CPT2

carnitine palmitoyltransferase 2

Basic information

Region (hg38): 1:53196792-53214197

Previous symbols: [ "CPT1" ]

Links

ENSG00000157184 ∙ NCBI:1376 ∙ OMIM:600650 ∙ HGNC:2330 ∙ Uniprot:P23786 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• carnitine palmitoyltransferase II deficiency (Definitive), mode of inheritance: AR
• carnitine palmitoyl transferase II deficiency, severe infantile form (Strong), mode of inheritance: AR
• carnitine palmitoyl transferase II deficiency, neonatal form (Strong), mode of inheritance: AR
• carnitine palmitoyl transferase II deficiency, myopathic form (Strong), mode of inheritance: AR
• carnitine palmitoyl transferase II deficiency, myopathic form (Supportive), mode of inheritance: AR
• carnitine palmitoyl transferase II deficiency, severe infantile form (Supportive), mode of inheritance: AR
• carnitine palmitoyl transferase II deficiency, neonatal form (Supportive), mode of inheritance: AR
• carnitine palmitoyl transferase II deficiency, neonatal form (Strong), mode of inheritance: AR
• encephalopathy, acute, infection-induced, susceptibility to, 4 (Limited), mode of inheritance: Unknown
• carnitine palmitoyltransferase II deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Carnitine palmitoyltransferase II deficiency, myopathic, stress-induced; Carnitine palmitoyltransferaseII deficiency, infantile	AR	Biochemical; Musculoskeletal; Pharmacogenomic; Renal	There are diverse presentations, including a severe infantile hepatocardiomuscular and myopathic forms, and optimal treatment may vary according to the phenotype; Severe, life-threatening rhabdomyolytic episodes can be precipitated by illness, prolonged exercise, dehydration, or fasting, and medical therapy (eg, with fibrates), along with avoidance of these precipitating factors (and interventions such as IV glucose in the instance of acute episodes) can be beneficial; Dietary measures (high-carbohydrate/low-fat diet) and medications (eg, carnitine, triheptanoin) can be beneficial; Certain medications should be avoided, including valproate, general anesthesia, ibuprofen, and high-dose diazepam	Biochemical; Cardiovascular; Gastrointestinal; Musculoskeletal; Neurologic; Renal	5416202; 123038; 187736; 736528; 272487; 2748260; 2712755; 1999498; 1940982; 1528846; 8358442; 8201482; 8651281; 8786066; 8682496; 11389301; 11477613; 11595519; 12410208; 12673791; 15363638; 15642848; 15622536; 18471680; 18550408; 18925671; 19228633; 19335026; 20661589; 20301431; 20505667; 20543534; 20810031; 21641254; 21913903; 23184072; 23326270; 33610471

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CPT2 gene.

• Carnitine_palmitoyltransferase_II_deficiency (945 variants)
• Carnitine_palmitoyl_transferase_II_deficiency,_severe_infantile_form (262 variants)
• Encephalopathy,_acute,_infection-induced,_susceptibility_to,_4 (241 variants)
• Carnitine_palmitoyl_transferase_II_deficiency,_neonatal_form (228 variants)
• Carnitine_palmitoyl_transferase_II_deficiency,_myopathic_form (223 variants)
• not_provided (156 variants)
• Inborn_genetic_diseases (71 variants)
• not_specified (55 variants)
• CPT2-related_disorder (30 variants)
• Pes_planus (2 variants)
• Generalized_hypotonia (2 variants)
• Rhabdomyolysis (2 variants)
• See_cases (2 variants)
• Myopathic_facies (2 variants)
• Hyperextensibility_at_elbow (2 variants)
• Genu_valgum (2 variants)
• Hyperextensible_hand_joints (2 variants)
• Hyperextensibility_of_the_finger_joints (2 variants)
• Abnormality_of_the_musculature (1 variants)
• Kidney_damage (1 variants)
• Microcephaly (1 variants)
• Abnormality_of_the_nervous_system (1 variants)
• Seizure (1 variants)
• Myopathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CPT2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000098.3. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous	1		11	350	1	363
missense	9	39	375	31		454
nonsense	21	27	1			49
start loss						0
frameshift	56	70	5			131
splice donor/acceptor (+/-2bp)	3	6	1			10
Total	90	142	393	381	1

Highest pathogenic variant AF is 0.0016730893

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CPT2	protein_coding	protein_coding	ENST00000371486	5	17769

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.60e-10	0.359	125613	0	135	125748	0.000537

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.397	337	358	0.941	0.0000200	4322
Missense in Polyphen		125	139.84	0.8939		1652
Synonymous	-1.17	165	147	1.12	0.00000831	1330
Loss of Function	0.946	17	21.8	0.781	0.00000118	234

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000688	0.000687
Ashkenazi Jewish	0.00486	0.00487
East Asian	0.000381	0.000381
Finnish	0.000185	0.000185
European (Non-Finnish)	0.000423	0.000422
Middle Eastern	0.000381	0.000381
South Asian	0.000327	0.000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Disease: DISEASE: Carnitine palmitoyltransferase 2 deficiency, myopathic, stress-induced (CPT2D) [MIM:255110]: An autosomal recessive disorder of mitochondrial long-chain fatty acid oxidation, characterized by recurrent myoglobinuria, episodes of muscle pain, stiffness, and rhabdomyolysis. These symptoms are exacerbated by prolonged exercise, fasting, cold, or viral infection. CPT2DM affects most frequently children or young adults, and severity of attacks is highly variable. Myoglobinuria can cause kidney failure and death. {ECO:0000269|PubMed:10090476, ECO:0000269|PubMed:11477613, ECO:0000269|PubMed:14605500, ECO:0000269|PubMed:14615409, ECO:0000269|PubMed:1528846, ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:15622536, ECO:0000269|PubMed:7711730, ECO:0000269|PubMed:8358442, ECO:0000269|PubMed:8651281, ECO:0000269|PubMed:9600456, ECO:0000269|PubMed:9758712, ECO:0000269|Ref.13, ECO:0000269|Ref.17}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Carnitine palmitoyltransferase 2 deficiency, infantile (CPT2DI) [MIM:600649]: An autosomal recessive disorder of mitochondrial long-chain fatty acid oxidation, characterized by hepatic or hepato-cardio-muscular manifestations with onset in infancy. Clinical features include hypoketotic hypoglycemia, lethargy, seizures, hepatomegaly, liver dysfunction, cardiomegaly and dilated cardiomyopathy. {ECO:0000269|PubMed:1528846, ECO:0000269|PubMed:8651281}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Carnitine palmitoyltransferase 2 deficiency, lethal neonatal (CPT2DLN) [MIM:608836]: An autosomal recessive disorder of mitochondrial long-chain fatty acid oxidation with fatal outcome, presenting shortly after birth. It is characterized by respiratory distress, seizures, altered mental status, hepatomegaly, cardiomegaly, cardiac arrhythmia, and, in many cases, dysmorphic features, renal dysgenesis, and migration defects. recessive. {ECO:0000269|PubMed:11477613}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Encephalopathy, acute, infection-induced, 4 (IIAE4) [MIM:614212]: A severe neurologic complication of an infection. It manifests within days in otherwise healthy children after common viral infections, without evidence of viral infection of the brain or inflammatory cell infiltration. In affected children, high- grade fever is accompanied within 12 to 48 hours by febrile convulsions, often leading to coma, multiple-organ failure, brain edema, and high morbidity and mortality. The infections are usually viral, particularly influenza, although other viruses and even mycoplasma have been found to cause the disorder. {ECO:0000269|PubMed:15811315, ECO:0000269|PubMed:21697855}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. CPT2 polymorphic variants do not cause classical carnitine palmitoyltransferase 2 deficiency, and patients harboring any of them are asymptomatic most of the time. However, they are prone to viral infection (high fever)-related encephalopathy (PubMed:21697855). {ECO:0000269|PubMed:21697855}.
• Pathway: Thermogenesis - 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);Beta Oxidation of Very Long Chain Fatty Acids;Short Chain Acyl CoA Dehydrogenase Deficiency (SCAD Deficiency);Fatty acid Metabolism;Oxidation of Branched Chain Fatty Acids;Glutaric Aciduria Type I;Ethylmalonic Encephalopathy;Mitochondrial Beta-Oxidation of Long Chain Saturated Fatty Acids;Adrenoleukodystrophy, X-linked;Carnitine-acylcarnitine translocase deficiency;Carnitine palmitoyl transferase deficiency (I);Fatty Acid Beta Oxidation;Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha);PPAR Alpha Pathway;Nuclear Receptors Meta-Pathway;Mitochondrial LC-Fatty Acid Beta-Oxidation;PPAR signaling pathway;Liver steatosis AOP;mitochondrial L-carnitine shuttle;Metabolism of lipids;Import of palmitoyl-CoA into the mitochondrial matrix;Metabolism;Fatty acid metabolism (Consensus)

Recessive Scores

• pRec: 0.101

Intolerance Scores

• loftool: 0.131
• rvis_EVS: 0.51
• rvis_percentile_EVS: 80.31

Haploinsufficiency Scores

• pHI: 0.140
• hipred: N
• hipred_score: 0.466
• ghis: 0.453

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.763

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cpt2
• 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); normal phenotype; 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); embryo phenotype; respiratory system phenotype; immune system phenotype; skeleton phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: fatty acid beta-oxidation;carnitine shuttle;regulation of lipid metabolic process;positive regulation of cold-induced thermogenesis
• Cellular component: nucleoplasm;nucleolus;mitochondrion;mitochondrial inner membrane
• Molecular function: carnitine O-palmitoyltransferase activity