TUSC3

Gene Facts

• HGNC Symbol: TUSC3 (HGNC:30242)
• HGNC Name: tumor suppressor candidate 3
• Gene type: protein-coding gene
• Locus type: gene with protein product
• Previous symbols: MRT22
• Alias symbols: MGC13453, N33, OST3A, MRT7, MagT2, SLC58A2
• %HI: 34.41
• pLI: 0
• LOEUF: 1.31
• Cytoband: 8p22
• Genomic Coordinates:

  GRCh37/hg19:	chr8:15397596-15624158
  GRCh38/hg38:	chr8:15417188-15852091

• MANE Select Transcript: NM_006765.4 ENST00000503731.6
• Function: Acts as accessory component of the N-oligosaccharyl transferase (OST) complex which catalyzes the transfer of a high mannose oligosaccharide from a lipid-linked oligosaccharide donor to an asparagine residue within an Asn-X-Ser/Thr consensus motif in nascent polypeptide chains. Involved in N-glycosylation of STT3B-dependent substrates. Specifically required for the glycosylation of a subset of acceptor sites that are near cysteine residues; in this function seems to act redundantly with MAGT1. I... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

• Dosage ID: ISCA-10658
• ClinGen Curation ID: CCID:008069
• Curation Status: Complete
• Issue Type: Dosage Curation - Gene
• Haploinsufficiency: Gene Associated with Autosomal Recessive Phenotype (30)
• Triplosensitivity: Not Yet Evaluated
• Last Evaluated: 12/01/2021

Haploinsufficiency (HI) Score Details

• HI Score: 30
• HI Evidence Strength: Gene Associated with Autosomal Recessive Phenotype

HI Disease

• Intellectual Disability

HI Evidence

• PUBMED: 18452889
  Garshasbi et al (2008) reported a 121.6 kb homozygous deletion involving the first exon of TUSC3 in a large consanguineous Iranian family comprising seven patients with nonsyndromic intellectual disability.
• PUBMED: 21513506
  Khan et al (2011) reported a novel 170 kb homozygous deletion of entire TUSC3 in six affected individuals from three different extended branches of a large consanguineous Pakistani family with autosomal recessive nonsyndromic intellectual disability.
• PUBMED: 23825019
  Loddo et al (2013) identified a 203 kb homozygous microdeletion of 8p22 encompassing the first exon of TUSC3 in male patient with dysmorphic features and moderate cognitive impairment. Both carrier nonconsanguineous parents were from a small Sicilian village.
• PUBMED: 25626710
  El Chehadeh (2014) reported a 238 kb homozygous intragenic exon 2–7 duplication in TUSC3, leading to a premature termination codon and truncated protein, in two affected individuals with intellectual disability and unspecific dysmorphic features from a consanguineous family. The authors also reviewed previously reported 19 affected members from 5 families. All of the previously reported patients with homozygous TUSC3 variants/rearrangements had speech delay, moderate-to-severe intellectual disability, and no or moderate facial dysmorphism.
• PUBMED: 27148795
  Al-Amri et al (2016) identified a homozygous single base deletion (c.225delA) in TUSC3 in a large consanguineous Omani family with four affected individuals with intellectual disability, developmental delay, and variably present features including short stature, microcephaly, moderate facial dysmorphism, and congenital malformations of the toes or hands.

• HI Evidence Comments: The TUSC3 gene, composed of 11 exons spanning about 224 kb on chromosome 8p22, encodes a predicted 348-amino-acid protein with five potential transmembrane domains. Bialleic TUSC3 variants have been identified in individuals with autosomal recessive intellectual disability. The variant spectrum includes sequence variants, intragenic/ full gene deletions, and intragenic duplications.

Triplosensitivity (TS) Score Details

• TS Evidence Strength: Not Yet Evaluated
• TS Evidence Comments: Triplosensitivity of TUSC3 has not yet been implicated in any clinical phenotypes.