STT3B

Summary

STT3B (STT3 oligosaccharyltransferase complex catalytic subunit B, HGNC:30611) is a protein-coding gene on chromosome 3p23, encoding Dolichyl-diphosphooligosaccharide–protein glycosyltransferase subunit STT3B (Q8TCJ2). 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 nasce….

The protein encoded by this gene is a catalytic subunit of a protein complex that transfers oligosaccharides onto asparagine residues. Defects in this gene are a cause of congenital disorder of glycosylation Ix (CDG1X).

Source: NCBI Gene 201595 — RefSeq curated summary.

At a glance

• Gene–disease (curated): STT3B-congenital disorder of glycosylation (Supportive, GenCC) — +1 more curated relationship
• GWAS associations: 5
• Clinical variants (ClinVar): 223 total — 1 pathogenic
• Phenotypes (HPO): 21
• Druggable target: yes
• MANE Select transcript: NM_178862

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30611
Approved symbol	STT3B
Name	STT3 oligosaccharyltransferase complex catalytic subunit B
Location	3p23
Locus type	gene with protein product
Status	Approved
Aliases	SIMP, FLJ90106, STT3-B
Ensembl gene	ENSG00000163527
Ensembl biotype	protein_coding
OMIM	608605
Entrez	201595

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 16 protein_coding, 2 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000295770, ENST00000423527, ENST00000436236, ENST00000453168, ENST00000462235, ENST00000463044, ENST00000488151, ENST00000718294, ENST00000868023, ENST00000868024, ENST00000868025, ENST00000935232, ENST00000935233, ENST00000935234, ENST00000935235, ENST00000945184, ENST00000945185, ENST00000945186, ENST00000945187, ENST00000945188

RefSeq mRNA: 1 — MANE Select: NM_178862 NM_178862

CCDS: CCDS2650

Canonical transcript exons

ENST00000295770 — 16 exons

Exon	Start	End
ENSE00001075690	31625954	31626127
ENSE00001075691	31624914	31625085
ENSE00001134635	31532925	31533312
ENSE00001141814	31623674	31623861
ENSE00001141821	31622097	31622308
ENSE00001299370	31635984	31637616
ENSE00003468925	31615105	31615203
ENSE00003481816	31579809	31580096
ENSE00003513163	31617940	31617988
ENSE00003522216	31596798	31596863
ENSE00003528335	31632935	31633147
ENSE00003533268	31629298	31629411
ENSE00003593887	31576396	31576504
ENSE00003646352	31616929	31617075
ENSE00003657996	31619676	31619830
ENSE00003660393	31600360	31600459

Expression profiles

Bgee: expression breadth ubiquitous, 263 present calls, max score 99.08.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 67.5856 / max 985.4565, expressed in 1825 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
35856	28.7278	1815
35857	19.1658	1794
35853	16.3329	1785
35858	1.3745	840
35854	1.0499	577
35855	0.9346	565

Top tissues by expression

264 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	99.08	gold quality
cardiac muscle of right atrium	UBERON:0003379	99.03	gold quality
upper arm skin	UBERON:0004263	98.79	gold quality
corpus epididymis	UBERON:0004359	98.76	gold quality
cortical plate	UBERON:0005343	98.50	gold quality
left ventricle myocardium	UBERON:0006566	98.46	gold quality
thymus	UBERON:0002370	98.39	gold quality
calcaneal tendon	UBERON:0003701	98.32	gold quality
pigmented layer of retina	UBERON:0001782	98.25	gold quality
retina	UBERON:0000966	98.22	gold quality
caput epididymis	UBERON:0004358	98.09	gold quality
tibialis anterior	UBERON:0001385	98.07	gold quality
myocardium	UBERON:0002349	97.96	gold quality
ovary	UBERON:0000992	97.75	gold quality
placenta	UBERON:0001987	97.74	gold quality
deltoid	UBERON:0001476	97.70	gold quality
left ovary	UBERON:0002119	97.61	gold quality
bone marrow cell	CL:0002092	97.55	gold quality
nasal cavity epithelium	UBERON:0005384	97.53	gold quality
seminal vesicle	UBERON:0000998	97.52	gold quality
penis	UBERON:0000989	97.50	gold quality
cauda epididymis	UBERON:0004360	97.46	gold quality
germinal epithelium of ovary	UBERON:0001304	97.39	gold quality
synovial joint	UBERON:0002217	97.37	gold quality
right ovary	UBERON:0002118	97.36	gold quality
bone marrow	UBERON:0002371	97.35	gold quality
endometrium	UBERON:0001295	97.34	gold quality
right testis	UBERON:0004534	97.31	gold quality
kidney epithelium	UBERON:0004819	97.31	gold quality
urethra	UBERON:0000057	97.30	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	13.07
E-HCAD-8	no	386.30
E-MTAB-6524	no	88.85

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

118 targeting STT3B, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-559	99.95	72.28	3609
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-3671	99.90	73.04	3897

Literature-anchored findings (GeneRIF, showing 13)

• STT3 proteins are the catalytic subunits of the oligosaccharyltransferase. Vertebrate, plant and insect genomes have an STT3A gene and a STT3B gene. SIMP is a member of the STT3B subfamily of STT3 proteins. (PMID:12887896)
• The STT3B isoform is required for efficient cotranslational glycosylation of an acceptor site adjacent to the N-terminal signal sequence of a secreted protein. (PMID:19167329)
• Data show that prolonged transthyretin (TTR) unfolding induces externalization of cryptic N-glycosylation site and triggers STT3B-dependent posttranslational N-glycosylation. (PMID:22607976)
• Extreme C-terminal sites are posttranslocationally glycosylated by the STT3B isoform of the OST. (PMID:23530066)
• Results show homozygous mutation in STT3A and in STT3B causes congenital disorders of glycosylation. (PMID:23842455)
• Post-translational modification of cotranslationally skipped sites by STT3B is hindered by the middle X residue, resulting in hypoglycosylation of consensus sites containing large hydrophobic and negatively charged side chains. (PMID:25029371)
• STT3B was significantly upregulated in hip osteoarthritis with affected versus intact cartilage, particularly in the analysis of hypertrophic and normotrophic compared with atrophic bone remodelling pattern. (PMID:27974301)
• These results reveal that the oxidoreductase activity of the STT3B-containing oligosaccharyltransferase is necessary for dengue virus infection. (PMID:28720733)
• The endoplasmic reticulum-localized mEGFP mutants contained an N-glycosylation sequon at their C-terminus and had increased fluorescence upon N-glycosylation. Among the mutants tested, the ER-mEGFP mutant containing the N185 -C186 -T187 sequon was the best substrate for the STT3B isoform in terms of glycosylation efficiency and fluorescence change. (PMID:29282902)
• Study reports that STT3B-oligosaccharyltransferase, but not STT3A-oligosaccharyltransferase, is a lipid-linked oligosaccharide hydrolase. (PMID:30181269)
• Acceptor sites located in short loops of multi-spanning membrane proteins represent a new class of STT3B-dependent site. (PMID:31296534)
• Proteome and Glycoproteome Analyses Reveal the Protein N-Linked Glycosylation Specificity of STT3A and STT3B. (PMID:36139350)
• Stabilization of EREG via STT3B-mediated N-glycosylation is critical for PDL1 upregulation and immune evasion in head and neck squamous cell carcinoma. (PMID:38945975)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	stt3b	ENSDARG00000001890
mus_musculus	Stt3b	ENSMUSG00000032437
rattus_norvegicus	Stt3b	ENSRNOG00000011922
drosophila_melanogaster	Stt3B	FBGN0011336
caenorhabditis_elegans		WBGENE00020437

Paralogs (2): STT3A (ENSG00000134910), RPL35 (ENSG00000136942)

Protein

Protein identifiers

Dolichyl-diphosphooligosaccharide–protein glycosyltransferase subunit STT3B — Q8TCJ2 (reviewed: Q8TCJ2)

Alternative names: Source of immunodominant MHC-associated peptides homolog

All UniProt accessions (1): Q8TCJ2

UniProt curated annotations — full annotation on UniProt →

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. STT3B is present in a small subset of OST complexes (OST-B) 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.

Subunit / interactions. Component of the oligosaccharyltransferase (OST) complex. There are 2 OST complexes, OST-A and OST-B, which contain STT3A or STT3B as catalytic subunit, respectively. OST-A and OST-B contain common core subunits RPN1, RPN2, OST48, OST4, DAD1 and TMEM258, and OST-B contains either MAGT1 or TUSC3 as specific accessory subunit.

Subcellular location. Endoplasmic reticulum. Endoplasmic reticulum membrane.

Tissue specificity. Expressed in heart, brain, placenta, lung, liver, muscle, kidney and pancreas. Expressed in skin fibroblasts (at protein level).

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. Despite low primary sequence conservation between eukaryotic catalytic subunits and bacterial and archaeal single subunit OSTs (ssOST), structural comparison revealed several common motifs at spatially equivalent positions, like the DXD motif 1 on the external loop 1 and the DXD motif 2 on the external loop 2 involved in binding of the metal ion cofactor and the carboxamide group of the acceptor asparagine, the conserved Glu residue of the TIXE/SVSE motif on the external loop 5 involved in catalysis, as well as the WWDYG and the DK/MI motifs in the globular domain that define the binding pocket for the +2 Ser/Thr of the acceptor sequon. In bacterial ssOSTs, an Arg residue was found to interact with a negatively charged side chain at the -2 position of the sequon. This Arg is conserved in bacterial enzymes and correlates with an extended sequon requirement (Asp-X-Asn-X-Ser/Thr) for bacterial N-glycosylation.

Pathway. Protein modification; protein glycosylation.

Similarity. Belongs to the STT3 family.

RefSeq proteins (1): NP_849193* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003674	Oligo_trans_STT3	Family
IPR048307	STT3_N	Domain
IPR048999	STT3-PglB_core	Domain

Pfam: PF02516, PF21436

Enzyme classification (BRENDA):

• EC 2.4.99.18 — dolichyl-diphosphooligosaccharide-protein glycotransferase (BRENDA: 84 organisms, 135 substrates, 28 inhibitors, 38 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

29 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
TYR-ASN-LEU-THR-SER-VAL	0.05–0.6	3
ACETYL-ASN-ALA-THR	0.08–0.143	2
ALA-LEU-GLN-ASN-ALA-THR-ARG	0.3–0.358	2
ASN-ALA-THR	0.56–2.09	2
DIPHENYL-ALA-LEU-GLU-ASN-ALA-THR-ARG-NH2	0.072–0.23	2
TYR-GLN-SER-ASN-SER-THR-MET	0.08–0.127	2
AC-ASN-ALA-THR-NH2	2	1
AC-ASN-LEU-THR-NH2	1	1
ACETYL-ASN-LYS-THR	0.278	1
ACETYL-DFNAT-(4-NITROPHENYLALANINE)-NH2	0.0009	1
ACETYL-DFNVT-(4-NITROPHENYLALANINE)-NH2	0.0012	1
ACETYL-DQNAT-(4-NITROPHENYLALANINE)-NH2	0.0008	1
ACETYL-DVNAS-(4-NITROPHENYLALANINE)-NH2	0.003	1
ACETYL-DVNAT-(4-NITROPHENYLALANINE)-NH2	0.0011	1
ACETYL-DVNVT-(4-NITROPHENYLALANINE)-NH2	0.0014	1

Catalyzed reactions (Rhea), 1 shown:

• a di-trans,poly-cis-dolichyl diphosphooligosaccharide + L-asparaginyl-[protein] = N(4)-(oligosaccharide-(1->4)-N-acetyl-beta-D-glucosaminyl-(1->4)-N-acetyl-beta-D-glucosaminyl)-L-asparaginyl-[protein] + a di-trans,poly-cis-dolichyl diphosphate + H(+) (RHEA:22980)

UniProt features (113 total): helix 32, topological domain 14, strand 14, transmembrane region 13, turn 9, modified residue 6, short sequence motif 5, binding site 5, site 4, glycosylation site 4, region of interest 3, initiator methionine 1, chain 1, compositionally biased region 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6S7T	ELECTRON MICROSCOPY	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TCJ2-F1	80.41	0.49

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (4): 103 (interacts with target acceptor peptide in protein substrate); 214 (important for catalytic activity); 405 (interacts with target acceptor peptide in protein substrate); 674 (interacts with target acceptor peptide in protein substrate)

Ligand- & substrate-binding residues (5): 103; 221; 223; 459; 609

Post-translational modifications (6): 2, 13, 18, 29, 498, 499

Glycosylation sites (4): 616, 623, 627, 641

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-446203	Asparagine N-linked glycosylation
R-HSA-9694548	Maturation of spike protein
R-HSA-9918432	Maturation of DENV proteins
R-HSA-9926550	Regulation of MITF-M-dependent genes involved in extracellular matrix, focal adhesion and epithelial-to-mesenchymal transition
R-HSA-9931295	PD-L1(CD274) glycosylation and translocation to plasma membrane
R-HSA-1266738	Developmental Biology
R-HSA-9730414	MITF-M-regulated melanocyte development
R-HSA-9856651	MITF-M-dependent gene expression

MSigDB gene sets: 284 (showing top): E2F_Q4, E2F_Q4_01, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, E2F4DP1_01, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_PROTEIN_N_LINKED_GLYCOSYLATION, CMYB_01, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, KEGG_N_GLYCAN_BIOSYNTHESIS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, E2F1DP1_01, E2F_Q3, E2F1DP2_01

GO Biological Process (8): protein N-linked glycosylation (GO:0006487), glycoprotein catabolic process (GO:0006516), response to unfolded protein (GO:0006986), obsolete protein N-linked glycosylation via asparagine (GO:0018279), ERAD pathway (GO:0036503), post-translational protein modification (GO:0043687), obsolete protein glycosylation (GO:0006486), obsolete co-translational protein modification (GO:0043686)

GO Molecular Function (6): dolichyl-diphosphooligosaccharide-protein glycotransferase activity (GO:0004579), metal ion binding (GO:0046872), oligosaccharyl transferase activity (GO:0004576), protein binding (GO:0005515), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757)

GO Cellular Component (6): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), oligosaccharyltransferase complex (GO:0008250), membrane (GO:0016020), protein-containing complex (GO:0032991), oligosaccharyltransferase complex B (GO:0160227)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Post-translational protein modification	1
Translation of Structural Proteins	1
Dengue Virus Genome Translation and Replication	1
MITF-M-dependent gene expression	1
Regulation of PD-L1(CD274) Post-translational modification	1
Developmental Biology	1
MITF-M-regulated melanocyte development	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
glycoprotein biosynthetic process	1
glycoprotein metabolic process	1
protein catabolic process	1
carbohydrate derivative catabolic process	1
response to topologically incorrect protein	1
proteasomal protein catabolic process	1
response to endoplasmic reticulum stress	1
response to chemical	1
protein modification process	1
oligosaccharyl transferase activity	1
cation binding	1
hexosyltransferase activity	1
binding	1
catalytic activity	1
transferase activity	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
endoplasmic reticulum membrane	1
membrane protein complex	1
endoplasmic reticulum protein-containing complex	1
transferase complex	1
cellular anatomical structure	1
cellular_component	1
oligosaccharyltransferase complex	1

Protein interactions and networks

STRING

2053 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
STT3B	DDOST	P39656	987
STT3B	DAD1	P46966	986
STT3B	OST4	P0C6T2	970
STT3B	RPN1	P04843	967
STT3B	RPN2	P04844	949
STT3B	TMEM258	P61165	943
STT3B	STT3A	P46977	921
STT3B	MAGT1	Q9H0U3	899
STT3B	TUSC3	Q13454	827
STT3B	KRTCAP2	Q8N6L1	780
STT3B	OSTC	Q9NRP0	761
STT3B	SEC61A1	P38378	676
STT3B	SEL1L	Q9UBV2	647
STT3B	ALG6	Q9Y672	644
STT3B	ALG12	Q9BV10	615

IntAct

153 interactions, top by confidence:

A	B	Type	Score
TCTN2	CLGN	psi-mi:“MI:0914”(association)	0.780
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
STT3B	RPN1	psi-mi:“MI:0915”(physical association)	0.690
RPN1	STT3B	psi-mi:“MI:0915”(physical association)	0.690
MLEC	RPN1	psi-mi:“MI:0915”(physical association)	0.690
CD27	TCAF2	psi-mi:“MI:0914”(association)	0.640
CANX	PGRMC1	psi-mi:“MI:0914”(association)	0.570
INSR	PIK3R2	psi-mi:“MI:2364”(proximity)	0.570
INCA1	STT3B	psi-mi:“MI:0915”(physical association)	0.560
DAD1	RPN1	psi-mi:“MI:0915”(physical association)	0.530
RPN1	APBB1	psi-mi:“MI:0914”(association)	0.530
RPN2	SMPD2	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
TINF2	STT3B	psi-mi:“MI:0915”(physical association)	0.400
CFAP74	STT3B	psi-mi:“MI:0915”(physical association)	0.400
TTN	STT3B	psi-mi:“MI:0915”(physical association)	0.400
TBC1D22A	STT3B	psi-mi:“MI:0915”(physical association)	0.400
DBX2	STT3B	psi-mi:“MI:0915”(physical association)	0.400
RXYLT1	STT3B	psi-mi:“MI:0915”(physical association)	0.400
PHKA2	STT3B	psi-mi:“MI:0915”(physical association)	0.400
GBP5	STT3B	psi-mi:“MI:0915”(physical association)	0.400
EML5	STT3B	psi-mi:“MI:0915”(physical association)	0.400
STT3B	CDC34	psi-mi:“MI:0915”(physical association)	0.400
SDC1	ILVBL	psi-mi:“MI:0915”(physical association)	0.400
Mad2l1	MAD1L1	psi-mi:“MI:0914”(association)	0.350
Nek9	EML1	psi-mi:“MI:0914”(association)	0.350
Ncstn	DERL1	psi-mi:“MI:0914”(association)	0.350
RAB7A		psi-mi:“MI:0914”(association)	0.350

BioGRID (409): STT3B (Affinity Capture-RNA), STT3B (Affinity Capture-MS), DDOST (Co-fractionation), RPN1 (Co-fractionation), STT3B (Co-fractionation), STT3B (Affinity Capture-Western), STT3B (Synthetic Growth Defect), STT3B (Proximity Label-MS), STT3B (Proximity Label-MS), STT3B (Proximity Label-MS), STT3B (Proximity Label-MS), STT3B (Proximity Label-MS), STT3B (Proximity Label-MS), STT3B (Proximity Label-MS), STT3B (Affinity Capture-MS)

ESM2 similar proteins: A2AJQ3, A6X919, A8Y3M2, D4AD75, E2RG47, F1PJP5, F1QYC4, G5EBX4, O13898, O59802, O76689, O94335, P0CW70, P34413, P46977, P46978, P53730, P53868, P54002, P97564, Q09216, Q09837, Q0VGW4, Q18600, Q2KJI2, Q2PZI1, Q3TDQ1, Q3UVK0, Q5R8N9, Q5RCE2, Q66J01, Q6CN27, Q6F2Z1, Q6NUT2, Q6UPR8, Q6ZN68, Q754G0, Q7Z2K6, Q7Z388, Q8BI36

Diamond homologs: E2RG47, F1PJP5, O29867, O94335, P39007, P46975, P46977, P46978, Q2KJI2, Q3TDQ1, Q54NM9, Q5RCE2, Q6F2Z1, Q7XQ88, Q8TCJ2, Q93ZY3, Q9FX21

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
STT3B	“form complex”	“OST-B complex”	binding
STT3B	“up-regulates quantity by stabilization”	CD274	glycosylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 169 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
PD-L1(CD274) glycosylation and translocation to plasma membrane	7	33.3×	3e-07
Maturation of spike protein	9	21.9×	1e-07
Regulation of CDH1 posttranslational processing and trafficking to plasma membrane	7	21.6×	6e-06
Maturation of DENV proteins	8	15.5×	7e-06
Defective CFTR causes cystic fibrosis	5	10.1×	7e-03
Anchoring of the basal body to the plasma membrane	7	7.3×	4e-03
Asparagine N-linked glycosylation	11	6.1×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
obsolete protein N-linked glycosylation via asparagine	6	29.1×	6e-05
protein N-linked glycosylation	7	13.3×	6e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

223 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	84
Likely benign	78
Benign	31

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
102449	NM_178862.3(STT3B):c.1539+20G>T	Pathogenic

SpliceAI

3762 predictions. Top by Δscore:

Variant	Effect	Δscore
3:31533309:CGTGG:C	donor_loss	1.0000
3:31533310:GTG:G	donor_gain	1.0000
3:31533310:GTGGT:G	donor_loss	1.0000
3:31533311:TGGTA:T	donor_loss	1.0000
3:31533313:G:GA	donor_loss	1.0000
3:31533313:G:GG	donor_gain	1.0000
3:31533314:TAAG:T	donor_loss	1.0000
3:31543800:G:GT	donor_gain	1.0000
3:31576391:TCTA:T	acceptor_loss	1.0000
3:31576394:A:AT	acceptor_loss	1.0000
3:31576500:GTACT:G	donor_gain	1.0000
3:31576503:CTGTA:C	donor_loss	1.0000
3:31576504:TG:T	donor_loss	1.0000
3:31576505:G:GG	donor_gain	1.0000
3:31576506:TAA:T	donor_loss	1.0000
3:31576507:AA:A	donor_loss	1.0000
3:31579807:A:AC	acceptor_loss	1.0000
3:31579807:A:AG	acceptor_gain	1.0000
3:31579808:G:GA	acceptor_gain	1.0000
3:31600354:CTATA:C	acceptor_loss	1.0000
3:31600355:TATAG:T	acceptor_loss	1.0000
3:31600357:TAGG:T	acceptor_loss	1.0000
3:31600359:G:GA	acceptor_loss	1.0000
3:31600457:TAGG:T	donor_loss	1.0000
3:31600460:G:A	donor_loss	1.0000
3:31600461:T:G	donor_loss	1.0000
3:31617938:A:G	acceptor_gain	1.0000
3:31622095:A:AG	acceptor_gain	1.0000
3:31622096:G:GG	acceptor_gain	1.0000
3:31622096:GTT:G	acceptor_gain	1.0000

AlphaMissense

5450 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:31533248:G:C	G84R	1.000
3:31533249:G:A	G84D	1.000
3:31533260:C:A	R88S	1.000
3:31533264:T:C	L89P	1.000
3:31533281:T:C	F95L	1.000
3:31533283:C:A	F95L	1.000
3:31533283:C:G	F95L	1.000
3:31533294:T:A	I99N	1.000
3:31533296:C:G	H100D	1.000
3:31533299:G:A	E101K	1.000
3:31533300:A:T	E101V	1.000
3:31533302:T:A	F102I	1.000
3:31533302:T:C	F102L	1.000
3:31533303:T:G	F102C	1.000
3:31533304:C:A	F102L	1.000
3:31533304:C:G	F102L	1.000
3:31533306:A:G	D103G	1.000
3:31533306:A:T	D103V	1.000
3:31533309:C:A	P104Q	1.000
3:31576397:T:C	F106L	1.000
3:31576398:T:C	F106S	1.000
3:31576398:T:G	F106C	1.000
3:31576399:T:A	F106L	1.000
3:31576399:T:G	F106L	1.000
3:31576402:C:A	N107K	1.000
3:31576402:C:G	N107K	1.000
3:31576472:T:A	W131R	1.000
3:31576472:T:C	W131R	1.000
3:31576488:G:C	R136T	1.000
3:31576489:A:C	R136S	1.000

dbSNP variants (sampled 300 via entrez): RS1000016096 (3:31619052 C>T), RS1000020847 (3:31533812 C>T), RS1000033641 (3:31637274 T>A), RS1000048049 (3:31550052 T>G), RS1000075778 (3:31600167 G>A,T), RS1000079475 (3:31593785 A>C,G), RS1000099107 (3:31598204 G>A), RS1000159147 (3:31538250 C>A), RS1000278823 (3:31573643 C>G), RS1000327364 (3:31624222 G>A), RS1000359467 (3:31606365 G>A,C), RS1000375176 (3:31535775 T>G), RS1000379098 (3:31610474 T>C,G), RS1000382269 (3:31576019 A>G), RS1000437061 (3:31616602 A>G)

Disease associations

OMIM: gene MIM:608605 | disease phenotypes: MIM:615597

GenCC curated gene-disease

Disease	Classification	Inheritance
STT3B-congenital disorder of glycosylation	Supportive	Autosomal recessive
congenital disorder of glycosylation	Limited	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
congenital disorder of glycosylation	Limited	AR

Mondo (2): STT3B-congenital disorder of glycosylation (MONDO:0014271), congenital disorder of glycosylation (MONDO:0015286)

Orphanet (1): STT3B-CDG (Orphanet:370924)

HPO phenotypes

21 total (21 of 21 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000046	Small scrotum
HP:0000054	Micropenis
HP:0000078	Abnormality of the genital system
HP:0000252	Microcephaly
HP:0000648	Optic atrophy
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001272	Cerebellar atrophy
HP:0001290	Generalized hypotonia
HP:0001508	Failure to thrive
HP:0001511	Intrauterine growth retardation
HP:0001873	Thrombocytopenia
HP:0002098	Respiratory distress
HP:0003819	Death in childhood
HP:0011461	Fetal onset
HP:0011968	Feeding difficulties
HP:0012345	Abnormal glycosylation

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002312_8	Periodontal disease-related phenotype (Socransky)	6.000000e-06
GCST007676_18	3-month functional outcome in ischaemic stroke (modified Rankin score)	3.000000e-06
GCST008971_62	Urate levels	7.000000e-06
GCST008972_37	Urate levels	2.000000e-08
GCST012174_1	Diabetic retinopathy in type 2 diabetes	7.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0009603	stroke outcome severity measurement
EFO:0004531	urate measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D018981	Congenital Disorders of Glycosylation	C16.320.565.202.125; C18.452.648.202.125
C535751	Congenital disorder of glycosylation type 1X (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066236 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

3 potent at pChembl≥5 of 3 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.10	Kd	7.943	nM	CHEMBL5583975
6.20	Kd	625.7	nM	CHEMBL3752910
6.20	ED50	625.7	nM	CHEMBL3752910

PubChem BioAssay actives

2 with measured affinity, of 3 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-methyl-3-(6-methyl-1H-indol-2-yl)-N-[2-[(3S)-3-methylmorpholin-4-yl]-2-oxoethyl]-4-pyrrolidin-1-ylbenzenesulfonamide	2114917: Binding affinity to STT3B in human HepG2 cells assessed as apparent dissociation constant incubated for 1 hr by competition binding assay	kd	0.0079	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149519: Binding affinity to human STT3B incubated for 45 mins by Kinobead based pull down assay	kd	0.6257	uM

CTD chemical–gene interactions

31 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, decreases methylation, affects cotreatment, increases expression, affects expression	4
trichostatin A	increases expression, affects cotreatment	3
sodium arsenite	affects binding, increases reaction, decreases expression	3
Air Pollutants	decreases expression, increases abundance	2
Tunicamycin	increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
methylmercuric chloride	decreases expression	1
bisphenol A	decreases methylation	1
perfluorooctanoic acid	decreases expression	1
mercuric bromide	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	decreases expression	1
bisphenol AF	increases expression	1
Atrazine	increases expression	1
Caffeine	increases phosphorylation	1
Isoniazid	increases expression	1
Ivermectin	decreases expression	1
Smoke	decreases expression, increases abundance	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Aflatoxin B1	decreases methylation	1
p-Chloromercuribenzoic Acid	decreases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5579433	Binding	Binding affinity to STT3B in human HepG2 cells assessed as apparent dissociation constant incubated for 1 hr by competition binding assay	Discovery of Potent STT3A/B Inhibitors and Assessment of Their Multipathogen Antiviral Potential and Safety. — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B3IK	Abcam HEK293T STT3B KO	Transformed cell line	Female

Clinical trials (associated diseases)

9 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT07572825	PHASE1	NOT_YET_RECRUITING	Assessing the Safety and Tolerability of NMN in DHDDS-CDG
NCT02089789	Not specified	RECRUITING	Clinical and Basic Investigations Into Known and Suspected Congenital Disorders of Glycosylation
NCT02503267	Not specified	UNKNOWN	Incidence and Consequences of Disorders of Glycosylation in Patients With Conotruncal and Septal Heart Defects
NCT02955264	Not specified	COMPLETED	Using D-Galactose as a Food Supplement in Congenital Disorders of Glycosylation
NCT03250728	Not specified	COMPLETED	Role of the Endothelium in Stroke-like Episode Among CDG Patients
NCT03560570	Not specified	COMPLETED	Study of Hemostasis in Patients With Congenital Disorder of Glycosylation
NCT04198987	Not specified	COMPLETED	Dietary Monosaccharide Supplementation in Patients With Congenital Disorders of Glycosylation
NCT04199000	Not specified	RECRUITING	Clinical and Basic Investigations Into Congenital Disorders of Glycosylation
NCT04201067	Not specified	COMPLETED	Large-Scale Metabolomic Profiling for the Diagnosis of Inborn Errors of Metabolism