STT3A

STT3 oligosaccharyltransferase complex catalytic subunit A, the group of Oligosaccharyltransferase complex subunits|STT3 oligosaccharyltransferase catalytic subunits

Basic information

Region (hg38): 11:125591712-125625215

Previous symbols: [ "ITM1" ]

Links

ENSG00000134910 ∙ NCBI:3703 ∙ OMIM:601134 ∙ HGNC:6172 ∙ Uniprot:P46977 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• STT3A-congenital disorder of glycosylation (Limited), mode of inheritance: AR
• STT3A-congenital disorder of glycosylation (Strong), mode of inheritance: AR
• STT3A-congenital disorder of glycosylation (Supportive), mode of inheritance: AR
• STT3A-congenital disorder of glycosylation (Moderate), mode of inheritance: AR
• congenital disorder of glycosylation, type Iw, autosomal dominant (Moderate), mode of inheritance: AD
• congenital disorder of glycosylation, type Iw, autosomal dominant (Strong), mode of inheritance: AD
• congenital disorder of glycosylation, type Iw, autosomal dominant (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Congenital disorder of glycosylation, type Iw, autosomal dominant; Congenital disorder of glycosylation, type Iw, autosomal recessive	AD/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	Biochemical; Craniofacial; Musculoskeletal; Neurologic	23842455; 34653363
Hepatic-metabolized agents should be avoided

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the STT3A gene.

• not_provided (112 variants)
• Inborn_genetic_diseases (43 variants)
• Congenital_disorder_of_glycosylation,_type_Iw,_autosomal_dominant (16 variants)
• not_specified (10 variants)
• STT3A-congenital_disorder_of_glycosylation (8 variants)
• STT3A-related_disorder (4 variants)
• Microcephaly (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the STT3A gene is commonly pathogenic or not. These statistics are base on transcript: NM_000152713.5. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	33	1	35
missense	1	6	82			89
nonsense			1			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1			1
Total	1	6	85	33	1

Highest pathogenic variant AF is 0.000024215331

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
STT3A	protein_coding	protein_coding	ENST00000392708	17	33504

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00204	0.998	125725	0	21	125746	0.0000835

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.62	205	412	0.498	0.0000229	4610
Missense in Polyphen		45	173.6	0.25921		2021
Synonymous	1.43	122	144	0.849	0.00000736	1385
Loss of Function	4.18	13	42.3	0.307	0.00000257	440

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000177	0.000177
Ashkenazi Jewish	0.00	0.00
East Asian	0.000218	0.000217
Finnish	0.000139	0.000139
European (Non-Finnish)	0.0000616	0.0000615
Middle Eastern	0.000218	0.000217
South Asian	0.0000327	0.0000327
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalytic subunit of the oligosaccharyl transferase (OST) complex that catalyzes the initial transfer of a defined glycan (Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipid carrier dolichol-pyrophosphate to an asparagine residue within an Asn-X-Ser/Thr consensus motif in nascent polypeptide chains, the first step in protein N-glycosylation. N-glycosylation occurs cotranslationally and the complex associates with the Sec61 complex at the channel-forming translocon complex that mediates protein translocation across the endoplasmic reticulum (ER). All subunits are required for a maximal enzyme activity. This subunit contains the active site and the acceptor peptide and donor lipid- linked oligosaccharide (LLO) binding pockets (By similarity). STT3A is present in the majority of OST complexes and mediates cotranslational N-glycosylation of most sites on target proteins, while STT3B-containing complexes are required for efficient post- translational glycosylation and mediate glycosylation of sites that have been skipped by STT3A (PubMed:19167329). {ECO:0000250|UniProtKB:P39007, ECO:0000269|PubMed:19167329}.
• Disease: DISEASE: Congenital disorder of glycosylation 1W (CDG1W) [MIM:615596]: A form of congenital disorder of glycosylation, a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. {ECO:0000269|PubMed:23842455}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Protein processing in endoplasmic reticulum - Homo sapiens (human);N-Glycan biosynthesis - Homo sapiens (human);Post-translational protein modification;Metabolism of proteins;Asparagine N-linked glycosylation;N-Glycan biosynthesis (Consensus)

Intolerance Scores

• loftool: 0.276
• rvis_EVS: -0.65
• rvis_percentile_EVS: 16.36

Haploinsufficiency Scores

• pHI: 0.398
• hipred: Y
• hipred_score: 0.756
• ghis: 0.641

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.967

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Stt3a

Gene ontology

• Biological process: protein N-linked glycosylation via asparagine;co-translational protein modification
• Cellular component: endoplasmic reticulum membrane;oligosaccharyltransferase complex;membrane;integral component of membrane;oligosaccharyltransferase III complex
• Molecular function: dolichyl-diphosphooligosaccharide-protein glycotransferase activity;protein binding;metal ion binding