EDEM2

protein-coding

ER degradation enhancing alpha-mannosidase like protein 2, the group of Mannosidases alpha class 1

Gene summary

In the endoplasmic reticulum (ER), misfolded proteins are retrotranslocated to the cytosol and degraded by the proteasome in a process known as ER-associated degradation (ERAD). EDEM2 belongs to a family of proteins involved in ERAD of glycoproteins (Mast et al., 2005 [PubMed 15537790]).[supplied by OMIM, Mar 2008]

Previous symbols:

C20orf49
C20orf31

MANE transcript

NM_018217.3

Inheritance

—

ClinVar variants

U:89B:3

Top phenotype

Maturity-onset diabetes of the young

gnomAD constraint

pLI —, LoF o/e 0.5

Max pathogenic AF

—

Genomic locus

chr20:35,115,364-35,147,336

External References & Databases

Ensembl (ENSG00000088298)

Transcript & Mutation Effects

hg38 • Region Span ~32.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to EDEM2 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 80

not providedTotal: 1

Maturity-onset diabetes of the youngTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018217.3. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar		1 clinvar	3
missense			81 clinvar	2 clinvar		83
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	89	2	1	92

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 83 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_018217.3	RefSeq	NP_060687.2	11	MANE Select
ENST00000374492.8	Ensembl	ENSP00000363616.3	11	MANE Select
NM_001145025.2	RefSeq	NP_001138497.1	10	Standard
ENST00000374491.3	Ensembl	ENSP00000363615.2	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Protein processing in endoplasmic reticulum - Homo sapiens (human)
ER Quality Control Compartment (ERQC)
Calnexin/calreticulin cycle
Post-translational protein modification
Metabolism of proteins

Biological Process

response to unfolded protein
trimming of terminal mannose on B branch
trimming of terminal mannose on C branch
trimming of first mannose on A branch
trimming of second mannose on A branch

Molecular Function

mannosyl-oligosaccharide 1,2-alpha-mannosidase activity
calcium ion binding

Cellular Component

endoplasmic reticulum
endoplasmic reticulum lumen
membrane
endoplasmic reticulum quality control compartment

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000374492
Coding exons: 11
Length: 162762
Individuals with no LoFs: 125663
Homozygous LoFs: 0
Heterozygous LoFs: 85
Defined: 125748
p: 0.000338

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.54	254	333	0.763	0.0000181	3770
Missense (PolyPhen)		91	144.02	0.63185		1585
Synonymous	0.456	132	139	0.951	0.00000829	1155
Loss of Function	2.51	15	29.7	0.504	0.00000159	313

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00018	0.00018	rare
Latino/Admixed American	0.00043	0.00043	rare
Ashkenazi Jewish	0.00060	0.00060	rare
East Asian	0.00022	0.00022	rare
Finnish	0.00032	0.00032	rare
European (Non-Finnish)	0.00034	0.00034	rare
South Asian	0.00020	0.00020	rare
Other	0.00081	0.00081	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in the endoplasmic reticulum-associated degradation (ERAD) pathway that targets misfolded glycoproteins for degradation in an N-glycan-dependent manner (PubMed:15537790, PubMed:25092655). May initiate ERAD by promoting the first mannose trimming step of ERAD substrates, from Man9GlcNAc2 to Man8GlcNAc2 (PubMed:25092655). Seems to recognize and bind to exposed hydrophobic regions in target proteins (By similarity). {ECO:0000250|UniProtKB:Q8BJT9, ECO:0000269|PubMed:15537790, ECO:0000269|PubMed:25092655}.;

Recessive Scores

pRec: 0.119

Intolerance Scores

LoFtool: 0.888
RVIS EVS: -0.09
RVIS percentile EVS: 46.99

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.956

Gene Damage Prediction

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