A3GALT2

Summary

A3GALT2 (alpha 1,3-galactosyltransferase 2, HGNC:30005) is a protein-coding gene on chromosome 1p35.1, encoding Alpha-1,3-galactosyltransferase 2 (U3KPV4). Synthesizes the galactose-alpha(1,3)-galactose group on the glycosphingolipid isoglobotrihexosylceramide or isogloboside 3 (iGb3) by catalyzing the transfer of galactose from UDP-Galactose to its acceptor molecule Gal-beta-1,4-Glc-ceramide.

Predicted to enable N-acetyllactosaminide 3-alpha-galactosyltransferase activity and alpha-1,3-galactosyltransferase activity. Predicted to be involved in lipid glycosylation. Predicted to act upstream of or within glycosphingolipid biosynthetic process. Predicted to be located in Golgi cisterna membrane. Predicted to be active in Golgi apparatus and vesicle.

Source: NCBI Gene 127550 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 11 total — 3 pathogenic
• MANE Select transcript: NM_001080438

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30005
Approved symbol	A3GALT2
Name	alpha 1,3-galactosyltransferase 2
Location	1p35.1
Locus type	gene with protein product
Status	Approved
Aliases	IGBS3S, IGB3S
Ensembl gene	ENSG00000184389
Ensembl biotype	protein_coding
OMIM	619850
Entrez	127550

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000442999

RefSeq mRNA: 1 — MANE Select: NM_001080438 NM_001080438

CCDS: CCDS60080

Canonical transcript exons

ENST00000442999 — 5 exons

Exon	Start	End
ENSE00001820539	33312052	33312189
ENSE00001937348	33312501	33312590
ENSE00001945494	33312807	33312890
ENSE00003493334	33306766	33307453
ENSE00003699709	33321076	33321098

Expression profiles

Bgee: expression breadth broad, 98 present calls, max score 80.63.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.63	silver quality
blood	UBERON:0000178	58.43	gold quality
mucosa of stomach	UBERON:0001199	50.48	gold quality
bone marrow cell	CL:0002092	49.69	gold quality
granulocyte	CL:0000094	49.51	silver quality
left uterine tube	UBERON:0001303	48.24	gold quality
bone marrow	UBERON:0002371	48.20	gold quality
cerebellar hemisphere	UBERON:0002245	47.39	silver quality
cerebellar cortex	UBERON:0002129	47.36	silver quality
cerebellum	UBERON:0002037	47.35	silver quality
right hemisphere of cerebellum	UBERON:0014890	46.34	silver quality
metanephros cortex	UBERON:0010533	45.53	gold quality
gastrocnemius	UBERON:0001388	44.21	gold quality
mucosa of transverse colon	UBERON:0004991	43.49	silver quality
thoracic aorta	UBERON:0001515	43.06	gold quality
right lung	UBERON:0002167	43.00	gold quality
tibial artery	UBERON:0007610	42.90	gold quality
popliteal artery	UBERON:0002250	42.75	gold quality
ascending aorta	UBERON:0001496	42.71	gold quality
descending thoracic aorta	UBERON:0002345	42.69	gold quality
muscle of leg	UBERON:0001383	42.62	gold quality
omental fat pad	UBERON:0010414	42.05	gold quality
upper lobe of left lung	UBERON:0008952	41.82	gold quality
spleen	UBERON:0002106	41.78	gold quality
monocyte	CL:0000576	41.75	silver quality
leukocyte	CL:0000738	41.48	silver quality
stromal cell of endometrium	CL:0002255	41.29	silver quality
cortical plate	UBERON:0005343	41.28	silver quality
smooth muscle tissue	UBERON:0001135	41.19	silver quality
ectocervix	UBERON:0012249	41.01	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.64

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• iGb3 is unlikely to represent natural ligand for NKT cells in humans. Furthermore, the absence of iGb3 in humans implies that it is another source of foreign Galalpha(1,3)Gal xenoantigen, with obvious significance in the field of xenotransplantation. (PMID:18630988)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	A3galt2	ENSMUSG00000028794
rattus_norvegicus	A3galt2	ENSRNOG00000005935

Paralogs (3): GBGT1 (ENSG00000148288), ABO (ENSG00000175164), GLT6D1 (ENSG00000204007)

Protein

Protein identifiers

Alpha-1,3-galactosyltransferase 2 — U3KPV4 (reviewed: U3KPV4)

Alternative names: Isoglobotriaosylceramide synthase

All UniProt accessions (1): U3KPV4

UniProt curated annotations — full annotation on UniProt →

Function. Synthesizes the galactose-alpha(1,3)-galactose group on the glycosphingolipid isoglobotrihexosylceramide or isogloboside 3 (iGb3) by catalyzing the transfer of galactose from UDP-Galactose to its acceptor molecule Gal-beta-1,4-Glc-ceramide. Can also catalyze the addition of galactose to iGb3 itself to form polygalactose structures.

Subcellular location. Golgi apparatus. Golgi stack membrane.

Tissue specificity. Expressed in thymus and monocyte derived dendritic cells.

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.

Similarity. Belongs to the glycosyltransferase 6 family.

RefSeq proteins (1): NP_001073907* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005076	Glyco_trans_6	Family
IPR029044	Nucleotide-diphossugar_trans	Homologous_superfamily

Pfam: PF03414

Catalyzed reactions (Rhea), 3 shown:

• a beta-D-galactosyl-(1->4)-N-acetyl-beta-D-glucosaminyl derivative + UDP-alpha-D-galactose = an alpha-D-galactosyl-(1->3)-beta-D-galactosyl-(1->4)-N-acetyl-beta-D-glucosaminyl derivative + UDP + H(+) (RHEA:13013)
• a beta-D-Gal-(1->4)-beta-D-Glc-(1<->1)-Cer(d18:1(4E)) + UDP-alpha-D-galactose = an isogloboside iGb3Cer (d18:1(4E)) + UDP + H(+) (RHEA:42000)
• a globoside Gb3Cer + UDP-alpha-D-galactose = a globoside GalGb3Cer + UDP + H(+) (RHEA:56740)

UniProt features (8 total): topological domain 2, binding site 2, glycosylation site 2, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-U3KPV4-F1	91.08	0.74

Functional residue map

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

Ligand- & substrate-binding residues (2): 199; 201

Glycosylation sites (2): 58, 100

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 34 (showing top): GOBP_GLYCOLIPID_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_SPHINGOLIPID_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_GLYCOSPHINGOLIPID_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_LIPID_BIOSYNTHETIC_PROCESS, GOBP_SPHINGOLIPID_BIOSYNTHETIC_PROCESS, GOBP_LIPOSACCHARIDE_METABOLIC_PROCESS, GOBP_MEMBRANE_LIPID_METABOLIC_PROCESS, GOBP_MEMBRANE_LIPID_BIOSYNTHETIC_PROCESS, GOCC_GOLGI_STACK, GOCC_GOLGI_CISTERNA, chr1p35

GO Biological Process (4): carbohydrate metabolic process (GO:0005975), glycosphingolipid biosynthetic process (GO:0006688), lipid metabolic process (GO:0006629), obsolete lipid glycosylation (GO:0030259)

GO Molecular Function (5): glycosyltransferase activity (GO:0016757), metal ion binding (GO:0046872), N-acetyllactosaminide 3-alpha-galactosyltransferase activity (GO:0047276), transferase activity (GO:0016740), hexosyltransferase activity (GO:0016758)

GO Cellular Component (4): Golgi apparatus (GO:0005794), vesicle (GO:0031982), Golgi cisterna membrane (GO:0032580), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
primary metabolic process	2
glycosphingolipid metabolic process	1
glycolipid biosynthetic process	1
sphingolipid biosynthetic process	1
transferase activity	1
cation binding	1
UDP-galactosyltransferase activity	1
catalytic activity	1
glycosyltransferase activity	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
membrane-bounded organelle	1
organelle membrane	1
Golgi cisterna	1
cellular anatomical structure	1

Protein interactions and networks

STRING

212 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
A3GALT2	A4GALT	Q9NPC4	592
A3GALT2	CD1D	P15813	460
A3GALT2	B3GNT5	Q9BYG0	459
A3GALT2	B3GALT1	Q9Y5Z6	454
A3GALT2	B4GALT5	O43286	444
A3GALT2	FUT2	Q10981	430
A3GALT2	B3GALNT1	O75752	428
A3GALT2	UGCG	Q16739	427
A3GALT2	GLA	P06280	414
A3GALT2	B4GALNT2	Q8NHY0	370
A3GALT2	FUT1	P19526	360
A3GALT2	B3GALT5	Q9Y2C3	337
A3GALT2	B4GALT6	Q9UBX8	324
A3GALT2	B4GALT1	P15291	319
A3GALT2	B4GALNT1	Q00973	312

IntAct

0 interactions, top by confidence:

BioGRID (1): A3GALT2 (Proximity Label-MS)

ESM2 similar proteins: A0A4Z3, A1Y9I9, A4FUH1, B6CZ46, B6CZ56, B6CZ62, D3ZNQ3, G3V9Q9, O43505, O60512, O60909, O94766, P14616, P14617, P58158, Q09326, Q10469, Q2NKH9, Q2YDM8, Q3V1N9, Q3V5L5, Q4R5T7, Q5EA01, Q5EB73, Q5JU69, Q5M936, Q5NVN3, Q5R4S2, Q5R868, Q5YB40, Q5ZLK4, Q64716, Q6AYR4, Q765H6, Q7Z4J2, Q8BGT9, Q8BWP8, Q8IXK2, Q8NCL4, Q8R1J9

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

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	0
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
149963	GRCh38/hg38 1p36.11-34.2(chr1:24381206-41401517)x3	Pathogenic
1526762	GRCh37/hg19 1p35.1-33(chr1:33285582-47891811)	Pathogenic
59931	GRCh38/hg38 1p35.2-35.1(chr1:30766758-33359428)x1	Pathogenic

SpliceAI

1182 predictions. Top by Δscore:

Variant	Effect	Δscore
1:33307453:TC:T	acceptor_loss	0.9800
1:33307454:CT:C	acceptor_loss	0.9800
1:33310139:C:CT	acceptor_gain	0.9800
1:33310140:A:T	acceptor_gain	0.9800
1:33310289:C:CT	acceptor_gain	0.9600
1:33307454:C:CC	acceptor_gain	0.9500
1:33310365:C:CT	acceptor_gain	0.9500
1:33313056:T:TC	acceptor_gain	0.9300
1:33307451:TAT:T	acceptor_gain	0.9100
1:33310136:C:CT	acceptor_gain	0.9100
1:33310289:C:T	acceptor_gain	0.9100
1:33310290:G:C	acceptor_gain	0.9100
1:33320856:A:AT	donor_gain	0.9100
1:33309773:T:TA	donor_gain	0.9000
1:33312977:A:AC	donor_gain	0.9000
1:33312978:C:CC	donor_gain	0.9000
1:33307449:GGTAT:G	acceptor_gain	0.8900
1:33307450:GTAT:G	acceptor_gain	0.8900
1:33310139:C:T	acceptor_gain	0.8800
1:33310279:A:T	acceptor_gain	0.8800
1:33310350:C:CT	acceptor_gain	0.8800
1:33312200:C:CT	acceptor_gain	0.8800
1:33312495:TCTTA:T	donor_loss	0.8800
1:33312496:CTTAC:C	donor_loss	0.8800
1:33312497:TTA:T	donor_loss	0.8800
1:33312498:TACC:T	donor_loss	0.8800
1:33312499:A:AT	donor_loss	0.8800
1:33312500:C:CG	donor_loss	0.8800
1:33320927:C:CT	donor_gain	0.8800
1:33321071:CTCA:C	donor_loss	0.8800

AlphaMissense

2195 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:33306856:G:C	F311L	0.916
1:33306856:G:T	F311L	0.916
1:33306858:A:G	F311L	0.916
1:33312126:G:C	F87L	0.891
1:33312126:G:T	F87L	0.891
1:33312128:A:G	F87L	0.891
1:33307369:G:C	F140L	0.877
1:33307369:G:T	F140L	0.877
1:33307371:A:G	F140L	0.877
1:33312521:G:C	F59L	0.874
1:33312521:G:T	F59L	0.874
1:33312523:A:G	F59L	0.874
1:33312063:A:C	F108L	0.868
1:33312063:A:T	F108L	0.868
1:33312065:A:G	F108L	0.868
1:33306898:G:C	F297L	0.855
1:33306898:G:T	F297L	0.855
1:33306900:A:G	F297L	0.855
1:33307015:G:C	F258L	0.854
1:33307015:G:T	F258L	0.854
1:33307017:A:G	F258L	0.854
1:33307207:G:C	F194L	0.843
1:33307207:G:T	F194L	0.843
1:33307209:A:G	F194L	0.843
1:33307165:A:C	F208L	0.841
1:33307165:A:T	F208L	0.841
1:33307167:A:G	F208L	0.841
1:33307402:G:C	F129L	0.821
1:33307402:G:T	F129L	0.821
1:33307404:A:G	F129L	0.821

dbSNP variants (sampled 300 via entrez): RS1000200704 (1:33322004 AT>A), RS1000374629 (1:33315928 TGG>T), RS1000379407 (1:33318258 G>A), RS1000579329 (1:33310753 G>A), RS1001092550 (1:33312686 C>T), RS1001259608 (1:33313092 C>T), RS1001668437 (1:33310054 C>T), RS1001694264 (1:33314709 C>T), RS1001808751 (1:33314988 T>C), RS1001950771 (1:33309897 G>T), RS1002034499 (1:33313567 G>A), RS1002053153 (1:33317258 G>C), RS1002098202 (1:33314057 T>C), RS1002150592 (1:33313765 C>G), RS1002306473 (1:33319620 C>T)

Disease associations

OMIM: gene MIM:619850 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90002382_68	Eosinophil percentage of white cells	3.000000e-13

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007991	eosinophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Resveratrol	affects cotreatment, decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Ozone	affects expression, increases abundance	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	increases expression	1
Thiram	increases expression	1
Cadmium Chloride	increases expression	1

Clinical trials (associated diseases)

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