CPT1A

carnitine palmitoyltransferase 1A

Basic information

Region (hg38): 11:68754620-68844410

Previous symbols: [ "CPT1" ]

Links

ENSG00000110090

∙ NCBI:1374 ∙ OMIM:600528 ∙ HGNC:2328 ∙ Uniprot:P50416 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

carnitine palmitoyl transferase 1A deficiency (Strong), mode of inheritance: AR
carnitine palmitoyl transferase 1A deficiency (Strong), mode of inheritance: AR
carnitine palmitoyl transferase 1A deficiency (Supportive), mode of inheritance: AR
carnitine palmitoyl transferase 1A deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Carnitine palmitoyltransferase deficiency I	AR	Biochemical; Pharmacogenomic	Dietary management, including avoidance of fasting and prompt treatment of hypoglycemia, can prevent and treat metabolic decompensation, and can prevent neurologic damage; Surveillance for hepatic dysfunction may be beneficial, and potentially hepatoxic agents should be avoided	Biochemical; Cardiovascular; Gastrointestinal; Musculoskeletal; Neurologic; Renal	7014807; 3211616; 1598098; 1403388; 9691089; 10625081; 11286380; 11350182; 12189492; 15110323; 20301700; 20696606; 21962599

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CPT1A gene.

Carnitine_palmitoyl_transferase_1A_deficiency (1001 variants)
not_provided (92 variants)
Inborn_genetic_diseases (86 variants)
not_specified (53 variants)
CPT1A-related_disorder (33 variants)
CPT1A_POLYMORPHISM (1 variants)
Metabolic_disease (1 variants)
CPT1A_ARCTIC_VARIANT (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CPT1A gene is commonly pathogenic or not. These statistics are base on transcript: NM_000001876.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			11 clinvar	329 clinvar	5 clinvar	345
missense	6 clinvar	26 clinvar	248 clinvar	26 clinvar	3 clinvar	309
nonsense	25 clinvar	26 clinvar	5 clinvar			56
start loss	1					1
frameshift	31 clinvar	29 clinvar	3 clinvar			63
splice donor/acceptor (+/-2bp)	3 clinvar	33 clinvar	3 clinvar			39
Total	66	114	270	355	8

Highest pathogenic variant AF is 0.000331712

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CPT1A	protein_coding	protein_coding	ENST00000265641	18	89791

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.11e-9	1.00	125703	0	45	125748	0.000179

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.64	376	477	0.789	0.0000324	5079
Missense in Polyphen		78	136.08	0.57321		1424
Synonymous	0.284	190	195	0.974	0.0000155	1486
Loss of Function	3.43	22	47.5	0.463	0.00000278	486

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000275	0.000275
Ashkenazi Jewish	0.000996	0.000993
East Asian	0.000326	0.000326
Finnish	0.00	0.00
European (Non-Finnish)	0.000159	0.000149
Middle Eastern	0.000326	0.000326
South Asian	0.000196	0.000196
Other	0.000165	0.000163

dbNSFP

Source: dbNSFP

Function: FUNCTION: 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. Plays an important role in triglyceride metabolism.;
Disease: DISEASE: Carnitine palmitoyltransferase 1A deficiency (CPT1AD) [MIM:255120]: Rare autosomal recessive metabolic disorder of long- chain fatty acid oxidation characterized by severe episodes of hypoketotic hypoglycemia usually occurring after fasting or illness. Onset is in infancy or early childhood. {ECO:0000269|PubMed:11350182, ECO:0000269|PubMed:11441142, ECO:0000269|PubMed:12111367, ECO:0000269|PubMed:12189492, ECO:0000269|PubMed:14517221, ECO:0000269|PubMed:15110323, ECO:0000269|PubMed:15669684, ECO:0000269|PubMed:9691089}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Adipocytokine signaling pathway - Homo sapiens (human);Insulin resistance - Homo sapiens (human);AMPK signaling pathway - Homo sapiens (human);Thermogenesis - Homo sapiens (human);Glucagon signaling pathway - Homo sapiens (human);Fatty acid degradation - Homo sapiens (human);PPAR signaling pathway - Homo sapiens (human);Long chain acyl-CoA dehydrogenase deficiency (LCAD);Trifunctional protein deficiency;Carnitine palmitoyl transferase deficiency (II);Very-long-chain acyl coa dehydrogenase deficiency (VLCAD);Medium chain acyl-coa dehydrogenase deficiency (MCAD);Short Chain Acyl CoA Dehydrogenase Deficiency (SCAD Deficiency);Fatty acid Metabolism;Glutaric Aciduria Type I;Ethylmalonic Encephalopathy;Mitochondrial Beta-Oxidation of Long Chain Saturated Fatty Acids;Carnitine palmitoyl transferase deficiency (I);AMP-activated Protein Kinase (AMPK) Signaling;Fatty Acid Beta Oxidation;Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha);PPAR Alpha Pathway;Nuclear Receptors Meta-Pathway;RORA activates gene expression;Mitochondrial LC-Fatty Acid Beta-Oxidation;Leptin and adiponectin;PPAR signaling pathway;Liver steatosis AOP;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;Signal Transduction;mechanism of gene regulation by peroxisome proliferators via ppara;Circadian Clock;mitochondrial L-carnitine shuttle;Metabolism of lipids;Import of palmitoyl-CoA into the mitochondrial matrix;RORA activates gene expression;Metabolism;Fatty acid metabolism;Signaling by Retinoic Acid;Signaling by Nuclear Receptors;FOXA2 and FOXA3 transcription factor networks (Consensus)

Recessive Scores

pRec: 0.575

Intolerance Scores

loftool: 0.0338
rvis_EVS: -0.48
rvis_percentile_EVS: 22.78

Haploinsufficiency Scores

pHI: 0.119
hipred: Y
hipred_score: 0.639
ghis: 0.494

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.976

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Cpt1a
Phenotype: cellular phenotype; homeostasis/metabolism phenotype; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); vision/eye phenotype;

Gene ontology

Biological process: long-chain fatty acid metabolic process;glucose metabolic process;fatty acid beta-oxidation;triglyceride metabolic process;carnitine shuttle;circadian rhythm;carnitine metabolic process;response to organic cyclic compound;regulation of lipid metabolic process;epithelial cell differentiation;positive regulation of fatty acid beta-oxidation;response to drug;eating behavior;regulation of insulin secretion;protein homooligomerization;cellular response to fatty acid
Cellular component: mitochondrion;mitochondrial outer membrane;membrane;integral component of mitochondrial outer membrane
Molecular function: carnitine O-palmitoyltransferase activity;identical protein binding;palmitoleoyltransferase activity