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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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GCNT2
glucosaminyl (N-acetyl) transferase 2 (I blood group)
Chromosome 6 · 6p24.3-p24.2
NCBI Gene: 2651Ensembl: ENSG00000111846.21HGNC: HGNC:4204UniProt: Q8N0V5
39PubMed Papers
1Diseases
0Drugs
12Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingN-acetyllactosaminide beta-1,6-N-acetylglucosaminyltransferase activityglycoprotein biosynthetic processpost-transcriptional regulation of gene expressionCataract 13, with adult i phenotype
✦AI Summary

GCNT2 encodes a β-1,6-N-acetylglucosaminyltransferase that determines expression of the blood group I antigen on erythrocytes by converting linear i-antigen to I-branched glycans 1. Beyond its canonical blood group function, GCNT2 plays a context-dependent role in human disease. In cancer biology, GCNT2 exhibits dual roles depending on cancer type. In melanoma, GCNT2 loss promotes tumor growth and survival by reducing I-branched glycan modifications on insulin-like growth factor receptors and integrins, thereby dampening critical signaling pathways 2. Conversely, GCNT2 overexpression drives progression in esophageal squamous cell carcinoma and prostate cancer by inducing epithelial-mesenchymal transition (EMT) and enhancing migration/invasion through α5β1 integrin signaling 34. In acute myeloid leukemia, hypomethylation of GCNT2 isoform A associates with high-risk disease and poor survival 5. Mechanistically, GCNT2 is regulated by miR-199a/b-5p during EMT in colon cancer 1, and its expression is controlled by DNA methylation in AML 5. In bone metabolism, GCNT2 suppression promotes osteoblast differentiation via PI3K/AKT/mTOR pathway activation, suggesting therapeutic potential in osteoporosis 6. GCNT2 represents an emerging biomarker and therapeutic target across multiple malignancies 7.

Sources cited
1
GCNT2 encodes β-1,6-N-acetylglucosaminyltransferase 2 for blood group I antigen synthesis and is upregulated during EMT; regulated by miR-199a/b-5p
PMID: 28542779
2
Loss of GCNT2/I-branched glycans enhances melanoma growth, colony formation, and survival; inversely correlates with clinical progression
PMID: 30135430
3
GCNT2 overexpression promotes EMT, migration, and invasion in esophageal squamous cell carcinoma; associated with poor overall survival
PMID: 30575058
4
GCNT2 regulates prostate cancer invasiveness by enhancing α5β1 integrin signaling and I-antigen expression on cell surface
PMID: 26678556
5
GCNT2 acts as oncogene in AML; epigenetically regulated by DNA methylation; hypomethylation predicts poor survival and immune cell infiltration
PMID: 40034691
6
GCNT2 knockdown promotes osteoblast differentiation by activating PI3K/AKT/mTOR pathway in osteoporosis model
PMID: 41298859
7
GCNT2 is emerging biomarker and therapeutic target in metastatic melanoma with role in aberrant glycosylation and pathogenesis
PMID: 33660254
8
GCNT2 identified as key regulator of γ-globin switching; modulated by hydroxyurea and metformin in fetal hemoglobin production
PMID: 40200166
Disease Associationsⓘ1
Cataract 13, with adult i phenotypeUniProt
Pathogenic Variants12
NM_145649.5(GCNT2):c.1046A>G (p.Tyr349Cys)Pathogenic
Cataract 13 with adult I phenotype
★★☆☆2024→ Residue 349
NM_145649.5(GCNT2):c.1049G>A (p.Gly350Glu)Pathogenic
Cataract 13 with adult I phenotype
★☆☆☆2025→ Residue 350
NM_001491.3(GCNT2):c.760dup (p.His254fs)Pathogenic
Inborn genetic diseases
★☆☆☆2025→ Residue 254
NM_145649.5(GCNT2):c.1000A>T (p.Arg334Ter)Pathogenic
Cataract 13 with adult I phenotype
★☆☆☆2023→ Residue 334
NM_001491.3(GCNT2):c.60del (p.Ile20fs)Pathogenic
Cataract 13 with adult I phenotype
★☆☆☆2023→ Residue 20
NM_001491.3(GCNT2):c.760del (p.His254fs)Pathogenic
Cataract 13 with adult I phenotype
★☆☆☆2023→ Residue 254
NM_145649.5(GCNT2):c.14G>A (p.Trp5Ter)Pathogenic
Cataract 13 with adult I phenotype|GCNT2-related disorder
★☆☆☆2021→ Residue 5
NM_001491.3(GCNT2):c.710_711insT (p.Lys237fs)Pathogenic
Cataract 13 with adult I phenotype
★☆☆☆2017→ Residue 237
NM_145649.5(GCNT2):c.1091T>C (p.Phe364Ser)Pathogenic
Developmental cataract
☆☆☆☆2016→ Residue 364
NM_145649.5(GCNT2):c.1169_1172del (p.Asn390fs)Likely pathogenic
Developmental cataract
☆☆☆☆2016→ Residue 390
NM_145649.5(GCNT2):c.683G>A (p.Arg228Gln)Pathogenic
ADULT i BLOOD GROUP PHENOTYPE
☆☆☆☆2003→ Residue 228
NM_145649.5(GCNT2):c.505G>A (p.Ala169Thr)Pathogenic
ADULT i BLOOD GROUP PHENOTYPE
☆☆☆☆2003→ Residue 169
View on ClinVar ↗
Related Genes
B4GALT1Protein interaction99%B3GNT3Protein interaction95%ST3GAL6Protein interaction95%B3GNT2Protein interaction93%B4GALT4Protein interaction92%FUT1Protein interaction92%
Tissue Expression

No tissue expression data available for this gene.

Gene Interaction Network
Click a node to explore
GCNT2B4GALT1B3GNT3ST3GAL6B3GNT2B4GALT4FUT1
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q8N0V5
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.37LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.99 [0.73–1.37]
RankingsWhere GCNT2 stands among ~20K protein-coding genes
  • #10,326of 20,598
    Most Researched39
  • #2,701of 5,498
    Most Pathogenic Variants12
  • #14,276of 17,882
    Most Constrained (LOEUF)1.37
Genes detectedGCNT2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Melanoma-associated glycosyltransferase GCNT2 as an emerging biomarker and therapeutic target.
PMID: 33660254
Br J Dermatol · 2021
1.00
2
Hypomethylation of
PMID: 40034691
Front Immunol · 2025
0.90
3
GCNT2 induces epithelial-mesenchymal transition and promotes migration and invasion in esophageal squamous cell carcinoma cells.
PMID: 30575058
Cell Biochem Funct · 2019
0.80
4
I-branching N-acetylglucosaminyltransferase regulates prostate cancer invasiveness by enhancing α5β1 integrin signaling.
PMID: 26678556
Cancer Sci · 2016
0.70
5
Knockdown of GCNT2 promoted osteoblast differentiation by activating PI3K/AKT/mTOR pathway in osteoblasts.
PMID: 41298859
Sci Rep · 2025
0.60