TUSC3

tumor suppressor candidate 3, the group of Oligosaccharyltransferase complex subunits|Solute carrier family 58

Basic information

Region (hg38): 8:15417214-15766649

Previous symbols: [ "MRT22" ]

Links

ENSG00000104723 ∙ NCBI:7991 ∙ OMIM:601385 ∙ HGNC:30242 ∙ Uniprot:Q13454 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, autosomal recessive 7 (Definitive), mode of inheritance: AR
• intellectual disability, autosomal recessive 7 (Strong), mode of inheritance: AR
• autosomal recessive non-syndromic intellectual disability (Supportive), mode of inheritance: AR
• intellectual disability (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, autosomal recessive 7	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	18452889; 18455129; 21739581

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TUSC3 gene.

• Congenital disorder of glycosylation (113 variants)
• not provided (64 variants)
• Intellectual disability, autosomal recessive 7 (50 variants)
• Inborn genetic diseases (39 variants)
• not specified (13 variants)
• Abnormality of the nervous system (1 variants)
• Intellectual disability (1 variants)
• Intellectual disability, autosomal recessive 24 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TUSC3 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	25		27
missense	1		48	1		50
nonsense	2	3	1			6
start loss			1			1
frameshift	1	1	1			3
inframe indel			1			1
splice donor/acceptor (+/-2bp)		3	1			4
splice region			5	5	1	11
non coding			71	20	39	130
Total	4	7	126	46	39

Highest pathogenic variant AF is 0.0000395

Variants in TUSC3

This is a list of pathogenic ClinVar variants found in the TUSC3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
8-15540073-A-G		Congenital disorder of glycosylation	Uncertain significance (Jan 12, 2018)
8-15540127-G-T		Congenital disorder of glycosylation	Uncertain significance (Jan 13, 2018)
8-15540128-C-G		Congenital disorder of glycosylation	Uncertain significance (Jan 13, 2018)
8-15540142-A-G		Congenital disorder of glycosylation	Uncertain significance (Jan 13, 2018)
8-15540158-G-A		Congenital disorder of glycosylation	Likely benign (Jan 13, 2018)
8-15540177-C-A		Congenital disorder of glycosylation	Uncertain significance (Jan 12, 2018)
8-15540225-C-T		Congenital disorder of glycosylation	Uncertain significance (Jan 12, 2018)
8-15540233-GTCT-G		Congenital disorder of glycosylation	Uncertain significance (Jun 14, 2016)
8-15540240-C-T		Congenital disorder of glycosylation	Uncertain significance (Jan 13, 2018)
8-15540241-C-T		Congenital disorder of glycosylation	Uncertain significance (Apr 27, 2017)
8-15540255-GCT-G		Congenital disorder of glycosylation	Uncertain significance (Jun 14, 2016)
8-15540264-G-A		Congenital disorder of glycosylation	Uncertain significance (Jan 12, 2018)
8-15540272-C-T		Congenital disorder of glycosylation	Uncertain significance (Jan 13, 2018)
8-15540281-C-T		Congenital disorder of glycosylation	Uncertain significance (Jun 14, 2016)
8-15540301-C-G		Congenital disorder of glycosylation	Uncertain significance (Jan 13, 2018)
8-15540311-C-T		Congenital disorder of glycosylation	Benign (Jul 27, 2018)
8-15540320-C-A		Congenital disorder of glycosylation	Uncertain significance (Jan 12, 2018)
8-15540323-G-A		Congenital disorder of glycosylation	Likely benign (Jan 13, 2018)
8-15540340-G-A		Congenital disorder of glycosylation	Likely benign (Jan 12, 2018)
8-15540343-T-G		Congenital disorder of glycosylation	Likely benign (Jan 13, 2018)
8-15540344-C-T		Congenital disorder of glycosylation	Likely benign (Apr 12, 2020)
8-15540349-A-G		Congenital disorder of glycosylation	Uncertain significance (Jan 12, 2018)
8-15540380-G-A		Congenital disorder of glycosylation	Uncertain significance (Jan 12, 2018)
8-15540383-C-T		Congenital disorder of glycosylation	Uncertain significance (Jan 13, 2018)
8-15540385-G-C		Congenital disorder of glycosylation	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TUSC3	protein_coding	protein_coding	ENST00000503731	10	349435

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000346	0.946	125699	0	49	125748	0.000195

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0491	197	195	1.01	0.0000106	2263
Missense in Polyphen		42	58.353	0.71976		657
Synonymous	-3.13	101	68.2	1.48	0.00000350	677
Loss of Function	1.82	12	21.0	0.572	0.00000113	234

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000177	0.000177
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000545	0.0000544
Finnish	0.000324	0.000323
European (Non-Finnish)	0.000248	0.000246
Middle Eastern	0.0000545	0.0000544
South Asian	0.000134	0.000131
Other	0.000691	0.000652

dbNSFP

Source: dbNSFP

• Function: 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. In its oxidized form proposed to form transient mixed disulfides with a glycoprotein substrate to facilitate access of STT3B to the unmodified acceptor site. Has also oxidoreductase-independent functions in the STT3B-containing OST complex possibly involving substrate recognition. {ECO:0000269|PubMed:25135935, ECO:0000305|PubMed:12887896, ECO:0000305|PubMed:24685145}.
• Pathway: Protein processing in endoplasmic reticulum - Homo sapiens (human);N-Glycan biosynthesis - Homo sapiens (human);EMT transition in Colorectal Cancer;Post-translational protein modification;Metabolism of proteins;Transport of small molecules;Asparagine N-linked glycosylation;Miscellaneous transport and binding events (Consensus)

Recessive Scores

• pRec: 0.125

Intolerance Scores

• loftool: 0.635
• rvis_EVS: -0.34
• rvis_percentile_EVS: 30.37

Haploinsufficiency Scores

• pHI: 0.643
• hipred: N
• hipred_score: 0.445
• ghis: 0.575

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.536

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Tusc3

Gene ontology

• Biological process: protein N-linked glycosylation;magnesium ion transport;protein N-linked glycosylation via asparagine;cognition;transmembrane transport;magnesium ion transmembrane transport
• Cellular component: mitochondrion;endoplasmic reticulum membrane;plasma membrane;integral component of plasma membrane;oligosaccharyltransferase complex
• Molecular function: dolichyl-diphosphooligosaccharide-protein glycotransferase activity;magnesium ion transmembrane transporter activity