EDEM3

Chr 1AR

ER degradation enhancing alpha-mannosidase like protein 3

Also known as: C1orf22, CDG2V

NCBI Gene: 80267ENSG00000116406UniProt: Q9BZQ6OMIM: 610214

EDEM3 encodes a mannosidase that accelerates endoplasmic reticulum-associated degradation (ERAD) by trimming mannose residues from N-glycans on glycoproteins targeted for proteasomal degradation. No human diseases have been definitively associated with EDEM3 mutations in the current medical literature.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismARLOEUF 0.461 OMIM phenotype
Clinical Summary— EDEM3
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Gene-Disease Validity (ClinGen)
congenital disorder of glycosylation, type 2v · ARStrong

Strong evidence — appropriate for clinical testing

⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.
📋
ClinVar Variants
40 unique Pathogenic / Likely Pathogenic· 119 VUS of 183 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.46LOEUF
pLI 0.002
Z-score 4.48
OE 0.30 (0.20–0.46)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.22Z-score
OE missense 0.84 (0.78–0.92)
409 obs / 484.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.30 (0.20–0.46)
0≤0.351.4
Missense OE0.84 (0.78–0.92)
0≤0.61.4
Synonymous OE0.89
0≤1.21.6
LoF obs/exp: 14 / 47.2Missense obs/exp: 409 / 484.4Syn Z: 1.17
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongEDEM3-related congenital disorder of glycosylationLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6648th %ile
GOF
0.5856th %ile
LOF
0.2970th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

183 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic36
Likely Pathogenic4
VUS119
Likely Benign5
Benign2
36
Pathogenic
4
Likely Pathogenic
119
VUS
5
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
11
2
23
0
36
Likely Pathogenic
2
1
1
0
4
VUS
1
112
6
0
119
Likely Benign
0
1
1
3
5
Benign
0
2
0
0
2
Total14118313166

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

EDEM3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients