MOGS

Summary

MOGS (mannosyl-oligosaccharide glucosidase, HGNC:24862) is a protein-coding gene on chromosome 2p13.1, encoding Mannosyl-oligosaccharide glucosidase (Q13724). In the context of N-glycan degradation, cleaves the distal alpha 1,2-linked glucose residue from the Glc(3)Man(9)GlcNAc(2) oligosaccharide precursor in a highly specific manner.

This gene encodes the first enzyme in the N-linked oligosaccharide processing pathway. The enzyme cleaves the distal alpha-1,2-linked glucose residue from the Glc(3)-Man(9)-GlcNAc(2) oligosaccharide precursor. This protein is located in the lumen of the endoplasmic reticulum. Defects in this gene are a cause of type IIb congenital disorder of glycosylation (CDGIIb). Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 7841 — RefSeq curated summary.

At a glance

• Gene–disease (curated): MOGS-congenital disorder of glycosylation (Definitive, ClinGen)
• Clinical variants (ClinVar): 600 total — 22 pathogenic, 12 likely-pathogenic
• Phenotypes (HPO): 59
• Druggable target: yes
• MANE Select transcript: NM_006302

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24862
Approved symbol	MOGS
Name	mannosyl-oligosaccharide glucosidase
Location	2p13.1
Locus type	gene with protein product
Status	Approved
Aliases	GCS1, CWH41, DER7
Ensembl gene	ENSG00000115275
Ensembl biotype	protein_coding
OMIM	601336
Entrez	7841

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 12 protein_coding, 5 retained_intron, 4 nonsense_mediated_decay

ENST00000409065, ENST00000414701, ENST00000448666, ENST00000452063, ENST00000462189, ENST00000462443, ENST00000486036, ENST00000489655, ENST00000647723, ENST00000647753, ENST00000647771, ENST00000647915, ENST00000648768, ENST00000648810, ENST00000649075, ENST00000649601, ENST00000649777, ENST00000649854, ENST00000650523, ENST00000690565, ENST00000691308

RefSeq mRNA: 2 — MANE Select: NM_006302 NM_001146158, NM_006302

CCDS: CCDS42700, CCDS54370

Canonical transcript exons

ENST00000448666 — 4 exons

Exon	Start	End
ENSE00001853789	74461057	74463012
ENSE00003462747	74464496	74464722
ENSE00003542785	74463190	74463386
ENSE00003832319	74464896	74465382

Expression profiles

Bgee: expression breadth ubiquitous, 202 present calls, max score 95.91.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 26.9174 / max 340.8976, expressed in 1818 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
29212	26.8067	1818
29211	0.0654	13
29210	0.0453	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	95.91	gold quality
body of stomach	UBERON:0001161	95.20	gold quality
granulocyte	CL:0000094	94.70	gold quality
stromal cell of endometrium	CL:0002255	94.54	gold quality
right uterine tube	UBERON:0001302	94.20	gold quality
small intestine Peyer’s patch	UBERON:0003454	94.13	gold quality
right lobe of thyroid gland	UBERON:0001119	93.97	gold quality
mucosa of transverse colon	UBERON:0004991	93.94	gold quality
minor salivary gland	UBERON:0001830	93.86	gold quality
right lobe of liver	UBERON:0001114	93.47	gold quality
left lobe of thyroid gland	UBERON:0001120	93.44	gold quality
adenohypophysis	UBERON:0002196	93.35	gold quality
stomach	UBERON:0000945	93.14	gold quality
metanephros cortex	UBERON:0010533	93.03	gold quality
transverse colon	UBERON:0001157	92.82	gold quality
small intestine	UBERON:0002108	92.64	gold quality
pancreas	UBERON:0001264	92.54	gold quality
upper lobe of left lung	UBERON:0008952	92.38	gold quality
left adrenal gland	UBERON:0001234	92.31	gold quality
left adrenal gland cortex	UBERON:0035825	92.29	gold quality
right lung	UBERON:0002167	92.19	gold quality
right adrenal gland	UBERON:0001233	92.17	gold quality
pituitary gland	UBERON:0000007	92.08	gold quality
spleen	UBERON:0002106	91.98	gold quality
mucosa of stomach	UBERON:0001199	91.86	gold quality
thyroid gland	UBERON:0002046	91.80	gold quality
right adrenal gland cortex	UBERON:0035827	91.80	gold quality
skin of abdomen	UBERON:0001416	91.62	gold quality
endometrium epithelium	UBERON:0004811	91.59	silver quality
right ovary	UBERON:0002118	91.50	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.26

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

20 targeting MOGS, 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-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-4698	99.84	71.41	4303
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-143-3P	99.49	69.05	1457
HSA-MIR-4770	99.49	69.09	1451
HSA-MIR-183-3P	99.41	69.41	1598
HSA-MIR-6088	99.29	68.45	1284
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-4324	99.04	70.14	1569
HSA-MIR-4646-3P	98.65	66.98	693
HSA-MIR-5187-5P	98.54	67.94	952
HSA-MIR-6728-5P	97.79	66.33	891
HSA-MIR-4708-5P	97.77	67.82	831
HSA-MIR-299-3P	97.73	66.67	773
HSA-MIR-6802-3P	97.29	65.42	613
HSA-MIR-3622A-3P	97.06	66.43	1000
HSA-MIR-3622B-3P	96.82	66.36	988
HSA-MIR-4654	95.86	65.72	751

Literature-anchored findings (GeneRIF, showing 6)

• Perturbation of free oligosaccharide trafficking in endoplasmic reticulum glucosidase I-deficient and castanospermine-treated cells. (PMID:11942856)
• MafF/NFE2 hetrodimers act as weak transcriptional activators, and, in particular, are able to stimulate activity of the GCS1 promoter. (PMID:12490281)
• identification of sequence motifs responsible for endoplasmic reticulum localization (PMID:12626409)
• A shortened immunoglobulin half-life was determined to be the mechanism underlying the hypogammaglobulinemia in congenital disorder of glycosylation type IIb (CDG-IIb). (PMID:24716661)
• Compound heterozygous variants in MOGS gene is associated with congenital disorders of glycosylation IIb. (PMID:30587846)
• Congenital disorders of glycosylation type IIb with MOGS mutations cause early infantile epileptic encephalopathy, dysmorphic features, and hepatic dysfunction. (PMID:33261925)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	mogs	ENSDARG00000060252
mus_musculus	Mogs	ENSMUSG00000030036
rattus_norvegicus	Mogs	ENSRNOG00000054176
drosophila_melanogaster	GCS1	FBGN0030289
caenorhabditis_elegans		WBGENE00008775

Protein

Protein identifiers

Mannosyl-oligosaccharide glucosidase — Q13724 (reviewed: Q13724)

Alternative names: Processing A-glucosidase I

All UniProt accessions (15): Q13724, A0A384MDR6, A0A3B3IRI1, A0A3B3IRI7, A0A3B3IRK6, A0A3B3IRW2, A0A3B3IS52, A0A3B3ITC1, A0A3B3ITU6, A0A3B3IU81, A0A8I5KQG9, A0A8I5KTK5, B4E3B8, B8ZZE2, C9JDQ1

UniProt curated annotations — full annotation on UniProt →

Function. In the context of N-glycan degradation, cleaves the distal alpha 1,2-linked glucose residue from the Glc(3)Man(9)GlcNAc(2) oligosaccharide precursor in a highly specific manner.

Subcellular location. Endoplasmic reticulum membrane.

Disease relevance. Type IIb congenital disorder of glycosylation (CDGIIb) [MIM:606056] Characterized by marked generalized hypotonia and hypomotility of the neonate, dysmorphic features, including a prominent occiput, short palpebral fissures, retrognathia, high arched palate, generalized edema, and hypoplastic genitalia. Symptoms of the infant included hepatomegaly, hypoventilation, feeding problems and seizures. The clinical course was progressive and the infant did not survive more than a few months. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by 1-deoxynojirimycin (40% inhibition) and N,N-dimethyl-deoxynojirimycin (85% inhibition).

Pathway. Glycan metabolism; N-glycan degradation.

Similarity. Belongs to the glycosyl hydrolase 63 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q13724-1	1	yes
Q13724-2	2

RefSeq proteins (2): NP_001139630, NP_006293* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004888	Glycoside_hydrolase_63	Family
IPR008928	6-hairpin_glycosidase_sf	Homologous_superfamily
IPR012341	6hp_glycosidase-like_sf	Homologous_superfamily
IPR031335	Glyco_hydro_63_C	Domain
IPR031631	Glyco_hydro_63N	Domain
IPR038518	Glyco_hydro_63N_sf	Homologous_superfamily

Pfam: PF03200, PF16923

Catalyzed reactions (Rhea), 1 shown:

• N(4)-(alpha-D-Glc-(1->2)-alpha-D-Glc-(1->3)-alpha-D-Glc-(1->3)-alpha-D-Man-(1->2)-alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-[alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-[alpha-D-Man-(1->2)-alpha-D-Man-(1->6)]-alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-beta-D-GlcNAc)-L-asparaginyl-[protein] + H2O = N(4)-(alpha-D-Glc-(1->3)-alpha-D-Glc-(1->3)-alpha-D-Man-(1->2)-alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-[alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-[alpha-D-Man-(1->2)-alpha-D-Man-(1->6)]-alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-beta-D-GlcNAc)-L-asparaginyl-[protein] + beta-D-glucose (RHEA:55988)

UniProt features (25 total): sequence variant 8, sequence conflict 4, topological domain 2, active site 2, region of interest 2, compositionally biased region 2, chain 1, glycosylation site 1, splice variant 1, transmembrane region 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13724-F1	92.42	0.86

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 (2): 807 (proton acceptor); 583 (proton donor)

Glycosylation sites (1): 657

Function

Pathways and Gene Ontology

Reactome pathways

20 pathways

ID	Pathway
R-HSA-4793954	Defective MOGS causes CDG-2b
R-HSA-532668	N-glycan trimming in the ER and Calnexin/Calreticulin cycle
R-HSA-9683686	Maturation of spike protein
R-HSA-9694548	Maturation of spike protein
R-HSA-9768727	Regulation of CDH1 posttranslational processing and trafficking to plasma membrane
R-HSA-1643685	Disease
R-HSA-3781860	Diseases associated with N-glycosylation of proteins
R-HSA-3781865	Diseases of glycosylation
R-HSA-392499	Metabolism of proteins
R-HSA-446203	Asparagine N-linked glycosylation
R-HSA-5663205	Infectious disease
R-HSA-5668914	Diseases of metabolism
R-HSA-597592	Post-translational protein modification
R-HSA-9678108	SARS-CoV-1 Infection
R-HSA-9679506	SARS-CoV Infections
R-HSA-9683701	Translation of Structural Proteins
R-HSA-9694516	SARS-CoV-2 Infection
R-HSA-9694635	Translation of Structural Proteins
R-HSA-9772573	Late SARS-CoV-2 Infection Events
R-HSA-9824446	Viral Infection Pathways

MSigDB gene sets: 303 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, GOBP_OLIGOSACCHARIDE_METABOLIC_PROCESS, GOBP_PROTEIN_N_LINKED_GLYCOSYLATION, KEGG_N_GLYCAN_BIOSYNTHESIS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, REACTOME_ADHERENS_JUNCTIONS_INTERACTIONS, GOBP_PROTEIN_MATURATION, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GROSS_HYPOXIA_VIA_HIF1A_UP, GROSS_HYPOXIA_VIA_ELK3_AND_HIF1A_DN, MORI_SMALL_PRE_BII_LYMPHOCYTE_DN, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, GOBP_PROTEIN_FOLDING, MILI_PSEUDOPODIA_CHEMOTAXIS_DN, GOBP_GLYCOPROTEIN_METABOLIC_PROCESS

GO Biological Process (5): protein folding (GO:0006457), protein N-linked glycosylation (GO:0006487), oligosaccharide metabolic process (GO:0009311), viral protein processing (GO:0019082), carbohydrate metabolic process (GO:0005975)

GO Molecular Function (4): Glc3Man9GlcNAc2 oligosaccharide glucosidase activity (GO:0004573), glucosidase activity (GO:0015926), hydrolase activity (GO:0016787), hydrolase activity, acting on glycosyl bonds (GO:0016798)

GO Cellular Component (4): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-16 pathways:

Category	Pathways
Disease	2
SARS-CoV Infections	2
Diseases associated with N-glycosylation of proteins	1
Asparagine N-linked glycosylation	1
Translation of Structural Proteins	1
Regulation of CDH1 Expression and Function	1
Diseases of glycosylation	1
Diseases of metabolism	1
Post-translational protein modification	1
Metabolism of proteins	1
Viral Infection Pathways	1
SARS-CoV-1 Infection	1
Late SARS-CoV-2 Infection Events	1
SARS-CoV-2 Infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular process	1
protein maturation	1
glycoprotein biosynthetic process	1
carbohydrate metabolic process	1
viral process	1
viral gene expression	1
primary metabolic process	1
alpha-glucosidase activity	1
hydrolase activity, hydrolyzing O-glycosyl compounds	1
catalytic activity	1
hydrolase 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
cellular anatomical structure	1
extracellular vesicle	1

Protein interactions and networks

STRING

2362 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MOGS	GANAB	Q14697	968
MOGS	ARFGAP1	Q8N6T3	896
MOGS	CANX	P27824	852
MOGS	MGAM	O43451	843
MOGS	SI	P14410	833
MOGS	UGGT1	Q9NYU2	815
MOGS	MAN1B1	Q9UKM7	770
MOGS	UGGT2	Q9NYU1	768
MOGS	CALR	P27797	764
MOGS	PMM2	O15305	759
MOGS	ARF1	P10947	719
MOGS	ALG6	Q9Y672	709
MOGS	MAN1A1	P33908	690
MOGS	DDOST	P39656	678
MOGS	EDEM1	Q92611	655

IntAct

110 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:0914”(association)	0.900
YBX1	HNRNPR	psi-mi:“MI:0914”(association)	0.770
GET3	GET1	psi-mi:“MI:0914”(association)	0.640
CANX	PGRMC1	psi-mi:“MI:0914”(association)	0.570
TUBB3	POTEF	psi-mi:“MI:0914”(association)	0.530
rep	AGPS	psi-mi:“MI:0914”(association)	0.530
GRK7	HSP90AA1	psi-mi:“MI:0914”(association)	0.530
COLGALT2	COL1A1	psi-mi:“MI:0914”(association)	0.530
MOGS	RRP1	psi-mi:“MI:0914”(association)	0.530
DNAJC3	DEDD	psi-mi:“MI:0914”(association)	0.530
vpr	AGPS	psi-mi:“MI:0914”(association)	0.460
GPC1	SNAP23	psi-mi:“MI:0915”(physical association)	0.400
GPC1	ATP6V1B2	psi-mi:“MI:0915”(physical association)	0.400
GPC1	GANAB	psi-mi:“MI:0915”(physical association)	0.400
MORC3	RDH10	psi-mi:“MI:0914”(association)	0.350
UBA5	P4HA1	psi-mi:“MI:0914”(association)	0.350
Smo	METTL8	psi-mi:“MI:0914”(association)	0.350
POLR2G	POLR2B	psi-mi:“MI:0914”(association)	0.350
Katna1	RIMS1	psi-mi:“MI:0914”(association)	0.350
USP11	CNOT8	psi-mi:“MI:0914”(association)	0.350
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
	NAP1L1	psi-mi:“MI:0914”(association)	0.350
		psi-mi:“MI:0914”(association)	0.350
	ESYT2	psi-mi:“MI:0914”(association)	0.350
E5	ESYT2	psi-mi:“MI:0914”(association)	0.350
TUBA1A	KIF2A	psi-mi:“MI:0914”(association)	0.350
MYC	ILVBL	psi-mi:“MI:0914”(association)	0.350
KSR1	DDX39A	psi-mi:“MI:0914”(association)	0.350
H3C1	IPO5	psi-mi:“MI:0914”(association)	0.350

BioGRID (233): MOGS (Co-fractionation), MOGS (Co-fractionation), MOGS (Affinity Capture-MS), MOGS (Affinity Capture-MS), MOGS (Proximity Label-MS), MOGS (Proximity Label-MS), MOGS (Affinity Capture-MS), MOGS (Affinity Capture-MS), MOGS (Affinity Capture-MS), MOGS (Affinity Capture-MS), MOGS (Affinity Capture-MS), MOGS (Affinity Capture-MS), MOGS (Affinity Capture-MS), MOGS (Affinity Capture-MS), MOGS (Affinity Capture-MS)

ESM2 similar proteins: A0A0U1RPR8, A1A4J8, A6H751, A6H784, A7YY46, D3ZBP4, F1MH07, O08644, O15197, O19179, O43542, O43819, O43824, O75880, O88561, O88941, P0C0K6, P0C0K7, P0C7A1, P50233, P51839, P51840, P51976, P52785, P55203, P80365, Q02846, Q05932, Q08DH8, Q13724, Q3U6U5, Q5JTZ9, Q5K4L6, Q5SS80, Q5SUC9, Q69ZP3, Q80UM7, Q8N490, Q8NFI3, Q8TDZ2

Diamond homologs: F4HTM3, O14255, O88941, Q13724, Q19426, Q80UM7, Q84M89, P53008, Q72K04

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	22
Likely pathogenic	12
Uncertain significance	322
Likely benign	203
Benign	7

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1039350	NM_006302.3(MOGS):c.1483C>T (p.Arg495Ter)	Pathogenic
127098	NM_006302.3(MOGS):c.370C>T (p.Gln124Ter)	Pathogenic
1323285	NM_006302.3(MOGS):c.1385G>A (p.Trp462Ter)	Pathogenic
1943297	NM_006302.3(MOGS):c.1513C>T (p.Gln505Ter)	Pathogenic
2022184	NM_006302.3(MOGS):c.1204del (p.Ile402fs)	Pathogenic
2096379	NM_006302.3(MOGS):c.1142dup (p.Leu383fs)	Pathogenic
2161830	NM_006302.3(MOGS):c.422del (p.Asp141fs)	Pathogenic
2203107	NM_006302.3(MOGS):c.832_833del (p.Lys278fs)	Pathogenic
2703760	NM_006302.3(MOGS):c.551G>A (p.Trp184Ter)	Pathogenic
2846552	NM_006302.3(MOGS):c.881del (p.Pro294fs)	Pathogenic
2913879	NM_006302.3(MOGS):c.54dup (p.Ala19fs)	Pathogenic
2976812	NM_006302.3(MOGS):c.1222del (p.Gln408fs)	Pathogenic
2982038	NM_006302.3(MOGS):c.1421G>A (p.Trp474Ter)	Pathogenic
3690170	NM_006302.3(MOGS):c.1516C>T (p.Arg506Ter)	Pathogenic
379238	NM_006302.3(MOGS):c.1801C>T (p.Arg601Ter)	Pathogenic
4717315	NM_006302.3(MOGS):c.1076dup (p.Ala360fs)	Pathogenic
4729233	NM_006302.3(MOGS):c.634_635del (p.Asp212fs)	Pathogenic
4797570	NM_006302.3(MOGS):c.451del (p.His151fs)	Pathogenic
8193	NM_006302.3(MOGS):c.1457G>C (p.Arg486Thr)	Pathogenic
8194	NM_006302.3(MOGS):c.1954T>C (p.Phe652Leu)	Pathogenic
831030	NC_000002.12:g.(?74461255)(74465267_?)del	Pathogenic
841487	NM_006302.3(MOGS):c.851G>A (p.Trp284Ter)	Pathogenic
1903342	NM_006302.3(MOGS):c.353-1G>A	Likely pathogenic
217735	NM_006302.3(MOGS):c.329G>A (p.Arg110His)	Likely pathogenic
2194178	NM_006302.3(MOGS):c.1603C>T (p.Arg535Ter)	Likely pathogenic
2500770	NM_006302.3(MOGS):c.1225G>A (p.Gly409Arg)	Likely pathogenic
2506426	NM_006302.3(MOGS):c.2305T>C (p.Tyr769His)	Likely pathogenic
2582979	NM_006302.3(MOGS):c.1336C>T (p.Arg446Ter)	Likely pathogenic
2690644	NM_006302.3(MOGS):c.455dup (p.Asp152fs)	Likely pathogenic
3586938	NM_006302.3(MOGS):c.1049del (p.Pro350fs)	Likely pathogenic

SpliceAI

763 predictions. Top by Δscore:

Variant	Effect	Δscore
2:74463014:T:C	acceptor_gain	1.0000
2:74463014:T:TC	acceptor_gain	1.0000
2:74463342:A:C	acceptor_gain	1.0000
2:74463396:C:CT	acceptor_gain	1.0000
2:74463397:A:T	acceptor_gain	1.0000
2:74463399:C:CT	acceptor_gain	1.0000
2:74465204:C:CA	donor_gain	1.0000
2:74463013:C:CC	acceptor_gain	0.9900
2:74463192:G:A	donor_gain	0.9900
2:74463197:A:AC	donor_gain	0.9900
2:74463198:C:CC	donor_gain	0.9900
2:74463339:CACA:C	acceptor_gain	0.9900
2:74463385:TCCT:T	acceptor_loss	0.9900
2:74463387:CTG:C	acceptor_loss	0.9900
2:74463388:T:C	acceptor_loss	0.9900
2:74463400:G:T	acceptor_gain	0.9900
2:74462856:TGG:T	donor_gain	0.9800
2:74462876:T:TA	donor_gain	0.9800
2:74463008:TGTAG:T	acceptor_gain	0.9800
2:74463009:GTAG:G	acceptor_gain	0.9800
2:74463010:TAG:T	acceptor_gain	0.9800
2:74463185:GTTA:G	donor_loss	0.9800
2:74463186:TTA:T	donor_loss	0.9800
2:74463189:CC:C	donor_loss	0.9800
2:74463210:ATCC:A	donor_gain	0.9800
2:74463249:G:C	donor_gain	0.9800
2:74463360:C:CT	acceptor_gain	0.9800
2:74463385:TC:T	acceptor_gain	0.9800
2:74463386:CC:C	acceptor_gain	0.9800
2:74463387:C:T	acceptor_gain	0.9800

AlphaMissense

5315 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:74462445:G:C	F448L	0.997
2:74462445:G:T	F448L	0.997
2:74462447:A:G	F448L	0.997
2:74462105:A:G	W562R	0.994
2:74462105:A:T	W562R	0.994
2:74464714:A:G	W121R	0.994
2:74464714:A:T	W121R	0.994
2:74461316:A:G	W825R	0.993
2:74461316:A:T	W825R	0.993
2:74462103:C:A	W562C	0.993
2:74462103:C:G	W562C	0.993
2:74461323:G:C	F822L	0.992
2:74461323:G:T	F822L	0.992
2:74461325:A:G	F822L	0.992
2:74462283:G:C	F502L	0.992
2:74462283:G:T	F502L	0.992
2:74462285:A:G	F502L	0.992
2:74464525:A:G	W184R	0.992
2:74464525:A:T	W184R	0.992
2:74464712:C:A	W121C	0.992
2:74464712:C:G	W121C	0.992
2:74462437:T:A	D451V	0.991
2:74464949:C:G	R100P	0.991
2:74464962:A:G	W96R	0.991
2:74464962:A:T	W96R	0.991
2:74462038:T:A	D584V	0.990
2:74462256:G:C	N511K	0.990
2:74462256:G:T	N511K	0.990
2:74462342:A:G	W483R	0.990
2:74462342:A:T	W483R	0.990

dbSNP variants (sampled 300 via entrez): RS1000070078 (2:74466870 A>G), RS1000448439 (2:74461214 G>C), RS1000756229 (2:74467194 T>A), RS1001042666 (2:74466787 A>C), RS1001503575 (2:74462513 G>A,T), RS1002341452 (2:74461041 A>C,T), RS1002509685 (2:74464108 C>A), RS1002673936 (2:74467219 A>G), RS1003464122 (2:74466407 A>G,T), RS1003516469 (2:74465929 A>C), RS1005540912 (2:74465477 G>A), RS1005556804 (2:74464508 A>G), RS1005609009 (2:74464132 T>A,C), RS1005904334 (2:74465879 G>A,C), RS1005946014 (2:74465467 A>G,T)

Disease associations

OMIM: gene MIM:601336 | disease phenotypes: MIM:606056

GenCC curated gene-disease

Disease	Classification	Inheritance
MOGS-congenital disorder of glycosylation	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
MOGS-congenital disorder of glycosylation	Definitive	AR

Mondo (1): MOGS-congenital disorder of glycosylation (MONDO:0011629)

Orphanet (1): MOGS-CDG (Orphanet:79330)

HPO phenotypes

59 total (30 of 59 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000034	Hydrocele testis
HP:0000218	High palate
HP:0000269	Prominent occiput
HP:0000278	Retrognathia
HP:0000407	Sensorineural hearing impairment
HP:0000445	Wide nose
HP:0000527	Long eyelashes
HP:0000581	Blepharophimosis
HP:0000648	Optic atrophy
HP:0000649	Abnormality of visual evoked potentials
HP:0000821	Hypothyroidism
HP:0000969	Edema
HP:0001007	Hirsutism
HP:0001188	Hand clenching
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001290	Generalized hypotonia
HP:0001332	Dystonia
HP:0001433	Hepatosplenomegaly
HP:0001561	Polyhydramnios
HP:0001596	Alopecia
HP:0001631	Atrial septal defect
HP:0001640	Cardiomegaly
HP:0001712	Left ventricular hypertrophy
HP:0001873	Thrombocytopenia
HP:0001999	Abnormal facial shape
HP:0002059	Cerebral atrophy
HP:0002079	Hypoplasia of the corpus callosum

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C565264	Congenital Disorder Of Glycosylation, Type IIB (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4684 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	decreases expression, increases expression	3
sodium arsenite	decreases expression, increases abundance	2
bisphenol S	increases expression, affects cotreatment, decreases expression	2
Cadmium Chloride	decreases expression	2
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases expression, increases oxidation, increases abundance	1
bisphenol A	increases expression	1
methacrylaldehyde	affects cotreatment, increases expression, increases oxidation, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
bisphenol B	increases expression	1
LDN 193189	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Acrolein	increases abundance, affects cotreatment, increases expression, increases oxidation	1
Air Pollutants	affects cotreatment, increases abundance, increases expression, increases oxidation	1
Arsenic	decreases expression, increases abundance	1
Dexamethasone	decreases expression, affects cotreatment	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Isoniazid	increases expression	1
Ivermectin	decreases expression	1
Lead	decreases expression	1
Ozone	affects cotreatment, increases expression, increases oxidation, increases abundance	1
Ribonucleotides	affects binding	1
Smoke	decreases expression	1
Dronabinol	decreases expression	1
Thiram	decreases expression	1
Tunicamycin	increases 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
CHEMBL834904	Binding	Inhibition of Glucosidase 1(of Endoplasmic reticulum processing alpha-glucosidase) at 2 umol/mL	Aglycon specificity profiling of alpha-glucosidases using synthetic probes. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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