EDEM1
protein-codingER degradation enhancing alpha-mannosidase like protein 1, the group of Mannosidases alpha class 1
Gene summary
Enables mannosyl-oligosaccharide 1,2-alpha-mannosidase activity and misfolded protein binding activity. Involved in several processes, including endoplasmic reticulum mannose trimming; positive regulation of retrograde protein transport, ER to cytosol; and protein catabolic process. Located in endoplasmic reticulum quality control compartment. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~32.3 kbGenCC 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 EDEM1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_014674.3. 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 | 4 | 4 | ||||
| missense | 93 | 3 | 96 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 100 | 3 | 0 | 103 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_055489.1 | 12 | MANE Select | |
| Ensembl | ENSP00000256497.4 | 12 | MANE Select | |
| Ensembl | ENSP00000393659.1 | 3 | Standard | |
| Ensembl | ENSP00000394615.1 | 1 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Protein processing in endoplasmic reticulum - Homo sapiens (human)
- XBP1(S) activates chaperone genes
- Photodynamic therapy-induced unfolded protein response
- er associated degradation (erad) pathway
Biological Process
- ubiquitin-dependent ERAD pathway
- IRE1-mediated unfolded protein response
- trimming of terminal mannose on C branch
- ubiquitin-dependent glycoprotein ERAD pathway
- positive regulation of retrograde protein transport, ER to cytosol
Molecular Function
- mannosyl-oligosaccharide 1,2-alpha-mannosidase activity
- calcium ion binding
- protein binding
- misfolded protein binding
Cellular Component
- endoplasmic reticulum
- aggresome
- integral component of endoplasmic reticulum membrane
- endoplasmic reticulum quality control compartment
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000256497
- Coding exons
- 12
- Length
- 32312
- Individuals with no LoFs
- 125675
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 73
- Defined
- 125748
- p
- 0.000290
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.370 | 327 | 346 | 0.944 | 0.0000179 | 4218 |
| Missense (PolyPhen) | 115 | 153.85 | 0.74747 | 1790 | ||
| Synonymous | -1.70 | 165 | 139 | 1.18 | 0.00000726 | 1300 |
| Loss of Function | 1.17 | 24 | 31.0 | 0.774 | 0.00000164 | 358 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00037 | 0.00037 | rare |
| Latino/Admixed American | 0.00043 | 0.00043 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00065 | 0.00065 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00027 | 0.00025 | rare |
| South Asian | 0.00030 | 0.00029 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Extracts misfolded glycoproteins, but not glycoproteins undergoing productive folding, from the calnexin cycle. It is directly involved in endoplasmic reticulum-associated degradation (ERAD) and targets misfolded glycoproteins for degradation in an N-glycan-independent manner, probably by forming a complex with SEL1L. It has low mannosidase activity, catalyzing mannose trimming from Man8GlcNAc2 to Man7GlcNAc2. {ECO:0000269|PubMed:12610306, ECO:0000269|PubMed:19524542, ECO:0000269|PubMed:19934218, ECO:0000269|PubMed:25092655}.;
Recessive Scores
- pRec
- 0.148
Intolerance Scores
- LoFtool
- 0.389
- RVIS EVS
- -0.96
- RVIS percentile EVS
- 9.17
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.852
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |