Terms
intracellular membrane-bounded organelle	2
cytoplasm	2
cellular anatomical structure	2
monocarboxylic acid metabolic process	1
pyruvate metabolic process	1
monocarboxylic acid catabolic process	1
oxoacid metabolic process	1
L-2-hydroxycarboxylate dehydrogenase (NAD+) activity	1
L-lactate dehydrogenase activity	1
molecular_function	1
binding	1
catalytic activity	1
oxidoreductase activity, acting on CH-OH group of donors	1
cilium	1
extracellular vesicle	1
intracellular anatomical structure	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 3 of 15 annotations. The rest are phylogenetic / computational / electronic (IEA).

3 experimentally-supported GO terms:

GO term	NS	Evidence
cytosol	CC	direct assay
extracellular exosome	CC	high-throughput assay
nucleus	CC	high-throughput assay

Protein interactions and networks

STRING

showing 15 of 1,746 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LDHC	KCNC1	P48547	761
LDHC	A0A096LPE2	A0A096LPE2	734
LDHC	CS	O75390	729
LDHC	SAA4	P35542	723
LDHC	GOT1L1	Q8NHS2	685
LDHC	ACP1	P24666	680
LDHC	LDHD	Q86WU2	647
LDHC	PKM	P14618	643
LDHC	PGK2	P07205	622
LDHC	GOT1	P17174	603
LDHC	GAPDHS	O14556	596
LDHC	TPI1	P00938	594
LDHC	CKMT1B	P12532	581
LDHC	CKMT2	P17540	581
LDHC	ALB	P02768	577

IntAct

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

6 partners by confidence:

Partner	Interaction type	MIscore	Records
LDHA	association	0.770	6
LDHB	physical association	0.740	1
EIPR1	association	0.530	2
ELMOD1	association	0.530	2
FMO1	association	0.350	1
ZNF675	association	0.350	1

BioGRID (139 interactions; top human partners by supporting records): LDHA (Affinity Capture-MS; 5 records), LDHB (Affinity Capture-MS; 5 records), ARF4 (Co-fractionation; 2 records), ELMOD1 (Affinity Capture-MS; 2 records), LIG4 (Two-hybrid; 2 records), TLE3 (Affinity Capture-MS; 2 records), TSSC1 (Affinity Capture-MS; 2 records), ACTA1 (Cross-Linking-MS (XL-MS)), ACTA2 (Cross-Linking-MS (XL-MS)), ACTB (Cross-Linking-MS (XL-MS)), ACTBL2 (Cross-Linking-MS (XL-MS)), ACTC1 (Cross-Linking-MS (XL-MS)), ACTG1 (Cross-Linking-MS (XL-MS)), ACTG2 (Cross-Linking-MS (XL-MS)), ACTN4 (Cross-Linking-MS (XL-MS))

Disease & clinical

Genetic variants

Variant evidence for LDHC: 48 ClinVar records (0 pathogenic / likely pathogenic); 3 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	39
Likely benign	1
Benign	1

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 25 predictions of 821):

Position(s)	Effect	Δscore	Sites
11:18412844–18412845	donor_loss	0.9900	5
11:18434738–18434739	acceptor_loss	0.9900	6
11:18434914–18434915	donor_loss	0.9900	5
11:18446203	acceptor_gain	0.9900
11:18415303	donor_gain	0.9800
11:18446201	acceptor_gain	0.9800
11:18412845	donor_loss	0.9700
11:18429736	acceptor_gain	0.9600
11:18429735	acceptor_gain	0.9500	2
11:18429735–18429736	acceptor_loss	0.9400	2

AlphaMissense

870 missense substitutions predicted likely pathogenic (of 2,175 scored), across 229 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D166	8	0.993	0.997
D64	8	0.985	0.994
D141	8	0.982	0.994
H193	8	0.982	0.990
D52	8	0.940	0.977
N113	8	0.932	0.987
F170	8	0.897	0.991
D195	8	0.871	0.965
H67	8	0.812	0.968
W201	7	0.971	0.996
E192	7	0.966	0.989
N138	7	0.953	0.995
W250	7	0.949	0.994
F71	7	0.943	0.982
E312	7	0.924	0.953
S290	7	0.923	0.997
E61	7	0.892	0.953
F288	7	0.886	0.985
C185	7	0.871	0.992
C163	7	0.870	0.997

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Disease associations

OMIM: gene MIM:150150 | disease phenotypes:

GWAS associations

3 associations:

Study	Trait	p-value
GCST000876_4	Amyloid A serum levels	3e-111
GCST000876_2	Amyloid A serum levels	4e-22
GCST002337_91	Amyotrophic lateral sclerosis (sporadic)	9e-6

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	2
Phthalic Acids	decreases methylation, increases abundance, increases methylation	2
bismuth tripotassium dicitrate	increases expression	1
sodium arsenite	increases expression	1
ochratoxin A	decreases acetylation	1
microcystin RR	decreases expression	1
CGP 52608	affects binding, increases reaction	1
bisphenol S	decreases expression	1
monoethyl phthalate	decreases methylation, increases abundance	1
Air Pollutants	increases expression, increases abundance	1
Air Pollutants, Occupational	affects expression	1
Vehicle Emissions	increases abundance, increases expression	1
Dimethyl Sulfoxide	affects expression	1
Formaldehyde	decreases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Cadmium Chloride	increases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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