Alternative titles; symbols
HGNC Approved Gene Symbol: CPT1B
Cytogenetic location: 22q13.33 Genomic coordinates (GRCh38): 22:50,568,861-50,578,612 (from NCBI)
The mitochondrial carnitine palmitoyltransferases (CPTs; EC 2.3.1.21) are required to allow net transport of long-chain fatty acyl-CoAs from the cytoplasm into the mitochondria for beta-oxidation. Type I CPT resides in the outer mitochondrial membrane (Yamazaki et al., 1996). CPT1B is specific to skeletal muscle, CPT1A (600529) is specific to liver, and CPT1C (608846) is specific to brain (Ji et al., 2008).
At least 2 isoforms of type I CPT are expressed in human and rat. Yamazaki et al. (1996) used a cDNA probe for the rat muscle-type CPT I to isolate cDNA clones for the human homolog. By Northern analysis, they determined that this isoform is expressed primarily in heart and skeletal muscle.
Van der Leij et al. (1997) isolated and sequenced cDNA and genomic DNA fragments of the human CPT1B gene, encoding muscle type carnitine palmitoyltransferase I. Analysis of CPT1B cDNA sequences revealed the presence of an untranslated 5-prime exon and differential processing of introns 13 and 19. The alternative splicing of intron 13 caused an in-frame deletion leading to a protein smaller by 10 amino acids. By using different splice acceptor sites, van der Leij et al. (1997) found that intron 19 was spliced in most cases, but 4 of 14 sequenced CPT1B 3-prime cDNA clones contained part of intron 19 instead of exon 20.
By RT-PCR of human heart and skeletal muscle mRNA, Yamazaki et al. (2000) identified fusion transcripts in which 3-prime exons from the upstream choline kinase-beta (CHKB; 612395) gene were spliced to either exon 1A or exon 2 of the MCPT1 gene.
By genomic sequence analysis, Yamazaki et al. (1997) determined that the CPT1B gene contains 21 exons, of which 18 are coding, and spans approximately 10 kb. The first 2 exons, exons 1A and 1B, are noncoding and alternatively spliced. Analysis of the 5-prime flanking region revealed that the CHKB gene is only 314 bp upstream from exon 1A.
By fluorescence in situ hybridization using a recombinant P1 phage containing CPT1B, van der Leij et al. (1997) mapped the gene to chromosome 22qter. This indicated that the 'liver type' (CPT1A) and 'muscle type' isoforms of CPT I are encoded by different loci. (CPT1A maps to 11q.) By fluorescence in situ hybridization, Britton et al. (1997) mapped the CPT1B gene to chromosome 22q13.3.
Ji et al. (2008) found that homozygous Cpt1b deficiency in mouse was embryonic lethal before embryonic day 9.5 to 11.5. Heterozygous mice appeared normal, but heterozygous females in a heterozygous breeding pair had decreased numbers of fetuses, suggesting that the females were either less prone to conceive or more prone to undergo spontaneous abortion. Cpt1b activity in muscle of heterozygous mice ranged from 55 to 60%. Heterozygous mice showed decreased cold tolerance and increased fatal hypothermia after a cold-challenge test compared to wildtype. Ji et al. (2008) noted that the findings were consistent with the paucity of human cases of homozygous CPT1B deficiency.
Britton, C. H., Mackey, D. W., Esser, V., Foster, D. W., Burns, D. K., Yarnall, D. P., Froguel, P., McGarry, J. D. Fine chromosome mapping of the genes for human liver and muscle carnitine palmitoyltransferase I (CPT1A and CPT1B). Genomics 40: 209-211, 1997. [PubMed: 9070950] [Full Text: https://doi.org/10.1006/geno.1996.4539]
Ji, S., You, Y., Kerner, J., Hoppel, C. L., Schoeb, T. R., Chick, W. S. H., Hamm, D. A., Sharer, J. D., Wood, P. A. Homozygous carnitine palmitoyltransferase 1b (muscle isoform) deficiency is lethal in the mouse. Molec. Genet. Metab. 93: 314-322, 2008. [PubMed: 18023382] [Full Text: https://doi.org/10.1016/j.ymgme.2007.10.006]
van der Leij, F. R., Takens, J., van der Veen, A. Y., Terpstra, P., Kuipers, J. R. G. Localization and intron usage analysis of the human CPT1B gene for muscle type carnitine palmitoyltransferase I. Biochim. Biophys. Acta 1352: 123-128, 1997. [PubMed: 9199240] [Full Text: https://doi.org/10.1016/s0167-4781(97)00037-7]
Yamazaki, N., Shinohara, Y., Kajimoto, K., Shindo, M., Terada, H. Novel expression of equivocal messages containing both regions of choline/ethanolamine kinase and muscle type carnitine palmitoyltransferase I. J. Biol. Chem. 275: 31739-31746, 2000. [PubMed: 10918069] [Full Text: https://doi.org/10.1074/jbc.M006322200]
Yamazaki, N., Shinohara, Y., Shima, A., Yamanaka, Y., Terada, H. Isolation and characterization of cDNA and genomic clones encoding human muscle type carnitine palmitoyltransferase I. Biochim. Biophys. Acta 1307: 157-161, 1996. [PubMed: 8679700] [Full Text: https://doi.org/10.1016/0167-4781(96)00069-3]
Yamazaki, N., Yamanaka, Y., Hashimoto, Y., Shinohara, Y., Shima, A., Terada, H. Structural features of the gene encoding human muscle type carnitine palmitoyltransferase I. FEBS Lett. 409: 401-406, 1997. [PubMed: 9224698] [Full Text: https://doi.org/10.1016/s0014-5793(97)00561-9]