EDEM1

Chr 3

ER degradation enhancing alpha-mannosidase like protein 1

Also known as: EDEM

EDEM1 encodes an ER-associated degradation (ERAD) protein that extracts misfolded glycoproteins from the calnexin cycle and targets them for degradation, while also having mannosidase activity that trims mannose residues from N-glycans. Mutations cause autosomal recessive developmental and epileptic encephalopathy with microcephaly, featuring early-onset seizures and severe intellectual disability. The gene shows very low constraint to loss-of-function variants, consistent with recessive inheritance where heterozygous carriers are unaffected.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
9
Pubs (1 yr)
75
P/LP submissions
0%
P/LP missense
1.09
LOEUF
Mechanism
Clinical SummaryEDEM1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
75 unique Pathogenic / Likely Pathogenic· 104 VUS of 198 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.09LOEUF
pLI 0.000
Z-score 1.17
OE 0.77 (0.561.09)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.37Z-score
OE missense 0.94 (0.861.03)
327 obs / 346.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.77 (0.561.09)
00.351.4
Missense OE0.94 (0.861.03)
00.61.4
Synonymous OE1.18
01.21.6
LoF obs/exp: 24 / 31.0Missense obs/exp: 327 / 346.4Syn Z: -1.70

ClinVar Variant Classifications

198 submitted variants in ClinVar

Classification Summary

Pathogenic70
Likely Pathogenic5
VUS104
Likely Benign4
70
Pathogenic
5
Likely Pathogenic
104
VUS
4
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
70
0
70
Likely Pathogenic
0
0
5
0
5
VUS
0
91
13
0
104
Likely Benign
0
3
1
0
4
Benign
0
0
0
0
0
Total094890183

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

View in ClinVar →

Protein Context — Lollipop Plot

EDEM1 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →