Alternative titles; symbols
HGNC Approved Gene Symbol: MBOAT7
Cytogenetic location: 19q13.42 Genomic coordinates (GRCh38) : 19:54,173,415-54,189,580 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 19q13.42 | Intellectual developmental disorder, autosomal recessive 57 | 617188 | Autosomal recessive | 3 |
The MBOAT7 gene encodes lysophosphatidylinositol acyltransferase, an enzyme that contributes to the regulation of free arachidonic acid (AA) in the cell through the remodeling of phospholipids (summary by Johansen et al., 2016).
Overexpression of genes is one of the genetic alterations that may have a role in the development and progression of cancers. By immunoscreening a bladder tumor cell cDNA expression library with antibody to AN43, a bladder tumor-associated antigen, Fukunaga-Johnson et al. (1996) isolated a cDNA encoding BB1. The deduced 343-amino acid protein contains both hydrophilic and hydrophobic regions, suggesting that it may be a transmembrane protein. Northern blot analysis revealed elevated expression of a 2.0-kb transcript in breast and bladder tumor cells compared with normal cells. Expression in the cancer cells could be reduced by treatment with gamma-interferon (IFNG; 147570). Because of a lack of reactivity of the expressed BB1 protein on Western blots, Fukunaga-Johnson et al. (1996) concluded that BB1 is distinct from the AN43 antigen.
By genomic sequence analysis, Wende et al. (2000) mapped the BB1 gene, which they termed LENG4, to chromosome 19q13.4. They noted that the LENG genes, unlike other genes in the leukocyte receptor cluster on 19q13.4, do not encode proteins with immunoglobulin domains.
In 16 patients from 6 different consanguineous families of Middle Eastern descent with autosomal recessive intellectual developmental disorder-57 (MRT57; 617188), Johansen et al. (2016) identified 5 different homozygous mutations in the MBOAT7 gene (606048.0001-606048.0005). The mutations resulted in truncated proteins, abnormal splicing, or intragenic deletion affecting critical domains. The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. Functional studies of the variants and studies of patient cells were not performed.
Lee et al. (2012) found that Mboat7-null mice were significantly smaller than controls and showed reduced postnatal survival. Histologic analysis of embryonic mutant mouse brains showed a smaller cerebral cortex and hippocampus, abnormal cortical lamination, delayed neuronal migration, gyral abnormalities, and increased number of apoptotic cells in the cortex.
In 3 patients from a consanguineous Egyptian family (FAM1) with autosomal recessive intellectual developmental disorder-57 (MRT57; 617188), Johansen et al. (2016) identified a homozygous 20-bp deletion (c.126_145del, NM_024298.3) in exon 3 of the MBOAT7 gene, resulting in a frameshift and premature termination (Leu43HisfsTer69) in the first transmembrane domain. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family and was not found in the dbSNP, 1000 Genomes Project, or ExAC databases, or in over 5,000 in-house control exomes. Functional studies of the variant and studies of patient cells were not performed.
In 5 patients from a 2 unrelated consanguineous Pakistani families (FAM2/3) with autosomal recessive intellectual developmental disorder-57 (MRT57; 617188), Johansen et al. (2016) identified a homozygous 21-bp deletion (c.758_778del, NM_024298.3) in exon 6 of the MBOAT7 gene, resulting in an in-frame deletion (Gln253_Ala259del) in the fourth transmembrane domain. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family and was not found in the dbSNP, 1000 Genomes Project, or ExAC databases, or in over 5,000 in-house control exomes. Haplotype analysis suggested a founder effect. Functional studies of the variant and studies of patient cells were not performed.
In 2 sisters, born of consanguineous Jordanian parents (FAM4), with autosomal recessive intellectual developmental disorder-57 (MRT57; 617188), Johansen et al. (2016) identified a homozygous 1-bp deletion (c.423delG, NM_024298.3) in exon 5 of the MBOAT7 gene, resulting in a frameshift and premature termination (Leu142CysfsTer8) in the catalytic domain. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family and was not found in the dbSNP, 1000 Genomes Project, or ExAC databases, or in over 5,000 in-house control exomes. Functional studies of the variant and studies of patient cells were not performed.
In 2 sisters, born of consanguineous Iraqi parents (FAM5), with autosomal recessive intellectual developmental disorder-57 (MRT57; 617188), Johansen et al. (2016) identified a homozygous G-to-C transversion in intron 6 of the MBOAT7 gene (c.854+1G-C, NM_024298.3), resulting in a splice site alteration predicted to affect the catalytic domain. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family and was not found in the dbSNP, 1000 Genomes Project, or ExAC databases, or in over 5,000 in-house control exomes. Functional studies of the variant and studies of patient cells were not performed.
In 4 patients from a large consanguineous Pakistani family (FAM6) with autosomal recessive intellectual developmental disorder-57 (MRT57; 617188), Johansen et al. (2016) identified a homozygous 7-bp deletion (c.820_826del, NM_024298.3) in exon 6 of the MBOAT7 gene, resulting in a frameshift and premature termination (Gly274ProfsTer47) in the catalytic domain. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family and was not found in the dbSNP, 1000 Genomes Project, or ExAC databases, or in over 5,000 in-house control exomes. Functional studies of the variant and studies of patient cells were not performed.
Fukunaga-Johnson, N., Lee, S. W., Liebert, M., Grossman, H. B. Molecular analysis of a gene, BB1, overexpressed in bladder and breast carcinoma. Anticancer Res. 16: 1085-1090, 1996. [PubMed: 8702217]
Johansen, A., Rosti, R. O., Musaev, D., Sticca, E., Harripaul, R., Zaki, M., Caglayan, A. O., Azam, M., Sultan, T., Froukh, T., Reis, A., Popp, B., Ahmed, I., John, P., Ayub, M., Ben-Omran, T., Vincent, J. B., Gleeson, J. G., Abou Jamra, R. Mutations in MBOAT7, encoding lysophosphatidylinositol acyltransferase I, lead to intellectual disability accompanied by epilepsy and autistic features. Am. J. Hum. Genet. 99: 912-916, 2016. [PubMed: 27616480] [Full Text: https://doi.org/10.1016/j.ajhg.2016.07.019]
Lee, H.-C., Inoue, T., Sasaki, J., Kubo, T., Matsuda, S., Nakasaki, Y., Hattori, M., Tanaka, F., Udagawa, O., Kono, N., Itoh, T., Ogiso, H., Taguchi, R., Arita, M., Sasaki, T., Arai, H. LPIAT1 regulates arachidonic acid content in phosphatidylinositol and is required for cortical lamination in mice. Molec. Biol. Cell. 23: 4689-4700, 2012. [PubMed: 23097495] [Full Text: https://doi.org/10.1091/mbc.E12-09-0673]
Wende, H., Volz, A., Ziegler, A. Extensive gene duplications and a large inversion characterize the human leukocyte receptor cluster. Immunogenetics 51: 703-713, 2000. Note: Erratum: Immunogenetics 52: 308 only, 2001. [PubMed: 10941842] [Full Text: https://doi.org/10.1007/s002510000187]