ALG6

ALG6 alpha-1,3-glucosyltransferase, the group of Alpha-1,3-glucosyltransferases

Basic information

Region (hg38): 1:63367574-63438553

Links

ENSG00000088035 ∙ NCBI:29929 ∙ OMIM:604566 ∙ HGNC:23157 ∙ Uniprot:Q9Y672 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• ALG6-congenital disorder of glycosylation 1C (Definitive), mode of inheritance: AR
• ALG6-congenital disorder of glycosylation 1C (Strong), mode of inheritance: AR
• ALG6-congenital disorder of glycosylation 1C (Strong), mode of inheritance: AR
• ALG6-congenital disorder of glycosylation 1C (Definitive), mode of inheritance: AR
• ALG6-congenital disorder of glycosylation 1C (Supportive), mode of inheritance: AR
• ALG6-congenital disorder of glycosylation 1C (Definitive), mode of inheritance: AR
• cystic kidney disease (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Congenital disorder of glycosylation, type Ic	AR	Hematologic	Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	Biochemical; Endocrine; Gastrointestinal; Hematologic; Neurologic; Ophthalmologic	10359825; 10914684; 10924277; 16007612; 21334936
Hepatic-metabolized agents should be avoided

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ALG6 gene.

• ALG6-congenital disorder of glycosylation 1C (618 variants)
• not provided (68 variants)
• not specified (39 variants)
• Inborn genetic diseases (10 variants)
• Congenital disorder of glycosylation (5 variants)
• ALG6-related condition (2 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ALG6 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			2	152	2	156
missense	1	4	158	7	1	171
nonsense	11	16				27
start loss		1				1
frameshift	24	24	2			50
inframe indel		1	10			11
splice donor/acceptor (+/-2bp)	1	24				25
splice region		3	16	37	3	59
non coding			25	95	31	151
Total	37	70	197	254	34

Highest pathogenic variant AF is 0.0000329

Variants in ALG6

This is a list of pathogenic ClinVar variants found in the ALG6 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-63367655-A-AGGCGCGAATCCCAGCGGCC			Likely benign (Mar 16, 2018)
1-63367674-C-G		ALG6-congenital disorder of glycosylation 1C • not specified	Conflicting classifications of pathogenicity (Jan 12, 2018)
1-63367697-T-C		ALG6-congenital disorder of glycosylation 1C	Uncertain significance (Jan 13, 2018)
1-63367765-C-G			Benign (Jul 12, 2019)
1-63367779-G-T			Benign (Jul 12, 2019)
1-63367802-C-G			Likely benign (May 20, 2021)
1-63367903-G-T			Benign (May 23, 2021)
1-63370674-T-C			Likely benign (May 11, 2021)
1-63370753-C-CT		not specified	Likely benign (Apr 28, 2017)
1-63370759-T-C		ALG6-congenital disorder of glycosylation 1C • not specified • ALG6-related disorder	Conflicting classifications of pathogenicity (Oct 18, 2021)
1-63370782-A-G		not specified	Likely benign (Jul 18, 2017)
1-63370837-A-G		ALG6-congenital disorder of glycosylation 1C	Uncertain significance (Jan 13, 2018)
1-63370842-C-G		ALG6-congenital disorder of glycosylation 1C	Benign (Jun 23, 2018)
1-63370850-C-T		ALG6-congenital disorder of glycosylation 1C	Uncertain significance (Jan 13, 2018)
1-63370857-T-G		ALG6-congenital disorder of glycosylation 1C	Likely benign (May 24, 2021)
1-63370858-C-T		ALG6-congenital disorder of glycosylation 1C	Uncertain significance (Jan 13, 2018)
1-63370978-A-G		ALG6-congenital disorder of glycosylation 1C	Conflicting classifications of pathogenicity (Feb 04, 2022)
1-63370979-T-C		ALG6-congenital disorder of glycosylation 1C	Likely pathogenic (Apr 25, 2018)
1-63370981-G-A		ALG6-congenital disorder of glycosylation 1C	Uncertain significance (Apr 11, 2022)
1-63370983-G-T		ALG6-congenital disorder of glycosylation 1C	Uncertain significance (Mar 09, 2022)
1-63370986-A-G		ALG6-congenital disorder of glycosylation 1C	Likely benign (Feb 06, 2022)
1-63370989-G-A		ALG6-congenital disorder of glycosylation 1C	Pathogenic (May 01, 2023)
1-63370992-C-T		ALG6-congenital disorder of glycosylation 1C	Likely benign (Jun 09, 2022)
1-63370993-T-C		ALG6-congenital disorder of glycosylation 1C	Likely benign (Dec 06, 2022)
1-63370996-A-G		ALG6-congenital disorder of glycosylation 1C	Uncertain significance (Jun 13, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ALG6	protein_coding	protein_coding	ENST00000371108	14	70973

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000305	0.999	125708	0	38	125746	0.000151

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.53	191	260	0.734	0.0000128	3310
Missense in Polyphen		65	95.091	0.68355		1161
Synonymous	0.604	86	93.4	0.920	0.00000487	948
Loss of Function	3.03	11	28.4	0.387	0.00000129	364

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000417	0.000417
Ashkenazi Jewish	0.0000997	0.0000992
East Asian	0.000109	0.000109
Finnish	0.0000464	0.0000462
European (Non-Finnish)	0.000106	0.000105
Middle Eastern	0.000109	0.000109
South Asian	0.000327	0.000327
Other	0.000165	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Adds the first glucose residue to the lipid-linked oligosaccharide precursor for N-linked glycosylation. Transfers glucose from dolichyl phosphate glucose (Dol-P-Glc) onto the lipid-linked oligosaccharide Man(9)GlcNAc(2)-PP-Dol.
• Disease: DISEASE: Congenital disorder of glycosylation 1C (CDG1C) [MIM:603147]: 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:10359825, ECO:0000269|PubMed:10914684, ECO:0000269|PubMed:10924277, ECO:0000269|PubMed:11106564, ECO:0000269|PubMed:11134235, ECO:0000269|PubMed:12357336, ECO:0000269|PubMed:14517965}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: N-Glycan biosynthesis - Homo sapiens (human);GPCRs, Other;Post-translational protein modification;Metabolism of proteins;dolichyl-diphosphooligosaccharide biosynthesis;Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein;Asparagine N-linked glycosylation (Consensus)

Recessive Scores

• pRec: 0.176

Intolerance Scores

• loftool: 0.291
• rvis_EVS: 0.29
• rvis_percentile_EVS: 71.5

Haploinsufficiency Scores

• pHI: 0.303
• hipred: N
• hipred_score: 0.448
• ghis: 0.486

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.272

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Alg6

Gene ontology

• Biological process: protein N-linked glycosylation;dolichol-linked oligosaccharide biosynthetic process;oligosaccharide-lipid intermediate biosynthetic process
• Cellular component: endoplasmic reticulum membrane;membrane;integral component of membrane
• Molecular function: dolichyl-phosphate-glucose-glycolipid alpha-glucosyltransferase activity;dolichyl pyrophosphate Man9GlcNAc2 alpha-1,3-glucosyltransferase activity;glucosyltransferase activity