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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SLC25A45
solute carrier family 25 member 45
Chromosome 11 · 11q13.1
NCBI Gene: 283130Ensembl: ENSG00000162241.13HGNC: HGNC:27442UniProt: E9PJQ3
13PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
mitochondrial inner membraneN(6),N(6),N(6)-trimethyl-L-lysine transmembrane transporter activitydimethylarginine transmembrane transporter activitycarnitine biosynthetic processgoutCOVID-19candidiasisosteosarcoma
✦AI Summary

SLC25A45 is a mitochondrial inner membrane transporter that mediates the import of methylated amino acids into mitochondria, playing a crucial role in carnitine biosynthesis 12. The protein specifically transports methylated basic amino acids including asymmetric dimethylarginine (ADMA) and trimethyllysine (TML), but shows no affinity for unmethylated arginine and lysine 2. Mechanistically, SLC25A45 facilitates mitochondrial TML import, which serves as a precursor for carnitine synthesis, thereby connecting protein catabolism to carnitine production and sustaining β-oxidation during fasting conditions 1. The transporter is essential for maintaining mitochondrial protein synthesis, biogenesis of the oxidative phosphorylation system, and mitochondrial morphology 3. Disease relevance includes associations with cardiovascular function, as a non-synonymous mutation (R285C) associates with altered plasma methylated amino acid levels and lower resting heart rate 4. Additionally, rare variants in SLC25A45 have been linked to serum creatinine levels and chr11 kidney disease 5, and genomic variations show associations with preterm birth risk 6. The protein may also regulate mitochondrial NMN levels, affecting local NMN/NAD+ ratios 7.

Sources cited
1
SLC25A45 is a mitochondrial transporter that imports methylated basic amino acids including TML for carnitine synthesis
PMID: 41075780
2
SLC25A45 specifically binds dimethylarginine and trimethyllysine but not unmethylated amino acids
PMID: 41075794
3
SLC25A45 is crucial for mitochondrial translation, biogenesis, and mitochondrial morphology
PMID: 41739937
4
R285C mutation in SLC25A45 associates with altered plasma methylated amino acids and heart rate
PMID: 24159190
5
Rare SLC25A45 variants associate with serum creatinine levels and chronic kidney disease
PMID: 25082825
6
SLC25A45 genomic variations show evolutionary link to preterm birth
PMID: 27466897
7
SLC25A45 identified as potential mitochondrial NMN regulator affecting NMN/NAD+ ratios
PMID: 39418868
Disease Associationsⓘ20
goutOpen Targets
0.02Suggestive
COVID-19Open Targets
0.02Suggestive
candidiasisOpen Targets
0.02Suggestive
osteosarcomaOpen Targets
0.02Suggestive
systemic primary carnitine deficiency diseaseOpen Targets
0.01Suggestive
neoplasmOpen Targets
0.01Suggestive
tuberculosisOpen Targets
0.01Suggestive
cancerOpen Targets
0.00Suggestive
chronic kidney diseaseOpen Targets
0.00Suggestive
head and neck squamous cell carcinomaOpen Targets
0.00Suggestive
obesityOpen Targets
0.00Suggestive
periodontitisOpen Targets
0.00Suggestive
papillary thyroid carcinomaOpen Targets
0.00Suggestive
clear cell adenocarcinomaOpen Targets
0.00Suggestive
gliomaOpen Targets
0.00Suggestive
ovarian cancerOpen Targets
0.00Suggestive
pancreatic adenocarcinomaOpen Targets
0.00Suggestive
thyroid carcinomaOpen Targets
0.00Suggestive
urinary bladder cancerOpen Targets
0.00Suggestive
urinary bladder carcinomaOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
SLC25A47Shared pathway33%TMLHEShared pathway33%BBOX1Shared pathway33%SLC38A10Shared pathway25%SLC38A8Shared pathway25%SLC38A11Shared pathway25%
Tissue Expression6 tissues
Liver
100%
Bone Marrow
62%
Lung
54%
Heart
39%
Ovary
26%
Brain
13%
Gene Interaction Network
Click a node to explore
SLC25A45SLC25A47TMLHEBBOX1SLC38A10SLC38A8SLC38A11
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q8N413
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.22LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.89 [0.65–1.22]
RankingsWhere SLC25A45 stands among ~20K protein-coding genes
  • #16,299of 20,598
    Most Researched13
  • #12,872of 17,882
    Most Constrained (LOEUF)1.22
Genes detectedSLC25A45
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Machine-learning-guided discovery of SLC25A45 as a mediator of mitochondrial methylated amino acid import and carnitine synthesis.
PMID: 41075780
Cell Metab · 2025
1.00
2
SLC25A45 is required for mitochondrial uptake of methylated amino acids and de novo carnitine biosynthesis.
PMID: 41075794
Mol Cell · 2025
0.90
3
Quantitative dynamics of intracellular NMN by genetically encoded biosensor.
PMID: 39418868
Biosens Bioelectron · 2025
0.80
4
Genome-wide association study on dimethylarginines reveals novel AGXT2 variants associated with heart rate variability but not with overall mortality.
PMID: 24159190
Eur Heart J · 2014
0.70
5
An orphan no more: SLC25A45 controls mitochondrial import of methylated amino acids.
PMID: 41202802
Mol Cell · 2025
0.60