Alternative titles; symbols
HGNC Approved Gene Symbol: STT3B
SNOMEDCT: 733112007;
Cytogenetic location: 3p23 Genomic coordinates (GRCh38): 3:31,532,925-31,637,616 (from NCBI)
Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
---|---|---|---|---|
3p23 | Congenital disorder of glycosylation, type Ix | 615597 | Autosomal recessive | 3 |
The STT3B gene encodes a catalytic subunit of the oligosaccharide (OST) protein complex that carries out glycan chain transfer to proteins in the endoplasmic reticulum. The STT3 proteins (see also STT3A; 601134) specifically transfer oligosaccharides onto asparagine residues. STT3A and STT3B exist in different OST complexes with different kinetic properties and substrate preferences, but they have overlapping roles (summary by Shrimal et al., 2013).
B6(dom1) is a highly immunogenic minor histocompatibility antigen in mice. Using the sequence of B6(dom1) suggested by Edman degradation analysis to search protein and cDNA databases, McBride et al. (2002) identified a candidate polymorphic mouse gene, which they termed Simp. The B6(dom1) antigen corresponds to amino acids 770 to 778 of the 823-amino acid Simp protein, and analysis of cytotoxic T-lymphocyte activity in different mouse strains confirmed the presence of a polymorphism at amino acid 776. By searching a genomic database and degenerate PCR analysis, McBride et al. (2002) obtained a human cDNA encoding SIMP. The 826-amino acid human protein shares 97% identity with the mouse protein. Sequence analysis of SIMP cDNA from 14 individuals failed to reveal polymorphism of human SIMP.
By genomic sequence analysis, McBride et al. (2002) mapped the SIMP gene to chromosome 3p22.3, a region that shows homology of synteny to the telomeric end of mouse chromosome 9, where the mouse Simp gene is localized.
Dumax-Vorzet et al. (2013) found that human OST4 (618932) assembled into distinct OST complexes through association with STT3A or STT3B, as well as with the OST accessory subunit, ribophorin I (RPN1; 180470). Knockdown experiments showed that OST4 preferentially stabilized STT3A and its interacting partner, KCP2 (KRTCAP2; 619029). STT3A and/or ribophorin I, in turn, stabilized OST4 in the complex. Depletion of OST4 destabilized both STT3A- and STT3B-containing OST complexes and released a ribophorin I-containing subcomplex. OST4 and ribophorin I stabilized whole OST complexes, and both proteins modulated the efficiency of N-glycosylation of endogenous prosaposin (PSAP; 176801) in HeLa cells.
In a boy, born of consanguineous Iraqi parents, with congenital disorder of glycosylation type Ix (CDG1X; 615597), Shrimal et al. (2013) identified a homozygous mutation in the STT3B gene (608605.0001). The mutation was found by homozygosity mapping and candidate gene sequencing. The patient had severely delayed psychomotor development with microcephaly, hypotonia, seizures, and optic atrophy, and died at age 4 years. Serum transferrin showed only a mildly abnormal type I pattern of glycosylation. Patient cells showed no STT3B mRNA and severely reduced protein expression. Patient cells also showed incomplete N-glycosylation of a GFP biomarker that was complemented by wildtype STT3B, as well as lower glycosylation of the STT3B substrates SHBG (182205) and beta-glucuronidase (GUSB; 611499) compared to control cells.
In a Turkish boy, born of consanguineous parents, with CDG1X, Kilic and Akkus (2020) identified a homozygous missense mutation in the STT3B gene (S13W; 608605.0002). The mutation, which was found by next-generation sequencing and confirmed by Sanger sequencing, was present in heterozygous state in the parents. Functional studies were not performed.
In a boy, born of consanguineous Iraqi parents, with congenital disorder of glycosylation type Ix (CDG1X; 615597), Shrimal et al. (2013) identified a homozygous G-to-T transversion in an intron of the STT3B gene (c.1539+20G-T). The mutation was found by homozygosity mapping and candidate gene sequencing. It was not present in the dbSNP, 1000 Genomes Project, or Exome Variant Server databases, or in 1,110 Middle Eastern control exomes. Patient cells showed no STT3B mRNA and severely reduced protein expression. The patient had severe developmental and congenital anomalies, including microcephaly, failure to thrive, lack of visual tracking and optic nerve hypoplasia, cerebellar atrophy, seizures, hypotonia, liver involvement, thrombocytopenia, micropenis, hypoplastic scrotum, and undescended testes. He died at age 4 years. Serum transferrin showed an only slightly abnormal glycosylation pattern. Patient cells showed incomplete N-glycosylation of a GFP biomarker complemented by wildtype STT3B as well as lower glycosylation of the STT3B substrates SHBG (182205) and beta-glucuronidase (GUSB; 611499) compared to control cells.
In a boy, born of consanguineous Turkish parents, with congenital disorder of glycosylation type Ix (CDG1X; 615597), Kilic and Akkus (2020) identified a homozygous c.38C-G transversion in the STT3B gene, resulting in a ser13-to-trp (S13W) substitution. The mutation, which was found by next-generation sequencing and confirmed by Sanger sequencing, was present in heterozygous state in the parents. Functional studies were not performed.
Dumax-Vorzet, A., Roboti, P., High, S. OST4 is a subunit of the mammalian oligosaccharyltransferase required for efficient N-glycosylation. J. Cell Sci. 126: 2595-2606, 2013. [PubMed: 23606741] [Full Text: https://doi.org/10.1242/jcs.115410]
Kilic, B., Akkus, N. Novel mutation and severe respiratory failure in congenital disorders of glycosylation type Ix. Turk. J. Pediat. 62: 114-118, 2020. [PubMed: 32253875] [Full Text: https://doi.org/10.24953/turkjped.2020.01.016]
McBride, K., Baron, C., Picard, S., Martin, S., Boismenu, D., Bell, A., Bergeron, J., Perreault, C. The model B6(dom1) minor histocompatibility antigen is encoded by a mouse homolog of the yeast STT3 gene. Immunogenetics 54: 562-569, 2002. [PubMed: 12439619] [Full Text: https://doi.org/10.1007/s00251-002-0502-4]
Shrimal, S., Ng, B. G., Losfeld, M.-E., Gilmore, R., Freeze, H. H. Mutations in STT3A and STT3B cause two congenital disorders of glycosylation. Hum. Molec. Genet. 22: 4638-4645, 2013. [PubMed: 23842455] [Full Text: https://doi.org/10.1093/hmg/ddt312]