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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
ALG12
ALG12 alpha-1,6-mannosyltransferase
Chromosome 22 Β· 22q13.33
NCBI Gene: 79087Ensembl: ENSG00000182858.15HGNC: HGNC:19358UniProt: Q9BV10
30PubMed Papers
21Diseases
0Drugs
43Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
dolichol-linked oligosaccharide biosynthetic processdol-P-Man:Man(7)GlcNAc(2)-PP-Dol alpha-1,6-mannosyltransferase activityprotein N-linked glycosylationmembraneALG12-congenital disorder of glycosylationgenetic disordercongenital disorder of glycosylationcongenital disorder of glycosylation type I
✦AI Summary

ALG12 encodes an alpha-1,6-mannosyltransferase that catalyzes a critical step in N-linked glycosylation by adding the eighth mannose residue to Man(7)GlcNAc(2)-PP-dolichol in the endoplasmic reticulum lumen 1. This enzymatic activity is essential for assembling the 14-sugar dolichol-linked oligosaccharide precursor that is subsequently transferred to nascent proteins by oligosaccharyltransferases 2. Biallelic ALG12 mutations cause congenital disorder of glycosylation type 1G (ALG12-CDG), characterized by impaired N-glycosylation of multiple proteins 2. Clinically, ALG12-CDG presents with broad multisystem manifestations including developmental delay, hypotonia, intellectual disability, coagulation abnormalities, recurrent infections, and dysmorphic features 1. Additional phenotypic features include skeletal dysplasia, cardiac defects, genitourinary abnormalities including hydronephrosis and multicystic kidneys, and brain anomalies 34. Phenotypic heterogeneity suggests modifying genetic and environmental factors influence disease severity 1. Beyond rare inherited disease, ALG12 dysfunction contributes to chemoresistance in intrahepatic cholangiocarcinoma through impaired N-glycosylation of ABCC1 drug transporters 5. ALG12 is also implicated in cardiac complications in carbohydrate metabolism disorders 6.

Sources cited
1
ALG12-CDG enzyme function and primary clinical features including intellectual disability, hypotonia, coagulation abnormalities, and infections
PMID: 31481313
2
ALG12 catalyzes alpha-1,6-mannosyltransferase activity in dolichol-oligosaccharide assembly and biochemical markers of ALG12-CDG
PMID: 34467644
3
ALG12-CDG phenotypic expansion including multicystic kidneys and expanded prenatal presentation
PMID: 38717015
4
ALG12-CDG clinical features and novel presentation of hydronephrosis as additional phenotypic manifestation
PMID: 34092405
5
ALG12 role in N-glycan biosynthesis and involvement in chemoresistance mechanisms in intrahepatic cholangiocarcinoma
PMID: 40683603
6
ALG12 involvement in cardiomyopathies and cardiac defects among congenital disorders of glycosylation
PMID: 37239976
7
ALG12-CDG presentation with severe skeletal dysplasia features including rhizomelic short stature and talipes equinovarus
PMID: 25019053
8
ALG12-CDG phenotypic heterogeneity and expanded clinical spectrum including cardiac and skeletal manifestations without typical facial dysmorphism
PMID: 32530140
Disease Associationsβ“˜21
ALG12-congenital disorder of glycosylationOpen Targets
0.83Strong
genetic disorderOpen Targets
0.41Moderate
congenital disorder of glycosylationOpen Targets
0.41Moderate
congenital disorder of glycosylation type IOpen Targets
0.37Weak
acneOpen Targets
0.13Weak
ovarian neoplasmOpen Targets
0.12Weak
osteoarthritis, hipOpen Targets
0.12Weak
osteoporosisOpen Targets
0.10Suggestive
essential tremorOpen Targets
0.09Suggestive
Young adult-onset ParkinsonismOpen Targets
0.08Suggestive
movement disorderOpen Targets
0.07Suggestive
Hereditary late-onset Parkinson diseaseOpen Targets
0.07Suggestive
dystonia 27Open Targets
0.07Suggestive
total hip arthroplastyOpen Targets
0.06Suggestive
Cranio-cervical dystonia with laryngeal and upper-limb involvementOpen Targets
0.06Suggestive
X-linked dystonia-parkinsonismOpen Targets
0.06Suggestive
Primary dystonia, DYT13 typeOpen Targets
0.06Suggestive
episodic kinesigenic dyskinesia 1Open Targets
0.06Suggestive
X-linked parkinsonism-spasticity syndromeOpen Targets
0.06Suggestive
spinocerebellar ataxia type 20Open Targets
0.06Suggestive
Congenital disorder of glycosylation 1GUniProt
Pathogenic Variants43
NM_024105.4(ALG12):c.295+1G>ALikely pathogenic
ALG12-congenital disorder of glycosylation|not provided
β˜…β˜…β˜†β˜†2026
NM_024105.4(ALG12):c.200C>T (p.Thr67Met)Pathogenic
ALG12-congenital disorder of glycosylation
β˜…β˜…β˜†β˜†2025β†’ Residue 67
NM_024105.4(ALG12):c.1156dup (p.Gln386fs)Pathogenic
ALG12-congenital disorder of glycosylation
β˜…β˜…β˜†β˜†2025β†’ Residue 386
NM_024105.4(ALG12):c.437G>A (p.Arg146Gln)Pathogenic
ALG12-congenital disorder of glycosylation|not provided|ALG12-related disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 146
NM_024105.4(ALG12):c.301G>A (p.Gly101Arg)Likely pathogenic
ALG12-congenital disorder of glycosylation|not provided|ALG12-related disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 101
NM_024105.4(ALG12):c.1001del (p.Asn334fs)Pathogenic
ALG12-congenital disorder of glycosylation|not provided|Inborn genetic diseases
β˜…β˜…β˜†β˜†2025β†’ Residue 334
NM_024105.4(ALG12):c.117del (p.Gln40fs)Pathogenic
ALG12-congenital disorder of glycosylation|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 40
NM_024105.4(ALG12):c.930_931del (p.Arg311fs)Pathogenic
ALG12-congenital disorder of glycosylation
β˜…β˜…β˜†β˜†2025β†’ Residue 311
NM_024105.4(ALG12):c.768+1dupPathogenic
ALG12-congenital disorder of glycosylation
β˜…β˜…β˜†β˜†2024
NM_024105.4(ALG12):c.1246_1247del (p.Lys416fs)Likely pathogenic
ALG12-congenital disorder of glycosylation|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 416
NM_024105.4(ALG12):c.30del (p.Leu12fs)Pathogenic
ALG12-congenital disorder of glycosylation
β˜…β˜…β˜†β˜†2024β†’ Residue 12
NM_024105.4(ALG12):c.768+1G>ALikely pathogenic
ALG12-congenital disorder of glycosylation
β˜…β˜…β˜†β˜†2022
NM_024105.4(ALG12):c.904_908del (p.Tyr302fs)Pathogenic
ALG12-congenital disorder of glycosylation
β˜…β˜†β˜†β˜†2025β†’ Residue 302
NM_024105.4(ALG12):c.1129C>T (p.Gln377Ter)Pathogenic
ALG12-congenital disorder of glycosylation
β˜…β˜†β˜†β˜†2025β†’ Residue 377
NM_024105.4(ALG12):c.1162+2T>GLikely pathogenic
ALG12-congenital disorder of glycosylation
β˜…β˜†β˜†β˜†2025
NM_024105.4(ALG12):c.604C>T (p.Arg202Ter)Pathogenic
ALG12-related disorder|ALG12-congenital disorder of glycosylation
β˜…β˜†β˜†β˜†2025β†’ Residue 202
NM_024105.4(ALG12):c.861del (p.Thr288fs)Pathogenic
ALG12-congenital disorder of glycosylation
β˜…β˜†β˜†β˜†2025β†’ Residue 288
NM_024105.4(ALG12):c.502G>T (p.Glu168Ter)Pathogenic
ALG12-congenital disorder of glycosylation
β˜…β˜†β˜†β˜†2025β†’ Residue 168
NM_024105.4(ALG12):c.755del (p.Ser252fs)Pathogenic
ALG12-congenital disorder of glycosylation
β˜…β˜†β˜†β˜†2025β†’ Residue 252
NM_024105.4(ALG12):c.1015_1016del (p.Trp339fs)Pathogenic
ALG12-congenital disorder of glycosylation
β˜…β˜†β˜†β˜†2024β†’ Residue 339
View on ClinVar β†—
Related Genes
STT3AProtein interaction99%DPAGT1Protein interaction99%ALG1Protein interaction99%ALG2Protein interaction98%ALG8Protein interaction87%ALG13Protein interaction86%
Tissue Expression6 tissues
Liver
100%
Lung
77%
Ovary
73%
Heart
63%
Bone Marrow
45%
Brain
41%
Gene Interaction Network
Click a node to explore
ALG12STT3ADPAGT1ALG1ALG2ALG8ALG13
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q9BV10
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.96LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.73 [0.56–0.96]
RankingsWhere ALG12 stands among ~20K protein-coding genes
  • #11,849of 20,598
    Most Researched30
  • #1,477of 5,498
    Most Pathogenic Variants43
  • #9,141of 17,882
    Most Constrained (LOEUF)0.96
Genes detectedALG12
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Metabolic Cardiomyopathies and Cardiac Defects in Inherited Disorders of Carbohydrate Metabolism: A Systematic Review.
PMID: 37239976
Int J Mol Sci Β· 2023
1.00
2
Restoration of N-glycosylation via leucine-activated leucyl-tRNA synthetase 1 overcomes chemoresistance in intrahepatic cholangiocarcinoma.
PMID: 40683603
J Hepatol Β· 2026
0.90
3
Complex phenotypes in ALG12-congenital disorder of glycosylation (ALG12-CDG): Case series and review of the literature.
PMID: 31481313
Mol Genet Metab Β· 2019
0.80
4
A novel homozygous mutation in the human ALG12 gene results in an aberrant profile of oligomannose N-glycans in patient's serum.
PMID: 34467644
Am J Med Genet A Β· 2021
0.70
5
PMID: 20301507
0.60