ALG1

ALG1 chitobiosyldiphosphodolichol beta-mannosyltransferase, the group of Glycosyl transferases group 1 domain containing

Basic information

Region (hg38): 16:5033701-5087379

Links

ENSG00000033011 ∙ NCBI:56052 ∙ OMIM:605907 ∙ HGNC:18294 ∙ Uniprot:Q9BT22 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• ALG1-congenital disorder of glycosylation (Strong), mode of inheritance: AR
• ALG1-congenital disorder of glycosylation (Definitive), mode of inheritance: AR
• ALG1-congenital disorder of glycosylation (Strong), mode of inheritance: AR
• ALG1-congenital disorder of glycosylation (Definitive), mode of inheritance: AR
• ALG1-congenital disorder of glycosylation (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Congenital disorder of glycosylation, type Ik	AR	Hematologic	Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	Biochemical; Gastrointestinal; Hematologic; Neurologic; Renal	14709599; 14973782; 14973778; 20679665; 22966035
Hepatic-metabolized agents should be avoided

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ALG1 gene.

• ALG1-congenital disorder of glycosylation (562 variants)
• not provided (119 variants)
• not specified (41 variants)
• Inborn genetic diseases (41 variants)
• Congenital disorder of glycosylation (26 variants)
• ALG1-related condition (3 variants)
• Encephalopathy (2 variants)
• Finnish congenital nephrotic syndrome (2 variants)
• Kabuki syndrome 1 (1 variants)
• Congenital disorder of glycosylation type I (1 variants)
• ALG12-congenital disorder of glycosylation (1 variants)
• - (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ALG1 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			5	145	3	153
missense	7	12	194	9	4	226
nonsense	8	4				12
start loss			1			1
frameshift	12	2				14
inframe indel			9			9
splice donor/acceptor (+/-2bp)	3	10				13
splice region	2	2	12	17	1	34
non coding		2	11	118	36	167
Total	30	30	220	272	43

Highest pathogenic variant AF is 0.0000394

Variants in ALG1

This is a list of pathogenic ClinVar variants found in the ALG1 region.

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

Position	Type	Phenotype	Significance	ClinVar
16-5033832-G-A			Benign (Dec 31, 2019)
16-5033882-G-T			Likely benign (Nov 06, 2018)
16-5033896-G-T		not specified	Uncertain significance (Feb 28, 2024)
16-5060315-GT-G		not specified	Uncertain significance (Jan 23, 2024)
16-5062443-C-T		not specified	Uncertain significance (Aug 13, 2021)
16-5071691-C-A			Benign (Jun 23, 2018)
16-5071840-G-T		not specified	Likely benign (Mar 18, 2016)
16-5071855-G-T		ALG1-congenital disorder of glycosylation	Likely benign (Nov 01, 2022)
16-5071856-G-A		Inborn genetic diseases	Uncertain significance (Jan 05, 2022)
16-5071857-C-A		ALG1-congenital disorder of glycosylation	Benign/Likely benign (Jan 19, 2024)
16-5071858-C-T		ALG1-congenital disorder of glycosylation	Likely benign (Jan 26, 2024)
16-5071860-C-A		ALG1-congenital disorder of glycosylation	Pathogenic (Nov 28, 2022)
16-5071860-C-T		ALG1-congenital disorder of glycosylation	Uncertain significance (Dec 15, 2022)
16-5071861-A-G		ALG1-congenital disorder of glycosylation	Likely benign (Nov 18, 2023)
16-5071861-A-T		ALG1-congenital disorder of glycosylation	Likely benign (Jun 20, 2023)
16-5071862-T-C		ALG1-congenital disorder of glycosylation	Uncertain significance (Aug 31, 2021)
16-5071862-T-G		ALG1-congenital disorder of glycosylation	Uncertain significance (Oct 24, 2022)
16-5071864-C-A		Congenital disorder of glycosylation • ALG1-congenital disorder of glycosylation	Pathogenic (Aug 18, 2021)
16-5071864-C-T		ALG1-congenital disorder of glycosylation	Likely benign (Nov 27, 2023)
16-5071865-T-C		ALG1-congenital disorder of glycosylation	Likely benign (Dec 13, 2023)
16-5071867-G-T		ALG1-congenital disorder of glycosylation • Inborn genetic diseases	Conflicting classifications of pathogenicity (Jan 04, 2024)
16-5071868-G-A		ALG1-congenital disorder of glycosylation	Conflicting classifications of pathogenicity (Jan 18, 2024)
16-5071868-G-C		ALG1-congenital disorder of glycosylation	Uncertain significance (Dec 20, 2021)
16-5071869-T-G		ALG1-congenital disorder of glycosylation	Uncertain significance (Jul 16, 2022)
16-5071870-C-G		ALG1-congenital disorder of glycosylation	Likely benign (Jun 25, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ALG1	protein_coding	protein_coding	ENST00000262374	13	53678

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.62e-19	0.00131	125694	0	54	125748	0.000215

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-2.05	357	264	1.35	0.0000159	2969
Missense in Polyphen		93	86.836	1.071		1072
Synonymous	-3.74	162	112	1.45	0.00000702	932
Loss of Function	-0.405	27	24.8	1.09	0.00000126	277

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000177	0.000177
Ashkenazi Jewish	0.000301	0.000298
East Asian	0.000555	0.000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000279	0.000273
Middle Eastern	0.000555	0.000544
South Asian	0.000131	0.000131
Other	0.000165	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Participates in the formation of the lipid-linked precursor oligosaccharide for N-glycosylation. Involved in assembling the dolichol-pyrophosphate-GlcNAc(2)-Man(5) intermediate on the cytoplasmic surface of the ER. {ECO:0000269|PubMed:10704531, ECO:0000269|PubMed:26931382}.
• Disease: DISEASE: Congenital disorder of glycosylation 1K (CDG1K) [MIM:608540]: 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:14709599, ECO:0000269|PubMed:14973778, ECO:0000269|PubMed:14973782, ECO:0000269|PubMed:26931382}. 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;N-Glycan biosynthesis (Consensus)

Recessive Scores

• pRec: 0.190

Intolerance Scores

• loftool: 0.384
• rvis_EVS: 0.04
• rvis_percentile_EVS: 57.41

Haploinsufficiency Scores

• pHI: 0.108
• hipred: N
• hipred_score: 0.133
• ghis: 0.482

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.604

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Alg1
• Phenotype: integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); pigmentation phenotype

Gene ontology

• Biological process: protein glycosylation;dolichol-linked oligosaccharide biosynthetic process;mannosylation
• Cellular component: endoplasmic reticulum;endoplasmic reticulum membrane;membrane;integral component of membrane
• Molecular function: mannosyltransferase activity;chitobiosyldiphosphodolichol beta-mannosyltransferase activity