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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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LDHC
lactate dehydrogenase C
Chromosome 11 · 11p15.1
NCBI Gene: 3948Ensembl: ENSG00000166796.13HGNC: HGNC:6544UniProt: A0A140VKA7
55PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
cytosolnucleusextracellular exosomeprotein bindingneurodegenerative diseasespondylolisthesisneoplasmhepatocellular carcinoma
✦AI Summary

LDHC (lactate dehydrogenase C) is a testis-specific isozyme primarily localized to the sperm tail that plays critical roles in male fertility and metabolic regulation 1. In spermatozoa, LDHC catalyzes the interconversion of pyruvate and lactate as part of anaerobic glycolysis, providing energy for sperm motility and capacitation 2. Ldhc knockout mice exhibit impaired sperm motility and reduced fertilizing capacity, demonstrating its essential function in reproduction 3. Beyond reproduction, LDHC functions in lactate metabolism across tissues, oxidizing lactate to pyruvate to re-enter the TCA cycle 4. In cancer contexts, LDHC acts as a cancer-testis antigen with immunomodulatory properties. High LDHC expression in lung adenocarcinoma correlates with aggressive clinicopathological features and poor prognosis, operating through PI3K/Akt/GSK-3β pathway activation to promote proliferation and epithelial-mesenchymal transition 5. Conversely, LDHC knockdown in breast cancer enhances anti-tumor immunity by reducing T cell dysfunction and immune checkpoint expression 6. LDHC also suppresses B-cell mediated inflammation in osteoarthritis 7. These findings identify LDHC as a multifunctional target for contraceptive, immunotherapeutic, and metabolic interventions 8.

Sources cited
1
LDHC is the first testis-specific isozyme discovered, localized to early-pachytene primary spermatocytes and the principal piece of the sperm tail, required for fertilization
PMID: 19875487
2
Spermatozoa require Ldhc for capacitation, motility, and fertilizing capacity; LDHC catalyzes pyruvate-lactate interconversion as part of glycolytic energy metabolism
PMID: 23467744
3
Ldhc knockout mice exhibit impaired sperm motility; human LDHC can functionally rescue mouse Ldhc deficiency in fertility models
PMID: 36464740
4
LDHC oxidizes lactate to pyruvate for re-entry into the TCA cycle; LDHC overexpression improves metabolic efficiency and reduces lactate accumulation
PMID: 37805860
5
High LDHC expression in lung adenocarcinoma correlates with aggressive features and poor prognosis; LDHC promotes proliferation and EMT via PI3K/Akt/GSK-3β pathway activation
PMID: 33301764
6
LDHC expression in breast cancer associates with T cell dysfunction; LDHC knockdown enhances anti-tumor immunity by reducing immune checkpoint expression and increasing pro-inflammatory cytokines
PMID: 40108668
7
LDHC downregulation in osteoarthritis impairs chondrocyte function; LDHC expression is mediated through B-cell-dependent mechanisms
PMID: 41339282
8
LDHC functions as a cancer-testis antigen in lung adenocarcinoma; LDHC-derived peptides can be targets for immunotherapy
PMID: 40270965
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.34Weak
spondylolisthesisOpen Targets
0.12Weak
neoplasmOpen Targets
0.09Suggestive
hepatocellular carcinomaOpen Targets
0.09Suggestive
azoospermiaOpen Targets
0.09Suggestive
breast cancerOpen Targets
0.09Suggestive
lung adenocarcinomaOpen Targets
0.09Suggestive
cancerOpen Targets
0.07Suggestive
adolescent idiopathic scoliosisOpen Targets
0.07Suggestive
spermatogenic failure 3Open Targets
0.06Suggestive
spermatogenic failure 55Open Targets
0.06Suggestive
partial chromosome Y deletionOpen Targets
0.06Suggestive
Rare genetic female infertilityOpen Targets
0.06Suggestive
spermatogenic failure 83Open Targets
0.06Suggestive
spermatogenic failure 7Open Targets
0.06Suggestive
spermatogenic failure 16Open Targets
0.06Suggestive
spermatogenic failure 21Open Targets
0.06Suggestive
spermatogenic failure 29Open Targets
0.06Suggestive
spermatogenic failure 58Open Targets
0.06Suggestive
spermatogenic failure 79Open Targets
0.06Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
LDHAL6BShared pathway100%TPI1Protein interaction100%PDHBProtein interaction100%FHProtein interaction98%TALDO1Protein interaction97%CSProtein interaction97%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
52%
Liver
35%
Ovary
10%
Lung
6%
Heart
0%
Gene Interaction Network
Click a node to explore
LDHCLDHAL6BTPI1PDHBFHTALDO1CS
PROTEIN STRUCTURE
Preparing viewer…
PDB8ZKJ · 2.38 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.87LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.17 [0.62–1.87]
RankingsWhere LDHC stands among ~20K protein-coding genes
  • #8,215of 20,598
    Most Researched55
  • #16,984of 17,882
    Most Constrained (LOEUF)1.87
Genes detectedLDHC
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
LDHC: the ultimate testis-specific gene.
PMID: 19875487
J Androl · 2010
1.00
2
Lactylation Genes LDHA and LDHC Alleviate Osteoarthritis by Reducing Specific B-Cell Expression: Mechanistic Exploration and Experimental Validation.
PMID: 41339282
J Cell Mol Med · 2025
0.90
3
Immunomodulatory effects of tumor Lactate Dehydrogenase C (LDHC) in breast cancer.
PMID: 40108668
Cell Commun Signal · 2025
0.80
4
Generation of humanized LDHC knock-in mice as a tool to assess human LDHC-targeting contraceptive drugs.
PMID: 36464740
Andrology · 2023
0.70
5
Identification of new HLA-A*0201-restricted cytotoxic T lymphocyte epitopes from LDHC in lung adenocarcinoma.
PMID: 40270965
Front Immunol · 2025
0.60