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GeneE
10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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GBGT1
globoside alpha-1,3-N-acetylgalactosaminyltransferase 1 (FORS blood group)
Chromosome 9 · 9q34.2
NCBI Gene: 26301Ensembl: ENSG00000148288.14HGNC: HGNC:20460UniProt: J7Q0Z1
19PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
Golgi apparatusvesiclegloboside alpha-N-acetylgalactosaminyltransferase activityglycolipid biosynthetic processneurodegenerative diseaseCOVID-19rheumatoid arthritisovarian cancer
✦AI Summary

GBGT1 encodes globoside alpha-1,3-N-acetylgalactosaminyltransferase 1, a glycosyltransferase involved in glycosphingolipid metabolism. In most humans, GBGT1 is functionally inactive due to two conserved inactivating missense mutations (c.688G>A [p.Gly230Ser] and c.887A>G [p.Gln296Arg]) that prevent synthesis of the Forssman (FORS1) glycosphingolipid antigen 1. However, reversion of these mutations restores enzymatic activity to synthesize FORS1 on red blood cells and other tissues 1. Rare individuals carrying the c.887G>A mutation express functional GBGT1 and display the FORS1+ blood group phenotype 2. GBGT1 expression is epigenetically regulated by DNA methylation in various tissues, with particularly high expression in normal ovary tissue but silenced expression in most ovarian cancer cell lines through promoter hypermethylation 3. Most humans naturally produce anti-FORS1 antibodies, with notably no anti-FORS1 detected in ABO A1 or A1B blood groups 2. GBGT1 is evolutionarily conserved despite its pseudogene status in humans, suggesting continued selective pressure 4. Clinically, while GBGT1 is dispensable in humans, FORS1 serves as a receptor for various pathogens and has been detected in cancer tissues 5, and elevated GBGT1 protein levels show promise as a biomarker for unstable angina 6.

Sources cited
1
Two common inactivating missense mutations in human GBGT1 (c.688G>A and c.887A>G) prevent Forssman antigen synthesis; reversion restores activity
PMID: 23240079
2
GBGT1 is allelically diverse with multiple variants; c.887G>A mutation enables FORS1 expression; humans are viable GBGT1 knockouts; anti-FORS1 absent in A1/A1B blood groups
PMID: 30277576
3
GBGT1 expression is epigenetically regulated by DNA methylation; highly expressed in normal ovary but silenced in ovarian cancer through promoter hypermethylation
PMID: 25294702
4
GBGT1 is a pseudogene in catarrhine primates but remains evolutionarily conserved despite inactivation, suggesting ongoing selective pressure
PMID: 28044107
5
FORS1 antigen serves as receptor for pathogens and toxins; detected in various cancers; most people have naturally occurring anti-FORS1
PMID: 28657765
6
Elevated GBGT1 protein levels identified as diagnostic biomarker for unstable angina with area under curve of 0.900
PMID: 41445034
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.39Weak
COVID-19Open Targets
0.15Weak
rheumatoid arthritisOpen Targets
0.13Weak
ovarian cancerOpen Targets
0.08Suggestive
46,XX testicular disorder of sex developmentOpen Targets
0.05Suggestive
46,XY disorder of sex development due to 5-alpha-reductase 2 deficiencyOpen Targets
0.05Suggestive
46,XX ovotesticular disorder of sex developmentOpen Targets
0.05Suggestive
azoospermiaOpen Targets
0.05Suggestive
46,XY complete gonadal dysgenesisOpen Targets
0.05Suggestive
Testicular regression syndromeOpen Targets
0.05Suggestive
thrombocytopenia 4Open Targets
0.05Suggestive
hypogonadotropic hypogonadism 11 with or without anosmiaOpen Targets
0.05Suggestive
cryptorchidismOpen Targets
0.04Suggestive
spermatogenic failure 71Open Targets
0.04Suggestive
partial chromosome Y deletionOpen Targets
0.04Suggestive
hypogonadotropic hypogonadism 14 with or without anosmiaOpen Targets
0.04Suggestive
ring chromosome YOpen Targets
0.04Suggestive
Leydig cell hypoplasiaOpen Targets
0.04Suggestive
spermatogenic failure, X-linked, 2Open Targets
0.04Suggestive
familial adrenal hypoplasia with absent pituitary luteinizing hormoneOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
HEXAProtein interaction90%HEXBProtein interaction90%NAGAProtein interaction90%B3GALNT1Protein interaction90%B3GALT5Protein interaction90%IDNKShared pathway50%
Tissue Expression6 tissues
Ovary
100%
Lung
91%
Bone Marrow
56%
Heart
39%
Brain
14%
Liver
10%
Gene Interaction Network
Click a node to explore
GBGT1HEXAHEXBNAGAB3GALNT1B3GALT5IDNK
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q8N5D6
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.25LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.82 [0.55–1.25]
RankingsWhere GBGT1 stands among ~20K protein-coding genes
  • #14,434of 20,598
    Most Researched19
  • #13,140of 17,882
    Most Constrained (LOEUF)1.25
Genes detectedGBGT1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Expression of the
PMID: 31933576
Transfus Med Hemother · 2019
1.00
2
Evolutionary divergence of the ABO and GBGT1 genes specifying the ABO and FORS blood group systems through chromosomal rearrangements.
PMID: 28839219
Sci Rep · 2017
0.90
3
Molecular Evolution of the Glycosyltransferase 6 Gene Family in Primates.
PMID: 28044107
Biochem Res Int · 2016
0.80
4
Expression of GBGT1 is epigenetically regulated by DNA methylation in ovarian cancer cells.
PMID: 25294702
BMC Mol Biol · 2014
0.70
5
GBGT1 is allelically diverse but dispensable in humans and naturally occurring anti-FORS1 shows an ABO-restricted pattern.
PMID: 30277576
Transfusion · 2018
0.60