CPT1A

Chr 11

carnitine palmitoyltransferase 1A

Also known as: CPT I, CPT1, CPT1-L, CPTI-L, L-CPT1

NCBI Gene: 1374 ENSG00000110090 UniProt: P50416

This enzyme catalyzes the rate-limiting step of mitochondrial fatty acid beta-oxidation by facilitating carnitine-dependent transport of long-chain fatty acids across the outer mitochondrial membrane. Mutations cause autosomal recessive CPT1A deficiency, presenting as hepatic-type carnitine palmitoyltransferase I deficiency with impaired fatty acid oxidation. The pathogenic mechanism involves dominant-negative effects that disrupt normal enzyme function.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

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]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtCarnitine palmitoyltransferase 1A deficiency

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · carnitine palmitoyl transferase 1A deficiency · AR · ClinGen 2018

Active trials

560

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.66

LOEUF

Mechanism· predicted

📖

GeneReview available — CPT1A

Authoritative clinical overview · Recommended first read

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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.66LOEUF

pLI 0.000

Z-score 3.43

OE 0.46 (0.33–0.66)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.64Z-score

OE missense 0.79 (0.72–0.86)

376 obs / 476.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.46 (0.33–0.66)

0≤0.351.4

Missense OE?0.79 (0.72–0.86)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 22 / 47.5Missense obs/exp: 376 / 476.7Syn Z: 0.28

Background carrier burden — how many people carry a rare variant somewhere in CPT1A?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 62

859 rare PASS variants

Rare truncating (LoF)

1 in 1,800

114 rare PASS variants

Rare synonymous (reference)

1 in 70

382 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CPT1A. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 97	1 in 2,200
South Asian	~43k	1 in 45	1 in 920
Remaining (unassigned)	~30k	1 in 71	1 in 4,300
European (Finnish)	~27k	1 in 260	≈ 1 in 8,900
Admixed American	~22k	1 in 68	≈ 1 in 4,500
African / African American	~21k	1 in 73	1 in 2,000
East Asian	~20k	1 in 60	1 in 700
Ashkenazi Jewish	~13k	1 in 140	1 in 390
Middle Eastern	~2,884	1 in 56	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 18 coding exons well covered in gnomAD exomes and genomes.? see exons ↓