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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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MAN2C1
mannosidase alpha class 2C member 1
Chromosome 15 · 15q24.2
NCBI Gene: 4123Ensembl: ENSG00000140400.19HGNC: HGNC:6827UniProt: A0A140VJN9
55PubMed Papers
21Diseases
0Drugs
9Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
alpha-mannosidase activityoligosaccharide catabolic processcytosolcarbohydrate metabolic processcongenital disorder of deglycosylation 2complex neurodevelopmental disorderfrozen shouldertype 2 diabetes mellitus
✦AI Summary

MAN2C1 encodes a cytosolic alpha-mannosidase that cleaves α1,2-, α1,3-, and α1,6-linked mannose residues from free oligosaccharides (fOSs) generated during N-glycoprotein degradation pathways 1. This enzyme plays a critical role in fOS catabolism, with deficiency leading to accumulation and delayed processing of these substrates 1. Pathogenic variants in MAN2C1 cause congenital disorder of deglycosylation 2 (CDDG2), characterized by neurodevelopmental abnormalities including dysmorphic facial features, intellectual disability, and brain malformations such as polymicrogyria, interhemispheric cysts, and cerebellar hypoplasia 12. Beyond its metabolic function, MAN2C1 appears to have broader cellular roles. In cancer contexts, the protein can attenuate PTEN function by direct binding, thereby promoting AKT activation and tumor growth in prostate cancer 3. Additionally, MAN2C1 influences cell adhesion through modulation of CD54-LFA-1 interactions in T cells 4 and affects microtubule organization, with suppression causing mitotic arrest and apoptosis in cancer cells 5. The gene has also been implicated in late-onset Parkinson's disease susceptibility and PTSD-associated epigenetic modifications 67.

Sources cited
1
MAN2C1 cleaves mannose residues from free oligosaccharides and variants cause neurodevelopmental disorder with brain malformations
PMID: 35045343
2
MAN2C1 variants are associated with polymicrogyria
PMID: 37486637
3
MAN2C1 attenuates PTEN function by direct binding and promotes AKT activation in prostate cancer
PMID: 21556061
4
MAN2C1 inhibition enhances T cell adhesion through CD54-LFA-1 interactions
PMID: 16721356
5
MAN2C1 suppression causes microtubule disorganization, mitotic arrest and apoptosis
PMID: 19018777
6
MAN2C1 is implicated in late-onset Parkinson's disease susceptibility
PMID: 34148545
7
MAN2C1 methylation is associated with PTSD
PMID: 21508515
Disease Associationsⓘ21
congenital disorder of deglycosylation 2Open Targets
0.64Moderate
complex neurodevelopmental disorderOpen Targets
0.37Weak
frozen shoulderOpen Targets
0.21Weak
type 2 diabetes mellitusOpen Targets
0.12Weak
hypogonadotropic hypogonadism 27 without anosmiaOpen Targets
0.12Weak
breast carcinomaOpen Targets
0.07Suggestive
diabetes mellitusOpen Targets
0.06Suggestive
coffee consumptionOpen Targets
0.06Suggestive
non-alcoholic fatty liver diseaseOpen Targets
0.05Suggestive
health study participationOpen Targets
0.04Suggestive
transient infantile hypertriglyceridemia and hepatosteatosisOpen Targets
0.03Suggestive
diarrhea 13Open Targets
0.03Suggestive
post-traumatic stress disorderOpen Targets
0.02Suggestive
neoplasmOpen Targets
0.01Suggestive
breast cancerOpen Targets
0.01Suggestive
infectionOpen Targets
0.01Suggestive
esophageal carcinomaOpen Targets
0.01Suggestive
breast ductal carcinoma in situOpen Targets
0.01Suggestive
cancerOpen Targets
0.01Suggestive
prostate cancerOpen Targets
0.01Suggestive
Congenital disorder of deglycosylation 2UniProt
Pathogenic Variants9
NM_006715.4(MAN2C1):c.351+1G>ALikely pathogenic
Congenital disorder of deglycosylation 2|Familial cancer of breast
★★☆☆2024
NM_006715.4(MAN2C1):c.2569del (p.Asp857fs)Likely pathogenic
Congenital disorder of deglycosylation 2
★☆☆☆2024→ Residue 857
NM_006715.4(MAN2C1):c.600+1delLikely pathogenic
Congenital disorder of deglycosylation 2
★☆☆☆2024
NM_006715.4(MAN2C1):c.2109_2141+4delinsAGTLikely pathogenic
Congenital disorder of deglycosylation 2
★☆☆☆2024
NM_006715.4(MAN2C1):c.2612G>C (p.Cys871Ser)Likely pathogenic
Congenital disorder of deglycosylation 2
★☆☆☆2023→ Residue 871
NM_006715.4(MAN2C1):c.607G>A (p.Gly203Arg)Likely pathogenic
Congenital disorder of deglycosylation 2
★☆☆☆2023→ Residue 203
NM_006715.4(MAN2C1):c.1235G>A (p.Trp412Ter)Likely pathogenic
Congenital disorder of deglycosylation 2
★☆☆☆2023→ Residue 412
NM_006715.4(MAN2C1):c.2733_2734del (p.His911fs)Likely pathogenic
Congenital disorder of deglycosylation 2
★☆☆☆2022→ Residue 911
NM_006715.4(MAN2C1):c.2791_2792del (p.Leu931fs)Likely pathogenic
Congenital disorder of deglycosylation 2
★☆☆☆→ Residue 931
View on ClinVar ↗
Related Genes
MAN1B1Protein interaction97%EDEM1Protein interaction94%MMP24-AS1-EDEM2Protein interaction94%EDEM2Protein interaction92%MAN2B2Protein interaction86%MOGSProtein interaction85%
Tissue Expression6 tissues
Ovary
100%
Bone Marrow
85%
Lung
79%
Liver
63%
Heart
59%
Brain
8%
Gene Interaction Network
Click a node to explore
MAN2C1MAN1B1EDEM1MMP24-AS1-EDEM2EDEM2MAN2B2MOGS
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q9NTJ4
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.01LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.87 [0.74–1.01]
RankingsWhere MAN2C1 stands among ~20K protein-coding genes
  • #8,220of 20,598
    Most Researched55
  • #2,965of 5,498
    Most Pathogenic Variants9
  • #9,887of 17,882
    Most Constrained (LOEUF)1.01
Genes detectedMAN2C1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Impaired catabolism of free oligosaccharides due to MAN2C1 variants causes a neurodevelopmental disorder.
PMID: 35045343
Am J Hum Genet · 2022
1.00
2
Exome Sequencing and the Identification of New Genes and Shared Mechanisms in Polymicrogyria.
PMID: 37486637
JAMA Neurol · 2023
0.90
3
Gene expression and methylation signatures of MAN2C1 are associated with PTSD.
PMID: 21508515
Dis Markers · 2011
0.80
4
Identification of sixteen novel candidate genes for late onset Parkinson's disease.
PMID: 34148545
Mol Neurodegener · 2021
0.70
5
Inhibition of alpha-mannosidase Man2c1 gene expression suppresses growth of esophageal carcinoma cells through mitotic arrest and apoptosis.
PMID: 19018777
Cancer Sci · 2008
0.60