CPT1B

protein-coding

carnitine palmitoyltransferase 1B

Gene summary

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]

MANE transcript

NM_152246.3

Inheritance

—

ClinVar variants

U:134B:10

Top phenotype

CPT1B-related disorder

gnomAD constraint

pLI —, LoF o/e 0.59

Max pathogenic AF

—

Genomic locus

chr22:50,568,861-50,578,465

External References & Databases

Ensembl (ENSG00000205560)

Transcript & Mutation Effects

hg38 • Region Span ~9.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

inherited fatty acid metabolism disorderNO_KNOWN

Inheritance Pattern: Unknown

Disease ID:MONDO:0037858

Submitter: ClinGen

No human disease has been genetically linked to variation in CPT1B. CPT1B, like CPT1A, is a carnitine palmitoyltransferase involved in transport of long-chain fatty acyl-CoAs from the cytoplasm into the mitochondrial. While CPT1A is specific to the liver, CPT1B is specific to skeletal muscle. PMID: 18023382 reported homozygous Cpt1b-deficient mice that were embryonic lethal, while heterozygous mice exhibited decreased cold tolerance and fatal hypothermia after a cold-challenge test, suggesting the possibility that variation in CPT1B could be disease- causing in humans or homozygous lethal. However, no cases have been reported in the literature. No convincing evidence for a causal role for CPT1B in an inherited fatty acid metabolism disorder has been reported. This gene-disease pair was originally evaluated by the FAO GCEP on 09/25/2018. It was reevaluated on 01/25/2021. As a result of this reevaluation, the classification did not change as no new information is contributing to the classification.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CPT1B variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 133

not providedTotal: 9

CPT1B-related disorderTotal: 8

High myopiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_152246.3. 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				4 clinvar	2 clinvar	6
missense			128 clinvar	4 clinvar		132
nonsense			2 clinvar			2
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	134	8	2	144

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 168 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_152246.3	RefSeq	NP_689452.1	18	MANE Select
ENST00000312108.12	Ensembl	ENSP00000312189.8	18	MANE Select
NM_001145134.2	RefSeq	NP_001138606.1	17	Standard
NM_001145135.2	RefSeq	NP_001138607.1	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

fatty acid beta-oxidation
carnitine shuttle
carnitine metabolic process
long-chain fatty acid transport

Molecular Function

carnitine O-palmitoyltransferase activity
protein binding

Cellular Component

mitochondrion
mitochondrial outer membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000360719
Coding exons: 18
Length: 10610
Individuals with no LoFs: 125637
Homozygous LoFs: 1
Heterozygous LoFs: 107
Defined: 125745
p: 0.000430

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.494	449	479	0.936	0.0000301	5077
Missense (PolyPhen)		106	120.19	0.88191		1210
Synonymous	0.251	181	185	0.977	0.0000116	1493
Loss of Function	2.44	24	40.8	0.588	0.00000190	459

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.00055	0.00055	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00066	0.00065	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00044	0.00043	rare
South Asian	0.00069	0.00065	rare
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.348

Intolerance Scores

LoFtool: 0.0174
RVIS EVS: -0.66
RVIS percentile EVS: 16.02

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.539

Gene Damage Prediction

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