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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SLC12A8
solute carrier family 12 member 8
Chromosome 3 · 3q21.2
NCBI Gene: 84561Ensembl: ENSG00000221955.12HGNC: HGNC:15595UniProt: A0AV02
19PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingpotassium:chloride symporter activitypotassium ion transmembrane transportapical plasma membranetype 2 diabetes mellitusdiabetes mellitusperitonsillar abscesstonsillitis
✦AI Summary

SLC12A8 (solute carrier family 12 member 8) functions primarily as a specific nicotinamide mononucleotide (NMN) transporter that plays a critical role in cellular NAD+ metabolism 1. The protein facilitates sodium-dependent NMN uptake into cells, particularly in the small intestine where it is highly expressed and regulated by NAD+ levels 1. SLC12A8 is essential for maintaining intestinal NAD+ homeostasis, with deficiency significantly decreasing NAD+ levels in jejunum and ileum tissues 1. Beyond its metabolic functions, SLC12A8 has emerged as an important factor in cancer biology. The gene is upregulated in multiple cancer types including colorectal cancer, non-small cell lung cancer, and bladder cancer, where high expression correlates with poor patient prognosis 234. Mechanistically, SLC12A8 promotes cancer progression by facilitating epithelial-mesenchymal transition, reducing apoptosis, decreasing reactive oxygen species production, and activating JAK/STAT signaling pathways 24. Additionally, SLC12A8 upregulation contributes to chemotherapy resistance, particularly to oxaliplatin treatment 2. The protein has also been identified as a potential therapeutic target for immunotherapy due to its associations with immune checkpoint genes and tumor microenvironment regulation 5.

Sources cited
1
SLC12A8 is a specific NMN transporter that facilitates sodium-dependent NMN uptake and maintains intestinal NAD+ homeostasis
PMID: 31131364
2
SLC12A8 is upregulated in colorectal cancer, promotes EMT, reduces apoptosis and ROS production, and contributes to oxaliplatin resistance
PMID: 39145047
3
SLC12A8 is highly expressed in NSCLC tissues and promotes cell proliferation, migration, invasion, and EMT
PMID: 39140681
4
SLC12A8 promotes bladder cancer progression through JAK/STAT signaling pathway activation and EMT promotion
PMID: 37814877
5
SLC12A8 serves as a pan-cancer biomarker associated with poor prognosis and immune checkpoint regulation across multiple tumor types
PMID: 38280496
Disease Associationsⓘ20
type 2 diabetes mellitusOpen Targets
0.51Moderate
diabetes mellitusOpen Targets
0.47Moderate
peritonsillar abscessOpen Targets
0.45Moderate
tonsillitisOpen Targets
0.42Moderate
disorder of pharynxOpen Targets
0.33Weak
lymphatic system diseaseOpen Targets
0.33Weak
upper respiratory tract disorderOpen Targets
0.33Weak
diabetic neuropathyOpen Targets
0.32Weak
Abnormality of the skeletal systemOpen Targets
0.29Weak
obesityOpen Targets
0.26Weak
pituitary gland diseaseOpen Targets
0.23Weak
kidney diseaseOpen Targets
0.22Weak
liver diseaseOpen Targets
0.12Weak
urinary bladder carcinomaOpen Targets
0.08Suggestive
colorectal carcinomaOpen Targets
0.07Suggestive
atrial fibrillationOpen Targets
0.07Suggestive
bone fractureOpen Targets
0.07Suggestive
breast cancerOpen Targets
0.05Suggestive
poisoningOpen Targets
0.05Suggestive
neoplasmOpen Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
SLC12A9Shared pathway100%CSTAProtein interaction96%SLC12A7Shared pathway50%KCNU1Shared pathway50%KCNQ5Shared pathway50%SLC12A4Shared pathway43%
Tissue Expression6 tissues
Liver
100%
Lung
27%
Brain
15%
Ovary
5%
Heart
3%
Bone Marrow
3%
Gene Interaction Network
Click a node to explore
SLC12A8SLC12A9CSTASLC12A7KCNU1KCNQ5SLC12A4
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt A0AV02
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.10LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.89 [0.72–1.10]
RankingsWhere SLC12A8 stands among ~20K protein-coding genes
  • #14,532of 20,598
    Most Researched19
  • #11,311of 17,882
    Most Constrained (LOEUF)1.10
Genes detectedSLC12A8
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
NAD
PMID: 33353981
Nat Rev Mol Cell Biol · 2021
1.00
2
Slc12a8 is a nicotinamide mononucleotide transporter.
PMID: 31131364
Nat Metab · 2019
0.90
3
SLC12A8 upregulation promotes colorectal cancer progression and chemoresistance.
PMID: 39145047
Transl Cancer Res · 2024
0.80
4
SLC12A8 promotes the migration and invasion of non-small cell lung cancer (NSCLC) cells.
PMID: 39140681
Gen Physiol Biophys · 2024
0.70
5
Identification of SLC12A8 as a valuable prognostic biomarker and immunotherapeutic target by comprehensive pan-cancer analysis.
PMID: 38280496
Gene · 2024
0.60