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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SLC25A33
solute carrier family 25 member 33
Chromosome 1 · 1p36.22
NCBI Gene: 84275Ensembl: ENSG00000171612.8HGNC: HGNC:29681UniProt: Q9BSK2
22PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
pyrimidine nucleotide transmembrane transporter activityregulation of oxidative phosphorylationmitochondrial transcriptionmitochondrial respiratory chain complex III assemblyatrial fibrillationVaricose veinsenteritisallergic rhinitis
✦AI Summary

SLC25A33 encodes a mitochondrial pyrimidine nucleotide transporter that plays essential roles in mitochondrial genome maintenance and cellular metabolism 1. The protein selectively transports uridine, thymidine, guanosine, cytosine, and inosine nucleoside di- and triphosphates across the inner mitochondrial membrane via an antiport mechanism, importing nucleoside triphosphates in exchange for diphosphates to support mitochondrial DNA and RNA synthesis 1. SLC25A33 is critical for mitochondrial biogenesis and function, particularly in response to IGF-1 signaling, where it regulates cell growth and proliferation by controlling mitochondrial DNA replication and transcription 2. Recent studies demonstrate that SLC25A33 contributes to inflammatory responses in M1 macrophages by facilitating mitochondrial DNA synthesis and release, which promotes mitochondrial ROS production and VDAC oligomerization, ultimately activating the cGAS-STING inflammatory pathway 3. The transporter is also involved in metabolic reprogramming, as its deficiency affects methionine metabolism and promotes fibrosis through the mTOR pathway 4. Additionally, SLC25A33 enhances dendritic cell endocytosis and may associate with mitochondrial oxidative phosphorylation 5. The gene shows widespread expression across tissues, particularly in the central nervous system, and is enriched in luminal tumor cells in prostate cancer 67.

Sources cited
1
SLC25A33 transports pyrimidine nucleotides across mitochondrial membrane via antiport mechanism
PMID: 25320081
2
SLC25A33 promotes inflammatory responses in M1 macrophages through mtDNA synthesis and ROS production
PMID: 40384854
3
SLC25A33 responds to IGF-1 signaling to regulate mitochondrial biogenesis and cell growth
PMID: 28821609
4
SLC25A33 deficiency affects methionine metabolism and promotes fibrosis via mTOR pathway
PMID: 40580027
5
SLC25A33 enhances dendritic cell endocytosis and associates with oxidative phosphorylation
PMID: 14715278
6
SLC25A33 is widely expressed in central nervous system tissues
PMID: 16949250
7
SLC25A33 is enriched in luminal tumor cells in prostate cancer
PMID: 41632930
Disease Associationsⓘ20
atrial fibrillationOpen Targets
0.41Moderate
Varicose veinsOpen Targets
0.30Weak
enteritisOpen Targets
0.24Weak
allergic rhinitisOpen Targets
0.18Weak
carpal tunnel syndromeOpen Targets
0.18Weak
Inguinal herniaOpen Targets
0.18Weak
Peyronie diseaseOpen Targets
0.17Weak
HerniaOpen Targets
0.17Weak
acute tonsillitisOpen Targets
0.11Weak
SepsisOpen Targets
0.05Suggestive
Chronic Obstructive AsthmaOpen Targets
0.04Suggestive
connective tissue neoplasmOpen Targets
0.02Suggestive
Duane retraction syndromeOpen Targets
0.02Suggestive
bone neoplasmOpen Targets
0.02Suggestive
vascular diseaseOpen Targets
0.01Suggestive
Reunion island Larsen syndromeOpen Targets
0.01Suggestive
Reunion Island's Larsen syndromeOpen Targets
0.01Suggestive
infectionOpen Targets
0.01Suggestive
cancerOpen Targets
0.01Suggestive
Peripheral arterial stenosisOpen Targets
0.01Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
MTCH1Protein interaction83%MTCH2Protein interaction80%SLC25A36Co-mentioned in literature20%UQCC2Shared pathway17%CEP43Shared pathway17%BCS1LShared pathway17%
Tissue Expression6 tissues
Liver
100%
Brain
94%
Bone Marrow
85%
Heart
29%
Lung
25%
Ovary
21%
Gene Interaction Network
Click a node to explore
SLC25A33MTCH1MTCH2SLC25A36UQCC2CEP43BCS1L
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q9BSK2
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.74LoF Tolerant
pLIⓘ
0.03Tolerant
Observed/Expected LoF0.48 [0.32–0.74]
RankingsWhere SLC25A33 stands among ~20K protein-coding genes
  • #13,739of 20,598
    Most Researched22
  • #5,847of 17,882
    Most Constrained (LOEUF)0.74
Genes detectedSLC25A33
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
The human SLC25A33 and SLC25A36 genes of solute carrier family 25 encode two mitochondrial pyrimidine nucleotide transporters.
PMID: 25320081
J Biol Chem · 2014
1.00
2
SLC25A33-mediated mitochondrial DNA synthesis plays a critical role in the inflammatory response of M1 macrophages by contributing to mitochondrial ROS and VDAC oligomerization.
PMID: 40384854
Int J Biol Sci · 2025
0.90
3
Insulin-like growth factor 1 signaling is essential for mitochondrial biogenesis and mitophagy in cancer cells.
PMID: 28821609
J Biol Chem · 2017
0.80
4
Fourteen novel human members of mitochondrial solute carrier family 25 (SLC25) widely expressed in the central nervous system.
PMID: 16949250
Genomics · 2006
0.70
5
Happening in the Prostate Tumor Microenvironment: Ion Channels and Extrachromosomal DNA Driving Phenotypic Plasticity.
PMID: 41632930
Prostate · 2026
0.60