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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
MAN2A2
mannosidase alpha class 2A member 2
Chromosome 15 Β· 15q26.1
NCBI Gene: 4122Ensembl: ENSG00000196547.16HGNC: HGNC:6825UniProt: A0A0C4DGL1
42PubMed Papers
20Diseases
0Drugs
2Pathogenic Variants
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingalpha-mannosidase activityN-glycan processingGolgi membraneNeurodevelopmental delaycoronary artery diseasehypertensionangina pectoris
✦AI Summary

MAN2A2 encodes an alpha-mannosidase enzyme localized to the Golgi apparatus that catalyzes a critical step in N-glycan maturation 1. The enzyme controls the conversion of high mannose to complex N-glycans by trimming mannose residues, representing the final hydrolytic step in the N-glycan processing pathway 1. MAN2A2 functions as a central hub in multi-enzyme assemblies within Golgi membranes, forming distinct molecular complexes with other N-glycan processing enzymes including MGAT1, MGAT2, MGAT3, and MGAT4B to facilitate efficient complex N-glycan synthesis 2. The gene is highly expressed in brain regions, and pathogenic variants cause autosomal recessive congenital disorders of glycosylation (CDG) characterized by neurological involvement, autism spectrum disorder, cognitive delay, and facial dysmorphism 13. Functionally defective MAN2A2 results in accumulation of immature hybrid-type N-glycans and decreased complex N-glycans 13. Beyond developmental roles, MAN2A2 expression is upregulated in pathological conditions including cholangiocarcinoma progression under high glucose-ROS conditions 4 and shows altered expression in cardiovascular disease contexts 5. The enzyme's dysfunction in neuroinflammatory conditions is evidenced by downregulated MAN2A2 in LPS-activated microglia 6.

Sources cited
1
MAN2A2 encodes an alpha-mannosidase localized to Golgi apparatus that catalyzes N-glycan trimming/maturation
PMID: 40628855
2
MAN2A2 acts as central hub forming molecular assemblies with other N-glycan processing enzymes in Golgi membranes
PMID: 30737517
3
Gene is highly expressed in brain regions and pathogenic variants cause autism spectrum disorder and cognitive delay
PMID: 40628855
4
Pathogenic variants cause autosomal recessive CDG with neurological involvement and facial dysmorphism
PMID: 36357165
5
Defective MAN2A2 results in accumulation of immature hybrid-type N-glycans
PMID: 40628855
6
MAN2A2 is upregulated in cholangiocarcinoma under high glucose-ROS conditions
PMID: 33141432
7
MAN2A2 shows altered expression in cardiovascular disease contexts
PMID: 33836805
8
MAN2A2 is downregulated in LPS-activated microglia
PMID: 40210651
Disease Associationsβ“˜20
Neurodevelopmental delayOpen Targets
0.33Weak
coronary artery diseaseOpen Targets
0.20Weak
hypertensionOpen Targets
0.19Weak
angina pectorisOpen Targets
0.17Weak
response to xenobiotic stimulusOpen Targets
0.15Weak
Myocardial IschemiaOpen Targets
0.13Weak
Aganglionic megacolonOpen Targets
0.11Weak
Hirschsprung diseaseOpen Targets
0.11Weak
azoospermiaOpen Targets
0.10Weak
cardiovascular diseaseOpen Targets
0.09Suggestive
Increased blood pressureOpen Targets
0.09Suggestive
response to statinOpen Targets
0.08Suggestive
partial chromosome Y deletionOpen Targets
0.08Suggestive
coronary atherosclerosisOpen Targets
0.08Suggestive
cholangiocarcinomaOpen Targets
0.07Suggestive
spermatogenic failure 25Open Targets
0.07Suggestive
spermatogenic failure 57Open Targets
0.07Suggestive
spermatogenic failure 50Open Targets
0.07Suggestive
spermatogenic failure, X-linked, 2Open Targets
0.07Suggestive
spermatogenic failure 48Open Targets
0.07Suggestive
Pathogenic Variants2
NM_006122.4(MAN2A2):c.1679G>A (p.Arg560Gln)Likely pathogenic
Neurodevelopmental delay
β˜…β˜†β˜†β˜†2025β†’ Residue 560
NM_006122.4(MAN2A2):c.3292C>T (p.Gln1098Ter)Likely pathogenic
Neurodevelopmental delay
β˜…β˜†β˜†β˜†2025β†’ Residue 1098
View on ClinVar β†—
Related Genes
MGAT2Protein interaction98%MGAT1Protein interaction97%FUT8Protein interaction91%MAN1A1Protein interaction91%SLC35C1Protein interaction83%SLC35D2Protein interaction82%
Tissue Expression6 tissues
Bone Marrow
100%
Liver
55%
Lung
54%
Brain
45%
Heart
44%
Ovary
28%
Gene Interaction Network
Click a node to explore
MAN2A2MGAT2MGAT1FUT8MAN1A1SLC35C1SLC35D2
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt P49641
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.72LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.60 [0.50–0.72]
RankingsWhere MAN2A2 stands among ~20K protein-coding genes
  • #9,902of 20,598
    Most Researched42
  • #4,462of 5,498
    Most Pathogenic Variants2
  • #5,579of 17,882
    Most Constrained (LOEUF)0.72
Genes detectedMAN2A2
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Exploring Genetic Associations of 3 Types of Risk Factors With Ischemic Stroke: An Integrated Bioinformatics Study.
PMID: 38591222
Stroke Β· 2024
1.00
2
MAN2A2-related glycosylation defects in autism and cognitive delay.
PMID: 40628855
Sci Rep Β· 2025
0.90
3
High glucose-ROS conditions enhance the progression in cholangiocarcinoma via upregulation of MAN2A2 and CHD8.
PMID: 33141432
Cancer Sci Β· 2021
0.80
4
N-acetylglucosaminyltransferases and nucleotide sugar transporters form multi-enzyme-multi-transporter assemblies in golgi membranes in vivo.
PMID: 30737517
Cell Mol Life Sci Β· 2019
0.70
5
Homozygous truncating variant in
PMID: 36357165
J Med Genet Β· 2023
0.60