ALG8 (ALG8 alpha-1,3-glucosyltransferase)

Gene

• Entrez ID: 79053
• Gene name: ALG8 alpha-1,3-glucosyltransferase
• Gene symbol: ALG8
• Synonyms (NCBI Gene): CDG1H, PCLD3
• Chromosome: 11
• Chromosome location: 11q14.1
• Summary: This gene encodes a member of the ALG6/ALG8 glucosyltransferase family. The encoded protein catalyzes the addition of the second glucose residue to the lipid-linked oligosaccharide precursor for N-linked glycosylation of proteins. Mutations in this gene h

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs121908293	T>A,C,G	Pathogenic	Coding sequence variant, non coding transcript variant, 5 prime UTR variant, missense variant
rs121908294	C>A,T	Pathogenic	Coding sequence variant, non coding transcript variant, missense variant
rs139832787	C>T	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Splice donor variant
rs146603801	G>A	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Coding sequence variant, non coding transcript variant, missense variant
rs200888240	G>A,C	Pathogenic	5 prime UTR variant, non coding transcript variant, missense variant, stop gained, coding sequence variant
rs202112771	C>A	Pathogenic	Splice donor variant
rs376161880	G>A	Pathogenic	Stop gained, coding sequence variant, intron variant, non coding transcript variant
rs387906277	G>-	Pathogenic	Coding sequence variant, frameshift variant, non coding transcript variant
rs753631154	->T	Pathogenic	Frameshift variant, coding sequence variant, non coding transcript variant
rs762811727	G>A	Pathogenic	Coding sequence variant, stop gained, non coding transcript variant
rs794727931	A>C	Pathogenic, uncertain-significance	Missense variant, non coding transcript variant, coding sequence variant
rs867450807	C>A,T	Conflicting-interpretations-of-pathogenicity	Missense variant, stop gained, non coding transcript variant, coding sequence variant, intron variant
rs1470636347	T>C,G	Pathogenic	Intron variant
rs1555073109	T>C	Pathogenic	Splice acceptor variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT027758	hsa-miR-98-5p	Microarray	19088304
MIRT482094	hsa-miR-665	PAR-CLIP	23592263
MIRT482092	hsa-miR-4459	PAR-CLIP	23592263
MIRT482093	hsa-miR-5681a	PAR-CLIP	23592263
MIRT482091	hsa-miR-6730-5p	PAR-CLIP	23592263
MIRT482090	hsa-miR-7854-3p	PAR-CLIP	23592263
MIRT482089	hsa-miR-3689d	PAR-CLIP	23592263
MIRT482088	hsa-miR-6851-5p	PAR-CLIP	23592263
MIRT482087	hsa-miR-488-3p	PAR-CLIP	23592263
MIRT443236	hsa-miR-1972	PAR-CLIP	22100165
MIRT443234	hsa-miR-5008-5p	PAR-CLIP	22100165
MIRT443235	hsa-miR-874-5p	PAR-CLIP	22100165
MIRT443233	hsa-miR-520a-5p	PAR-CLIP	22100165
MIRT443232	hsa-miR-525-5p	PAR-CLIP	22100165
MIRT443231	hsa-miR-3180-5p	PAR-CLIP	22100165
MIRT482094	hsa-miR-665	PAR-CLIP	23592263
MIRT482092	hsa-miR-4459	PAR-CLIP	23592263
MIRT482093	hsa-miR-5681a	PAR-CLIP	23592263
MIRT482091	hsa-miR-6730-5p	PAR-CLIP	23592263
MIRT482090	hsa-miR-7854-3p	PAR-CLIP	23592263
MIRT482089	hsa-miR-3689d	PAR-CLIP	23592263
MIRT482088	hsa-miR-6851-5p	PAR-CLIP	23592263
MIRT482087	hsa-miR-488-3p	PAR-CLIP	23592263
MIRT443236	hsa-miR-1972	PAR-CLIP	22100165
MIRT443234	hsa-miR-5008-5p	PAR-CLIP	22100165
MIRT443235	hsa-miR-874-5p	PAR-CLIP	22100165
MIRT443233	hsa-miR-520a-5p	PAR-CLIP	22100165
MIRT443232	hsa-miR-525-5p	PAR-CLIP	22100165
MIRT443231	hsa-miR-3180-5p	PAR-CLIP	22100165

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004583	Function	Dolichyl-phosphate-glucose-glycolipid alpha-glucosyltransferase activity	TAS
GO:0005515	Function	Protein binding	IPI	25910212, 32296183, 33961781
GO:0005783	Component	Endoplasmic reticulum	IEA
GO:0005789	Component	Endoplasmic reticulum membrane	IBA
GO:0005789	Component	Endoplasmic reticulum membrane	IEA
GO:0005789	Component	Endoplasmic reticulum membrane	IGI	15235028
GO:0005789	Component	Endoplasmic reticulum membrane	TAS
GO:0006486	Process	Protein glycosylation	IEA
GO:0006487	Process	Protein N-linked glycosylation	IMP	12480927, 15235028
GO:0006488	Process	Dolichol-linked oligosaccharide biosynthetic process	IBA
GO:0006488	Process	Dolichol-linked oligosaccharide biosynthetic process	IMP	12480927, 15235028
GO:0006488	Process	Dolichol-linked oligosaccharide biosynthetic process	TAS
GO:0016020	Component	Membrane	IEA
GO:0016740	Function	Transferase activity	IEA
GO:0016757	Function	Glycosyltransferase activity	IEA
GO:0016758	Function	Hexosyltransferase activity	IEA
GO:0018279	Process	Protein N-linked glycosylation via asparagine	IEA
GO:0018279	Process	Protein N-linked glycosylation via asparagine	ISS
GO:0042283	Function	Dolichyl pyrophosphate Glc1Man9GlcNAc2 alpha-1,3-glucosyltransferase activity	IBA
GO:0042283	Function	Dolichyl pyrophosphate Glc1Man9GlcNAc2 alpha-1,3-glucosyltransferase activity	IEA
GO:0042283	Function	Dolichyl pyrophosphate Glc1Man9GlcNAc2 alpha-1,3-glucosyltransferase activity	IMP	12480927, 15235028
GO:0098553	Component	Lumenal side of endoplasmic reticulum membrane	IC	15235028

Other IDs

• MIM: 608103
• HGNC: 23161
• e!Ensembl: ENSG00000159063

Protein

• UniProt ID: Q9BVK2
• Protein name: Dolichyl pyrophosphate Glc1Man9GlcNAc2 alpha-1,3-glucosyltransferase (EC 2.4.1.265) (Asparagine-linked glycosylation protein 8 homolog) (Dol-P-Glc:Glc(1)Man(9)GlcNAc(2)-PP-dolichyl alpha-1,3-glucosyltransferase) (Dolichyl-P-Glc:Glc1Man9GlcNAc2-PP-dolichyl
• Protein function: Dolichyl pyrophosphate Glc1Man9GlcNAc2 alpha-1,3-glucosyltransferase that operates in the biosynthetic pathway of dolichol-linked oligosaccharides, the glycan precursors employed in protein asparagine (N)-glycosylation. The assembly of dolichol-
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF03155	Alg6_Alg8	21 → 510	ALG6, ALG8 glycosyltransferase family	Family

• Sequence:

  MAALTIATGTGNWFSALALGVTLLKCLLIPTYHSTDFEVHRNWLAITHSLPISQWYYEAT
  SEWTLDYPPFFAWFEYILSHVAKYFDQEMLNVHNLNYSSSRTLLFQRFSVIFMDVLFVYA
  VRECCKCIDGKKVGKELTEKPKFILSVLLLWNFGLLIVDHIHFQYNGFLFGLMLLSIARL
  FQKRHMEGAFLFAVLLHFKHIYLYVAPAYGVYLLRSYCFTANKPDGSIRWKSFSFVRVIS
  LGLVVFLVSALSLGPFLALNQLPQVFSRLFPFKRGLCHAYWAPNFWALYNALDKVLSVIG
  LKLKFLDPNNIPKASMTSGLVQQFQHTVLPSVTPLATLICTLIAILPSIFCLWFKPQGPR
  GFLRCLTLCALSSFMFGWHVHEKAILLAILPMSLLSVGKAGDASIFLILTTTGHYSLFPL
  LFTAPELPIKILLMLLFTIYSISSLKTLFRKEKPLFNWMETFYLLGLGPLEVCCEFVFPF
  TSWKVKYPFIPLLLTSVYCAVGITYAWFKLYVSVLIDSAIGKTKKQ

• Sequence length: 526

Pathways

KEGG:

N-Glycan biosynthesis
Metabolic pathways

Reactome:

Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein
Defective ALG8 causes ALG8-CDG (CDG-1h)

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
ALG8 congenital disorder of glycosylation	Likely pathogenic; Pathogenic	rs200888240, rs398124391, rs2136915887, rs533704173, rs2136876881, rs1323512637, rs772492143, rs2136899636, rs387906277, rs1555073109, rs121908293, rs1470636347, rs121908294, rs2497145277, rs2497144761, rs2497114826, rs2497114146, rs376161880, rs866578354, rs1288977289, rs2497066474, rs2497112638, rs2496889084, rs745894763, rs867450807, rs762811727, rs968741434, rs756894409, rs1859771094, rs777686455	RCV001334177 RCV004786359 RCV001374721 RCV005006055 RCV001842227 RCV002489904 RCV001915953 RCV001965056 RCV000002667 RCV000002669 RCV000002670 RCV000002671 RCV000002672 RCV002839540 RCV003053689 RCV003035656 RCV005011112 RCV001535890 RCV005012825 RCV005061378 RCV005003653 RCV003606029 RCV003834369 RCV003842941 RCV005004155 RCV002506394 RCV001059616 RCV001070562 RCV001196678 RCV001229117	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
ALG8-related disorder	Likely pathogenic; Pathogenic	rs376161880, rs1288977289, rs2497066474, rs762811727, rs777686455	RCV004757187 RCV004529669 RCV004757592 RCV003596048 RCV004538480	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Autosomal dominant polycystic liver disease	Likely pathogenic; Pathogenic	rs533704173, rs376161880, rs2497144999, rs866578354, rs2497085175, rs2496886120, rs777686455	RCV003448986 RCV003448977 RCV003448995 RCV003448996 RCV003448997 RCV003448999 RCV003448985	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Familial cystic renal disease	Likely pathogenic; Pathogenic	rs200888240, rs376161880, rs762811727, rs777686455	RCV005429223 RCV005429236 RCV005429257 RCV005429317	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Polycystic liver disease 3 with or without kidney cysts	Likely pathogenic; Pathogenic	rs200888240, rs533704173, rs2136903056, rs1323512637, rs2136899636, rs121908293, rs1470636347, rs121908294, rs2497114146, rs376161880, rs866578354, rs2497066474, rs745894763, rs867450807, rs762811727, rs968741434, rs756894409, rs777686455	RCV002490722 RCV005006055 RCV001808200 RCV002489904 RCV002492025 RCV002496232 RCV002496233 RCV002496234 RCV005011112 RCV000584794 RCV005012825 RCV003484554 RCV005003735 RCV005004155 RCV000584773 RCV002505624 RCV002489709 RCV002497778	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ALG8-CONGENITAL DISORDER OF GLYCOSYLATION	—	GenCC	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE	—	ClinGen, GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cholangiocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Clear cell carcinoma of kidney	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital disorder of glycosylation	Benign; Uncertain significance; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL DISORDER OF GLYCOSYLATION TYPE 1H	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL DISORDER OF GLYCOSYLATION, TYPE IH	—	HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL DISORDERS OF GLYCOSYLATION	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEPRESSIVE DISORDER	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MAJOR DEPRESSIVE DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mesothelioma	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
POLYCYSTIC KIDNEY, AUTOSOMAL DOMINANT	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
POLYCYSTIC LIVER DISEASE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thymoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine carcinosarcoma	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
ALG8-CDG	Congenital Disorder Of Glycosylation	Orphanet			★☆☆☆☆ Found in Text Mining only
Anemia	Anemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Autism Spectrum Disorder	Autism	Pubtator	35716054	Associate	★☆☆☆☆ Found in Text Mining only
Cataract	Cataract	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cholestasis	Cholestasis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital Camptodactyly	Congenital Camptodactyly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital clubfoot	Congenital Clubfoot	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital disorder of glycosylation type 1H	Congenital disorder of glycosylation	UNIPROT_DG	15235028		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital disorder of glycosylation type 1H	Congenital disorder of glycosylation	GENOMICS_ENGLAND_DG	15235028, 19688606, 27604308, 31420886		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital disorder of glycosylation type 1H	Congenital disorder of glycosylation	BEFREE	19648040, 19688606, 22306853, 26066342		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital disorder of glycosylation type 1H	Congenital disorder of glycosylation	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital disorder of glycosylation type 1H	Congenital disorder of glycosylation	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital disorder of glycosylation type 1s	Congenital disorder of glycosylation	BEFREE	24555185, 30420707		★☆☆☆☆ Found in Text Mining only
Congenital Disorders of Glycosylation	Congenital disorder of glycosylation	BEFREE	22306853, 24555185, 26066342, 30420707, 31420886		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital Disorders of Glycosylation	Congenital disorder of glycosylation	Pubtator	35211808, 38323760	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cryptorchidism	Cryptorchidism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cystic Kidney Diseases	Cystic Kidney Disease	GENOMICS_ENGLAND_DG	30135240		★☆☆☆☆ Found in Text Mining only
Cystic liver disease	Cystic liver disease	GENOMICS_ENGLAND_DG	30135240		★☆☆☆☆ Found in Text Mining only
Depressive disorder	Mental Depression	PSYGENET_DG	22348086		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Depressive Disorder	Major depressive disorder	Pubtator	22348086	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Diabetes Mellitus Type 2	Diabetes mellitus, type 2	Pubtator	22348086	Associate	★☆☆☆☆ Found in Text Mining only
Dysmorphic features	Dysmorphic Features	BEFREE	24555185		★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	BEFREE	24555185		★☆☆☆☆ Found in Text Mining only
Heart Septal Defects	Heart Septal Defects	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hydrops Fetalis, Non-Immune	Hydrops Fetalis	BEFREE	31420886		★☆☆☆☆ Found in Text Mining only
Hypoalbuminemia	Hypoalbuminemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypothyroidism	Hypothyroidism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypothyroidism	Hypothyroidism	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Intellectual developmental disorder	Pubtator	35716054	Associate	★☆☆☆☆ Found in Text Mining only
Intestinal Diseases	Intestinal Diseases	BEFREE	26066342		★☆☆☆☆ Found in Text Mining only
Isolated polycystic liver disease	Polycystic liver disease	BEFREE	30652979		★☆☆☆☆ Found in Text Mining only
Kidney Diseases Cystic	Kidney disease	Pubtator	36573973, 37628703	Associate	★☆☆☆☆ Found in Text Mining only
Liver cyst	Liver Cyst	HPO_DG			★☆☆☆☆ Found in Text Mining only
Liver Failure	Liver failure	HPO_DG			★☆☆☆☆ Found in Text Mining only
Macroglossia	Macroglossia	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Micrognathism	Micrognathism	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Ovarian Neoplasms	Ovarian neoplasm	Pubtator	35281472	Associate	★☆☆☆☆ Found in Text Mining only
Patent ductus arteriosus	Patent ductus arteriosus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Polycystic Kidney Autosomal Dominant	Polycystic kidney disease	Pubtator	30135240	Associate	★☆☆☆☆ Found in Text Mining only
Polycystic liver disease	Polycystic liver disease	GENOMICS_ENGLAND_DG	30135240		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Polycystic liver disease	Polycystic liver disease	Pubtator	30135240, 37628703	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Polycystic liver disease	Polycystic liver disease	BEFREE	30652979		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
POLYCYSTIC LIVER DISEASE 3 WITH OR WITHOUT KIDNEY CYSTS	Polycystic liver disease	GENOMICS_ENGLAND_DG	15235028		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Protein-Losing Enteropathies	Protein-losing enteropathy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Simple renal cyst	Renal cyst	HPO_DG			★☆☆☆☆ Found in Text Mining only