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
• MANE Select transcript: NM_017448

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: 11 — 8 protein_coding, 3 nonsense_mediated_decay

ENST00000280704, ENST00000396215, ENST00000535809, ENST00000536880, ENST00000537486, ENST00000539369, ENST00000541669, ENST00000544105, ENST00000545848, ENST00000546146, ENST00000940409

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.

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

279 total, 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

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

Regulation

Is transcription factor: no

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

miRNA regulators (miRDB)

6 targeting LDHC, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-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

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)

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), 1 shown:

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

UniProt features (43 total): helix 13, strand 13, binding site 7, sequence conflict 3, turn 3, chain 1, active site 1, sequence variant 1, modified residue 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
8ZKJ	X-RAY DIFFRACTION	2.38
7EPM	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

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

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 193 (proton acceptor)

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

Post-translational modifications (1): 301

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-70268	Pyruvate metabolism
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 (6): lactate metabolic process (GO:0006089), ATP biosynthetic process (GO:0006754), pyruvate fermentation to lactate (GO:0019244), flagellated sperm motility (GO:0030317), 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 (12): nucleus (GO:0005634), mitochondrion (GO:0005739), cytosol (GO:0005829), extracellular exosome (GO:0070062), sperm midpiece (GO:0097225), sperm principal piece (GO:0097228), sperm end piece (GO:0097229), oxidoreductase complex (GO:1990204), cytoplasm (GO:0005737), cilium (GO:0005929), membrane (GO:0016020), motile cilium (GO:0031514)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Aerobic respiration and respiratory electron transport	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
sperm flagellum	3
intracellular membrane-bounded organelle	2
cytoplasm	2
monocarboxylic acid metabolic process	1
purine ribonucleotide biosynthetic process	1
purine ribonucleoside triphosphate biosynthetic process	1
ATP metabolic process	1
lactate metabolic process	1
pyruvate fermentation	1
cilium-dependent cell motility	1
cilium movement involved in cell motility	1
sperm motility	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
extracellular vesicle	1
catalytic complex	1
intracellular anatomical structure	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cilium	1

Protein interactions and networks

STRING

3561 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LDHC	LDHA	P00338	895
LDHC	CS	O75390	830
LDHC	KCNC1	P48547	769
LDHC	PKLR	P11973	768
LDHC	GOT1L1	Q8NHS2	733
LDHC	A0A096LPE2	A0A096LPE2	730
LDHC	PKM	P14618	719
LDHC	CKMT1B	P12532	707
LDHC	SAA4	P35542	697
LDHC	CKMT2	P17540	686
LDHC	SAA1	P02735	684
LDHC	GOT1	P17174	682
LDHC	CKB	P12277	679
LDHC	GAPDH	P00354	670
LDHC	ACP1	P24666	668

IntAct

34 interactions, top by confidence:

A	B	Type	Score
RAD51B	RAD51C	psi-mi:“MI:0914”(association)	0.940
LDHA	LDHB	psi-mi:“MI:0914”(association)	0.800
LDHB	LDHA	psi-mi:“MI:0914”(association)	0.800
LDHA	LDHC	psi-mi:“MI:0914”(association)	0.770
LDHA	LDHC	psi-mi:“MI:0915”(physical association)	0.770
LDHC	LDHA	psi-mi:“MI:0914”(association)	0.770
LDHB	LDHC	psi-mi:“MI:0915”(physical association)	0.740
MED24	MED19	psi-mi:“MI:0914”(association)	0.730
EIPR1	LDHC	psi-mi:“MI:0914”(association)	0.530
ELMOD1	LDHC	psi-mi:“MI:0914”(association)	0.530
TLE3	ATP2A1	psi-mi:“MI:0914”(association)	0.350
TEX101	PSMD12	psi-mi:“MI:0914”(association)	0.350
TEX101	NDUFA4	psi-mi:“MI:0914”(association)	0.350
TEX101	GGT3P	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
SSB	RPS3A	psi-mi:“MI:0914”(association)	0.350
SLC24A3	GPR89A	psi-mi:“MI:0914”(association)	0.350
NPAP1	ACACB	psi-mi:“MI:0914”(association)	0.350
DNAJC12	CYB5R3	psi-mi:“MI:0914”(association)	0.350
TLE3	COL1A1	psi-mi:“MI:0914”(association)	0.350
FMO1	LDHC	psi-mi:“MI:0914”(association)	0.350
ZNF675	LDHC	psi-mi:“MI:0914”(association)	0.350
TM2D3	SPINT1	psi-mi:“MI:0914”(association)	0.350

BioGRID (139): ARF4 (Co-fractionation), ARF5 (Co-fractionation), LDHC (Co-fractionation), LDHC (Co-fractionation), LDHC (Co-fractionation), LDHC (Co-fractionation), LDHC (Co-fractionation), MDH1 (Co-fractionation), NME1-NME2 (Co-fractionation), NME2 (Co-fractionation), TALDO1 (Co-fractionation), TPI1 (Co-fractionation), UBE2N (Co-fractionation), LDHC (Biochemical Activity), LDHC (Affinity Capture-MS)

ESM2 similar proteins: A3KP37, E9Q3E1, O06543, O09174, O13277, O13278, O65781, O93401, O93537, O93539, O93541, O93542, O93545, O93546, P07864, P20373, P33571, P42122, P43353, P69083, P69084, P69085, P69086, P70473, Q10G56, Q1JPA0, Q27888, Q29563, Q4R3Y4, Q5RDY4, Q68FU4, Q6DGK2, Q6K2E1, Q6P1M0, Q7TNE1, Q80VQ0, Q8J0F0, Q8LNZ3, Q91VE0, Q92055

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

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

1478 predictions. Top by Δscore:

Variant	Effect	Δscore
11:18434738:A:AG	acceptor_gain	1.0000
11:18434738:AGT:A	acceptor_gain	1.0000
11:18434739:G:GA	acceptor_gain	1.0000
11:18434739:GT:G	acceptor_gain	1.0000
11:18434739:GTG:G	acceptor_gain	1.0000
11:18434739:GTGGA:G	acceptor_gain	1.0000
11:18434909:TAGTG:T	donor_gain	1.0000
11:18434911:GTG:G	donor_gain	1.0000
11:18434912:TG:T	donor_gain	1.0000
11:18434913:GG:G	donor_gain	1.0000
11:18434914:G:GG	donor_gain	1.0000
11:18412841:AAG:A	donor_loss	0.9900
11:18412842:AG:A	donor_loss	0.9900
11:18412843:GGT:G	donor_loss	0.9900
11:18412846:G:GT	donor_loss	0.9900
11:18434735:CTTA:C	acceptor_loss	0.9900
11:18434737:TA:T	acceptor_loss	0.9900
11:18434738:AGTG:A	acceptor_gain	0.9900
11:18434739:GTGG:G	acceptor_gain	0.9900
11:18434910:AGTG:A	donor_gain	0.9900
11:18434910:AGTGG:A	donor_loss	0.9900
11:18434911:GTGG:G	donor_gain	0.9900
11:18434912:TGG:T	donor_loss	0.9900
11:18434912:TGGT:T	donor_gain	0.9900
11:18434914:G:T	donor_loss	0.9900
11:18434915:TAA:T	donor_loss	0.9900
11:18434916:AA:A	donor_loss	0.9900
11:18446200:A:AG	acceptor_gain	0.9900
11:18446202:A:AG	acceptor_gain	0.9900
11:18446203:A:G	acceptor_gain	0.9900

AlphaMissense

2175 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:18434810:T:G	C163W	0.997
11:18434818:A:T	D166V	0.997
11:18434893:G:A	G191E	0.997
11:18446317:T:A	V273D	0.997
11:18450996:A:C	S290R	0.997
11:18450998:T:A	S290R	0.997
11:18450998:T:G	S290R	0.997
11:18415251:T:C	L65P	0.996
11:18434800:G:A	G160E	0.996
11:18434806:G:A	G162D	0.996
11:18438536:T:A	W201R	0.996
11:18438536:T:C	W201R	0.996
11:18446234:G:C	K245N	0.996
11:18446234:G:T	K245N	0.996
11:18429906:T:A	N138K	0.995
11:18429906:T:G	N138K	0.995
11:18434802:A:C	S161R	0.995
11:18434804:T:A	S161R	0.995
11:18434804:T:G	S161R	0.995
11:18434806:G:T	G162V	0.995
11:18434817:G:C	D166H	0.995
11:18434818:A:C	D166A	0.995
11:18434818:A:G	D166G	0.995
11:18446257:G:A	G253E	0.995
11:18412797:G:A	G27E	0.994
11:18415247:G:C	D64H	0.994
11:18429758:C:T	S89F	0.994
11:18434742:G:C	D141H	0.994
11:18434893:G:T	G191V	0.994
11:18438552:T:A	V206D	0.994

dbSNP variants (sampled 300 via entrez): RS1000030420 (11:18446090 A>G), RS1000143442 (11:18417994 C>A,T), RS1000156791 (11:18427008 A>C), RS1000265224 (11:18412095 A>C), RS1000271672 (11:18445897 C>A), RS1000391129 (11:18449798 G>A), RS1000477066 (11:18415778 C>T), RS1000500122 (11:18442712 G>T), RS1000502270 (11:18439250 A>G), RS1000517422 (11:18421762 C>G,T), RS1000518195 (11:18418374 T>A,C), RS1000653302 (11:18422006 C>A), RS1000726686 (11:18436367 C>T), RS1000785836 (11:18415410 G>A), RS1000917119 (11:18434438 A>G)

Disease associations

OMIM: gene MIM:150150 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST000876_2	Amyloid A serum levels	4.000000e-22
GCST000876_4	Amyloid A serum levels	3.000000e-111
GCST002337_91	Amyotrophic lateral sclerosis (sporadic)	9.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	2
Phthalic Acids	increases methylation, decreases methylation, increases abundance	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, Occupational	affects 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

Clinical trials (associated diseases)

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