GeneBe

MOGS

protein-coding

mannosyl-oligosaccharide glucosidase, the group of Glycoside hydrolases

Gene summary

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. [provided by RefSeq, Mar 2009]

MANE transcript

NM_006302.3

Inheritance

AR

ClinVar variants

P:41U:336B:210

Top phenotype

Congenital disorder of glycosylation, type IIb

gnomAD constraint

pLI —, LoF o/e 0.66

Max pathogenic AF

—

Genomic locus

chr2:74,461,057-74,465,410

External References & Databases

Ensembl (ENSG00000115275)NCBI Gene (7841)OMIM (601336)HGNC:24862GenCCUniProt (Q13724)AlphaFoldClinVar (MOGS)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~4.4 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

MOGS-congenital disorder of glycosylationSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0011629

Submitter: PanelApp Australia

MOGS-congenital disorder of glycosylationMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0011629

Submitter: Ambry Genetics

MOGS-congenital disorder of glycosylationSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0011629

Submitter: Orphanet

MOGS-congenital disorder of glycosylationSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0011629

Submitter: Labcorp Genetics (formerly Invitae)

MOGS-congenital disorder of glycosylationSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0011629

Submitter: G2P

MOGS-congenital disorder of glycosylationDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0011629

Submitter: ClinGen

The mannosyl-oligosaccharide glucosidase (MOGS) gene was first reported in relation to an autosomal recessive condition known as congenital disorder of glycosylation type IIB (CDG2B) or MOGS-CDG in 2000 (De Praeter et al., PMID:10788335). This inherited disorder is caused by variants that decrease or abolish the expression or function of the MOGS enzyme, which normally functions in the endoplasmic reticulum (ER) to catalyze a cleavage step in the processing of oligosaccharides for N-linked attachment to nascent glycoproteins. MOGS loss-of-function results in the accumulation of abnormal N-linked glycoproteins and oligosaccharides, as well as ER stress. These molecular events trigger a variety of phenotypes in affected individuals that span a range of categories from morphological to neuromuscular and immunological ((PMID: 24716661). This curation includes fifteen variants (ten missense, four nonsense, and one single amino acid deletion) from nine probands reported in eight publications (PMID:32246563, PMID:10788335, PMID:24716661, PMID:29235540, PMID:30587846, PMID:31925597, PMID:33058492, and PMID:33261925). Two of the nonsense variants and the single amino acid deletion have been found to recur in multiple probands (PMID:32246563, PMID:33261925, PMID:29235540). The mechanism of pathogenicity appears to be biallelic loss of function. All genotyped patients were compound heterozygotes within the MOGS locus. This gene-disease association is supported by experimental evidence showing that the function of the MOGS enzyme is consistent with disease phenotypes (PMID:7635146) which is disrupted in patient cells (PMID:12145188) and non-patient cells (PMID: 15383536). Experimental evidence also includes C. elegans and S. pombe models that disrupt orthologs of MOGS and recapitulate some of the features of the affected patients (PMID:23836288, PMID:30389790). More evidence is available in the literature, but the maximum score for functional evidence (6 points) has been reached. In summary, MOGS is definitively associated with autosomal recessive MOGS-CDG. This has been repeatedly demonstrated in both research and diagnostic settings, and has been upheld over time without emergence of contradictory evidence.

Clinical Genomic Database (CGD)

Congenital disorder of glycosylation, type IIbAR

Manifestation: Biochemical; Craniofacial; Gastrointestinal; Genitourinary; Hematologic; Musculoskeletal; Neurologic

Intervention: Hematologic

Rationale: At least theoretically, awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery

Comments: Hepatic-metabolized agents should be avoided

Refs: 10788335; 20301507; 24716661Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MOGS variants in ClinVar

6 Conditions Cataloged
MOGS-congenital disorder of glycosylationTotal: 532
Inborn genetic diseasesTotal: 124
not providedTotal: 57
not specifiedTotal: 44
MOGS-related disorderTotal: 27
Fetal anomalies with a likely genetic causeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006302.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
189
clinvar
2
clinvar
 191
missense
2
clinvar
5
clinvar
320
clinvar
19
clinvar
 346
nonsense
8
clinvar
8
clinvar
8
clinvar
 24
start loss
0
frameshift
11
clinvar
6
clinvar
7
clinvar
 24
splice donor/acceptor (+/-2bp)
1
clinvar
1
clinvar
 2
Total21203362082587

Highest pathogenic variant AF is 0.000038412498

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 27 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_006302.3RefSeqNP_006293.24MANE Select
ENST00000448666.7EnsemblENSP00000410992.34MANE Select
NM_001146158.2RefSeqNP_001139630.14Standard
ENST00000409065.5EnsemblENSP00000386493.14Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Protein processing in endoplasmic reticulum - Homo sapiens (human)
  • N-Glycan biosynthesis - Homo sapiens (human)
  • er associated degradation (erad) pathway
  • Post-translational protein modification
  • Metabolism of proteins

Biological Process

  • protein folding
  • protein N-linked glycosylation
  • oligosaccharide metabolic process

Molecular Function

  • mannosyl-oligosaccharide glucosidase activity
  • glucosidase activity

Cellular Component

  • endoplasmic reticulum
  • endoplasmic reticulum membrane
  • membrane
  • integral component of membrane
  • extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000233616
Coding exons
4
Length
4354
Individuals with no LoFs
124707
Homozygous LoFs
0
Heterozygous LoFs
111
Defined
124818
p
0.000445
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.6624344750.9140.00002835267
Missense (PolyPhen)149177.320.840292040
Synonymous-0.5122092001.050.00001051907
Loss of Function1.752131.60.6640.00000202289

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000710.00065rare
Latino/Admixed American0.000380.00038rare
Ashkenazi Jewish00.0absent
East Asian0.000500.00050rare
Finnish0.000280.00028rare
European (Non-Finnish)0.000430.00043rare
South Asian0.000590.00059rare
Other0.000990.00099rare

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Cleaves the distal alpha 1,2-linked glucose residue from the Glc(3)Man(9)GlcNAc(2) oligosaccharide precursor in a highly specific manner.;
Disease
DISEASE: 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. {ECO:0000269|PubMed:10788335}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Intolerance Scores

LoFtool
0.891
RVIS EVS
1.13
RVIS percentile EVS
92.29

Essentials

Essential (CRISPR)
E
Essential (CRISPR2)
S
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.652

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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