EDEM3

Chr 1AR

ER degradation enhancing alpha-mannosidase like protein 3

Also known as: C1orf22, CDG2V

NCBI Gene: 80267 ENSG00000116406 UniProt: Q9BZQ6 OMIM: 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.

OMIM ResearchSummary from RefSeq, UniProt

Quality control in the endoplasmic reticulum (ER) ensures that only properly folded proteins are retained in the cell through recognition and degradation of misfolded or unassembled proteins. EDEM3 belongs to a group of proteins that accelerate degradation of misfolded glycoproteins in the ER (Hirao et al., 2006 [PubMed 16431915]).[supplied by OMIM, Mar 2008]

OMIM ResearchGenerating clinical summary…

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

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.

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ClinVar Variants

16 unique Pathogenic / Likely Pathogenic· 115 VUS of 155 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 OE?0.30 (0.20–0.46)

0≤0.351.4

Missense OE?0.84 (0.78–0.92)

0≤0.61.4

Synonymous OE?0.89

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

This gene — mechanism propensity

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

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

155 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic13

Likely Pathogenic3

VUS115

Likely Benign5

Benign2

Pathogenic

Likely Pathogenic

115

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	11	2	0	0	13
Likely Pathogenic	2	1	0	0	3
VUS	1	112	2	0	115
Likely Benign	0	1	1	3	5
Benign	0	2	0	0	2
Total	14	118	3	3	138

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

View in ClinVar →

25 pathogenic / likely-pathogenic (of 30) ClinVar copy-number / structural variants overlap EDEM3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →