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UDP-Gal + Galbeta1,4Glc-PAA
UDP + ?
i.e. Lac-PAA, precursor to Pk
-
-
?
UDP-Gal + Galbeta1,4GlcNAcbeta1,3Galbeta1,4Glc-PAA
UDP + ?
i.e. nLc4-PAA, precursor to P1
-
-
?
UDP-Gal + GalNAcbeta1,3Galalpha1,4Galbeta1,4Glc-PAA
UDP + ?
i.e. Gbeta4-PAA, precursor to NOR1
-
-
?
UDP-galactose + beta-D-galactosyl-(1,4)-D-glucosylceramide
UDP + alpha-D-galactosyl-(1,4)-beta-D-galactosyl-(1,4)-D-glucosylceramide
-
-
-
-
?
UDP-galactose + beta-D-galactosyl-(1,4)-N-acetyl-beta-D-glucosaminyl-alpha-D-galactosyl-(1,4)-beta-D-glucosylceramide
UDP + alpha-D-galactosyl-(1,4)-beta-D-galactosyl-(1,4)-N-acetyl-beta-D-glucosaminyl-alpha-D-galactosyl-(1,4)-beta-D-glucosylceramide
-
P1 antigen synthesis
-
-
?
UDP-galactose + beta-D-galactosyl-(1-4)-D-glucosyl-(1-1)-ceramide
UDP + alpha-D-galactosyl-(1-4)-beta-D-galactosyl-(1-4)-D-glucosyl-(1-1)-ceramide
UDP-galactose + beta-D-galactosyl-(1-4)-D-glucosylceramide
UDP + alpha-D-galactosyl-(1-4)-beta-D-galactosyl-(1-4)-D-glucosylceramide
UDP-galactose + galactosylceramide
?
-
-
-
-
?
UDP-galactose + lactose
?
UDP-galactose + lactosylceramide
UDP + globotriaosylceramide
additional information
?
-
UDP-galactose + beta-D-galactosyl-(1-4)-D-glucosyl-(1-1)-ceramide
UDP + alpha-D-galactosyl-(1-4)-beta-D-galactosyl-(1-4)-D-glucosyl-(1-1)-ceramide
-
-
-
-
?
UDP-galactose + beta-D-galactosyl-(1-4)-D-glucosyl-(1-1)-ceramide
UDP + alpha-D-galactosyl-(1-4)-beta-D-galactosyl-(1-4)-D-glucosyl-(1-1)-ceramide
-
-
-
?
UDP-galactose + beta-D-galactosyl-(1-4)-D-glucosylceramide
UDP + alpha-D-galactosyl-(1-4)-beta-D-galactosyl-(1-4)-D-glucosylceramide
-
-
-
?
UDP-galactose + beta-D-galactosyl-(1-4)-D-glucosylceramide
UDP + alpha-D-galactosyl-(1-4)-beta-D-galactosyl-(1-4)-D-glucosylceramide
-
-
-
?
UDP-galactose + beta-D-galactosyl-(1-4)-D-glucosylceramide
UDP + alpha-D-galactosyl-(1-4)-beta-D-galactosyl-(1-4)-D-glucosylceramide
-
-
-
?
UDP-galactose + beta-D-galactosyl-(1-4)-D-glucosylceramide
UDP + alpha-D-galactosyl-(1-4)-beta-D-galactosyl-(1-4)-D-glucosylceramide
-
-
-
?
UDP-galactose + beta-D-galactosyl-(1-4)-D-glucosylceramide
UDP + alpha-D-galactosyl-(1-4)-beta-D-galactosyl-(1-4)-D-glucosylceramide
-
-
-
?
UDP-galactose + beta-D-galactosyl-(1-4)-D-glucosylceramide
UDP + alpha-D-galactosyl-(1-4)-beta-D-galactosyl-(1-4)-D-glucosylceramide
-
-
-
?
UDP-galactose + beta-D-galactosyl-(1-4)-D-glucosylceramide
UDP + alpha-D-galactosyl-(1-4)-beta-D-galactosyl-(1-4)-D-glucosylceramide
-
-
-
?
UDP-galactose + lactose
?
-
-
-
-
?
UDP-galactose + lactose
?
-
-
-
-
?
UDP-galactose + lactosylceramide
UDP + globotriaosylceramide
-
-
-
?
UDP-galactose + lactosylceramide
UDP + globotriaosylceramide
-
-
-
?
UDP-galactose + lactosylceramide
UDP + globotriaosylceramide
-
-
-
-
?
UDP-galactose + lactosylceramide
UDP + globotriaosylceramide
-
UDP-galactose is the sole sugar donor
-
?
UDP-galactose + lactosylceramide
UDP + globotriaosylceramide
-
reduction of enzyme activity following retinoic acid induced differentiation
-
?
UDP-galactose + lactosylceramide
UDP + globotriaosylceramide
-
in the small p cells in vitro only
-
?
UDP-galactose + lactosylceramide
UDP + globotriaosylceramide
-
-
-
?
UDP-galactose + lactosylceramide
UDP + globotriaosylceramide
-
UDP-galactose is the sole sugar donor
-
?
additional information
?
-
-
substrate specificity
-
-
?
additional information
?
-
-
globotriaosylceramide, Gb3, is synthesized from lactosylceramide by alpha1,4-galactosyltransferase Gb3/CD77 synthase
-
-
?
additional information
?
-
the consensus enzyme synthesizes both the Pk and P1 antigens, while its p.Q211E variant additionally synthesizes the NOR antigen
-
-
?
additional information
?
-
-
the consensus enzyme synthesizes both the Pk and P1 antigens, while its p.Q211E variant additionally synthesizes the NOR antigen
-
-
?
additional information
?
-
-
targeted disruption of Gb3/CD77 synthase gene results in the complete deletion of globo-series glycosphingolipids and loss of sensitivity to verotoxins
-
-
?
additional information
?
-
-
no substrates: galactosylceramide, glucosylceramide, neolactotetraose, neolactotetraosylceramide
-
-
?
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UDP-galactose + beta-D-galactosyl-(1,4)-D-glucosylceramide
UDP + alpha-D-galactosyl-(1,4)-beta-D-galactosyl-(1,4)-D-glucosylceramide
-
-
-
-
?
UDP-galactose + beta-D-galactosyl-(1,4)-N-acetyl-beta-D-glucosaminyl-alpha-D-galactosyl-(1,4)-beta-D-glucosylceramide
UDP + alpha-D-galactosyl-(1,4)-beta-D-galactosyl-(1,4)-N-acetyl-beta-D-glucosaminyl-alpha-D-galactosyl-(1,4)-beta-D-glucosylceramide
-
P1 antigen synthesis
-
-
?
UDP-galactose + beta-D-galactosyl-(1-4)-D-glucosyl-(1-1)-ceramide
UDP + alpha-D-galactosyl-(1-4)-beta-D-galactosyl-(1-4)-D-glucosyl-(1-1)-ceramide
UDP-galactose + beta-D-galactosyl-(1-4)-D-glucosylceramide
UDP + alpha-D-galactosyl-(1-4)-beta-D-galactosyl-(1-4)-D-glucosylceramide
UDP-galactose + lactosylceramide
UDP + globotriaosylceramide
-
-
-
-
?
additional information
?
-
UDP-galactose + beta-D-galactosyl-(1-4)-D-glucosyl-(1-1)-ceramide
UDP + alpha-D-galactosyl-(1-4)-beta-D-galactosyl-(1-4)-D-glucosyl-(1-1)-ceramide
-
-
-
-
?
UDP-galactose + beta-D-galactosyl-(1-4)-D-glucosyl-(1-1)-ceramide
UDP + alpha-D-galactosyl-(1-4)-beta-D-galactosyl-(1-4)-D-glucosyl-(1-1)-ceramide
-
-
-
?
UDP-galactose + beta-D-galactosyl-(1-4)-D-glucosylceramide
UDP + alpha-D-galactosyl-(1-4)-beta-D-galactosyl-(1-4)-D-glucosylceramide
-
-
-
?
UDP-galactose + beta-D-galactosyl-(1-4)-D-glucosylceramide
UDP + alpha-D-galactosyl-(1-4)-beta-D-galactosyl-(1-4)-D-glucosylceramide
-
-
-
?
UDP-galactose + beta-D-galactosyl-(1-4)-D-glucosylceramide
UDP + alpha-D-galactosyl-(1-4)-beta-D-galactosyl-(1-4)-D-glucosylceramide
-
-
-
?
UDP-galactose + beta-D-galactosyl-(1-4)-D-glucosylceramide
UDP + alpha-D-galactosyl-(1-4)-beta-D-galactosyl-(1-4)-D-glucosylceramide
-
-
-
?
UDP-galactose + beta-D-galactosyl-(1-4)-D-glucosylceramide
UDP + alpha-D-galactosyl-(1-4)-beta-D-galactosyl-(1-4)-D-glucosylceramide
-
-
-
?
UDP-galactose + beta-D-galactosyl-(1-4)-D-glucosylceramide
UDP + alpha-D-galactosyl-(1-4)-beta-D-galactosyl-(1-4)-D-glucosylceramide
-
-
-
?
UDP-galactose + beta-D-galactosyl-(1-4)-D-glucosylceramide
UDP + alpha-D-galactosyl-(1-4)-beta-D-galactosyl-(1-4)-D-glucosylceramide
-
-
-
?
additional information
?
-
-
globotriaosylceramide, Gb3, is synthesized from lactosylceramide by alpha1,4-galactosyltransferase Gb3/CD77 synthase
-
-
?
additional information
?
-
-
targeted disruption of Gb3/CD77 synthase gene results in the complete deletion of globo-series glycosphingolipids and loss of sensitivity to verotoxins
-
-
?
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malfunction
-
overexpression of the truncated form of N-methyl-D-asparate-associated protein 1, GRINA-C, and some members of the full-length TMBIM family, including FAS inhibitory molecule 2, reduces Gb3, leading to accumulation of lactosylceramide. The change of glycolipid composition is restored by overexpression of Gb3 synthase, although the mRNA level of Gb3 synthase is unchanged. GRINA-C is associated with Gb3 synthase. Reduction of only the mature form of Gb3 synthase by the expression of GRINA-C is restored by addition of lysosome inhibitors, reduction of Gb3 synthase after overexpression through increased lysosomal degenaration. Phenotypes, overview
malfunction
-
the inhibitory effect of 1-deoxygalactonojirimycin on alpha-galactosidase A activity causes Gb3 accumulation in G3S/COS-7 cells. Fabry disease is a lysosomal storage disorder caused by an alpha-galactosidase A deficiency and resulting in the accumulation of glycosphingolipids, predominantly globotriaosylceramide
malfunction
-
effect of GCS inhibitor DL-threo-1-phenyl-2-palmitoylamino-3-morpholino-1-propanol and multidrug resistance 1/P-glycoprotein, MDR1, pump inhibitor cyclosporin A on expression and cisplatin cytotoxicity. Enzyme inhibition potentiates cisplatin cytotoxicity in H1299 cells and abolishes cell surface globotriaosylceramide (Gb3) expression of resistant cells
malfunction
deletion of A4GALT significantly increases the number of extravasated cells and more clusters are formed as compared with parental cells. The deletion of A4GALT leads to increased cell motility and invasiveness in vitro as well as in vivo, features commonly accompanied with epithelial-to-mesenchymal transition
malfunction
habitual abortion in a Chinese woman is caused by the synonymous 903C>G mutation in the A4GALT gene. The synonymous mutation of 903C>G in the A4GALT gene causes the p phenotype in P1Pk blood system and it is the in vivo anti-PP1Pk antibody of the patient that causes habitual abortion
metabolism
single nucleotide polymorphisms in A4GALT spur extra products of the human Gb3/CD77 synthase and underlie the P1PK blood group system
metabolism
the enzyme is responsible for biosynthesis of Gal(alpha1-4)Gal moiety in Gb3 (CD77, Pk antigen) and P1 glycosphingolipids
physiological function
-
globotriaosylceramide, Gb3, synthesized from lactosylceramide by alpha1,4-galactosyltransferase Gb3/CD77 synthase, is a well known receptor for Shiga toxin, Stx, produced by enterohemorrhagic Escherichia coli and Shigella dysenteriae
physiological function
the enzyme is involved in the biosynthesis of unique globoside (Gb4Cer) derivatives, NOR1, NORint, and NOR2, in which Gal(alpha1-4), GalNAc(beta1-3)Gal(alpha1-4), and Gal(alpha1-4)GalNAc(beta1-3)Gal(alpha1-4), respectively, are linked to the terminal GalNAc residue of Gb4Cer, transfer of Gal to GalNAc, overview
physiological function
-
Ceramide increases in response to chemotherapy, leading to proliferation arrest and apoptosis. A tumour stress activation of glucosylceramide synthase follows to eliminate ceramide by formation of glycosphingolipids (GSLs) such as globotriaosylceramide (Gb3), the functional receptor of verotoxin-1
physiological function
the enzyme catalyzes the synthesis of Gal(alpha1-4)Gal moiety in globotriaosylceramide (Gb3Cer, CD77, Pk blood group antigen), a glycosphingolipid of the globo series
physiological function
the A4GALT gene encodes the alpha1-4 galactosyltransferase, a key enzyme responsible for synthesis of globoside glycosphingolipids. Globo series-related genes, and in particular, A4GALT, are elevated in epithelial cancer cells and associated with improved patient's outcome
additional information
-
overexpression of Gb3 synthase in transgenic TgG3S mice, phenotype, overview. Age-related increase in the kidney Gb3 content in TgG3S(+/-)M(+/-)/KO mice, while neither the Gb3 content in the heart nor the alpha-galactosidase A activity in the heart or kidney change during this time
additional information
the naturally occuring mutation Q211E enables the Gb3/CD77 synthase mutant to synthesize unique globoside (Gb4Cer) NOR derivatives, overview. The NOR antigen appears as a result of the C631G mutation in the gene encoding Gb3/CD77 synthase. Expression of NOR antigen is correlated with expression of the P1 antigen
additional information
-
the naturally occuring mutation Q211E enables the Gb3/CD77 synthase mutant to synthesize unique globoside (Gb4Cer) NOR derivatives, overview. The NOR antigen appears as a result of the C631G mutation in the gene encoding Gb3/CD77 synthase. Expression of NOR antigen is correlated with expression of the P1 antigen
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Taniguchi, N.; Yanagisawa, K.; Makita, A.; Naiki, M.
Purification and properties of rat liver globotriaosylceramide synthase, UDP-galactose:lactosylceramide alpha1-4-galactosyltransferase
J. Biol. Chem.
260
4908-4913
1985
Rattus norvegicus
brenda
Bailly, P.; Piller, F.; Cartron, J.P.; Leroy, Y.; Fournet, B.
Identification of UDP-galactose:lactose (lactosylceramide) alpha-4 and beta-3 galactosyltransferases in human kidney
Biochem. Biophys. Res. Commun.
141
84-91
1986
Homo sapiens
brenda
Iizuka, S.; Chen, S.H.; Yoshida, A.
Studies on the human blood group P system: an existence of UDP-Gal: lactosylceramide alpha 1 -> 4 galactosyltransferase in the small p type cells
Biochem. Biophys. Res. Commun.
137
1187-1195
1986
Homo sapiens
brenda
Chen, C.; Fenderson, B.A.; Andrews, P.W.; Hakomori, S.
Glycolipid glycosyltransferases in human embryonal carcinoma cells during retinoic acid induced differentiation
Biochemistry
28
2229-2238
1989
Homo sapiens
brenda
Stults, C.L.M.; Larsen, R.D.; Macher, B.A.
alpha-1,4Galactosyltransferase activity and Gbeta3Cer expression in human leukemia/lymphoma cell lines
Glycoconj. J.
12
680-689
1995
Homo sapiens
brenda
Mobassaleh, M.; Koul, O.; Mishra, K.; McCluer, R.H.; Keusch, G.T.
Developmentally regulated Gb3 galactosyltransferase and alpha-galactosidase determine Shiga toxin receptors in intestine
Am. J. Physiol.
267
G618-G624
1994
Oryctolagus cuniculus
brenda
Kojima, Y.; Fukumoto, S.; Furukawa, K.; Okajima, T.; Wiels, J.; Yokoyama, K.; Suzuki, Y.; Urano, T.; Ohta, M.; Furukawa, K.
Molecular cloning of globotriaosylceramide/CD77 synthase, a glycosyltransferase that initiates the synthesis of Globo series glycosphingolipids
J. Biol. Chem.
275
15152-15156
2000
Homo sapiens
brenda
Steffensen, R.; Carlier, K.; Wiels, J.; Levery, S.B.; Stroud, M.; Cedergren, B.; Sojka, B.N.; Bennett, E.P.; Jersild, C.; Clausen, H.
Cloning and expression of the histo-blood group Pk UDP-galactose: Galbeta1-4Glcbeta1-Cer alpha1,4-galactosyltransferase. Molecular genetic basis of the p phenotype
J. Biol. Chem.
275
16723-16729
2000
Homo sapiens (Q9NPC4), Homo sapiens
brenda
Iwamura, K.; Furukawa, K.; Uchikawa, M.; Sojka, B.N.; Kojima, Y.; Wiels, J.; Shiku, H.; Urano, T.; Furukawa, K.
The blood group P1 synthase gene is identical to the Gb3/CD77 synthase gene: a clue to the solution of the P1/P2/p puzzle
J. Biol. Chem.
278
44429-44438
2003
Homo sapiens
brenda
Okuda, T.; Tokuda, N.; Numata, S.; Ito, M.; Ohta, M.; Kawamura, K.; Wiels, J.; Urano, T.; Tajima, O.; Furukawa, K.; Furukawa, K.
Targeted disruption of Gb3/CD77 synthase gene resulted in the complete deletion of globo-series glycosphingolipids and loss of sensitivity to verotoxins
J. Biol. Chem.
281
10230-10235
2006
Mus musculus
brenda
Okuda, T.; Nakayama, K.I.
Identification and characterization of the human Gb3/CD77 synthase gene promoter
Glycobiology
18
1028-1035
2008
Homo sapiens
brenda
Schweppe, C.H.; Bielaszewska, M.; Pohlentz, G.; Friedrich, A.W.; Buentemeyer, H.; Alexander Schmidt, M.; Kim, K.S.; Peter-Katalini?, J.; Karch, H.; Muething, J.
Glycosphingolipids in vascular endothelial cells: relationship of heterogeneity in Gb3Cer/CD77 receptor expression with differential Shiga toxin 1 cytotoxicity
Glycoconj. J.
25
291-304
2008
Homo sapiens (Q9NPC4), Homo sapiens
brenda
Shin, I.S.; Ishii, S.; Shin, J.S.; Sung, K.I.; Park, B.S.; Jang, H.Y.; Kim, B.W.
Globotriaosylceramide (Gb3) content in HeLa cells is correlated to Shiga toxin-induced cytotoxicity and Gb3 synthase expression
BMB Rep.
42
310-314
2009
Homo sapiens
brenda
Okuda, T.; Furukawa, K.; Nakayama, K.
A novel, promoter-based, target-specific assay identifies 2-deoxy-D-glucose as an inhibitor of globotriaosylceramide biosynthesis
FEBS J.
276
5191-5202
2009
Homo sapiens
brenda
Ramkumar, S.; Sakac, D.; Binnington, B.; Branch, D.R.; Lingwood, C.A.
Induction of HIV-1 resistance: cell susceptibility to infection is an inverse function of globotriaosyl ceramide levels
Glycobiology
19
76-82
2009
Homo sapiens
brenda
Shiozuka, C.; Taguchi, A.; Matsuda, J.; Noguchi, Y.; Kunieda, T.; Uchio-Yamada, K.; Yoshioka, H.; Hamanaka, R.; Yano, S.; Yokoyama, S.; Mannen, K.; Kulkarni, A.B.; Furukawa, K.; Ishii, S.
Increased globotriaosylceramide levels in a transgenic mouse expressing human alpha1,4-galactosyltransferase and a mouse model for treating Fabry disease
J. Biochem.
149
161-170
2011
Homo sapiens
brenda
Yamaji, T.; Nishikawa, K.; Hanada, K.
Transmembrane BAX inhibitor motif containing (TMBIM) family proteins perturbs a trans-Golgi network enzyme, Gb3 synthase, and reduces Gb3 biosynthesis
J. Biol. Chem.
285
35505-35518
2010
Homo sapiens
brenda
Suchanowska, A.; Kaczmarek, R.; Duk, M.; Lukasiewicz, J.; Smolarek, D.; Majorczyk, E.; Jaskiewicz, E.; Laskowska, A.; Wasniowska, K.; Grodecka, M.; Lisowska, E.; Czerwinski, M.
A single point mutation in the gene encoding Gb3/CD77 synthase causes a rare inherited polyagglutination syndrome
J. Biol. Chem.
287
38220-38230
2012
Homo sapiens (Q9NPC4), Homo sapiens
brenda
Kaczmarek, R.; Duk, M.; Szymczak, K.; Korchagina, E.; Tyborowska, J.; Mikolajczyk, K.; Bovin, N.; Szewczyk, B.; Jaskiewicz, E.; Czerwinski, M.
Human Gb3/CD77 synthase reveals specificity toward two or four different acceptors depending on amino acid at position 211, creating Pk, P1 and NOR blood group antigens
Biochem. Biophys. Res. Commun.
470
168-174
2016
Homo sapiens (Q9NPC4), Homo sapiens
brenda
Tyler, A.; Johansson, A.; Karlsson, T.; Gudey, S.K.; Braennstroem, T.; Grankvist, K.; Behnam-Motlagh, P.
Targeting glucosylceramide synthase induction of cell surface globotriaosylceramide (Gb3) in acquired cisplatin-resistance of lung cancer and malignant pleural mesothelioma cells
Exp. Cell Res.
336
23-32
2015
Homo sapiens
brenda
Jacob, F.; Alam, S.; Konantz, M.; Liang, C.Y.; Kohler, R.S.; Everest-Dass, A.V.; Huang, Y.L.; Rimmer, N.; Fedier, A.; Schoetzau, A.; Lopez, M.N.; Packer, N.H.; Lengerke, C.; Heinzelmann-Schwarz, V.
Transition of mesenchymal and epithelial cancer cells depends on alpha1-4 galactosyltransferase-mediated glycosphingolipids
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78
2952-2965
2018
Homo sapiens (Q9NPC4)
brenda
Kaczmarek, R.; Mikolajewicz, K.; Szymczak, K.; Duk, M.; Majorczyk, E.; Krop-Watorek, A.; Buczkowska, A.; Czerwinski, M.
Evaluation of an amino acid residue critical for the specificity and activity of human Gb3/CD77 synthase
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33
963-973
2016
Homo sapiens (Q9NPC4), Homo sapiens
brenda
Lv, X.; Chen, Y.; Luo, Y.; Li, L.; Wang, H.
The synonymous 903C>G mutation in the alpha 1,4-galactosyltransferase gene in a Chinese woman with habitual abortion A case report
Medicine (Baltimore)
98
e16361
2019
Homo sapiens (Q9NPC4), Homo sapiens
brenda
Kaczmarek, R.; Szymczak-Kulus, K.; Bereznicka, A.; Mikolajczyk, K.; Duk, M.; Majorczyk, E.; Krop-Watorek, A.; Klausa, E.; Skowronska, J.; Michalewska, B.; Brojer, E.; Czerwinski, M.
Single nucleotide polymorphisms in A4GALT spur extra products of the human Gb3/CD77 synthase and underlie the P1PK blood group system
PLoS ONE
13
e0196627
2018
Homo sapiens (Q9NPC4), Homo sapiens
brenda