CPT1A

protein-coding

carnitine palmitoyltransferase 1A

Gene summary

The mitochondrial oxidation of long-chain fatty acids is initiated by the sequential action of carnitine palmitoyltransferase I (which is located in the outer membrane and is detergent-labile) and carnitine palmitoyltransferase II (which is located in the inner membrane and is detergent-stable), together with a carnitine-acylcarnitine translocase. 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. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Previous symbols:

CPT1

MANE transcript

NM_001876.4

Inheritance

ClinVar variants

P:213U:305B:367

Top phenotype

Carnitine palmitoyltransferase deficiency I

gnomAD constraint

pLI —, LoF o/e 0.46

Max pathogenic AF

—

Genomic locus

chr11:68,754,620-68,844,410

External References & Databases

Ensembl (ENSG00000110090)

Transcript & Mutation Effects

hg38 • Region Span ~89.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

carnitine palmitoyl transferase 1A deficiencyDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009705

Submitter: Natera

carnitine palmitoyl transferase 1A deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009705

Submitter: Labcorp Genetics (formerly Invitae)

carnitine palmitoyl transferase 1A deficiencyDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009705

Submitter: ClinGen

carnitine palmitoyl transferase 1A deficiencySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009705

Submitter: Orphanet

Clinical Genomic Database (CGD)

Carnitine palmitoyltransferase deficiency IAR

Manifestation: Biochemical; Cardiovascular; Gastrointestinal; Musculoskeletal; Neurologic; Renal

Intervention: Biochemical; Pharmacogenomic

Rationale: 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

Refs: 7014807; 3211616; 1598098; 1403388; 9691089; 10625081; 11286380; 11350182; 12189492; 15110323; 20301700; 20696606; 21962599

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CPT1A variants in ClinVar

9 Conditions Cataloged

Carnitine palmitoyl transferase 1A deficiencyTotal: 1053

not providedTotal: 102

Inborn genetic diseasesTotal: 94

not specifiedTotal: 69

CPT1A-related disorderTotal: 46

CPT1A-related disordersTotal: 3

CPT1A POLYMORPHISMTotal: 1

Metabolic diseaseTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001876.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			12 clinvar	333 clinvar	5 clinvar	350
missense	5 clinvar	26 clinvar	271 clinvar	26 clinvar	3 clinvar	331
nonsense	27 clinvar	32 clinvar	5 clinvar			64
start loss		1 clinvar				1
frameshift	49 clinvar	36 clinvar	3 clinvar			88
splice donor/acceptor (+/-2bp)	3 clinvar	34 clinvar	14 clinvar			51
Total	84	129	305	359	8	885

Highest pathogenic variant AF is 0.00033171164

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 29 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001876.4	RefSeq	NP_001867.2	18	MANE Select
ENST00000265641.10	Ensembl	ENSP00000265641.4	18	MANE Select
NM_001031847.3	RefSeq	NP_001027017.1	18	Standard
NM_001440358.1	RefSeq	NP_001427287.1	18	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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)

Biological Process

long-chain fatty acid metabolic process
glucose metabolic process
fatty acid beta-oxidation
triglyceride metabolic process
carnitine shuttle

Molecular Function

carnitine O-palmitoyltransferase activity
identical protein binding
palmitoleoyltransferase activity

Cellular Component

mitochondrion
mitochondrial outer membrane
membrane
integral component of mitochondrial outer membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000265641
Coding exons: 18
Length: 89791
Individuals with no LoFs: 125703
Homozygous LoFs: 0
Heterozygous LoFs: 45
Defined: 125748
p: 0.000179

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.64	376	477	0.789	0.0000324	5079
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0.0010	0.00099	rare
East Asian	0.00033	0.00033	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00016	0.00015	rare
South Asian	0.00020	0.00020	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.575

Intolerance Scores

LoFtool: 0.0338
RVIS EVS: -0.48
RVIS percentile EVS: 22.78

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.976

Gene Damage Prediction

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