SLC25A20

Carnitine-Acylcarnitine Translocase (CACT) Deficiency

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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 ID	Variant	Amino Acid Change	Gene Symbol	Variant Type	Effect Type	Display ACMG Call	Disease Subtype	Times Observed	Phenotype	PMID	Location	Present in ClinVar

SLC25A20_0060	c.?	Deletion (Exon 5-9)	SLC25A20	CNV	Deletion	Pathogenic	CACT	<5	Hyperammonemia, Hypoglycemia	21605995		Unknown
SLC25A20_0061	c.906A>G	p.302Trpext2	SLC25A20	SNV	Missense	Uncertain Significance	CACT	<5	Elevated circulating creatine kinase concentration, Liver abnormality, Other, Peripheral neuropathy		Exon 9	Yes
SLC25A20_0002	c.897dup	p.Asn300Glnfs*24	SLC25A20	Duplication	Frameshift	Pathogenic	CACT	5-10	Cardiac arrest, Cardiomyopathy, Cyanosis, Dehydration, Hypoglycemia, Liver abnormality, Muscle weakness, Seizure	11162577, 36109795, 9399886	Exon 9	Yes
SLC25A20_0003	c.868G>A	p.Ala290Thr	SLC25A20	SNV	Missense	Uncertain Significance	CACT	<5			Exon 9	Yes
SLC25A20_0004	c.843+4_843+50del	Intronic	SLC25A20	Deletion	Splice region	Likely Pathogenic	CACT	<5	Abnormality of metabolism/homeostasis, Anorexia, Arrhythmia, Cardiomyopathy, Gas....	10472533, 15365988	Intron 8	Yes
SLC25A20_0005	c.843+4A>G	Intronic	SLC25A20	SNV	Splice region	Uncertain Significance	CACT	<5	Liver abnormality		Intron 8	Yes
SLC25A20_0006	c.842C>T	p.Ala281Val	SLC25A20	SNV	Missense	Pathogenic	CACT	<5	Cardiac-other, Coma, Feeding refusal, Hyperammonemia, Hypoglycemia, Liver abnormality	15365988	Exon 8	Yes
SLC25A20_0007	c.824G>A	p.Arg275Gln	SLC25A20	SNV	Missense	Likely Pathogenic	CACT	5-10	Arrhythmia, Cardiac arrest, Cardiomyopathy, Decreased body weight, Developmental....	32337051	Exon 8	Yes
SLC25A20_0008	c.823C>T	p.Arg275*	SLC25A20	SNV	Nonsense	Pathogenic	CACT	<5	Hyperammonemia, Hypoglycemia	21605995	Exon 8	Yes
SLC25A20_0009	c.804del	p.Phe269Serfs*4	SLC25A20	Deletion	Frameshift	Pathogenic	CACT	5-10	Abnormality of metabolism/homeostasis, Encephalopathy, Hypertension, Hypoglycemi....	12559850, 21605995, 24088670, 31156707, 35360862	Exon 8	Yes
SLC25A20_0010	c.673_782del	p.Ala225Serfs*27	SLC25A20	Copy Number Loss	Deletion	Likely Pathogenic	CACT	<5	Abnormality of metabolism/homeostasis, Arrhythmia, Cardiomyopathy, Liver abnormality, Muscle weakness	21605995, 9686371	Exon 7-8, Intron 7	No
SLC25A20_0011	c.779_781del	p.Glu260del	SLC25A20	Deletion	Deletion	Uncertain Significance	CACT	<5	Abnormality of metabolism/homeostasis, Cardiac-other, Hyperbilirubinemia, Hypoglycemia, Lethargy, Liver abnormality	21605995	Exon 8	Yes
SLC25A20_0012	c.752_761del	p.Asp251Glyfs*3	SLC25A20	Deletion	Frameshift	Pathogenic	CACT	<5	Abnormality of metabolism/homeostasis, Arrhythmia, Hypoglycemia	21605995	Exon 8	No
SLC25A20_0013	c.719-9_719-1dup	Intronic	SLC25A20	Insertion	Intronic	Uncertain Significance	CACT	<5	Arrhythmia, Cardiomyopathy, Coma, Hyperammonemia, Hypoglycemia, Hypotonia, Lethargy, Liver abnormality, Pulmonary/respiratory, Seizure	31108048, 33194920	Intron 7	No
SLC25A20_0014	c.718+1G>C	Intronic	SLC25A20	SNV	Splice donor	Pathogenic	CACT	<5	Arrhythmia, Gastrointestinal-other, Hyperammonemia, Hypoglycemia, Hypotonia, Liver abnormality, Pulmonary/respiratory	15365988	Intron 7	Yes
SLC25A20_0015	c.715A>C	p.Thr239Pro	SLC25A20	SNV	Missense	Uncertain Significance	CACT	<5		31319225	Exon 7	Yes
SLC25A20_0016	c.713A>G	p.Gln238Arg	SLC25A20	SNV	Missense	Pathogenic	CACT	21-30	Arrhythmia, Cardiomyopathy, Hyperammonemia, Hypoglycemia, Hypothermia, Low blood pressure, Microcephaly, Pulmonary/respiratory	15057979, 23867825, 32906206	Exon 7	Yes
SLC25A20_0017	c.706C>T	p.Arg236*	SLC25A20	SNV	Nonsense	Pathogenic	CACT	<5		34626609	Exon 7	Yes
SLC25A20_0018	c.691G>C	p.Asp231His	SLC25A20	SNV	Missense	Pathogenic	CACT	<5	Hyperammonemia, Hypoglycemia, Liver abnormality	12559850, 15365988	Exon 7	Yes
SLC25A20_0019	c.689C>G	p.Pro230Arg	SLC25A20	SNV	Missense	Likely Pathogenic	CACT	<5		12559850	Exon 7	No
SLC25A20_0020	c.658G>A	p.Gly220Arg	SLC25A20	SNV	Missense	Uncertain Significance	CACT	<5	Cardiomyopathy, Encephalopathy, Hyperammonemia, Seizure	32905135	Exon 7	Yes
SLC25A20_0021	c.609-1G>A	Intronic	SLC25A20	SNV	Splice acceptor	Pathogenic	CACT	<5		12559850	Intron 6	No
SLC25A20_0022	c.609-3C>G	Intronic	SLC25A20	SNV	Splice region	Pathogenic	CACT	<5	Abnormal muscle tone, Abnormality of metabolism/homeostasis, Arrhythmia, Hypogly....	16919490, 25604974	Intron 6	No
SLC25A20_0023	c.576G>A	p.Trp192*	SLC25A20	SNV	Nonsense	Pathogenic	CACT	<5	Asphyxia, Cardiac arrest, Hypoglycemia, Hypotonia, Irritability, Liver abnormality, Oliguria, Pulmonary/respiratory, Rhabdomyolysis	24088670	Exon 6	Yes
SLC25A20_0024	c.536A>G	p.Asp179Gly	SLC25A20	SNV	Missense	Uncertain Significance	CACT	<5	Abnormality of metabolism/homeostasis, Cardiac arrest, Gastrointestinal-other, H....	25614308	Exon 6	Yes
SLC25A20_0025	c.533G>A	p.Arg178Gln	SLC25A20	SNV	Missense	Pathogenic	CACT	<5		12559850	Exon 5	Yes
SLC25A20_0026	c.532C>T	p.Arg178*	SLC25A20	SNV	Nonsense	Pathogenic	CACT	5-10	Abnormality of metabolism/homeostasis, Apnoea, Arrhythmia, Cardiomyopathy, Hyper....	12559850, 12801121, 15365988, 25614308	Exon 5	Yes
SLC25A20_0027	c.528del	p.Met177Cysfs*12	SLC25A20	Deletion	Frameshift	Pathogenic	CACT	<5		21605995	Exon 5	Yes
SLC25A20_0028	c.516T>C	p.Thr172=	SLC25A20	SNV	Silent	Uncertain Significance	CACT	<5		24088670	Exon 5	Yes
SLC25A20_0029	c.496C>T	p.Arg166*	SLC25A20	SNV	Nonsense	Pathogenic	CACT	<5	Abnormality of metabolism/homeostasis, Arterial hypertension, Cardiac-other, Com....	10384384, 10653336, 12559850, 21605995	Exon 5	Yes
SLC25A20_0030	c.463T>C	p.Cys155Arg	SLC25A20	SNV	Missense	Likely Pathogenic	CACT	<5	Discoloured stools, Jaundice	31561269	Exon 5	No
SLC25A20_0031	c.417+1G>T	Intronic	SLC25A20	SNV	Splice donor	Pathogenic	CACT	<5		23322164, 23850792	Intron 4	No
SLC25A20_0032	c.397C>T	p.Arg133Trp	SLC25A20	SNV	Missense	Pathogenic	CACT	<5	Abnormality of metabolism/homeostasis, Arrhythmia, Cardiac-other, Cardiomyopathy....	15365988, 21605995, 32905135	Exon 4	Yes
SLC25A20_0033	c.261_388del	p.Val88Trpfs*53	SLC25A20	Copy Number Loss	Deletion	Pathogenic	CACT	<5	Abnormality of metabolism/homeostasis, Arrhythmia, Cardiomyopathy, Liver abnormality, Muscle weakness	21605995, 9686371	Exon 3-4, Intron 3	No
SLC25A20_0034	c.383T>A	p.Met128Lys	SLC25A20	SNV	Missense	Uncertain Significance	CACT	<5		26589311	Exon 4	No
SLC25A20_0035	c.364G>A	p.Val122Ile	SLC25A20	SNV	Missense	Uncertain Significance	CACT	<5	Cardiomyopathy, Elevated circulating creatine kinase concentration, Myopathy, Other, Peripheral neuropathy		Exon 4	Yes
SLC25A20_0036	c.326+1del	Intronic	SLC25A20	Deletion	Splice donor	Pathogenic	CACT	5-10	Abnormal muscle tone, Abnormality of metabolism/homeostasis, Attention deficit h....	11592821, 15365988, 16919490, 25604974, 32070364, 36109795, 9290607	Intron 3	Yes
SLC25A20_0037	c.270del	p.Phe91Leufs*38	SLC25A20	Deletion	Frameshift	Pathogenic	CACT	<5	Abnormality of metabolism/homeostasis, Circulatory failure, Coma, Hypoglycemia, ....	11592821, 35360862, 8450053	Exon 3	Yes
SLC25A20_0038	c.269T>G	p.Phe90Cys	SLC25A20	SNV	Missense	Likely Pathogenic	CACT	<5	Hypoglycemia	36109795	Exon 3	No
SLC25A20_0062	c.254T>A	p.Met85Lys	SLC25A20	SNV	Missense	Uncertain Significance	CACT	<5			Exon 3	Yes
SLC25A20_0039	c.241G>A	p.Gly81Arg	SLC25A20	SNV	Missense	Pathogenic	CACT	<5		23322164, 23850792	Exon 3	Yes
SLC25A20_0040	c.226G>C	p.Ala76Pro	SLC25A20	SNV	Missense	Uncertain Significance	CACT	<5	Retinal/choroid disorder		Exon 3	Yes
SLC25A20_0041	c.199-10T>G	Intronic	SLC25A20	SNV	Intronic	Likely Pathogenic	CACT	30+	Abnormality of metabolism/homeostasis, Anemia, Arrhythmia, Asphyxia, Cardiac arr....	11592821, 12559850, 1598097, 24088670, 25459972, 25604974, 26117549, 27066551, 29137068, 31108048, 33194920, 34626609, 35314707, 35360862, 36419912, 8739960, 9290607	Intron 2	Yes
SLC25A20_0042	c.198+4G>A	Intronic	SLC25A20	SNV	Splice region	Uncertain Significance	CACT	<5			Intron 2	Yes
SLC25A20_0043	c.160_163delinsTGGG	p.Gly54_Thr55delinsTrpAla	SLC25A20	Delins	Missense	Pathogenic	CACT	5-10	Abnormality of metabolism/homeostasis, Cardiac-other, Encephalopathy, Hypoglycem....	15365988, 21605995, 25614308	Exon 2	Yes
SLC25A20_0044	c.110G>C	p.Arg37Pro	SLC25A20	SNV	Missense	Likely Pathogenic	CACT	<5	Hyperaminoaciduria	31575911	Exon 2	No
SLC25A20_0045	c.109C>T	p.Arg37*	SLC25A20	SNV	Nonsense	Pathogenic	CACT	<5		34626609	Exon 2	Yes
SLC25A20_0046	c.106-2A>T	Intronic	SLC25A20	SNV	Splice acceptor	Pathogenic	CACT	<5	Cardiac arrest	24088670	Intron 1	Yes
SLC25A20_0047	c.94G>A	p.Asp32Asn	SLC25A20	SNV	Missense	Likely Pathogenic	CACT	<5		12559850	Exon 1	No
SLC25A20_0048	c.84del	p.His29Thrfs*100	SLC25A20	Deletion	Frameshift	Pathogenic	CACT	<5	Arrhythmia, Cardiac-other, Coma, Hypoglycemia, Hypotension, Lethargy, Liver abno....	11592821, 1598097	Exon 1	Yes
SLC25A20_0049	c.82G>T	p.Gly28Cys	SLC25A20	SNV	Missense	Pathogenic	CACT	5-10	Abnormality of metabolism/homeostasis, Developmental delay, Hypoglycemia, Microcephaly	12559850, 33123633, 34374989, 9544911	Exon 1	Yes
SLC25A20_0050	c.67T>C	p.Cys23Arg	SLC25A20	SNV	Missense	Likely Pathogenic	CACT	<5	Cardiomyopathy, Hypoglycemia	21605995	Exon 1	No
SLC25A20_0051	c.65_69dup	p.Leu24Cysfs*107	SLC25A20	Insertion	Frameshift	Pathogenic	CACT	<5		12559850	Exon 1	No
SLC25A20_0052	c.59G>A	p.Gly20Asp	SLC25A20	SNV	Missense	Uncertain Significance	CACT	<5	Cardiomyopathy, Hyperammonemia, Hypoglycemia, Hypothermia, Hypotonia, Liver abnormality, Respiratory tract infection	25614308	Exon 1	No
SLC25A20_0053	c.50G>C	p.Gly17Ala	SLC25A20	SNV	Missense	Uncertain Significance	CACT	<5	Attention deficit hyperactivity disorder, Cardiac-other, Encephalopathy, Hypogly....	32070364	Exon 1	No
SLC25A20_0054	c.47C>T	p.Ala16Val	SLC25A20	SNV	Missense	Uncertain Significance	CACT	<5	Discoloured stools, Jaundice	31561269	Exon 1	Yes
SLC25A20_0055	c.10C>T	p.Gln4*	SLC25A20	SNV	Nonsense	Pathogenic	CACT	<5	Abnormality of metabolism/homeostasis, Cardiac arrest, Hypoglycemia, Hypotonia	36109795	Exon 1	Yes
SLC25A20_0056	c.3G>A	Intronic	SLC25A20	SNV	Missense	Pathogenic	CACT	<5		23322164, 23850792	Exon 1	No
SLC25A20_0063	c.1A>G	p.Met1Val	SLC25A20	SNV	Missense	Pathogenic	CACT	<5		29137068, 35360862	Exon 1	Yes

Notes:

* Click the PMID number to go to the corresponding publication.
* 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.
* Click the Present in ClinVar link to go to the corresponding ClinVar VariationID.

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

References:

Iacobazzi, V. et al., The structure and organization of the human carnitine/acylcarnitine translocase (CACT1) gene. Biochem Biophys Res Commun. 1998 Nov 27;252(3):770-4.
https://www.ncbi.nlm.nih.gov/gene/788
Pérez. P. et al. Functional analysis of mutations in the human carnitine/acylcarnitine translocase in Aspergillus nidulans. Fungal Genet Biol. 2003 Aug;39(3):211-20.
De Lucas, J. R. et al., Functional characterization of residues within the carnitine/acylcarnitine translocase RX2PANAAXF distinct motif. Mol Membr Biol. 2008 Feb;25(2):152-63.
https://www.uniprot.org/uniprotkb/O43772/entry#
Richbourg et al. (2023) Phenotype associations from a comprehensive database of long-chain fatty acid oxidation disorder gene variants (Abstract and poster presentation, ASHG 2023).

Carnitine-Acylcarnitine Translocase (CACT) Deficiency​

Introduction

Variant List

Gene Structure

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Carnitine-Acylcarnitine Translocase (CACT) Deficiency