ALG8

ALG8 alpha-1,3-glucosyltransferase, the group of Alpha-1,3-glucosyltransferases

Basic information

Region (hg38): 11:78095244-78139660

Links

ENSG00000159063 ∙ NCBI:79053 ∙ OMIM:608103 ∙ HGNC:23161 ∙ Uniprot:Q9BVK2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• polycystic liver disease 3 with or without kidney cysts (Strong), mode of inheritance: AD
• ALG8-congenital disorder of glycosylation (Strong), mode of inheritance: AR
• ALG8-congenital disorder of glycosylation (Moderate), mode of inheritance: AR
• polycystic liver disease 3 with or without kidney cysts (Limited), mode of inheritance: AD
• ALG8-congenital disorder of glycosylation (Definitive), mode of inheritance: AR
• ALG8-congenital disorder of glycosylation (Supportive), mode of inheritance: AR
• ALG8-congenital disorder of glycosylation (Strong), mode of inheritance: AR
• polycystic liver disease 3 with or without kidney cysts (Strong), mode of inheritance: AD
• polycystic liver disease 3 with or without kidney cysts (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Congenital disorder of glycosylation, type Ih	AR	Hematologic	Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	Biochemical; Gastrointestinal; Hematologic; Neurologic; Renal	12480927; 15235028; 19648040; 19688606; 22306853; 28375157
Hepatic-metabolized agents should be avoided

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ALG8 gene.

• ALG8_congenital_disorder_of_glycosylation (266 variants)
• Polycystic_liver_disease_3_with_or_without_kidney_cysts (119 variants)
• not_provided (91 variants)
• Inborn_genetic_diseases (57 variants)
• ALG8-related_disorder (39 variants)
• Autosomal_dominant_polycystic_liver_disease (9 variants)
• Familial_cystic_renal_disease (8 variants)
• not_specified (8 variants)
• Congenital_disorder_of_glycosylation (2 variants)
• See_cases (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ALG8 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000024079.5. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			7	42	2	51
missense	4	6	161	11		182
nonsense	4	13	2			19
start loss						0
frameshift	8	17	3			28
splice donor/acceptor (+/-2bp)	1	14				15
Total	17	50	173	53	2

Highest pathogenic variant AF is 0.000206002

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ALG8	protein_coding	protein_coding	ENST00000299626	13	38725

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.18e-8	0.986	125547	0	200	125747	0.000796

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.604	240	268	0.896	0.0000129	3381
Missense in Polyphen		88	91.844	0.95814		1180
Synonymous	-0.968	114	102	1.12	0.00000489	1039
Loss of Function	2.31	18	32.1	0.560	0.00000197	348

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00179	0.00179
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.00291	0.00291
European (Non-Finnish)	0.000784	0.000774
Middle Eastern	0.000163	0.000163
South Asian	0.000230	0.000229
Other	0.000337	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Adds the second 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 Glc(1)Man(9)GlcNAc(2)-PP-Dol before it is transferred to the nascent peptide (By similarity). Required for PKD1/Polycystin-1 maturation and localization to the plasma membrane of the primary cilia (By similarity). {ECO:0000250|UniProtKB:P40351, ECO:0000250|UniProtKB:Q6P8H8}.
• Disease: DISEASE: Congenital disorder of glycosylation 1H (CDG1H) [MIM:608104]: 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:15235028}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Polycystic liver disease 3 with or without kidney cysts (PCLD3) [MIM:617874]: A form of polycystic liver disease, an autosomal dominant hepatobiliary disease characterized by overgrowth of biliary epithelium and supportive connective tissue, resulting in multiple liver cysts. PCLD3 patients may also develop kidney cysts that usually do not result in clinically significant renal disease. {ECO:0000269|PubMed:28375157}. 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;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: 0.173

Intolerance Scores

• loftool: 0.159
• rvis_EVS: 0.49
• rvis_percentile_EVS: 79.46

Haploinsufficiency Scores

• pHI: 0.440
• hipred: N
• hipred_score: 0.429
• ghis: 0.502

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.720

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Alg8

Gene ontology

• Biological process: protein N-linked glycosylation;dolichol-linked oligosaccharide biosynthetic process;oligosaccharide-lipid intermediate biosynthetic process;mannosylation
• Cellular component: endoplasmic reticulum membrane;integral component of membrane
• Molecular function: alpha-1,3-mannosyltransferase activity;dolichyl-phosphate-glucose-glycolipid alpha-glucosyltransferase activity;protein binding;dolichyl pyrophosphate Man9GlcNAc2 alpha-1,3-glucosyltransferase activity;dolichyl pyrophosphate Glc1Man9GlcNAc2 alpha-1,3-glucosyltransferase activity