[email protected] (受疫情影响,东南亚目前只开放曼谷诊所)
全周 (9AM - 5PM)

我们和你在一起

Extra info thumb
  • 总部: 泰国曼谷市巴吞汪区仑披尼分区 普勒吉路齐隆巷5号.
  • [email protected]
PHOSPHATIDYLINOSITOL GLYCAN ANCHOR BIOSYNTHESIS CLASS S PROTEIN; PIGS

PHOSPHATIDYLINOSITOL GLYCAN ANCHOR BIOSYNTHESIS CLASS S PROTEIN; PIGS

HGNC Approved Gene Symbol: PIGSCytogenetic location: 17q11.2 Genomic coordinates (GRCh38): 17:28,553,386-28,571,523 (from NCBI)▼ DescriptionGlycosylphosphati...

HGNC Approved Gene Symbol: PIGS

Cytogenetic location: 17q11.2 Genomic coordinates (GRCh38): 17:28,553,386-28,571,523 (from NCBI)

▼ Description
Glycosylphosphatidylinositol (GPI) is a membrane anchor for cell surface proteins. PIGS is a subunit of the GPI transamidase complex that catalyzes the attachment of preformed GPI to proteins containing a C-terminal GPI attachment signal (Ohishi et al., 2001).

For information on the PIG gene family and the roles of PIG proteins in GPI biosynthesis, see PIGA (311770).

▼ Cloning and Expression
Ohishi et al. (2001) purified PIGS from the GPI transamidase complex isolated from a human myelogenous leukemia cell line. The full-length PIGS cDNA encodes a deduced 555-amino acid protein with 2 transmembrane domains near the N and C termini.

▼ Gene Function
By disruption of the Pigs gene in a mouse embryonal carcinoma cell line, Ohishi et al. (2001) found that Pigs is not required for GPI synthesis but is essential for attachment of GPI to proteins. During the GPI attachment process, GPI transamidase forms a carbonyl intermediate with the precursor protein, and in the absence of Pigs, the carbonyl intermediate was not generated. The lack of Pigs did not affect the expression of the other GPI transaminase subunits Gaa1 (GPAA1; 603048), Gpi8 (PIGK; 605087), or Pigt (610272). Coimmunoprecipitation experiments indicated that PIGS and PIGT associate with each other.

▼ Mapping
Gross (2020) mapped the PIGS gene to chromosome 17q11.2 based on an alignment of the PIGS sequence (GenBank BC069228) with the genomic sequence (GRCh38).

▼ Molecular Genetics
In 6 patients, including 2 fetuses, from 3 unrelated families with developmental and epileptic encephalopathy-95 (DEE95; 618143), Nguyen et al. (2018) identified homozygous and compound heterozygous mutations in the PIGS gene (610271.0001-610271.0005). The mutations were found by exome sequencing and segregated with the disorder in the families. Patient cells showed variably decreased levels of GPI-anchored proteins compared to controls, consistent with a hypomorphic or loss-of-function effect.

In 6 patients with DEE95, including 1 sib pair, from 5 families of various ethnicities (Pakistani, Egyptian, Chinese, and European), Efthymiou et al. (2021) identified homozygous or compound heterozygous mutations in the PIGS gene (610271.0006-610271.0010). The mutations, which were found by trio whole-exome sequencing, segregated with the disorder in the families.

▼ ALLELIC VARIANTS ( 10 Selected Examples):

.0001 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 95
PIGS, TRP36TER
In 2 monozygotic twin brothers of European descent (family 1) with developmental and epileptic encephalopathy-95 (DEE95; 618143), Nguyen et al. (2018) identified compound heterozygous mutations in exon 2 of the PIGS gene: a c.108G-A transition (c.108G-A, NM_033198.3), resulting in a trp36-to-ter (W36X) substitution, and a c.101T-C transition, resulting in a leu34-to-pro (L34P; 610271.0002) substitution at a highly conserved residue. The mutations, which were found by whole-exome sequencing, segregated with the disorder in the family. Both mutations occurred in the transmembrane domain. Analysis of patient cells showed about a 50% decrease in PIGS mRNA and protein levels, consistent with having a nonsense mutation on 1 allele. Patient cells also showed decreased amounts of GPI-AP in peripheral white blood cells. Expression of the Y36X variant in PIGS-deficient HEK293 cells showed only partial restoration of cell-surface GPI-APs, and expression of L34P had a reduction in restoration, suggesting that they are hypomorphic alleles.

.0002 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 95
PIGS, LEU34PRO
For discussion of the c.101T-C transition (c.101T-C, NM_033198.3) in the PIGS gene, resulting in a leu34-to-pro (L34P) substitution, that was found in compound heterozygous state in 2 sibs with developmental and epileptic encephalopathy-95 (DEE95; 618143) by Nguyen et al. (2018), see 610271.0001.

.0003 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 95
PIGS, 37-BP DEL/7-BP INS, NT1316
In 2 brothers, born of Mexican parents from the same small rural community (family 2), with developmental and epileptic encephalopathy-95 (DEE95; 618143), Nguyen et al. (2018) identified a homozygous deletion/insertion mutation in exon 11 of the PIGS gene (c.1316_1352delins, NM_033198.3), resulting in an in-frame deletion/insertion (Thr439_Lys451delinsArgLeuLeu) in the luminal domain. The mutation, which was found by whole-genome sequencing, occurred within a region of homozygosity and segregated with the disorder in the family. It was not found in the ExAC or Exome Sequencing Project databases. Patient cells showed decreased amounts of GPI-AP in peripheral white blood cells.

.0004 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 95
PIGS, GLU308GLY
In 2 fetus sibs (family 3) with developmental and epileptic encephalopathy-95 (DEE95; 618143), Nguyen et al. (2018) identified compound heterozygous mutations in the PIGS gene: a c.923A-G transition (c.923A-G, NM_033198.3) in exon 8, resulting in a glu308-to-gly (E208G) substitution, and a G-to-C transversion (c.468+1G-C; 610271.0005) in intron 4, predicted to result in a splice site alteration. Amniocytes from 1 of the fetuses showed decreased GPI-AP levels for all markers analyzed.

.0005 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 95
PIGS, IVS4DS, G-C, +1
For discussion of the c.468+1G-C transversion (c.468+1G-C, NM_033198.3) in intron 4 of the PIGS gene, predicted to result in a splice site alteration, that was found in compound heterozygous state in 2 fetus sibs with developmental and epileptic encephalopathy-95 (DEE95; 618143) by Nguyen et al. (2018), see 610271.0004.

.0006 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 95
PIGS, GLN58HIS
In 2 unrelated Pakistani patients (patients 1 and 2), born to consanguineous parents, with developmental and epileptic encephalopathy-95 (DEE95; 618143), Efthymiou et al. (2021) identified homozygosity for a c.174G-C transversion (c.174G-C, NM_033198.4) in exon 2 of the PIGS gene, resulting in a gln58-to-his (Q58H) substitution. The mutation was identified by trio whole-exome sequencing, segregated with the disorder in both families, and was located in a 15-Mb run of homozygosity. The mutation was not present in the gnomAD, Exome Sequencing Project, GME Variome, and Iranome databases or in an in-house database of 14,000 exomes. RNA analysis showed that the Q58H mutation in the PIGS gene resulted in abnormal splicing.

.0007 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 95
PIGS, GLY357ASP
In a Pakistani patient (patient 3), born to consanguineous parents, with developmental and epileptic encephalopathy-95 (DEE95; 618143), Efthymiou et al. (2021) identified homozygosity for a c.1070G-A transition (c.1070G-A, NM_033198.4) in the PIGS gene, resulting in a gly357-to-asp (G357D) substitution at a highly conserved residue. The mutation was identified by trio whole-exome sequencing, segregated with the disorder in the family, and was located in a 10-Mb run of homozygosity. The mutation was not present in the gnomAD, Exome Sequencing Project, GME Variome, and Iranome databases, or in an in-house database of 14,000 exomes. Functional studies were not performed.

.0008 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 95
PIGS, PRO329ARG
In 2 Egyptian sibs (patients 4 and 5, family 4), born to consanguineous parents, with developmental and epileptic encephalopathy-95 (DEE95; 618143), Efthymiou et al. (2021) identified homozygosity for a c.986C-G transversion (c.986C-G, NM_033198.4) in the PIGS gene, resulting in a pro329-to-arg (P329R) substitution at a conserved residue. The mutation, which was identified by trio whole-exome sequencing, segregated with the disorder in the family. The mutation was not present in the gnomAD, Exome Sequencing Project, GME Variome, and Iranome databases or in an in-house database of 14,000 exomes. Functional studies were not performed.

.0009 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 95
PIGS, 24-BP DUP, NT1141
In a Chinese patient (patient 6, family 5) with developmental and epileptic encephalopathy-95 (DEE95; 618143), Efthymiou et al. (2021) identified compound heterozygous mutations in the PIGS gene: a paternally inherited 24-bp duplication (c.1141_1164dup24, NM_033198.4) in exon 10, predicted to result in an in-frame insertion of 8 amino acids (Asp381_Val388dup), and a maternally inherited c.734G-A transition in exon 7, predicted to result in a trp245-to-ter (W245X; 610271.0010) substitution. The mutations, which were identified by trio whole-exome sequencing, segregated with the disorder in the family. The Asp381_Val388dup mutation was reported at an allele frequency of 0.029% in the East Asian population in the gnomAD database (v3). The W245X substitution was reported at an allele frequency of 0.0115% in the East Asian population in the gnomAD database (v.3). Testing in patient blood cells showed low CD14 in monocytes and FLAER in lymphocytes, consistent with reduced amounts of GPI-anchored proteins at the cell surface.

.0010 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 95
PIGS, TRP245TER
For discussion of the c.734G-A transition (c.734G-A, NM_033198.4) in exon 7 of the PIGS gene, predicted to result in a trp245-to-ter (W245X) substitution, that was identified in compound heterozygous state in a Chinese patient with developmental and epileptic encephalopathy-95 (DEE95; 618143) by Efthymiou et al. (2021), see 610271.0009.

Tags: 17q11.2