ALG3

ALG3 alpha-1,3- mannosyltransferase, the group of Dolichyl D-mannosyl phosphate dependent mannosyltransferases

Basic information

Region (hg38): 3:184242300-184249548

Links

ENSG00000214160 ∙ NCBI:10195 ∙ OMIM:608750 ∙ HGNC:23056 ∙ Uniprot:Q92685 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• ALG3-congenital disorder of glycosylation (Strong), mode of inheritance: AR
• ALG3-congenital disorder of glycosylation (Moderate), mode of inheritance: AR
• ALG3-congenital disorder of glycosylation (Strong), mode of inheritance: AR
• ALG3-congenital disorder of glycosylation (Definitive), mode of inheritance: AR
• ALG3-congenital disorder of glycosylation (Supportive), mode of inheritance: AR
• ALG3-congenital disorder of glycosylation (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Congenital disorder of glycosylation, type Id	AR	Hematologic	Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	Biochemical; Hematologic; Neurologic	8552211; 10581255; 15108280; 15840742; 17551933; 18679822
Hepatic-metabolized agents should be avoided

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ALG3 gene.

• ALG3-congenital disorder of glycosylation (138 variants)
• not provided (47 variants)
• not specified (17 variants)
• Inborn genetic diseases (17 variants)
• Intellectual disability (1 variants)
• Congenital disorder of glycosylation (1 variants)
• Seizure;Microcephaly;Intellectual disability (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ALG3 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		1	6	30	2	39
missense	4	8	69	2		83
nonsense	2					2
start loss	1					1
frameshift	1	2	1			4
inframe indel						0
splice donor/acceptor (+/-2bp)		2				2
splice region		1	3	2		6
non coding			5	18	4	27
Total	8	13	81	50	6

Highest pathogenic variant AF is 0.0000132

Variants in ALG3

This is a list of pathogenic ClinVar variants found in the ALG3 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-184242362-G-A		ALG3-congenital disorder of glycosylation	Uncertain significance (Jan 13, 2018)
3-184242406-A-G		ALG3-congenital disorder of glycosylation	Uncertain significance (Jan 13, 2018)
3-184242449-G-A		ALG3-congenital disorder of glycosylation	Uncertain significance (Jan 13, 2018)
3-184242464-A-C		not specified • ALG3-congenital disorder of glycosylation	Benign (Jun 29, 2018)
3-184242509-G-A		ALG3-related disorder	Likely benign (Feb 04, 2020)
3-184242551-A-T		ALG3-congenital disorder of glycosylation	Uncertain significance (May 16, 2022)
3-184242559-C-T		not specified • ALG3-congenital disorder of glycosylation	Benign/Likely benign (Oct 30, 2022)
3-184242560-G-A		not specified • ALG3-congenital disorder of glycosylation	Benign/Likely benign (Aug 06, 2023)
3-184242568-C-T		ALG3-congenital disorder of glycosylation	Pathogenic (-)
3-184242577-C-T		ALG3-congenital disorder of glycosylation	Likely benign (Mar 29, 2022)
3-184242588-C-T		ALG3-congenital disorder of glycosylation	Uncertain significance (Jul 11, 2022)
3-184242589-G-A		ALG3-congenital disorder of glycosylation • ALG3-related disorder	Likely benign (Jul 12, 2023)
3-184242616-G-A		ALG3-congenital disorder of glycosylation	Likely benign (Aug 21, 2020)
3-184242619-G-C		Inborn genetic diseases • ALG3-congenital disorder of glycosylation	Uncertain significance (Jul 24, 2022)
3-184242638-G-A			Uncertain significance (Dec 28, 2016)
3-184242642-T-TC		ALG3-congenital disorder of glycosylation	Uncertain significance (Jul 20, 2022)
3-184242643-C-T		ALG3-congenital disorder of glycosylation	Uncertain significance (Apr 03, 2023)
3-184242655-G-A		not specified • ALG3-congenital disorder of glycosylation	Likely benign (Nov 20, 2022)
3-184242661-C-A		ALG3-congenital disorder of glycosylation	Likely benign (May 11, 2023)
3-184242675-A-G		ALG3-congenital disorder of glycosylation	Uncertain significance (Jan 13, 2018)
3-184242808-G-A		ALG3-related disorder	Likely benign (Sep 25, 2020)
3-184242813-C-G		ALG3-congenital disorder of glycosylation	Pathogenic (-)
3-184242821-G-A		ALG3-congenital disorder of glycosylation	Uncertain significance (Jan 12, 2018)
3-184242835-G-A		ALG3-congenital disorder of glycosylation • Inborn genetic diseases	Uncertain significance (May 09, 2023)
3-184242839-A-G			Likely benign (Dec 12, 2017)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ALG3	protein_coding	protein_coding	ENST00000397676	9	7248

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.68e-10	0.322	124625	0	51	124676	0.000205

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.317	264	250	1.06	0.0000137	2794
Missense in Polyphen		99	106.67	0.92809		1242
Synonymous	-0.793	121	110	1.10	0.00000599	930
Loss of Function	0.891	17	21.5	0.792	0.00000107	213

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000465	0.000463
Ashkenazi Jewish	0.000299	0.000298
East Asian	0.000288	0.000278
Finnish	0.0000466	0.0000464
European (Non-Finnish)	0.000199	0.000186
Middle Eastern	0.000288	0.000278
South Asian	0.000296	0.000294
Other	0.000165	0.000165

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Adds the first Dol-P-Man derived mannose in an alpha-1,3 linkage to Man5GlcNAc2-PP-Dol. {ECO:0000269|PubMed:10581255}.
• Disease: DISEASE: Congenital disorder of glycosylation 1D (CDG1D) [MIM:601110]: A form of congenital disorder of glycosylation, a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. {ECO:0000269|PubMed:10581255, ECO:0000269|PubMed:15840742}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: N-Glycan biosynthesis - Homo sapiens (human);Post-translational protein modification;Metabolism of proteins;dolichyl-diphosphooligosaccharide biosynthesis;Phosphatidylinositol phosphate metabolism;Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein;Asparagine N-linked glycosylation;N-Glycan biosynthesis (Consensus)

Intolerance Scores

• loftool: 0.178
• rvis_EVS: -0.6
• rvis_percentile_EVS: 17.91

Haploinsufficiency Scores

• pHI: 0.221
• hipred: N
• hipred_score: 0.204
• ghis: 0.574

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.814

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Alg3

Gene ontology

• Biological process: protein glycosylation;dolichol-linked oligosaccharide biosynthetic process;mannosylation
• Cellular component: endoplasmic reticulum membrane;integral component of endoplasmic reticulum membrane
• Molecular function: alpha-1,3-mannosyltransferase activity;protein binding;dol-P-Man:Man(5)GlcNAc(2)-PP-Dol alpha-1,3-mannosyltransferase activity