ALG12

ALG12 alpha-1,6-mannosyltransferase, the group of Dolichyl D-mannosyl phosphate dependent mannosyltransferases

Basic information

Region (hg38): 22:49900229-49918438

Links

ENSG00000182858 ∙ NCBI:79087 ∙ OMIM:607144 ∙ HGNC:19358 ∙ Uniprot:Q9BV10 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• ALG12-congenital disorder of glycosylation (Definitive), mode of inheritance: AR
• ALG12-congenital disorder of glycosylation (Strong), mode of inheritance: AR
• ALG12-congenital disorder of glycosylation (Moderate), mode of inheritance: AR
• ALG12-congenital disorder of glycosylation (Strong), mode of inheritance: AR
• ALG12-congenital disorder of glycosylation (Supportive), mode of inheritance: AR
• ALG12-congenital disorder of glycosylation (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Congenital disorder of glycosylation, type Ig	AR	Allergy/Immunology/Infectious; Cardiovascular; Hematologic	As the condition can include immunodeficiency and frequent infections, prophylaxis and early and aggressive treatment of infections may be beneficial; Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery; Individuals have been described with congenital heart anomalies, and awareness may enable early diagnosis and management	Allergy/Immunology/Infectious; Biochemical; Cardiovascular; Craniofacial; Genitourinary; Hematologic; Musculoskeletal; Neurologic	11983712; 12217961; 17506107; 31481313
Hepatic-metabolized agents should be avoided

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ALG12 gene.

• ALG12-congenital disorder of glycosylation (15 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ALG12 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			6	142	4	152
missense		4	178	4	3	189
nonsense	8		1			9
start loss						0
frameshift	7	4	1			12
inframe indel			2			2
splice donor/acceptor (+/-2bp)		6				6
splice region			9	15		24
non coding			18	47	32	97
Total	15	14	206	193	39

Highest pathogenic variant AF is 0.00000657

Variants in ALG12

This is a list of pathogenic ClinVar variants found in the ALG12 region.

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

Position	Type	Phenotype	Significance	ClinVar
22-49903347-C-A		Congenital disorder of glycosylation	Uncertain significance (Jun 14, 2016)
22-49903352-G-T		ALG12-congenital disorder of glycosylation	Uncertain significance (Jan 12, 2018)
22-49903353-T-TG		Congenital disorder of glycosylation	Uncertain significance (Jun 14, 2016)
22-49903354-G-T		ALG12-congenital disorder of glycosylation	Uncertain significance (Jan 13, 2018)
22-49903363-C-T		ALG12-congenital disorder of glycosylation	Uncertain significance (Jan 13, 2018)
22-49903386-CCT-C		Congenital disorder of glycosylation	Likely benign (Jun 14, 2016)
22-49903445-G-A		ALG12-congenital disorder of glycosylation	Uncertain significance (Jan 13, 2018)
22-49903475-C-T		ALG12-congenital disorder of glycosylation	Uncertain significance (Jan 12, 2018)
22-49903484-C-T		ALG12-congenital disorder of glycosylation	Uncertain significance (Jan 13, 2018)
22-49903558-C-T		ALG12-congenital disorder of glycosylation	Benign (Jun 19, 2021)
22-49903562-A-C		ALG12-congenital disorder of glycosylation	Uncertain significance (Jan 13, 2018)
22-49903588-G-A		ALG12-congenital disorder of glycosylation	Uncertain significance (Jan 13, 2018)
22-49903598-C-T		ALG12-congenital disorder of glycosylation	Benign (Apr 25, 2021)
22-49903629-G-A		ALG12-congenital disorder of glycosylation	Uncertain significance (Jan 12, 2018)
22-49903707-G-T		ALG12-congenital disorder of glycosylation	Uncertain significance (Jan 12, 2018)
22-49903787-T-C		ALG12-congenital disorder of glycosylation	Benign (Oct 16, 2018)
22-49903805-G-A		ALG12-congenital disorder of glycosylation	Uncertain significance (Jan 13, 2018)
22-49903837-C-G		ALG12-congenital disorder of glycosylation	Uncertain significance (Jan 12, 2018)
22-49903838-T-G		ALG12-congenital disorder of glycosylation	Uncertain significance (Apr 29, 2022)
22-49903839-C-T		ALG12-congenital disorder of glycosylation	Uncertain significance (Aug 18, 2022)
22-49903842-G-A		ALG12-congenital disorder of glycosylation	Uncertain significance (Jun 24, 2021)
22-49903844-C-T		ALG12-congenital disorder of glycosylation	Likely benign (Sep 30, 2023)
22-49903845-G-A		ALG12-congenital disorder of glycosylation	Uncertain significance (Sep 07, 2022)
22-49903845-G-C		ALG12-congenital disorder of glycosylation	Uncertain significance (Aug 22, 2022)
22-49903845-GGCCGGGGGA-G		ALG12-congenital disorder of glycosylation	Uncertain significance (Jun 14, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ALG12	protein_coding	protein_coding	ENST00000330817	9	18230

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.18e-7	0.806	125677	0	70	125747	0.000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.193	295	286	1.03	0.0000199	3077
Missense in Polyphen		107	107.61	0.99431		1246
Synonymous	-1.87	166	138	1.20	0.0000107	1094
Loss of Function	1.45	14	21.2	0.661	0.00000102	234

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000883	0.000882
Ashkenazi Jewish	0.000198	0.000198
East Asian	0.000109	0.000109
Finnish	0.000277	0.000277
European (Non-Finnish)	0.000322	0.000273
Middle Eastern	0.000109	0.000109
South Asian	0.0000980	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Adds the eighth mannose residue in an alpha-1,6 linkage onto the dolichol-PP-oligosaccharide precursor (dolichol-PP- Man(7)GlcNAc(2)) required for protein glycosylation.
• 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;N-Glycan biosynthesis (Consensus)

Recessive Scores

• pRec: 0.141

Intolerance Scores

• loftool: 0.420
• rvis_EVS: -0.64
• rvis_percentile_EVS: 16.68

Haploinsufficiency Scores

• pHI: 0.0946
• hipred: N
• hipred_score: 0.331
• ghis: 0.520

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.352

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Alg12

Gene ontology

• Biological process: protein folding;protein N-linked glycosylation;dolichol-linked oligosaccharide biosynthetic process;mannosylation
• Cellular component: endoplasmic reticulum;endoplasmic reticulum lumen;endoplasmic reticulum membrane;membrane;integral component of membrane
• Molecular function: mannosyltransferase activity;dolichyl-pyrophosphate Man7GlcNAc2 alpha-1,6-mannosyltransferase activity;dol-P-Man:Man(7)GlcNAc(2)-PP-Dol alpha-1,6-mannosyltransferase activity