Alternative titles; symbols
HGNC Approved Gene Symbol: LIPI
Cytogenetic location: 21q11.2 Genomic coordinates (GRCh38) : 21:14,108,812-14,210,955 (from NCBI)
By screening a testis cDNA library using mouse Lpdl as probe, Wen et al. (2003) cloned human LIPI, which they called LPDL. The deduced 460-amino acid protein contains a hydrophobic leader sequence with a putative cleavage site after amino acid 15, a central lipase consensus sequence (GxSxG), a central 12-amino acid lipase lid sequence, and several conserved cysteines. The GxSxG sequence includes the active site ser159, which forms a putative catalytic triad with asp183 and his258. LPDL shares 71% amino acid identity with mouse Lpdl, 44% identity with LPDLR (LIPH; 607365), and 34% identity with phospholipase PLA1A (607460). Northern blot analysis of several human and mouse tissues detected strong expression of a 2.0-kb transcript only in testis. In situ hybridization of 2-week-old mice detected Lpdl expression in testis, with weaker expression in hepatocytes. In testis of adult mice, Lpdl was expressed in the cytoplasm of primary spermatocytes, but not in mature sperm or in Leydig cells.
Wen et al. (2003) determined that the LIPI gene contains 10 exons and spans more than 100 kb. Exon 3 encodes the lipase consensus sequence GxSxG. The mouse Lipi gene contains 10 exons and spans 110 kb.
By genomic sequence analysis, Wen et al. (2003) mapped the LIPI gene to chromosome 21q11.2, centromeric to the STCH gene (601100). They mapped the mouse Lipi gene to chromosome 16B1.
For discussion of a possible association between variation in the LIPI gene and hypercholesterolemia (see 238600), see 609252.0001.
Mice homozygous for the lipid defect (lpd) mutation have a phenotype that includes hepatic steatosis and hypertriglyceridemia. Wen et al. (2003) determined that the lpd mutation is a deletion of exon 10 in the Lpdl gene.
This variant, formerly titled HYPERTRIGLYCERIDEMIA, SUSCEPTIBILITY TO, has been reclassified based on a review of the gnomAD database by Hamosh (2019).
Wen et al. (2003) identified 2 Caucasians with moderate to severe hypertriglyceridemia who were heterozygous for a G-to-A transition at nucleotide 164 of the LIPI gene, resulting in substitution of tyrosine for a conserved cysteine at codon 55 (C55Y). The authors noted that C55 is predicted to participate in disulfide bridge formation and in determining lipase tertiary structure, suggesting that C55Y affects protein function.
Hamosh (2019) noted that the C55Y (C76Y) variant was present in 1,382 of 282,752 alleles and in 8 homozygotes in the gnomAD database (June 25, 2019).
Hamosh, A. Personal Communication. Baltimore, Md. 6/25/2019.
Wen, X.-Y., Hegele, R. A., Wang, J., Wang, D. Y., Cheung, J., Wilson, M., Yahyapour, M., Bai, Y., Zhuang, L., Skaug, J., Young, T. K., Connelly, P. W., Koop, B. F., Tsui, L.-C., Stewart, A. K. Identification of a novel lipase gene mutated in lpd mice with hypertriglyceridemia and associated with dyslipidemia in humans. Hum. Molec. Genet. 12: 1131-1143, 2003. [PubMed: 12719377] [Full Text: https://doi.org/10.1093/hmg/ddg124]