CPT1B

Chr 22

carnitine palmitoyltransferase 1B

Also known as: CPT1-M, CPT1M, CPTI, CPTI-M, M-CPT1, MCCPT1, MCPT1

NCBI Gene: 1375 ENSG00000205560 UniProt: Q92523 OMIM: 601987

CPT1B encodes carnitine palmitoyltransferase IB, the rate-controlling enzyme that catalyzes the transfer of long-chain fatty acids onto carnitine for mitochondrial uptake and subsequent beta-oxidation in muscle. Mutations cause CPT1B deficiency, an autosomal recessive disorder presenting with exercise intolerance, muscle weakness, and rhabdomyolysis triggered by prolonged exercise or fasting. The gene shows low constraint against loss-of-function variants, consistent with the recessive inheritance pattern of this fatty acid oxidation disorder.

GeneReviews OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene, a member of the carnitine/choline acetyltransferase family, is the rate-controlling enzyme of the long-chain fatty acid beta-oxidation pathway in muscle mitochondria. This enzyme is required for the net transport of long-chain fatty acyl-CoAs from the cytoplasm into the mitochondria. Multiple transcript variants encoding different isoforms have been found for this gene, and read-through transcripts are expressed from the upstream locus that include exons from this gene. [provided by RefSeq, Jun 2009]

GeneReviews OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.83

Clinical Summary— CPT1B

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Gene-Disease Validity (ClinGen)

inherited fatty acid metabolism disorder · UDNo Known Disease Relationship

No known disease relationship

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

128 VUS of 146 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — CPT1B

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.83LOEUF

pLI 0.000

Z-score 2.44

OE 0.59 (0.42–0.83)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.49Z-score

OE missense 0.94 (0.87–1.01)

449 obs / 479.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.59 (0.42–0.83)

0≤0.351.4

Missense OE?0.94 (0.87–1.01)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 24 / 40.8Missense obs/exp: 449 / 479.5Syn Z: 0.25

This gene — mechanism propensity

0.7229th %ile

GOF

0.5367th %ile

LOF

0.2582th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

146 submitted variants in ClinVar

ClinVar

Classification Summary

VUS128

Likely Benign8

Benign7

128

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	2	126	0	0	128
Likely Benign	0	4	2	2	8
Benign	0	1	3	3	7
Total	2	131	5	5	143

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

149 pathogenic / likely-pathogenic (of 170) ClinVar copy-number / structural variants overlap CPT1B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →