ALG11

ALG11 alpha-1,2-mannosyltransferase, the group of Glycosyl transferases group 1 domain containing

Basic information

Region (hg38): 13:52012391-52079232

Links

ENSG00000253710 ∙ NCBI:440138 ∙ OMIM:613666 ∙ HGNC:32456 ∙ Uniprot:Q2TAA5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• ALG11-congenital disorder of glycosylation (Strong), mode of inheritance: AR
• ALG11-congenital disorder of glycosylation (Moderate), mode of inheritance: AR
• ALG11-congenital disorder of glycosylation (Strong), mode of inheritance: AR
• ALG11-congenital disorder of glycosylation (Strong), mode of inheritance: AR
• ALG11-congenital disorder of glycosylation (Supportive), mode of inheritance: AR
• ALG11-congenital disorder of glycosylation (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Congenital disorder of glycosylation, type Ip	AR	Hematologic	Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	Biochemical; Hematologic; Neurologic	20080937; 22213132; 30676690
Hepatic-metabolized agents should be avoided

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ALG11 gene.

• ALG11-congenital_disorder_of_glycosylation (92 variants)
• not_provided (54 variants)
• Inborn_genetic_diseases (53 variants)
• not_specified (7 variants)
• ALG11-related_disorder (7 variants)
• Seizure (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ALG11 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001004127.3. 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			4	31		35
missense	4	8	94	6	1	113
nonsense	1		1			2
start loss		2				2
frameshift	2	1	3			6
splice donor/acceptor (+/-2bp)		1				1
Total	7	12	102	37	1

Highest pathogenic variant AF is 0.0000235487

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ALG11	protein_coding	protein_coding	ENST00000521508	4	17267

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.17e-9	0.248	125708	0	40	125748	0.000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0471	258	256	1.01	0.0000124	3221
Missense in Polyphen		70	93.101	0.75187		1130
Synonymous	0.789	88	97.9	0.899	0.00000528	966
Loss of Function	0.564	14	16.5	0.850	6.91e-7	239

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000595	0.000593
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000185	0.000185
Middle Eastern	0.00	0.00
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Mannosyltransferase involved in the last steps of the synthesis of Man5GlcNAc(2)-PP-dolichol core oligosaccharide on the cytoplasmic face of the endoplasmic reticulum. Catalyzes the addition of the 4th and 5th mannose residues to the dolichol- linked oligosaccharide chain. {ECO:0000269|PubMed:20080937}.
• Disease: DISEASE: Congenital disorder of glycosylation 1P (CDG1P) [MIM:613661]: 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:20080937, ECO:0000269|PubMed:22213132}. 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;Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein;Asparagine N-linked glycosylation (Consensus)

Intolerance Scores

• loftool: 0.880
• rvis_EVS: -0.49
• rvis_percentile_EVS: 22.51

Haploinsufficiency Scores

• hipred: N
• hipred_score: 0.204
• ghis: 0.414

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: N
• gene_indispensability_score: 0.231

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Alg11

Gene ontology

• Biological process: protein N-linked glycosylation;oligosaccharide-lipid intermediate biosynthetic process;mannosylation
• Cellular component: endoplasmic reticulum membrane;membrane;integral component of membrane
• Molecular function: GDP-Man:Man3GlcNAc2-PP-Dol alpha-1,2-mannosyltransferase activity