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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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SLC25A20
solute carrier family 25 member 20
Chromosome 3 Β· 3p21.31
NCBI Gene: 788Ensembl: ENSG00000178537.11HGNC: HGNC:1421UniProt: O43772
55PubMed Papers
21Diseases
0Drugs
75Pathogenic Variants
FUNCTIONAL ROLE
Transporter
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingmitochondrioncarnitine:O-acyl-L-carnitine antiporter activitycarnitine transmembrane transportcarnitine-acylcarnitine translocase deficiencygenetic disorderPancreatic pseudocystneoplasm
✦AI Summary

SLC25A20 encodes the carnitine-acylcarnitine translocase (CAC), a mitochondrial inner membrane transporter that catalyzes the electroneutral exchange of acylcarnitines with free carnitine across the mitochondrial membrane 1. This transporter is essential for fatty acid Ξ²-oxidation, facilitating the transport of short, medium, and long-chain acylcarnitines into the mitochondrial matrix where they undergo oxidation 1. The protein utilizes an alternating access mechanism involving conformational transitions between cytoplasmic (c-state) and matrix (m-state) conformations 2. Functionally, SLC25A20 acts as a tumor suppressor by promoting fatty acid oxidation; its down-regulation in hepatocellular carcinoma leads to suppressed fatty acid oxidation, enhanced cell growth, and increased metastasis through mTOR pathway inactivation 34. Clinically, SLC25A20 mutations cause carnitine-acylcarnitine translocase deficiency (CACTD), a rare autosomal recessive disorder presenting with severe metabolic decompensation, hypoglycemia, and often neonatal death 56. Pathogenic mutations such as Asp231His and Ala281Val disrupt the transporter's conformational dynamics 2. SLC25A20 also functions as an immunologic regulator, with dysregulation linked to inflammatory conditions including ankylosing spondylitis and uveitis 7.

Sources cited
1
SLC25A20 catalyzes electroneutral exchange of acylcarnitines with carnitine and is essential for fatty acid Ξ²-oxidation
PMID: 33807231
2
The transporter uses alternating access mechanism with conformational transitions and specific pathogenic mutations affect its dynamics
PMID: 36835358
3
SLC25A20 acts as tumor suppressor in hepatocellular carcinoma through fatty acid oxidation regulation
PMID: 33824298
4
SLC25A20 knockdown reduces ATP production via mTOR inactivation in pancreatic cancer
PMID: 40521210
5
SLC25A20 mutations cause CACTD with severe metabolic decompensation and neonatal death
PMID: 34784499
6
CACTD presents with hypoglycemia and is caused by compound heterozygous or homozygous SLC25A20 variants
PMID: 38565514
7
SLC25A20 functions as immunologic regulator in ankylosing spondylitis and uveitis
PMID: 40929101
Disease Associationsβ“˜21
carnitine-acylcarnitine translocase deficiencyOpen Targets
0.83Strong
genetic disorderOpen Targets
0.19Weak
Pancreatic pseudocystOpen Targets
0.10Weak
neoplasmOpen Targets
0.10Suggestive
Abnormality of the skeletal systemOpen Targets
0.08Suggestive
hepatocellular carcinomaOpen Targets
0.08Suggestive
atrial fibrillationOpen Targets
0.08Suggestive
hyperinsulinemic hypoglycemia, familial, 4Open Targets
0.05Suggestive
uveitisOpen Targets
0.04Suggestive
cancerOpen Targets
0.04Suggestive
carcinomaOpen Targets
0.03Suggestive
renal-hepatic-pancreatic dysplasia 1Open Targets
0.03Suggestive
familial idiopathic dilatation of the right atriumOpen Targets
0.03Suggestive
Autosomal dominant polycystic kidney diseaseOpen Targets
0.03Suggestive
alcohol drinkingOpen Targets
0.03Suggestive
nicotine dependenceOpen Targets
0.03Suggestive
dilated cardiomyopathyOpen Targets
0.02Suggestive
diabetes mellitusOpen Targets
0.02Suggestive
obstructive sleep apneaOpen Targets
0.01Suggestive
nasopharyngeal carcinomaOpen Targets
0.01Suggestive
Carnitine-acylcarnitine translocase deficiencyUniProt
Pathogenic Variants75
NM_000387.6(SLC25A20):c.326+1delPathogenic
Carnitine acylcarnitine translocase deficiency|not provided|SLC25A20-related disorder
β˜…β˜…β˜†β˜†2026
NM_000387.6(SLC25A20):c.121C>T (p.Gln41Ter)Pathogenic
Carnitine acylcarnitine translocase deficiency
β˜…β˜…β˜†β˜†2026β†’ Residue 41
NM_000387.6(SLC25A20):c.199-10T>GPathogenic
Carnitine acylcarnitine translocase deficiency|not provided|SLC25A20-related disorder
β˜…β˜…β˜†β˜†2026
NM_000387.6(SLC25A20):c.397C>T (p.Arg133Trp)Pathogenic
Carnitine acylcarnitine translocase deficiency|SLC25A20-related disorder
β˜…β˜…β˜†β˜†2026β†’ Residue 133
NM_000387.6(SLC25A20):c.496C>T (p.Arg166Ter)Pathogenic
Carnitine acylcarnitine translocase deficiency|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 166
NM_000387.6(SLC25A20):c.10C>T (p.Gln4Ter)Pathogenic
not provided|Carnitine acylcarnitine translocase deficiency
β˜…β˜…β˜†β˜†2025β†’ Residue 4
NM_000387.6(SLC25A20):c.301C>T (p.Gln101Ter)Pathogenic
Carnitine acylcarnitine translocase deficiency
β˜…β˜…β˜†β˜†2025β†’ Residue 101
NM_000387.6(SLC25A20):c.191_192del (p.Leu63_Phe64insTer)Pathogenic
Carnitine acylcarnitine translocase deficiency|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 63
NM_000387.6(SLC25A20):c.198+2T>CLikely pathogenic
Carnitine acylcarnitine translocase deficiency|SLC25A20-related disorder
β˜…β˜…β˜†β˜†2025
NM_000387.6(SLC25A20):c.533G>A (p.Arg178Gln)Pathogenic
Carnitine acylcarnitine translocase deficiency
β˜…β˜…β˜†β˜†2025β†’ Residue 178
NM_000387.6(SLC25A20):c.824G>A (p.Arg275Gln)Pathogenic
Carnitine acylcarnitine translocase deficiency
β˜…β˜…β˜†β˜†2025β†’ Residue 275
NM_000387.6(SLC25A20):c.823C>T (p.Arg275Ter)Pathogenic
Carnitine acylcarnitine translocase deficiency
β˜…β˜…β˜†β˜†2025β†’ Residue 275
NM_000387.6(SLC25A20):c.532C>T (p.Arg178Ter)Pathogenic
not provided|Carnitine acylcarnitine translocase deficiency
β˜…β˜…β˜†β˜†2024β†’ Residue 178
NM_000387.6(SLC25A20):c.713A>G (p.Gln238Arg)Pathogenic
Carnitine acylcarnitine translocase deficiency|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 238
NM_000387.6(SLC25A20):c.691G>C (p.Asp231His)Pathogenic
Carnitine acylcarnitine translocase deficiency
β˜…β˜…β˜†β˜†2024β†’ Residue 231
NM_000387.6(SLC25A20):c.84del (p.His29fs)Pathogenic
Carnitine acylcarnitine translocase deficiency|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 29
NM_000387.6(SLC25A20):c.706C>T (p.Arg236Ter)Pathogenic
Carnitine acylcarnitine translocase deficiency
β˜…β˜…β˜†β˜†2024β†’ Residue 236
NM_000387.6(SLC25A20):c.718+1G>CPathogenic
Carnitine acylcarnitine translocase deficiency
β˜…β˜…β˜†β˜†2024
NM_000387.6(SLC25A20):c.109C>T (p.Arg37Ter)Pathogenic
Carnitine acylcarnitine translocase deficiency
β˜…β˜…β˜†β˜†2024β†’ Residue 37
NM_000387.6(SLC25A20):c.105+2T>GLikely pathogenic
Carnitine acylcarnitine translocase deficiency
β˜…β˜…β˜†β˜†2024
View on ClinVar β†—
Related Genes
HADHAProtein interaction99%HADHBProtein interaction99%ACADVLProtein interaction93%CPT2Protein interaction92%PPARAProtein interaction92%ACADMProtein interaction92%
Tissue Expression6 tissues
Liver
100%
Heart
44%
Lung
15%
Brain
7%
Bone Marrow
7%
Ovary
6%
Gene Interaction Network
Click a node to explore
SLC25A20HADHAHADHBACADVLCPT2PPARAACADM
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt O43772
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
1.05LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.77 [0.57–1.05]
RankingsWhere SLC25A20 stands among ~20K protein-coding genes
  • #8,250of 20,598
    Most Researched55
  • #983of 5,498
    Most Pathogenic Variants75 Β· top quartile
  • #10,534of 17,882
    Most Constrained (LOEUF)1.05
Genes detectedSLC25A20
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
A 20-year Clinical and Genetic Neuromuscular Cohort Analysis in Lebanon: An International Effort.
PMID: 34602496
J Neuromuscul Dis Β· 2022
1.00
2
In Silico Analysis of the Structural Dynamics and Substrate Recognition Determinants of the Human Mitochondrial Carnitine/Acylcarnitine SLC25A20 Transporter.
PMID: 36835358
Int J Mol Sci Β· 2023
0.90
3
Loss of
PMID: 40521210
Theranostics Β· 2025
0.80
4
Neonatal sudden death caused by a novel heterozygous mutation in SLC25A20 gene: A case report and brief literature review.
PMID: 34784499
Leg Med (Tokyo) Β· 2022
0.70
5
[Clinical and genetic analysis of two pedigrees affected with Carnitine-acylcarnitine translocase deficiency due to variant of SLC25A20 gene].
PMID: 38565514
Zhonghua Yi Xue Yi Chuan Xue Za Zhi Β· 2024
0.60