STT3B

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

Basic information

Region (hg38): 3:31532637-31637616

Links

ENSG00000163527 ∙ NCBI:201595 ∙ OMIM:608605 ∙ HGNC:30611 ∙ Uniprot:Q8TCJ2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• STT3B-congenital disorder of glycosylation (Limited), mode of inheritance: AR
• STT3B-congenital disorder of glycosylation (Supportive), mode of inheritance: AR
• STT3B-congenital disorder of glycosylation (Limited), mode of inheritance: AR
• STT3B-congenital disorder of glycosylation (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Congenital disorder of glycosylation, type Ix	AR	Hematologic	Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	Biochemical; Gastrointestinal; Genitourinary; Hematologic; Neurologic; Ophthalmologic	23842455
Hepatic-metabolized agents should be avoided

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the STT3B gene.

• STT3B-congenital disorder of glycosylation (70 variants)
• not provided (55 variants)
• not specified (24 variants)
• Inborn genetic diseases (12 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the STT3B 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			1	40	3	44
missense			34		1	35
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1	7	2	10
non coding				28	24	52
Total	0	0	35	68	28

Variants in STT3B

This is a list of pathogenic ClinVar variants found in the STT3B region.

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

Position	Type	Phenotype	Significance	ClinVar
3-31532647-C-T			Likely benign (Apr 25, 2021)
3-31532766-A-C			Benign (Jun 29, 2018)
3-31532901-T-TTCCTCC			Benign (May 24, 2021)
3-31532992-G-C		STT3B-related disorder	Likely benign (Jul 12, 2019)
3-31533009-C-T		STT3B-congenital disorder of glycosylation	Uncertain significance (Jun 15, 2020)
3-31533011-T-C		STT3B-congenital disorder of glycosylation	Uncertain significance (Jan 09, 2023)
3-31533013-G-C			Likely benign (Jun 08, 2018)
3-31533018-C-T		not specified	Uncertain significance (Feb 28, 2024)
3-31533030-A-G		STT3B-congenital disorder of glycosylation	Uncertain significance (Aug 10, 2023)
3-31533031-C-T		STT3B-congenital disorder of glycosylation	Likely benign (Jul 03, 2023)
3-31533036-C-G		STT3B-congenital disorder of glycosylation	Pathogenic (May 19, 2022)
3-31533043-C-T		not specified	Likely benign (Jan 24, 2017)
3-31533054-C-T		not specified	Uncertain significance (Aug 30, 2021)
3-31533085-C-T			Likely benign (Apr 03, 2018)
3-31533104-C-T		not specified	Uncertain significance (Sep 21, 2023)
3-31533134-G-A		STT3B-congenital disorder of glycosylation	Benign (Jan 20, 2023)
3-31533139-C-T		not specified • STT3B-congenital disorder of glycosylation	Benign/Likely benign (Apr 26, 2023)
3-31533151-G-C		STT3B-congenital disorder of glycosylation	Likely benign (Jan 08, 2024)
3-31533169-G-A		STT3B-congenital disorder of glycosylation	Likely benign (Dec 31, 2019)
3-31533199-G-C		STT3B-congenital disorder of glycosylation	Likely benign (Sep 20, 2023)
3-31533223-C-T		STT3B-congenital disorder of glycosylation	Likely benign (Oct 22, 2023)
3-31533233-C-T			Likely benign (Jun 19, 2018)
3-31533247-C-T			Likely benign (Nov 01, 2022)
3-31533262-C-T		STT3B-congenital disorder of glycosylation	Likely benign (Apr 23, 2021)
3-31533305-G-T		STT3B-congenital disorder of glycosylation	Uncertain significance (Jan 27, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
STT3B	protein_coding	protein_coding	ENST00000295770	16	104983

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.00104	125717	0	8	125725	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.76	205	422	0.486	0.0000201	5409
Missense in Polyphen		59	201.28	0.29312		2492
Synonymous	-0.184	149	146	1.02	0.00000703	1528
Loss of Function	5.29	5	42.0	0.119	0.00000220	508

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000618	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000934	0.0000924
European (Non-Finnish)	0.0000357	0.0000352
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

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). STT3B is present in a small subset of OST complexes and mediates both cotranslational and post-translational N-glycosylation of target proteins: STT3B-containing complexes are required for efficient post-translational glycosylation and while they are less competent than STT3A-containing complexes for cotranslational glycosylation, they have the ability to mediate glycosylation of some nascent sites that are not accessible for STT3A. STT3B- containing complexes also act post-translationally and mediate modification of skipped glycosylation sites in unfolded proteins. Plays a role in ER-associated degradation (ERAD) pathway that mediates ubiquitin-dependent degradation of misfolded endoplasmic reticulum proteins by mediating N-glycosylation of unfolded proteins, which are then recognized by the ERAD pathway and targeted for degradation. Mediates glycosylation of the disease variant AMYL-TTR 'Asp-38' of TTR at 'Asn-118', leading to its degradation (PubMed:19167329, PubMed:22607976). {ECO:0000250|UniProtKB:P39007, ECO:0000269|PubMed:19167329, ECO:0000269|PubMed:22607976}.
• Disease: DISEASE: Congenital disorder of glycosylation 1X (CDG1X) [MIM:615597]: 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);N-Glycan biosynthesis (Consensus)

Recessive Scores

• pRec: 0.168

Intolerance Scores

• loftool: 0.0734
• rvis_EVS: -0.76
• rvis_percentile_EVS: 13.33

Haploinsufficiency Scores

• pHI: 0.600
• hipred: Y
• hipred_score: 0.685
• ghis: 0.714

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: H
• gene_indispensability_pred: N
• gene_indispensability_score: 0.319

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Stt3b

Gene ontology

• Biological process: glycoprotein catabolic process;response to unfolded protein;protein N-linked glycosylation via asparagine;ubiquitin-dependent ERAD pathway;co-translational protein modification;post-translational protein modification
• Cellular component: endoplasmic reticulum;oligosaccharyltransferase complex;membrane;integral component of membrane;protein-containing complex;oligosaccharyltransferase I complex
• Molecular function: dolichyl-diphosphooligosaccharide-protein glycotransferase activity;metal ion binding