ABO

Summary

ABO (ABO, alpha 1-3-N-acetylgalactosaminyltransferase and alpha 1-3-galactosyltransferase, HGNC:79) is a protein-coding gene on chromosome 9q34.2, encoding Histo-blood group ABO system transferase (P16442). This protein is the basis of the ABO blood group system.

This gene encodes proteins related to the first discovered blood group system, ABO. Variation in the ABO gene (chromosome 9q34.2) is the basis of the ABO blood group, thus the presence of an allele determines the blood group in an individual. The ‘O’ blood group is caused by a deletion of guanine-258 near the N-terminus of the protein which results in a frameshift and translation of an almost entirely different protein. Individuals with the A, B, and AB alleles express glycosyltransferase activities that convert the H antigen into the A or B antigen. Other minor alleles have been found for this gene.

Source: NCBI Gene 28 — RefSeq curated summary.

At a glance

• GWAS associations: 364
• Clinical variants (ClinVar): 45 total
• Druggable target: yes
• MANE Select transcript: NM_020469

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:79
Approved symbol	ABO
Name	ABO, alpha 1-3-N-acetylgalactosaminyltransferase and alpha 1-3-galactosyltransferase
Location	9q34.2
Locus type	gene with protein product
Status	Approved
Aliases	A3GALNT, A3GALT1
Ensembl gene	ENSG00000175164
Ensembl biotype	protein_coding
OMIM	110300
Entrez	28

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding_CDS_not_defined, 3 protein_coding

ENST00000453660, ENST00000538324, ENST00000611156, ENST00000647353, ENST00000651471, ENST00000679909, ENST00000680600

RefSeq mRNA: 1 — MANE Select: NM_020469 NM_020469

Canonical transcript exons

ENST00000611156 — 8 exons

Exon	Start	End
ENSE00002288274	133275162	133275214
ENSE00003723632	133258097	133258132
ENSE00003725550	133257409	133257521
ENSE00003728794	133259819	133259866
ENSE00003732073	133261318	133261374
ENSE00003733191	133262099	133262168
ENSE00003736043	133255176	133256356
ENSE00003742406	133257524	133257542

Expression profiles

Bgee: expression breadth ubiquitous, 169 present calls, max score 97.06.

FANTOM5 (CAGE): breadth broad, TPM avg 3.5453 / max 358.8404, expressed in 465 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
102974	1.7164	333
102971	0.4848	130
102970	0.4701	121
102972	0.4543	141
102968	0.2474	78
102973	0.0757	35
102967	0.0596	30
102976	0.0225	10
102975	0.0145	6

Top tissues by expression

269 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	97.06	gold quality
buccal mucosa cell	CL:0002336	96.79	gold quality
right lobe of thyroid gland	UBERON:0001119	95.13	gold quality
right uterine tube	UBERON:0001302	94.97	gold quality
left lobe of thyroid gland	UBERON:0001120	94.00	gold quality
left ovary	UBERON:0002119	93.76	gold quality
rectum	UBERON:0001052	93.57	gold quality
right adrenal gland cortex	UBERON:0035827	93.16	gold quality
thyroid gland	UBERON:0002046	92.52	gold quality
left adrenal gland	UBERON:0001234	92.50	gold quality
right adrenal gland	UBERON:0001233	92.49	gold quality
left adrenal gland cortex	UBERON:0035825	92.36	gold quality
lower esophagus mucosa	UBERON:0035834	92.34	gold quality
mucosa of transverse colon	UBERON:0004991	91.91	gold quality
right ovary	UBERON:0002118	91.66	gold quality
sural nerve	UBERON:0015488	91.47	gold quality
small intestine Peyer’s patch	UBERON:0003454	91.40	gold quality
transverse colon	UBERON:0001157	91.25	gold quality
adrenal cortex	UBERON:0001235	90.78	gold quality
esophagus mucosa	UBERON:0002469	90.54	gold quality
metanephros cortex	UBERON:0010533	89.80	gold quality
small intestine	UBERON:0002108	88.21	gold quality
adrenal gland	UBERON:0002369	88.18	gold quality
ovary	UBERON:0000992	87.44	gold quality
minor salivary gland	UBERON:0001830	85.55	gold quality
adult mammalian kidney	UBERON:0000082	85.11	gold quality
right lung	UBERON:0002167	84.91	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	84.76	gold quality
body of pancreas	UBERON:0001150	84.00	gold quality
right testis	UBERON:0004534	83.70	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.36
E-MTAB-6678	no	3.40

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NFYB, RUNX1, SP1

miRNA regulators (miRDB)

45 targeting ABO, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-379-3P	99.69	69.60	1524
HSA-MIR-411-3P	99.69	69.63	1524
HSA-MIR-567	99.63	68.57	1219
HSA-MIR-4743-3P	99.62	68.12	2095
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-297	99.40	69.58	1418
HSA-MIR-4652-3P	99.33	70.02	2742
HSA-MIR-223-5P	99.24	68.82	1206
HSA-MIR-593-3P	99.22	67.28	1327
HSA-MIR-491-5P	99.13	65.98	1468
HSA-MIR-8070	99.07	69.30	1303
HSA-MIR-4711-3P	98.97	66.87	1020
HSA-MIR-511-5P	98.97	70.94	2268
HSA-MIR-935	98.82	69.36	1072
HSA-MIR-6895-3P	98.79	65.69	996
HSA-MIR-6830-3P	98.62	68.07	1760
HSA-MIR-6818-3P	98.56	68.23	1307

Literature-anchored findings (GeneRIF, showing 40)

• su(f) is required for the cleavage of pre-mRNA during mRNA 3’ end formation (PMID:12149458)
• Data show that overexpression of either heat-shock proteins 26 or 27 extended the mean lifespan by 30%, and the flies also displayed increased stress resistance. (PMID:15308776)
• The data suggest that the Drosophila HSP27 protein acts as a chaperone to provide cellular stress resistance, although its function may be limited to a subset of the stress response such as the starvation resistance. (PMID:18229455)
• study identifies two distinct sets of sequences respectively mediating the nuclear import of Hsp27 and its association to nuclear speckles. (PMID:18339325)
• The functional similarities and differences of neuronal expression of hsp26 and hsp27 in adult Drosophila were demonstrated. (PMID:18796296)
• We propose that Atg7 acts downstream of Hsp27 in the regulation of eye morphology, polyglutamine toxicity, and lifespan in Drosophila. (PMID:22621211)
• The study evidenced the neuroprotective efficacy of hsp27 overexpression against prolonged dichlorvos exposure. (PMID:26033218)
• Altogether, the results characterize wild-type Hsp27 and its alpha-crystallin domain (ACD) arginine mutants and may give insight into protection mechanism of small heat shock proteins. (PMID:27933579)
• We show that while Hsp70 or Hsp83 expression under normal or stress conditions was not affected by AR feeding, Hsp27 levels were elevated in AR-fed wild-type control as well as heat-shocked larvae (PMID:27966490)
• Hsp27, a potential EcR target, protects nonylphenol-induced cellular and organismal toxicity in Drosophila melanogaster. (PMID:34774861)
• Hsp27 over expression protect against cadmium induced nephrotoxicity in Drosophila melanogaster. (PMID:37586579)
• The expression of the ABO promoter is influenced by the binding of transcription factor Sp1 or Sp1-like protein(s) in both erythroid and epithelial cell lineages. (PMID:11856466)
• Alternative promoter identified between a hypermethylated upstream region of repetitive elements and a CpG island in these genes (PMID:12151392)
• Active enzyme expressed from a synthetic gene corresponding to GTB with a P234S mutation shows a dramatic and complete reversal of donor specificity. (PMID:12529355)
• 502C>T missense mutation in the B allele, for the Bel phenotype and an association of the Bel502C>T allele with the Bel phenotype in the Taiwanese population (PMID:14516453)
• Novel O1v-A2 hybrid allele of the ABO blood group that causes missense mutations in the A transferase. (PMID:14617382)
• Genetic and epigenetic alterations of the blood group ABO gene is associated with oral squamous cell carcinoma (PMID:14750174)
• Results suggest that loss of the ABO gene and/or its promoter hypermethylation is a specific marker for transitional cell carcinoma of the bladder. (PMID:15880137)
• Amino acid substitution in the disordered loop of blood group B-glycosyltransferase causes weak B phenotyype. (PMID:15987364)
• We studied the molecular genetic background of the B subgroup in the Chinese Han population and identified a novel allele at the ABO locus. (PMID:16081582)
• Weak A & B subgroups can arise from ABO transferases with single or multiple missense mutations casuing amino acid changes in the N-terminal domain, particularly in AB phenotypes, where normal A1 or B1 glycosyltransferases compete for the same substrates. (PMID:16181218)
• a hypothesis for understanding the association between blood group O and the risk of infection with V. cholerae O1 and O139 as well as the risk of developing severe symptoms once infected (PMID:16239542)
• The probiotic Lactobacillus binds to human blood type-A antigen expressed in the intestinal mucosa which may aid in colonization of the gut. (PMID:16631357)
• characterization of a novel B(A) allele which differs from those reported previously (PMID:16871363)
• Substitution of M214 can cause alternative conformation. (PMID:17259183)
• structure of a single mutant C209A has been determined in the presence and absence of heavy atoms (PMID:17642512)
• Data suggests that weak blood group B phenotypes may be caused by sequence variations in the CBF/NF-Y regulatory region. (PMID:17764507)
• The researchers assessed the admixture genetic components of samples from two socioeconomic levels in Venezuela to identify various genetic aspects in the population. (PMID:18027815)
• study reports the molecular analysis of a novel A(el) allele; a unique 816insG mutation occurred on the A102 background that results in a frame shift leading to a 37-amino acid longer polypeptide than the normal A1 transferase (PMID:18063521)
• ABO genotyping in leukemia patients reveals new ABO variant alleles. (PMID:18273824)
• most A2B genotypes belong to the A205/B allele in Taiwan; we report for the first time the presence of the A205, A201, and cis-AB02 alleles in Taiwan. (PMID:18651204)
• Two novel heterozygous mutations 905A>G and 541T>C were identified, respectively, which resulted in the amino acid changes D302G and W181R in the B glycosyltransferases. (PMID:18680548)
• 2 unrelated Chinese individuals with the A1B3 phenotype were found to have a 425T>C mutation in exon 7 of the B allele, causing an M142T substitution. (PMID:19054377)
• Blood group ABO is a risk factor for pre-eclampsia. (PMID:19110300)
• E-selectin levels have been associated with the ABO blood group phenotype. (PMID:19729612)
• Data show that ABO genotypes were significantly associated with pancreatic cancer risk. (PMID:20103627)
• Genetic variants at ABO locus affect plasma sE-selectin levels and the risk of type 2 diabetes. (PMID:20147318)
• in general the binding of acceptor substrates to retaining glycosyltransferases modulates the rate of glycosyl transfer (PMID:20154292)
• sP-selectin and sICAM-1 were associated with A1 allele variants of the ABO gene. (PMID:20167578)
• the M142T (425 T>C) mutation is responsible for the B subtype phenotype produced by the B305 allele (PMID:20197725)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Abo	ENSMUSG00000015787
rattus_norvegicus	Abo3	ENSRNOG00000039906
rattus_norvegicus	Abo2	ENSRNOG00000077667
rattus_norvegicus		ENSRNOG00000086621

Paralogs (3): GBGT1 (ENSG00000148288), A3GALT2 (ENSG00000184389), GLT6D1 (ENSG00000204007)

Protein

Protein identifiers

Histo-blood group ABO system transferase — P16442 (reviewed: P16442)

Alternative names: Fucosylglycoprotein 3-alpha-galactosyltransferase, Fucosylglycoprotein alpha-N-acetylgalactosaminyltransferase, Glycoprotein-fucosylgalactoside alpha-N-acetylgalactosaminyltransferase, Glycoprotein-fucosylgalactoside alpha-galactosyltransferase, Histo-blood group A transferase, Histo-blood group B transferase, NAGAT

All UniProt accessions (3): A0A087X009, A0A087X0C2, A0A7P0TA91

UniProt curated annotations — full annotation on UniProt →

Function. This protein is the basis of the ABO blood group system. The histo-blood group ABO involves three carbohydrate antigens: A, B, and H. A, B, and AB individuals express a glycosyltransferase activity that converts the H antigen to the A antigen (by addition of N-acetyl-alpha-D-galactosamine (GalNAc)) or to the B antigen (by addition of galactose (Gal)), whereas O individuals lack such activity and express the H antigen precursor unmodified. Catalyzes the transfer of GalNAc or Gal in an alpha1,3 linkage to the terminal Gal of all five types of naturally occurring H antigens, forming the antigenic structures of the A and B blood groups.

Subcellular location. Golgi apparatus. Golgi stack membrane. Secreted.

Tissue specificity. Expressed at high levels in testis. Also expressed in pancreas, uterus and lung and salivary gland.

Post-translational modifications. The soluble form derives from the membrane form by proteolytic processing.

Cofactor. Binds 1 Mn(2+) ion per subunit.

Domain organisation. The conserved DXD motif is involved in cofactor binding. The manganese ion interacts with the beta-phosphate group of UDP and may also have a role in catalysis.

Pathway. Protein modification; protein glycosylation.

Polymorphism. Genetic variations in ABO define the ABO blood group system [MIM:616093]. The ABO blood group system is one of the most important blood group systems in transfusion medicine. The ABO blood group involves 3 carbohydrate antigens: A, B, and H. A, B, and AB individuals express a glycosyltransferase activity that converts the H antigen to the A antigen (by addition of GalNAc) or to the B antigen (by addition of Gal). There are only 4 amino acid differences between A and B transferases in the catalytic domain, two of which (Leu266Met and Gly268Ala) are primarily responsible for the substrate specificity. The group O phenotype results from variations in ABO that cause a loss of glycosyltransferase activity. The most common group O allele results from a single nucleotide deletion near the 5’ end of the gene (NM_020469.2:c.261del) that causes a frameshift and early termination with no active enzyme production (p.Thr88Profs31). The sequence shown is that of ABOA1.01.

Similarity. Belongs to the glycosyltransferase 6 family.

RefSeq proteins (1): NP_065202* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005076	Glyco_trans_6	Family
IPR029044	Nucleotide-diphossugar_trans	Homologous_superfamily

Pfam: PF03414

Enzyme classification (BRENDA):

• EC 2.4.1.37 — fucosylgalactoside 3-alpha-galactosyltransferase (BRENDA: 12 organisms, 84 substrates, 31 inhibitors, 90 Km, 49 kcat entries)
• EC 2.4.1.40 — glycoprotein-fucosylgalactoside alpha-N-acetylgalactosaminyltransferase (BRENDA: 12 organisms, 33 substrates, 15 inhibitors, 33 Km, 14 kcat entries)
• EC 2.4.1.88 — globoside alpha-N-acetylgalactosaminyltransferase (BRENDA: 6 organisms, 21 substrates, 33 inhibitors, 5 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

50 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
UDP-GALACTOSE	0.01–4.5	17
UDP-ALPHA-D-GALACTOSE	0.023–0.78	11
ALPHA-FUC-(1->2)-BETA-D-GAL-(CH2)7CH3	0.088–2.64	8
BETA-D-GALACTOSYL-(1->4)-BETA-D-GLUCOSYL-(1<->1)	0.032–0.35	6
L-FUCOSYL-ALPHA-1,2-BETA-D-GALACTOSYL-O(CH2)7CH3	0.022–0.281	6
ALPHA-FUC-(1->2)-BETA-D-GAL-(CH2)7CH3	0.0099–0.4	6
UDP-N-ACETYL-ALPHA-D-GALACTOSAMINE	0.0087–0.086	6
UDP-GALNAC	0.0099–3.74	5
L-FUCOSYL-ALPHA-1,2-BETA-GALACTOSYL-O(CH2)7CH3	0.027–0.116	4
UDP-GLUCOSE	0.12–0.238	4
L-FUCOSYL-ALPHA-1,2-BETA-GALACTOSYL-O(CH2)7CH3	0.0087–0.167	4
UDP-GALNAC	0.023–0.78	3
UDP-N-ACETYLGALACTOSAMINE	0.285–0.34	3
2’-FUCOSYLLACTOSE	0.27–0.47	3
GLOBOSIDE	0.0016–0.5	3

Catalyzed reactions (Rhea), 9 shown:

• an alpha-L-fucosyl-(1->2)-beta-D-galactosyl derivative + UDP-alpha-D-galactose = an alpha-D-galactosyl-(1->3)-[alpha-L-fucosyl-(1->2)]-beta-D-galactosyl derivative + UDP + H(+) (RHEA:14349)
• an alpha-L-fucosyl-(1->2)-beta-D-galactosyl derivative + UDP-N-acetyl-alpha-D-galactosamine = an N-acetyl-alpha-D-galactosaminyl-(1->3)-[alpha-L-fucosyl-(1->2)]-beta-D-galactosyl derivative + UDP + H(+) (RHEA:19021)
• an alpha-L-Fuc-(1->2)-beta-D-Gal-(1->3)-beta-D-GlcNAc derivative + UDP-N-acetyl-alpha-D-galactosamine = an alpha-D-GalNAc-(1->3)-[alpha-L-Fuc-(1->2)]-beta-D-Gal-(1->3)-beta-D-GlcNAc derivative + UDP + H(+) (RHEA:84499)
• an alpha-L-Fuc-(1->2)-beta-D-Gal-(1->4)-beta-D-GlcNAc derivative + UDP-N-acetyl-alpha-D-galactosamine = an alpha-D-GalNAc-(1->3)-[alpha-L-Fuc-(1->2)]-beta-D-Gal-(1->4)-beta-D-GlcNAc derivative + UDP + H(+) (RHEA:84507)
• an alpha-L-Fuc-(1->2)-beta-D-Gal-(1->3)-beta-D-GlcNAc derivative + UDP-alpha-D-galactose = an alpha-D-Gal-(1->3)-[alpha-L-Fuc-(1->2)]-beta-D-Gal-(1->3)-beta-D-GlcNAc derivative + UDP + H(+) (RHEA:84519)
• an alpha-L-Fuc-(1->2)-beta-D-Gal-(1->4)-beta-D-GlcNAc derivative + UDP-alpha-D-galactose = an alpha-D-Gal-(1->3)-[alpha-L-Fuc-(1->2)]-beta-D-Gal-(1->4)-beta-D-GlcNAc derivative + UDP + H(+) (RHEA:84523)
• an alpha-L-Fuc-(1->2)-beta-D-Gal-(1->3)-alpha-D-GalNAc derivative + UDP-alpha-D-galactose = an alpha-D-Gal-(1->3)-[alpha-L-Fuc-(1->2)]-beta-D-Gal-(1->3)-alpha-D-GalNAc derivative + UDP + H(+) (RHEA:84527)
• an alpha-L-Fuc-(1->2)-beta-D-Gal-(1->3)-beta-D-GalNAc derivative + UDP-alpha-D-galactose = an alpha-D-Gal-(1->3)-[alpha-L-Fuc-(1->2)]-beta-D-Gal-(1->3)-beta-D-GalNAc derivative + UDP + H(+) (RHEA:84739)
• an alpha-L-Fuc-(1->2)-beta-D-Gal-(1->4)-beta-D-Glc derivative + UDP-alpha-D-galactose = an alpha-D-Gal-(1->3)-[alpha-L-Fuc-(1->2)]-beta-D-Gal-(1->4)-beta-D-Glc derivative + UDP + H(+) (RHEA:84743)

UniProt features (80 total): sequence variant 27, binding site 18, helix 13, strand 11, mutagenesis site 3, chain 2, topological domain 2, glycosylation site 1, transmembrane region 1, active site 1, turn 1

Structure

Experimental structures (PDB)

151 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
6GX2	X-RAY DIFFRACTION	1.07
5M7D	X-RAY DIFFRACTION	1.2
3IOH	X-RAY DIFFRACTION	1.25
6GX0	X-RAY DIFFRACTION	1.25
4Y63	X-RAY DIFFRACTION	1.3
5M79	X-RAY DIFFRACTION	1.3
5M7A	X-RAY DIFFRACTION	1.3
1LZJ	X-RAY DIFFRACTION	1.32
5C3A	X-RAY DIFFRACTION	1.33
1LZI	X-RAY DIFFRACTION	1.35
5C3D	X-RAY DIFFRACTION	1.39
5C47	X-RAY DIFFRACTION	1.39
3I0G	X-RAY DIFFRACTION	1.4
5BXC	X-RAY DIFFRACTION	1.4
5C1L	X-RAY DIFFRACTION	1.4
5C3B	X-RAY DIFFRACTION	1.4
5C4D	X-RAY DIFFRACTION	1.4
6GWY	X-RAY DIFFRACTION	1.4
2RJ6	X-RAY DIFFRACTION	1.41
5C4F	X-RAY DIFFRACTION	1.41
3SX7	X-RAY DIFFRACTION	1.42
2RIT	X-RAY DIFFRACTION	1.43
3SX5	X-RAY DIFFRACTION	1.43
4FRA	X-RAY DIFFRACTION	1.43
5C4C	X-RAY DIFFRACTION	1.43
2RIZ	X-RAY DIFFRACTION	1.45
2RJ5	X-RAY DIFFRACTION	1.45
3IOI	X-RAY DIFFRACTION	1.45
3SX3	X-RAY DIFFRACTION	1.45
5C38	X-RAY DIFFRACTION	1.45

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P16442-F1	89.59	0.82

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 303 (nucleophile)

Ligand- & substrate-binding residues (18): 213; 233; 233; 233; 235; 245; 245; 245; 303; 303; 303; 326 …

Glycosylation sites (1): 113

Mutagenesis-validated functional residues (3):

Position	Phenotype
214	alters substrate specificity so that both udp-n-acetyl-d-galactosamine and udp-galactose are utilized.
234	alters donor nucleotide-sugar specificity switching from udp-galactose to udp-n-acetyl-d-galactosamine.
303	almost complete loss of specific activity in group b transferase.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9033807	ABO blood group biosynthesis

MSigDB gene sets: 133 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, MORF_FLT1, MORF_MSH3, MORF_BRCA1, MORF_ESR1, MORF_RAD51L3, JAZAG_TGFB1_SIGNALING_DN, MORF_IL4, MORF_PRKCA, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, MORF_THPO, MORF_ETV3, MODULE_113, KIM_GASTRIC_CANCER_CHEMOSENSITIVITY, MORF_ATF2

GO Biological Process (1): carbohydrate metabolic process (GO:0005975)

GO Molecular Function (9): nucleotide binding (GO:0000166), antigen binding (GO:0003823), glycoprotein-fucosylgalactoside alpha-N-acetylgalactosaminyltransferase activity (GO:0004380), fucosylgalactoside 3-alpha-galactosyltransferase activity (GO:0004381), manganese ion binding (GO:0030145), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757), hexosyltransferase activity (GO:0016758), metal ion binding (GO:0046872)

GO Cellular Component (6): Golgi membrane (GO:0000139), extracellular region (GO:0005576), Golgi apparatus (GO:0005794), vesicle (GO:0031982), Golgi cisterna membrane (GO:0032580), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Blood group systems biosynthesis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
primary metabolic process	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
acetylgalactosaminyltransferase activity	1
catalytic activity, acting on a glycoprotein	1
UDP-galactosyltransferase activity	1
transition metal ion binding	1
catalytic activity	1
transferase activity	1
glycosyltransferase activity	1
cation binding	1
Golgi apparatus	1
bounding membrane of organelle	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
membrane-bounded organelle	1
organelle membrane	1
Golgi cisterna	1

Protein interactions and networks

STRING

222 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ABO	FOXK1	P85037	603
ABO	PTK2	Q05397	460
ABO	FUT1	P19526	374
ABO	DAB2	P98082	343
ABO	C1GALT1C1L	P0DN25	325
ABO	AFF2	P51816	297
ABO	FUT2	Q10981	292
ABO	CLN3	Q13286	291
ABO	TKFC	Q3LXA3	273
ABO	MGAT2	Q10469	272
ABO	GLCE	O94923	270
ABO	PPT1	P50897	252
ABO	MFSD8	Q8NHS3	252
ABO	FAM177A1	Q8N128	245
ABO	GCNT1	Q02742	245

IntAct

2 interactions, top by confidence:

A	B	Type	Score
	AP3D1	psi-mi:“MI:0914”(association)	0.460
	ABO	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (3): GRAMD3 (Two-hybrid), TMEM79 (Two-hybrid), ABO (Affinity Capture-MS)

ESM2 similar proteins: A2AIG8, A6NFX1, O15315, O35083, O35719, O35790, O43502, O54783, O54804, O55229, O73884, P16442, P20417, P35790, P35821, P47802, Q01134, Q08DW9, Q27HK4, Q2TBS1, Q3T9M1, Q3U129, Q4R3I0, Q4R766, Q4R7M4, Q5E9H2, Q5E9T4, Q5SUV1, Q5SX19, Q5VYX0, Q6GV29, Q86XW9, Q8BVM4, Q8CIW5, Q8N2K0, Q8NBA8, Q8QGV6, Q8R2J9, Q8TCT0, Q924H5

Diamond homologs: A0A4Z3, A1YGR5, A1YGR6, A2AUQ7, D3ZNQ3, G3V9Q9, P14769, P16442, P23336, P38649, P50127, Q2NKH9, Q2YDM8, Q3L7M0, Q3V1N9, Q4R5T7, Q5ZLK4, Q7Z4J2, Q8CFC4, Q8HY56, Q8HYB2, Q8N5D6, Q8SPR2, Q8SQ20, Q8VI38, Q95158, Q9ET32, U3KPV4, Q4G0N0, Q5JBG6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

45 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	6
Likely benign	3
Benign	15

Top pathogenic / likely-pathogenic (0)

SpliceAI

1234 predictions. Top by Δscore:

Variant	Effect	Δscore
9:133257407:A:AC	donor_gain	1.0000
9:133257408:C:CC	donor_gain	1.0000
9:133257408:CTT:C	donor_gain	1.0000
9:133275156:ACTC:A	donor_loss	1.0000
9:133275158:TCAC:T	donor_loss	1.0000
9:133275159:CA:C	donor_loss	1.0000
9:133275160:A:AC	donor_gain	1.0000
9:133275160:A:T	donor_loss	1.0000
9:133275160:ACCGG:A	donor_gain	1.0000
9:133275161:C:CA	donor_loss	1.0000
9:133275161:C:CC	donor_gain	1.0000
9:133275161:CCGG:C	donor_gain	1.0000
9:133275161:CCGGC:C	donor_gain	1.0000
9:133256352:CGTAT:C	acceptor_gain	0.9900
9:133257410:T:TA	donor_gain	0.9900
9:133257540:CTA:C	acceptor_gain	0.9900
9:133257543:C:CC	acceptor_gain	0.9900
9:133257549:A:C	acceptor_gain	0.9900
9:133257538:TCCTA:T	acceptor_gain	0.9800
9:133257539:CCTAC:C	acceptor_gain	0.9800
9:133257541:TA:T	acceptor_gain	0.9800
9:133275160:AC:A	donor_gain	0.9800
9:133275161:CC:C	donor_gain	0.9800
9:133275161:CCG:C	donor_gain	0.9800
9:133256357:C:CC	acceptor_gain	0.9700
9:133275110:C:A	donor_gain	0.9700
9:133256353:GTATC:G	acceptor_loss	0.9600
9:133256354:TATCT:T	acceptor_loss	0.9600
9:133256357:CTGC:C	acceptor_loss	0.9600
9:133256358:T:G	acceptor_loss	0.9600

AlphaMissense

2309 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000231760 (9:133262387 G>A), RS1000288182 (9:133269205 A>G,T), RS1000627084 (9:133270548 A>G), RS1000692217 (9:133276584 G>T), RS1000756404 (9:133275340 C>G,T), RS1000776958 (9:133255590 T>C), RS1000878063 (9:133253440 C>T), RS1001027870 (9:133258411 C>T), RS1001141261 (9:133263688 G>A), RS1001228947 (9:133276399 G>A), RS1001246634 (9:133253261 C>T), RS1001573084 (9:133257621 C>G), RS1001595759 (9:133275611 C>T), RS1001655797 (9:133269824 T>C), RS1001895636 (9:133258707 A>G)

Disease associations

OMIM: gene MIM:110300 | disease phenotypes: MIM:191100

GenCC curated gene-disease

Mondo (2): Ehlers-Danlos syndrome, classic type (MONDO:0007522), tuberous sclerosis 1 (MONDO:0008612)

Orphanet (2): Classical Ehlers-Danlos syndrome (Orphanet:287), Tuberous sclerosis complex (Orphanet:805)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

364 associations (top):

Study	Trait	p-value
GCST000189_32	Protein quantitative trait loci	7.000000e-40
GCST000210_4	Soluble ICAM-1	5.000000e-29
GCST000248_2	Liver enzyme levels	2.000000e-30
GCST000354_1	Venous thromboembolism	4.000000e-15
GCST000456_1	Pancreatic cancer	5.000000e-08
GCST000476_1	Soluble E-selectin levels	1.000000e-29
GCST000565_1	Angiotensin-converting enzyme activity	3.000000e-08
GCST000582_6	Mean corpuscular hemoglobin concentration	4.000000e-08
GCST000583_11	Hematological and biochemical traits	4.000000e-59
GCST000583_26	Hematological and biochemical traits	1.000000e-11
GCST000583_6	Hematological and biochemical traits	6.000000e-10
GCST000588_1	Red blood cell count	3.000000e-12
GCST000599_3	Soluble levels of adhesion molecules	1.000000e-15
GCST000599_5	Soluble levels of adhesion molecules	2.000000e-41
GCST000606_1	E-selectin levels	2.000000e-82
GCST000626_1	Factor VIII levels	4.940656e-324
GCST000627_2	vWF levels	4.940656e-324
GCST000694_3	Phytosterol levels	9.000000e-13
GCST000759_16	LDL cholesterol	8.000000e-22
GCST000760_26	Cholesterol, total	9.000000e-21
GCST000946_1	Myocardial infarction in coronary artery disease	8.000000e-09
GCST000998_19	Coronary heart disease	4.000000e-14
GCST001047_2	Soluble ICAM-1	3.000000e-91
GCST001049_12	D-dimer levels	7.000000e-06
GCST001200_10	Graves’ disease	8.000000e-06
GCST001217_21	Metabolic traits	9.000000e-40
GCST001233_14	Metabolite levels	6.000000e-09
GCST001253_3	Venous thromboembolism	1.000000e-34
GCST001276_3	Liver enzyme levels (alkaline phosphatase)	3.000000e-123
GCST001385_7	Inflammatory biomarkers	9.000000e-25

EFO canonical traits (83, from GWAS)

EFO ID	Trait name
EFO:0004520	ICAM-1 measurement
EFO:0004533	alkaline phosphatase measurement
EFO:0004509	hemoglobin measurement
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0004348	hematocrit
EFO:0004305	erythrocyte count
EFO:0004522	adhesion molecule measurement
EFO:0004519	soluble P-selectin measurement
EFO:0004630	factor VIII measurement
EFO:0004862	phytosterol measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004574	total cholesterol measurement
EFO:0004507	D dimer measurement
EFO:0004725	metabolite measurement
EFO:0004810	interleukin-6 measurement
EFO:0004747	protein measurement
EFO:0005127	cancer biomarker measurement
EFO:0004730	hormone measurement
EFO:0005116	urinary metabolite measurement
EFO:0005760	serum carcinoembryonic antigen measurement
EFO:0004695	intraocular pressure measurement
EFO:0004459	ferritin measurement
EFO:0004461	iron biomarker measurement
EFO:0006902	angiopoietin-2 receptor measurement
EFO:0003907	deep vein thrombosis
EFO:0004297	clinical laboratory measurement
EFO:0007904	susceptibility to childhood ear infection measurement
EFO:0007924	tonsillectomy risk measurement
EFO:0004866	autoantibody measurement
EFO:0004309	platelet count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C565346	Tuberous Sclerosis 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2321639 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

3 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs495828	Toxicity	3	Ace Inhibitors;Plain
rs56392308	Toxicity	3	hormonal contraceptives for systemic use
rs8176719	Toxicity	3	hormonal contraceptives for systemic use

PharmGKB variants

5 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs495828	ABO	3	5.50	2	Ace Inhibitors;Plain;enalapril
rs8176740	ABO		0.00	0
rs8176746	ABO		0.00	0
rs8176719	ABO	3	3.00	1	hormonal contraceptives for systemic use
rs56392308	ABO	3	3.00	1	hormonal contraceptives for systemic use

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases methylation	2
bufotalin	decreases expression	1
tebuconazole	decreases expression	1
CGP 52608	affects binding, increases reaction	1
(+)-JQ1 compound	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Aflatoxin B1	increases methylation	1
Gold Compounds	increases expression	1
Lactic Acid	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2329770	Binding	Competitive inhibition of human blood group B Galactosyltransferase using UDP-Gal as substrate by Michaelis-Menten equation analysis in presence of magnesium ions	A nonionic inhibitor with high specificity for the UDP-Gal donor binding site of human blood group B galactosyltransferase: design, synthesis, and characterization. — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B5SI	MUSIi016-A	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

6 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT02201212	PHASE2	COMPLETED	Everolimus for Cancer With TSC1 or TSC2 Mutation
NCT05103358	PHASE2	ACTIVE_NOT_RECRUITING	Phase 2 Basket Trial of Nab-sirolimus in Patients With Malignant Solid Tumors With Pathogenic Alterations in TSC1/TSC2 Genes (PRECISION 1)
NCT05429996	Not specified	UNKNOWN	Ultrastructural Collagen Markers in Ehlers Danlos Syndromes
NCT05434728	Not specified	UNKNOWN	Characterization of Bleeding Disorders in EDS
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns
NCT03817515	Not specified	APPROVED_FOR_MARKETING	Expanded Access for ABI-009 in Patients With Advanced PEComa and Patients With a Malignancy With Relevant Genetic Mutations or mTOR Pathway Activation