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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SLC25A25
solute carrier family 25 member 25
Chromosome 9 · 9q34.11
NCBI Gene: 114789Ensembl: ENSG00000148339.14HGNC: HGNC:20663UniProt: Q6KCM7
35PubMed Papers
20Diseases
0Drugs
1Pathogenic Variants
FUNCTIONAL ROLE
Transporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
mitochondrionATP:phosphate antiporter activityATP transportATP transmembrane transporter activitynephrolithiasispathological myopiamyopianon-small cell lung carcinoma
✦AI Summary

SLC25A25 is a mitochondrial electroneutral antiporter that mediates calcium-dependent ATP-Mg²⁺/inorganic phosphate exchange across the inner mitochondrial membrane 1. By regulating the mitochondrial adenyl nucleotide pool, it adapts cellular metabolism to changing energetic demands 1. SLC25A25 acts downstream of the ciliary calcium-permeable channel TRPP2, establishing a conserved molecular link between ciliary signaling and mitochondrial metabolism 2. This pathway is essential for left-right patterning and other ciliary-dependent physiological functions 2. Clinically, SLC25A25 dysfunction has disease relevance across multiple conditions. Loss-of-function mutations impair oxidative phosphorylation and increase oxidative stress 1, while a heterozygous dominant variant (p.Gln349His) reducing calcium-regulated ATP transport to ~20% of wild-type activity was identified in families with recurrent kidney stones, likely through impaired ATP provision for renal solute transport 3. The gene is also implicated in cancer biology, with its antisense RNA (SLC25A25-AS1) acting as a tumor suppressor—decreased expression in colorectal cancer promotes proliferation, chemoresistance, and epithelial-mesenchymal transition 4. Additionally, SLC25A25 expression changes in delayed-onset muscle soreness correlate with mitochondrial damage and inflammatory immune responses 5. Exercise acutely upregulates SLC25A25 in endothelial cells, suggesting metabolic adaptation roles 6.

Sources cited
1
SLC25A25 promotes ATP-Mg²⁺/phosphate exchange, accumulates adenine nucleotides in mitochondria, and mutations cause diverse human diseases through loss-of-function or dominant mechanisms
PMID: 37449547
2
SLC25A25 acts downstream of TRPP2 ciliary calcium signaling in an evolutionarily conserved pathway linking cilia-dependent functions to mitochondrial metabolism and left-right patterning
PMID: 30080851
3
Heterozygous SLC25A25 variant p.Gln349His reduces calcium-regulated ATP transport to ~20% of wild-type and is associated with kidney stone formation in multiple families
PMID: 34346195
4
SLC25A25-AS1 downregulation in colorectal cancer promotes proliferation, chemoresistance, and EMT, establishing SLC25A25-AS1 as a tumor suppressor
PMID: 27553025
5
SLC25A25 is a hub gene differentially expressed in delayed-onset muscle soreness, linked to mitochondrial damage and abnormal immune microenvironment
PMID: 37612729
6
SLC25A25 is among canonical early response genes induced in endothelial cells during acute exercise, suggesting a role in vascular metabolic adaptation
PMID: 40789176
Disease Associationsⓘ20
nephrolithiasisOpen Targets
0.33Weak
myopiaOpen Targets
0.11Weak
pathological myopiaOpen Targets
0.11Weak
non-small cell lung carcinomaOpen Targets
0.08Suggestive
pachyonychia congenitaOpen Targets
0.07Suggestive
esophageal squamous cell carcinomaOpen Targets
0.04Suggestive
neoplasmOpen Targets
0.03Suggestive
melanomaOpen Targets
0.02Suggestive
heart conduction diseaseOpen Targets
0.02Suggestive
colorectal carcinomaOpen Targets
0.02Suggestive
cancerOpen Targets
0.02Suggestive
breast carcinomaOpen Targets
0.02Suggestive
colorectal cancerOpen Targets
0.01Suggestive
VitiligoOpen Targets
0.01Suggestive
prostate cancerOpen Targets
0.01Suggestive
cardiovascular diseaseOpen Targets
0.01Suggestive
IGA glomerulonephritisOpen Targets
0.01Suggestive
lung cancerOpen Targets
0.01Suggestive
Parkinson diseaseOpen Targets
0.01Suggestive
breast cancerOpen Targets
0.01Suggestive
Pathogenic Variants1
NM_001330988.2(SLC25A25):c.1083G>C (p.Gln361His)Pathogenic
Nephrolithiasis
☆☆☆☆2020→ Residue 361
View on ClinVar ↗
Related Genes
SLC35B1Shared pathway100%NDUFS4Protein interaction100%NDUFB9Protein interaction100%NDUFS3Protein interaction100%NDUFV1Protein interaction100%NDUFB10Protein interaction100%
Tissue Expression6 tissues
Liver
100%
Brain
33%
Lung
27%
Ovary
25%
Bone Marrow
10%
Heart
7%
Gene Interaction Network
Click a node to explore
SLC25A25SLC35B1NDUFS4NDUFB9NDUFS3NDUFV1NDUFB10
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q6KCM7
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.76LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.57 [0.43–0.76]
RankingsWhere SLC25A25 stands among ~20K protein-coding genes
  • #11,067of 20,598
    Most Researched35
  • #5,219of 5,498
    Most Pathogenic Variants1
  • #6,156of 17,882
    Most Constrained (LOEUF)0.76
Genes detectedSLC25A25
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Adenine nucleotide carrier protein dysfunction in human disease.
PMID: 37449547
IUBMB Life · 2023
1.00
2
Distinct endothelial gene responses to acute exercise in skeletal muscle.
PMID: 40789176
Am J Physiol Endocrinol Metab · 2025
0.90
3
The mitochondrial transporter SLC25A25 links ciliary TRPP2 signaling and cellular metabolism.
PMID: 30080851
PLoS Biol · 2018
0.80
4
[Bioinformatic analysis of immune-related lncRNA based on TCGA database in patients with prostate cancer].
PMID: 33504416
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi · 2021
0.70
5
Decreased expression of LncRNA SLC25A25-AS1 promotes proliferation, chemoresistance, and EMT in colorectal cancer cells.
PMID: 27553025
Tumour Biol · 2016
0.60