Rare Disease Genes

Introduction

The CPT1A gene, which stands for carnitine palmitoyltransferase 1A, is located on chromosome 11q13.3, has 19 exons spanning ~60kb and encodes a 773 amino acid protein, Carnitine Palmitoyltransferase I or CPT I (1). The mitochondrial oxidation of long-chain fatty acids is initiated by the sequential action of carnitine palmitoyltransferase I (located in the outer membrane) and carnitine palmitoyltransferase II (located in the inner membrane), together with a carnitine-acylcarnitine translocase (2). CPT I is the key enzyme in the carnitine-dependent transport across the mitochondrial inner membrane and its deficiency results in a decreased rate of fatty acid beta-oxidation (2). The protein catalyzes the transfer of the acyl group of long-chain fatty acid-CoA conjugates onto carnitine, an essential step for the mitochondrial uptake of long-chain fatty acids and their subsequent beta-oxidation in the mitochondrion (3).

The CPT I protein is expressed at high levels in kidney and heart and at lower levels in liver and skeletal muscle (3).

More than 94 unique disease-causing variants in the CPT1A gene have been identified in CPT I patients and are represented in this database (4). The variants occur across the entire length of the gene and include frameshift, splice site, copy-number, nonsense and missense variants.

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

Show entries

Search by any gene or variant detail to filter the table below:

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

CPT1A_0001	c.2246G>A	p.Arg749His	CPT1A	SNV	Missense	Likely Pathogenic	CPT I	<5	Developmental delay	34374989, 35360862	Exon 19	No
CPT1A_0002	c.2238T>G	p.Asp746Glu	CPT1A	SNV	Missense	Uncertain Significance	CPT I	<5	Myopathy		Exon 19	Yes
CPT1A_0003	c.2215A>G	p.Lys739Glu	CPT1A	SNV	Missense	Likely Pathogenic	CPT I	<5		33123633	Exon 18	No
CPT1A_0004	c.2201T>C	p.Phe734Ser	CPT1A	SNV	Missense	Uncertain Significance	CPT I	<5		34233743	Exon 18	No
CPT1A_0005	c.2198A>G	p.Asn733Ser	CPT1A	SNV	Missense	Uncertain Significance	CPT I	<5		34023347	Exon 18	Yes
CPT1A_0006	c.2156G>A	p.Gly719Asp	CPT1A	SNV	Missense	Likely Pathogenic	CPT I	<5		19345525	Exon 18	No
CPT1A_0007	c.2142G>A	p.Pro714=	CPT1A	SNV	Silent	Uncertain Significance	CPT I	<5			Exon 17	Yes
CPT1A_0009	c.2136del	p.Phe712Leufs*43	CPT1A	Deletion	Frameshift	Likely Pathogenic	CPT I	<5		30887117	Exon 17	Yes
CPT1A_0010	c.2129G>A	p.Gly710Glu	CPT1A	SNV	Missense	Likely Pathogenic	CPT I	11-20	Deep vein thrombosis, Dehydration, Developmental delay, Diarrhea, Encephalopathy Show More >>	11350182, 11350183, 1403388	Exon 17	Yes
CPT1A_0011	c.2126G>A	p.Gly709Glu	CPT1A	SNV	Missense	Likely Pathogenic	CPT I	<5	Abnormality of metabolism/homeostasis, Arrhythmia, Cardiac-other, Hypoglycemia, Hypotonic, Liver abnormality, Peripheral oedema	14517221, 9048718	Exon 17	Yes

Showing 1 to 10 of 105 entries

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Column Name	Table View	Detail View
Variant ID
Variant
Amino Acid Change
Gene Symbol
Variant Type
Effect Type
Display ACMG Call
Disease Subtype
Times Observed
Phenotype
PMID
Article Count
Location
Protein Domain
ACMG Call Last Revised Date
GRCh38
Record Last Revised Date
Present in ClinVar
ACMG Call
Predicted ACMG Call
Thousand Genomes Allele Frequency
Ontology Relations
ExAC Allele Frequency
GnomAD Alleles
Associated Geography
Variants Seen With

Notes:

Click the PMID number to go to the corresponding publication.
All variants are referencing NM_001876.4 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:

Gobin, S. et al., Organization of the human liver carnitine palmitoyltransferase 1 gene (CPT1A) and identification of novel mutations in hypoketotic hypoglycaemia. Hum Genet. 2002 Aug;111(2):179-89.
https://www.ncbi.nlm.nih.gov/gene/1374
https://www.genecards.org/cgi-bin/carddisp.pl?gene=CPT1A&keywords=cpt1a
Richbourg et al. (2023) Phenotype associations from a comprehensive database of long-chain fatty acid oxidation disorder gene variants (Abstract and poster presentation, American Society of Human Genetics 2023).

Carnitine Palmitoyltransferase I (CPT I) Deficiency

Introduction

Variant List

Gene Structure