EDEM3

ER degradation enhancing alpha-mannosidase like protein 3, the group of Mannosidases alpha class 1

Basic information

Region (hg38): 1:184690237-184754907

Previous symbols: [ "C1orf22" ]

Links

ENSG00000116406 ∙ NCBI:80267 ∙ OMIM:610214 ∙ HGNC:16787 ∙ Uniprot:Q9BZQ6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital disorder of glycosylation, type 2v (Strong), mode of inheritance: AR
• congenital disorder of glycosylation, type 2v (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Congenital disorder of glycosylation, type 2V	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Craniofacial; Neurologic	34143952

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EDEM3 gene.

• not provided (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EDEM3 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				3		3
missense			42		2	44
nonsense	1					1
start loss						0
frameshift		1				1
inframe indel						0
splice donor/acceptor (+/-2bp)	1		1			2
splice region						0
non coding			1			1
Total	2	1	44	3	2

Variants in EDEM3

This is a list of pathogenic ClinVar variants found in the EDEM3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-184694286-G-T		Inborn genetic diseases	Uncertain significance (Aug 28, 2023)
1-184694431-C-A		Short stature • Inborn genetic diseases	Uncertain significance (Jan 22, 2024)
1-184702861-C-T		Inborn genetic diseases	Uncertain significance (May 14, 2024)
1-184702862-G-A		Inborn genetic diseases	Uncertain significance (Jan 30, 2024)
1-184702942-T-C		Inborn genetic diseases	Uncertain significance (Feb 06, 2024)
1-184702964-G-A		Congenital disorder of glycosylation, type 2v	Benign (May 04, 2023)
1-184702981-C-T		Inborn genetic diseases	Uncertain significance (Apr 09, 2024)
1-184706679-T-G		EDEM3-related disorder	Uncertain significance (May 16, 2024)
1-184706727-C-T		Inborn genetic diseases	Uncertain significance (Feb 12, 2024)
1-184706774-T-C		Inborn genetic diseases	Uncertain significance (Jun 01, 2024)
1-184706793-C-T		Inborn genetic diseases	Uncertain significance (Jul 26, 2022)
1-184708188-C-CT		Congenital disorder of glycosylation, type 2v	Pathogenic (Sep 11, 2021)
1-184708209-C-T		Inborn genetic diseases	Uncertain significance (May 28, 2024)
1-184708248-G-A			Pathogenic (Oct 01, 2023)
1-184708292-A-G		Inborn genetic diseases	Uncertain significance (May 26, 2024)
1-184708330-GA-G		Congenital disorder of glycosylation, type 2v	Pathogenic (Sep 11, 2021)
1-184708332-T-C		Inborn genetic diseases	Uncertain significance (Jan 03, 2022)
1-184708337-C-A		Inborn genetic diseases	Uncertain significance (Dec 17, 2023)
1-184710503-C-T			Uncertain significance (Feb 01, 2023)
1-184710519-G-A			Uncertain significance (Feb 01, 2023)
1-184710520-T-G		Inborn genetic diseases	Uncertain significance (Jul 12, 2022)
1-184710575-T-A		Congenital disorder of glycosylation, type 2v	Uncertain significance (Mar 22, 2023)
1-184711735-C-T		Inborn genetic diseases	Uncertain significance (May 09, 2023)
1-184711807-G-C		Inborn genetic diseases	Uncertain significance (May 08, 2023)
1-184711872-C-T		EDEM3-related disorder	Likely benign (Nov 20, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EDEM3	protein_coding	protein_coding	ENST00000318130	20	64683

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00247	0.998	125715	0	33	125748	0.000131

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.22	409	484	0.844	0.0000232	6169
Missense in Polyphen		108	175.55	0.6152		2150
Synonymous	1.17	150	169	0.886	0.00000833	1702
Loss of Function	4.48	14	47.2	0.296	0.00000233	601

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000228	0.000210
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000564	0.0000544
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000163	0.000158
Middle Eastern	0.0000564	0.0000544
South Asian	0.000135	0.000131
Other	0.000340	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in endoplasmic reticulum-associated degradation (ERAD). Accelerates the glycoprotein ERAD by proteasomes, by catalyzing mannose trimming from Man8GlcNAc2 to Man7GlcNAc2 in the N-glycans. Seems to have alpha 1,2-mannosidase activity (By similarity). {ECO:0000250, ECO:0000269|PubMed:25092655}.
• Pathway: Protein processing in endoplasmic reticulum - Homo sapiens (human) (Consensus)

Recessive Scores

• pRec: 0.120

Intolerance Scores

• loftool: 0.803
• rvis_EVS: -0.66
• rvis_percentile_EVS: 15.95

Haploinsufficiency Scores

• pHI: 0.864
• hipred: Y
• hipred_score: 0.544
• ghis: 0.577

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.319

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Edem3

Gene ontology

• Biological process: protein glycosylation;response to unfolded protein;mannose trimming involved in glycoprotein ERAD pathway
• Cellular component: endoplasmic reticulum lumen;membrane;endoplasmic reticulum quality control compartment
• Molecular function: mannosyl-oligosaccharide 1,2-alpha-mannosidase activity;calcium ion binding