Carnitine-Acylcarnitine Translocase (CACT) Deficiency​

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SLC25A20

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Introduction

The SLC25A20 gene, solute carrier family 25 member 20, is located on chromosome 3p21.31 and has 9 exons spanning ~16.5kb (1). It encodes a 302 amino acid protein that is one of several closely related mitochondrial-membrane carrier proteins shuttling substrates between cytosol and the intramitochondrial matrix space.

The SLC25A20 protein mediates the transport of acylcarnitines into mitochondrial matrix for oxidation by the mitochondrial fatty acid-oxidation pathway (2). It also mediates the electroneutral exchange of acylcarnitines (O-acyl-(R)-carnitine or L-acylcarnitine) of different acyl chain lengths (ranging from O-acetyl-(R)-carnitine to long-chain O-acyl-(R)-carnitines) with free carnitine ((R)-carnitine or L-carnitine) across the mitochondrial inner membrane (3,4).

​Variations in this gene are associated with carnitine-acylcarnitine translocase deficiency, which can cause a variety of pathological conditions such as hypoglycemia, cardiac arrest, hepatomegaly, hepatic dysfunction and muscle weakness, and is usually lethal in newborns and infants (1). The protein is expressed in liver, duodenum and other tissues (5).

More than 58 disease-causing variants in the SLC25A20 gene have been identified in patients and are represented in this database. The variants occur across the entire length of the gene and include frameshift, splice site, copy-number, nonsense and missense variants (6).

Variant List

To see more information, click on the Variant in the table. Hover on the Variant in the table to see its location on the gene. For more information on table headers, HGVS nomenclature, and ACMG classification please use the following links here.

Gene Structure
Variant_IDVariantAmino_Acid_ChangeProtein DomainDisplay ACMG CallACMG_Call_Last_Revised_DateVariant_TypeEffect_Typegene_symbolTimes_Observed_RangePMIDArticle_CountPhenotypeDisease subtypeVariant_StartLocation
SLC25A20_0001NC_000003.11:g.(?_48900092)_(48895143_?)delNC_000003.11:g.(?_48900092)_(48895143_?)delNot SpecifiedPathogenic03/01/2023SLC25A20<3216059951Hyperammonemia, Hypoketotic hypoglycemiaCACT
SLC25A20_0002c.897dupp.Asn300Glnfs*24cyt (Cytoplasmic)Pathogenic05/16/2023DuplicationFrameshiftSLC25A203-511162577, 36109795, 93998863Abnormal liver morphology, Cardiac arrest, Cardiomyopathy, Cyanosis, Dehydration, Hypoglycemia, Liver dysfunction, Muscle weakness, SeizureCACT897Exon 9
SLC25A20_0003c.868G>Ap.Ala290ThrSolcar Repeat 3Uncertain Significance05/16/2023SNVMissenseSLC25A20<30CACT868Exon 9
SLC25A20_0004c.843+4_843+50delIntronicNot SpecifiedLikely Pathogenic03/01/2023DeletionSplice regionSLC25A203-510472533, 153659882Abnormal liver morphology, Abnormality of metabolism/homeostasis, Anorexia, Arrhythmia, Gastrointestinal-other, Hypertrophic cardiomyopathy, Hypoglycemia, Hypotonia, SeizureCACT843Intron 8
SLC25A20_0005c.843+4A>GIntronicNot SpecifiedUncertain Significance05/16/2023SNVSplice regionSLC25A20<30CACT843Intron 8
SLC25A20_0006c.842C>Tp.Ala281ValSolcar Repeat 3Pathogenic03/01/2023SNVMissenseSLC25A203-5153659881Cardiac-other, Coma, Decreased liver function, Feeding refusal, Hyperammonemia, HypoglycemiaCACT842Exon 8
SLC25A20_0007c.824G>Ap.Arg275GlnSolcar Repeat 3Likely Pathogenic03/01/2023SNVMissenseSLC25A206-10323370511Abnormal liver morphology, Arrhythmia, Cardiac arrest, Decreased body weight, Developmental delay, Grunting, Hyperammonemia, Hypertrophic cardiomyopathy, Hypoglycemia, Intracranial bleeding, Pulmonary/respiratory, SeizureCACT824Exon 8
SLC25A20_0008c.823C>Tp.Arg275*Solcar Repeat 3Pathogenic03/01/2023SNVNonsenseSLC25A20<3216059951Hyperammonemia, Hypoketotic hypoglycemiaCACT823Exon 8
SLC25A20_0009c.804delp.Phe269Serfs*4Solcar Repeat 3Pathogenic03/01/2023DeletionFrameshiftSLC25A206-1012559850, 21605995, 24088670, 31156707, 353608625Encephalopathy, Hepatic failureCACT804Exon 8
SLC25A20_0010c.673_782delp.Ala225Serfs*27Solcar Repeat 3Likely Pathogenic03/01/2023Copy Number LossSLC25A20<321605995, 96863712Abnormal liver morphology, Abnormality of metabolism/homeostasis, Arrhythmia, Hypertrophic cardiomyopathy, Muscle weaknessCACT673Exon 7-8, Intron 7
SLC25A20_0011c.779_781delp.Glu260delSolcar Repeat 3Uncertain Significance03/01/2023DeletionDeletionSLC25A20<3216059951Abnormality of metabolism/homeostasis, Cardiac-other, Decreased liver function, Hyperbilirubinemia, Hypoketotic hypoglycemia, LethargyCACT779Exon 8
SLC25A20_0012c.752_761delp.Asp251Glyfs*3Solcar Repeat 3Pathogenic03/01/2023DeletionFrameshiftSLC25A20<3216059951Abnormality of metabolism/homeostasis, Arrhythmia, HypoglycemiaCACT752Exon 8
SLC25A20_0013c.719-9_719-1dupIntronicNot SpecifiedUncertain Significance03/01/2023InsertionIntronicSLC25A20<331108048, 331949202Arrhythmia, Cardiomyopathy, Coma, Hyperammonemia, Hypoketotic hypoglycemia, Hypotonia, Lethargy, Liver dysfunction, Pulmonary/respiratory, SeizureCACT719Intron 7
SLC25A20_0014c.718+1G>CIntronicNot SpecifiedPathogenic03/01/2023SNVSplice donorSLC25A20<3153659881Abnormal liver morphology, Arrhythmia, Gastrointestinal-other, Hepatic failure, Hyperammonemia, Hypoglycemia, Hypotonia, Pulmonary/respiratoryCACT718Intron 7
SLC25A20_0015c.715A>Cp.Thr239ProSolcar Repeat 3Uncertain Significance03/01/2023SNVMissenseSLC25A20<3313192251CACT715Exon 7
SLC25A20_0016c.713A>Gp.Gln238ArgSolcar Repeat 3Pathogenic03/01/2023SNVMissenseSLC25A2021-3015057979, 23867825, 329062063Arrhythmia, Cardiomyopathy, Hyperammonemia, Hypoketotic hypoglycemia, Hypothermia, Low blood pressure, Microcephaly, Pulmonary/respiratoryCACT713Exon 7
SLC25A20_0017c.706C>Tp.Arg236*Solcar Repeat 3Pathogenic03/01/2023SNVNonsenseSLC25A20<3346266091CACT706Exon 7
SLC25A20_0018c.691G>Cp.Asp231HisSolcar Repeat 3Pathogenic03/01/2023SNVMissenseSLC25A203-512559850, 153659882Hepatic failure, Hyperammonemia, HypoglycemiaCACT691Exon 7
SLC25A20_0019c.689C>Gp.Pro230ArgSolcar Repeat 3Likely Pathogenic03/01/2023SNVMissenseSLC25A20<3125598501CACT689Exon 7
SLC25A20_0020c.658G>Ap.Gly220ArgSolcar Repeat 3Uncertain Significance05/16/2023SNVMissenseSLC25A20<3329051351Encephalopathy, Hyperammonemia, Hypertrophic cardiomyopathy, SeizureCACT658Exon 7
SLC25A20_0021c.609-1G>AIntronicNot SpecifiedPathogenic03/01/2023SNVSplice acceptorSLC25A20<3125598501CACT609Intron 6
SLC25A20_0022c.609-3C>GIntronicNot SpecifiedPathogenic03/01/2023SNVSLC25A203-516919490, 256049742Abnormal liver morphology, Abnormal muscle tone, Abnormality of metabolism/homeostasis, Arrhythmia, Hypoglycemia, Hypothermia, Lethargy, Paleness, Poor oral intakeCACT609Intron 6
SLC25A20_0023c.576G>Ap.Trp192*Solcar Repeat 2Pathogenic03/01/2023SNVNonsenseSLC25A20<3240886701Asphyxia, Cardiac arrest, Decreased liver function, Hypoglycemia, Hypotonia, Irritability, Oliguria, Pulmonary/respiratory, RhabdomyolysisCACT576Exon 6
SLC25A20_0024c.536A>Gp.Asp179GlySolcar Repeat 2Uncertain Significance05/16/2023SNVMissenseSLC25A203-5256143081Abnormality of metabolism/homeostasis, Cardiac arrest, Gastrointestinal-other, Hyperammonemia, Hypocarnitinemia, Hypoglycemia, Respiratory tract infectionCACT536Exon 6
SLC25A20_0025c.533G>Ap.Arg178GlnSolcar Repeat 2Pathogenic03/01/2023SNVMissenseSLC25A203-5125598501CACT533Exon 5
SLC25A20_0026c.532C>Tp.Arg178*Solcar Repeat 2Pathogenic03/01/2023SNVNonsenseSLC25A206-1012559850, 12801121, 15365988, 256143084Abnormal liver morphology, Abnormality of metabolism/homeostasis, Apnoea, Arrhythmia, Cholestasis, Dilated cardiomyopathy, Hyperammonemia, Hypoglycemia, Hypothermia, Hypotonia, Renal insufficiency/failure, Seizure, VomitingCACT532Exon 5
SLC25A20_0027c.528delp.Met177Cysfs*12Solcar Repeat 2Pathogenic03/01/2023DeletionFrameshiftSLC25A20<3216059951CACT528Exon 5
SLC25A20_0028c.516T>Cp.Thr172=Solcar Repeat 2Uncertain Significance03/01/2023SNVSilentSLC25A20<3240886701CACT516Exon 5
SLC25A20_0029c.496C>Tp.Arg166*Solcar Repeat 2Pathogenic03/01/2023SNVNonsenseSLC25A203-510384384, 10653336, 12559850, 216059954Abnormal liver morphology, Abnormality of metabolism/homeostasis, Arterial hypertension, Cardiac-other, Coma, Hyperammonemia, Hypoglycemia, Hypothermia, Hypotonia, Mucocutaneous bleeding syndrome, Oesophagitis, PallorCACT496Exon 5
SLC25A20_0030c.463T>Cp.Cys155ArgSolcar Repeat 2Likely Pathogenic03/01/2023SNVMissenseSLC25A20<3315612691Discoloured stools, JaundiceCACT463Exon 5
SLC25A20_0031c.417+1G>TIntronicNot SpecifiedPathogenic03/01/2023SNVSplice donorSLC25A20<323322164, 238507922CACT417Intron 4
SLC25A20_0032c.397C>Tp.Arg133TrpSolcar Repeat 2Pathogenic03/01/2023SNVMissenseSLC25A203-515365988, 21605995, 329051353Abnormal liver morphology, Abnormality of metabolism/homeostasis, Arrhythmia, Cardiac-other, Decreased liver function, Encephalopathy, Gastrointestinal-other, Hepatic failure, Hyperammonemia, Hyperbilirubinemia, Hypertrophic cardiomyopathy, Hypoglycemia, Hypoketotic hypoglycemia, Hypotonia, Lethargy, Pulmonary/respiratory, SeizureCACT397Exon 4
SLC25A20_0033c.261_388delp.Val88Trpfs*53Solcar Repeat 1Pathogenic03/01/2023Copy Number LossSLC25A20<321605995, 96863712Abnormal liver morphology, Abnormality of metabolism/homeostasis, Arrhythmia, Hypertrophic cardiomyopathy, Muscle weaknessCACT261Exon 3-4, Intron 3
SLC25A20_0034c.383T>Ap.Met128LysSolcar Repeat 2Uncertain Significance03/01/2023SNVMissenseSLC25A20<3265893111CACT383Exon 4
SLC25A20_0035c.364G>Ap.Val122IleSolcar Repeat 2Uncertain Significance05/16/2023SNVMissenseSLC25A20<30CACT364Exon 4
SLC25A20_0036c.326+1delIntronicNot SpecifiedPathogenic03/01/2023DeletionSplice donorSLC25A206-1011592821, 15365988, 16919490, 25604974, 32070364, 36109795, 92906077Abnormal liver morphology, Abnormal muscle tone, Abnormality of metabolism/homeostasis, Attention deficit hyperactivity disorder, Cardiac arrest, Cardiac-other, Decreased liver function, Encephalopathy, Hepatic failure, Hyperammonemia, Hypoglycemia, Hypothermia, Hypotonia, Learning difficulties, Lethargy, Paleness, Poor oral intake, SeizureCACT326Intron 3
SLC25A20_0037c.270delp.Phe91Leufs*38Solcar Repeat 1Pathogenic03/01/2023DeletionFrameshiftSLC25A203-511592821, 35360862, 84500533Abnormal liver morphology, Abnormality of metabolism/homeostasis, Circulatory failure, Coma, Hepatic failure, Hypoglycemia, Hypothermia, Hypotonia, Lethargy, Macrovesicular steatosis, Pulmonary hemorrhage, Pulmonary/respiratory, SweatingCACT270Exon 3
SLC25A20_0038c.269T>Gp.Phe90CysSolcar Repeat 1Likely Pathogenic03/01/2023SNVMissenseSLC25A20<3361097951HypoglycemiaCACT269Exon 3
SLC25A20_0039c.241G>Ap.Gly81ArgSolcar Repeat 1Pathogenic03/01/2023SNVMissenseSLC25A203-523322164, 238507922CACT241Exon 3
SLC25A20_0040c.226G>Cp.Ala76ProSolcar Repeat 1Uncertain Significance03/01/2023SNVMissenseSLC25A2030+0CACT226Exon 3
SLC25A20_0041c.199-10T>GIntronicNot SpecifiedLikely Pathogenic03/01/2023SNVIntronicSLC25A2030+11592821, 12559850, 1598097, 24088670, 25459972, 25604974, 26117549, 27066551, 29137068, 31108048, 33194920, 34626609, 35314707, 35360862, 36419912, 8739960, 929060717Abnormal liver morphology, Abnormality of metabolism/homeostasis, Abnormality of the liver, Anemia, Arrhythmia, Asphyxia, Cardiac arrest, Cardiac-other, Cardiomyopathy, Cholestasis, Coma, Cyanosis, Decreased liver function, Developmental delay, Encephalopathy, Gastrointestinal-other, Hepatic failure, Hyperammonemia, Hypoglycemia, Hypoketotic hypoglycemia, Hypotension, Hypothermia, Hypotonia, Irritability, Lethargy, Liver dysfunction, Micro -macrovesicular steatosis of the liver, Muscle weakness, Myopathy, No interest in breastfeeding, Oliguria, Osteoporosis, Poor feeding, Poor response, Pulmonary/respiratory, Respiratory tract infection, Rhabdomyolysis, Seizure, VomitingCACT199Intron 2
SLC25A20_0042c.198+4G>AIntronicNot SpecifiedUncertain Significance05/16/2023SNVSplice regionSLC25A20<30CACT198Intron 2
SLC25A20_0043c.160_163delinsTGGGp.Gly54_Thr55delinsTrpAlaSolcar Repeat 1Pathogenic05/16/2023DelinsMissenseSLC25A206-1015365988, 21605995, 256143083Abnormal liver morphology, Abnormality of metabolism/homeostasis, Cardiac-other, Cholestasis, Encephalopathy, Hepatic failure, Hypoglycemia, Renal insufficiency/failure, Steatosis, VomitingCACT160Exon 2
SLC25A20_0044c.110G>Cp.Arg37ProSolcar Repeat 1Likely Pathogenic03/01/2023SNVMissenseSLC25A20<3315759111HyperaminoaciduriaCACT110Exon 2
SLC25A20_0045c.109C>Tp.Arg37*Solcar Repeat 1Pathogenic03/01/2023SNVNonsenseSLC25A20<3346266091CACT109Exon 2
SLC25A20_0046c.106-2A>TIntronicNot SpecifiedPathogenic03/01/2023SNVSplice acceptorSLC25A20<3240886701Cardiac arrestCACT106Intron 1
SLC25A20_0047c.94G>Ap.Asp32AsnSolcar Repeat 1Likely Pathogenic03/01/2023SNVMissenseSLC25A20<3125598501CACT94Exon 1
SLC25A20_0048c.84delp.His29Thrfs*100Solcar Repeat 1Pathogenic03/01/2023DeletionFrameshiftSLC25A20<311592821, 15980972Abnormal liver morphology, Arrhythmia, Cardiac-other, Coma, Hepatic failure, Hypoglycemia, Hypotension, Lethargy, Muscle weakness, Pulmonary/respiratory, Respiratory tract infection, Seizure, VomitingCACT84Exon 1
SLC25A20_0049c.82G>Tp.Gly28CysSolcar Repeat 1Pathogenic03/01/2023SNVMissenseSLC25A206-1012559850, 33123633, 34374989, 95449114Abnormality of metabolism/homeostasis, Developmental delay, Hypoglycemia, MicrocephalyCACT82Exon 1
SLC25A20_0050c.67T>Cp.Cys23ArgSolcar Repeat 1Likely Pathogenic03/01/2023SNVMissenseSLC25A203-5216059951Cardiomyopathy, HypoglycemiaCACT67Exon 1
SLC25A20_0051c.65_69dupp.Leu24Cysfs*107Solcar Repeat 1Pathogenic03/01/2023InsertionFrameshiftSLC25A20<3125598501CACT65Exon 1
SLC25A20_0052c.59G>Ap.Gly20AspSolcar Repeat 1Uncertain Significance03/01/2023SNVMissenseSLC25A20<3256143081Abnormal liver morphology, Cholestasis, Hyperammonemia, Hypertrophic cardiomyopathy, Hypoglycemia, Hypothermia, Hypotonia, Respiratory tract infectionCACT59Exon 1
SLC25A20_0053c.50G>Cp.Gly17AlaSolcar Repeat 1Uncertain Significance03/01/2023SNVMissenseSLC25A20<3320703641Attention deficit hyperactivity disorder, Cardiac-other, Decreased liver function, Encephalopathy, Hypoglycemia, Hypothermia, Learning difficulties, Lethargy, SeizureCACT50Exon 1
SLC25A20_0054c.47C>Tp.Ala16ValSolcar Repeat 1Uncertain Significance03/01/2023SNVMissenseSLC25A20<3315612691Discoloured stools, JaundiceCACT47Exon 1
SLC25A20_0055c.10C>Tp.Gln4*Modified residue(N-acetylalanine)Pathogenic05/16/2023SNVNonsenseSLC25A20<3361097951Abnormality of metabolism/homeostasis, Cardiac arrest, Hypoglycemia, HypotoniaCACT10Exon 1
SLC25A20_0056c.3G>AIntronicNot SpecifiedPathogenic03/01/2023SNVMissenseSLC25A20<323322164, 238507922CACT3Exon 1
SLC25A20_0057c.1A>GIntronicNot SpecifiedPathogenic03/01/2023SNVMissenseSLC25A20<3291370681Cardiac-other, Cyanosis, Hyperammonemia, Hypoglycemia, Hypotension, Hypothermia, Poor response, Pulmonary/respiratoryCACT1Exon 1
SLC25A20_0058c.1A>Gp.Met1?Not SpecifiedPathogenic03/01/2023SNVMissenseSLC25A20<3353608621CACT1Exon 1
    Notes:
  • * All variants are referencing NM_000387.6 and there is no change between these versions with respect to the coding sequence.
  • * Genomic coordinates are calculated based on variant data provided: in some cases coordinates are estimated in order to allow users to sort the variants linearly, by approximation.
    Definition of acronyms:
  • "*": Referenced a stop codon insertion when listed under amino acid change.
  • ACMG: American College of Medical Genetics and Genomics
  • CNV: Copy number variant which here describes a change 100 DNA nucleotides or larger.
  • SNV: Single DNA nucleotide variant
  • del: Deletion
  • dup: Duplication
  • fs: Frameshift
  • ins: Insertion

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