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GeneE
26 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
SLC25A1
solute carrier family 25 member 1
Chromosome 22 Β· 22q11.21
NCBI Gene: 6576Ensembl: ENSG00000100075.10HGNC: HGNC:10979UniProt: D3DX16
209PubMed Papers
22Diseases
0Drugs
24Pathogenic Variants
FUNCTIONAL ROLE
Transporter
RESEARCH IMPACT
Trending
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
mitochondrial membranenucleuscitrate secondary active transmembrane transporter activitymitochondrial citrate transmembrane transportD,L-2-hydroxyglutaric aciduriaPresynaptic congenital myasthenic syndromes2-hydroxyglutaric aciduriagenetic disorder
✦AI Summary

SLC25A1 encodes the mitochondrial citrate/malate antiporter, a critical transporter that exports citrate from the mitochondria to the cytosol in exchange for malate 1. The protein can also mediate exchange of citrate with other substrates including isocitrate, phosphoenolpyruvate, and cis-aconitate, operating through consecutive substrate transport with sequential binding and dissociation 1. In the cytoplasm, exported citrate serves as a precursor for acetyl-CoA synthesis by ATP citrate lyase (ACLY), supporting fatty acid and sterol synthesis, glycolysis regulation, and protein acetylation 1. SLC25A1 plays important roles in cancer metabolism, where oncogenic KRAS upregulates its expression via GLI1 to reprogram lipid metabolism in pancreatic cancer 2. The transporter also regulates ferroptosis susceptibility by maintaining cytosolic acetyl-CoA levels necessary for FSP1 acetylation and stability 1. Additionally, SLC25A1 supports DNMT3A-R882-mutant clonal hematopoiesis through enhanced oxidative phosphorylation 3. Disease associations include congenital myasthenic syndrome type 23, highlighting its importance in neuromuscular junction function 4. Therapeutic targeting of SLC25A1 shows promise in cancer treatment and prevention of clonal hematopoiesis progression 13.

Sources cited
1
SLC25A1 exports citrate from mitochondria in exchange for malate and regulates ferroptosis through FSP1 acetylation
PMID: 39881208
2
Oncogenic KRAS upregulates SLC25A1 via GLI1 to reprogram lipid metabolism in pancreatic cancer
PMID: 37695315
3
SLC25A1 supports DNMT3A-R882-mutant clonal hematopoiesis through enhanced oxidative phosphorylation
PMID: 40239706
4
SLC25A1 mutations cause congenital myasthenic syndrome type 23
PMID: 36835142
⚠Limited data available β€” This gene has 4 indexed publications. Summary and analysis may be incomplete.
Disease Associationsβ“˜22
D,L-2-hydroxyglutaric aciduriaOpen Targets
0.83Strong
Presynaptic congenital myasthenic syndromesOpen Targets
0.66Moderate
2-hydroxyglutaric aciduriaOpen Targets
0.51Moderate
genetic disorderOpen Targets
0.41Moderate
mitochondrial diseaseOpen Targets
0.37Weak
presynaptic congenital myasthenic syndromeOpen Targets
0.37Weak
neurodegenerative diseaseOpen Targets
0.31Weak
cancerOpen Targets
0.10Weak
neoplasmOpen Targets
0.08Suggestive
acute myeloid leukemiaOpen Targets
0.08Suggestive
colorectal carcinomaOpen Targets
0.07Suggestive
esophageal squamous cell carcinomaOpen Targets
0.07Suggestive
lung cancerOpen Targets
0.07Suggestive
coronary artery calcificationOpen Targets
0.06Suggestive
alcohol drinkingOpen Targets
0.05Suggestive
endometriosisOpen Targets
0.05Suggestive
Familial exudative vitreoretinopathyOpen Targets
0.04Suggestive
lung adenocarcinomaOpen Targets
0.04Suggestive
non-small cell lung carcinomaOpen Targets
0.04Suggestive
congenital heart diseaseOpen Targets
0.03Suggestive
Combined D-2- and L-2-hydroxyglutaric aciduriaUniProt
Myasthenic syndrome, congenital, 23, presynapticUniProt
Pathogenic Variants24
NM_005984.5(SLC25A1):c.517_526del (p.Arg173fs)Pathogenic
2-hydroxyglutaric aciduria|not provided|D,L-2-hydroxyglutaric aciduria
β˜…β˜…β˜†β˜†2025β†’ Residue 173
NM_005984.5(SLC25A1):c.520G>T (p.Glu174Ter)Pathogenic
not provided|SLC25A1-related disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 174
NM_005984.5(SLC25A1):c.578C>T (p.Ser193Leu)Likely pathogenic
2-hydroxyglutaric aciduria|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 193
NM_005984.5(SLC25A1):c.821+1G>APathogenic
2-hydroxyglutaric aciduria|Myasthenic syndrome, congenital, 23, presynaptic
β˜…β˜…β˜†β˜†2024
NM_005984.5(SLC25A1):c.740G>A (p.Arg247Gln)Pathogenic
Myasthenic syndrome, congenital, 23, presynaptic
β˜…β˜…β˜†β˜†2024β†’ Residue 247
NM_005984.5(SLC25A1):c.18_24dup (p.Ala9fs)Pathogenic
not provided
β˜…β˜…β˜†β˜†2023β†’ Residue 9
NM_005984.5(SLC25A1):c.844C>T (p.Arg282Cys)Pathogenic
2-hydroxyglutaric aciduria|D,L-2-hydroxyglutaric aciduria|not provided
β˜…β˜…β˜†β˜†2023β†’ Residue 282
NM_005984.5(SLC25A1):c.548dup (p.Leu184fs)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 184
NM_005984.5(SLC25A1):c.631+1G>TLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2025
NM_005984.5(SLC25A1):c.657_665delinsGACCTC (p.Asn219_Ile222delinsLysThrSer)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 219
NM_005984.5(SLC25A1):c.890A>G (p.Tyr297Cys)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 297
NM_005984.5(SLC25A1):c.95-3delLikely pathogenic
Myasthenic syndrome, congenital, 23, presynaptic
β˜…β˜†β˜†β˜†2024
NM_005984.5(SLC25A1):c.121T>C (p.Cys41Arg)Likely pathogenic
Myasthenic syndrome, congenital, 23, presynaptic
β˜…β˜†β˜†β˜†2024β†’ Residue 41
NM_005984.5(SLC25A1):c.845G>A (p.Arg282His)Likely pathogenic
D,L-2-hydroxyglutaric aciduria|not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 282
NM_005984.5(SLC25A1):c.628C>T (p.Arg210Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 210
NM_005984.5(SLC25A1):c.9_18del (p.Pro4fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 4
NM_005984.5(SLC25A1):c.844C>G (p.Arg282Gly)Likely pathogenic
D,L-2-hydroxyglutaric aciduria|not provided
β˜…β˜†β˜†β˜†2022β†’ Residue 282
NM_005984.5(SLC25A1):c.529del (p.Gly176_Leu177insTer)Pathogenic
not provided
β˜…β˜†β˜†β˜†2021β†’ Residue 176
NM_005984.5(SLC25A1):c.381_382del (p.Cys127fs)Pathogenic
Inborn genetic diseases
β˜…β˜†β˜†β˜†2021β†’ Residue 127
NM_005984.5(SLC25A1):c.499G>A (p.Gly167Arg)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2021β†’ Residue 167
View on ClinVar β†—
Related Genes
CLTCL1Protein interaction85%MRPL40Protein interaction82%ESS2Protein interaction81%DGCR2Protein interaction81%CSProtein interaction81%GRNProtein interaction80%
Tissue Expression6 tissues
Liver
100%
Ovary
27%
Lung
22%
Brain
14%
Bone Marrow
8%
Heart
8%
Gene Interaction Network
Click a node to explore
SLC25A1CLTCL1MRPL40ESS2DGCR2CSGRN
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt P53007
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
1.03LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.75 [0.55–1.03]
RankingsWhere SLC25A1 stands among ~20K protein-coding genes
  • #2,003of 20,598
    Most Researched209 Β· top 10%
  • #1,999of 5,498
    Most Pathogenic Variants24
  • #10,253of 17,882
    Most Constrained (LOEUF)1.03
Genes detectedSLC25A1
Sources retrieved26 papers
Response timeβ€”
πŸ“„ Sources
26β–Ό
1
SLC25A1 and ACLY maintain cytosolic acetyl-CoA and regulate ferroptosis susceptibility via FSP1 acetylation.
PMID: 39881208
EMBO J Β· 2025
1.00
2
Cytosolic acetyl-coenzyme A is a signalling metabolite to control mitophagy.
PMID: 41225001
Nature Β· 2026
0.90
3
Mitochondrial metabolism sustains DNMT3A-R882-mutant clonal haematopoiesis.
PMID: 40239706
Nature Β· 2025
0.80
4
Oncogenic KRASG12D Reprograms Lipid Metabolism by Upregulating SLC25A1 to Drive Pancreatic Tumorigenesis.
PMID: 37695315
Cancer Res Β· 2023
0.70
5
SLC25A1 regulates placental development to ensure embryonic heart morphogenesis.
PMID: 39591637
Development Β· 2024
0.68