GAL3ST3

Summary

GAL3ST3 (galactose-3-O-sulfotransferase 3, HGNC:24144) is a protein-coding gene on chromosome 11q13.1, encoding Galactose-3-O-sulfotransferase 3 (Q96A11). Catalyzes the transfer of a sulfate group from 3’-phosphoadenylyl sulfate (PAPS) to the C-3 hydroxyl group of terminal non-reducing beta-1,4-linked galactose residues in both N-glycans and O-glycans.

This gene encodes a member of the galactose-3-O-sulfotransferase protein family. The product of this gene catalyzes sulfonation by transferring a sulfate group to the 3’ position of galactose in N-acetyllactosamine in both type 2 (Gal-beta-1-4GlcNAc-R) oligosaccharides and core-2-branched O-glycans, but not on type 1 or core-1-branched structures. This gene, which has also been referred to as GAL3ST2, is different from the GAL3ST2 gene located on chromosome 2 that encodes a related enzyme with distinct tissue distribution and substrate specificities, compared to galactose-3-O-sulfotransferase 3.

Source: NCBI Gene 89792 — RefSeq curated summary.

At a glance

• GWAS associations: 19
• Clinical variants (ClinVar): 205 total — 1 likely-pathogenic
• MANE Select transcript: NM_033036

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24144
Approved symbol	GAL3ST3
Name	galactose-3-O-sulfotransferase 3
Location	11q13.1
Locus type	gene with protein product
Status	Approved
Aliases	GAL3ST2
Ensembl gene	ENSG00000175229
Ensembl biotype	protein_coding
OMIM	608234
Entrez	89792

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 retained_intron

ENST00000312006, ENST00000527048, ENST00000527878, ENST00000882250, ENST00000882251, ENST00000923257, ENST00000945048

RefSeq mRNA: 1 — MANE Select: NM_033036 NM_033036

CCDS: CCDS8128

Canonical transcript exons

ENST00000312006 — 3 exons

Exon	Start	End
ENSE00001189817	66040765	66043677
ENSE00001189831	66049011	66049161
ENSE00001384222	66045291	66045527

Expression profiles

Bgee: expression breadth ubiquitous, 101 present calls, max score 85.23.

FANTOM5 (CAGE): breadth broad, TPM avg 2.9500 / max 70.8245, expressed in 360 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
120753	2.8236	359
120754	0.1264	78

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.23	gold quality
left lobe of thyroid gland	UBERON:0001120	82.26	gold quality
right lobe of thyroid gland	UBERON:0001119	82.12	gold quality
cortical plate	UBERON:0005343	80.22	gold quality
thyroid gland	UBERON:0002046	80.21	gold quality
caudate nucleus	UBERON:0001873	77.12	gold quality
putamen	UBERON:0001874	76.79	gold quality
right atrium auricular region	UBERON:0006631	76.78	gold quality
nucleus accumbens	UBERON:0001882	76.03	gold quality
right hemisphere of cerebellum	UBERON:0014890	76.01	gold quality
cardiac atrium	UBERON:0002081	75.86	gold quality
cerebellar hemisphere	UBERON:0002245	74.35	gold quality
cerebellar cortex	UBERON:0002129	74.30	gold quality
right frontal lobe	UBERON:0002810	74.29	gold quality
prefrontal cortex	UBERON:0000451	74.25	gold quality
anterior cingulate cortex	UBERON:0009835	73.73	gold quality
cerebellum	UBERON:0002037	73.14	gold quality
Brodmann (1909) area 9	UBERON:0013540	72.88	gold quality
ganglionic eminence	UBERON:0004023	72.62	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	72.25	gold quality
ventricular zone	UBERON:0003053	71.33	gold quality
neocortex	UBERON:0001950	71.28	gold quality
frontal cortex	UBERON:0001870	71.14	gold quality
amygdala	UBERON:0001876	70.74	gold quality
apex of heart	UBERON:0002098	69.48	gold quality
forebrain	UBERON:0001890	69.39	gold quality
cerebral cortex	UBERON:0000956	69.34	gold quality
brain	UBERON:0000955	68.84	gold quality
hypothalamus	UBERON:0001898	67.97	gold quality
metanephros cortex	UBERON:0010533	67.56	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.47

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

87 targeting GAL3ST3, 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-5196-5P	100.00	67.98	2761
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-1296-3P	99.72	64.04	636
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-646	99.68	67.84	1645
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-3679-3P	99.64	69.88	1599
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-182-3P	99.57	67.57	825
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-6832-3P	99.52	70.44	1726

Literature-anchored findings (GeneRIF, showing 1)

• Gal3ST-2 and LS180 sulfotransferase is a substrate for the globo H backbone; Gal3ST-3 is a substrate for N-glycan multiterminal Galbeta1 (PMID:14701868)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	gal3st3	ENSDARG00000073728
mus_musculus	Gal3st3	ENSMUSG00000047658
rattus_norvegicus	Gal3st3	ENSRNOG00000028743

Paralogs (3): GAL3ST1 (ENSG00000128242), GAL3ST2 (ENSG00000154252), GAL3ST4 (ENSG00000197093)

Protein

Protein identifiers

Galactose-3-O-sulfotransferase 3 — Q96A11 (reviewed: Q96A11)

Alternative names: Beta-galactose-3-O-sulfotransferase 3, Gal-beta-1, 3-GalNAc 3’-sulfotransferase 3

All UniProt accessions (1): Q96A11

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the transfer of a sulfate group from 3’-phosphoadenylyl sulfate (PAPS) to the C-3 hydroxyl group of terminal non-reducing beta-1,4-linked galactose residues in both N-glycans and O-glycans. It acts efficiently on type 2 chains (Gal-beta-1,4-GlcNAc-R) found in N-glycans and core 2-branched O-glycans (Gal-beta-1,4-GlcNAc-beta-1,6(Gal-beta-1,3)GalNAc-R). In contrast, it shows poor activity on type 1 chains (Gal-beta-1,3-GlcNAc-R) and intermediate activity on core 1 structures (Gal-beta-1,3-GalNAc-R). Participates in the glycoconjugates sulfation namely the 3’-sulfated Lewis X epitope (Gal-beta-1,4(Fuc-alpha-1,3)GlcNAc), by sulfating N-acetyllactosamine (Gal-beta-1,4-GlcNAc) at the 3’ position; then the resulting modification is fucosylated by FUT5.

Subcellular location. Golgi apparatus. Golgi stack membrane.

Tissue specificity. Highly expressed in thyroid, brain, kidney. Also expressed in heart and spinal cord.

Activity regulation. Activated about 1.7-fold by 10 mM Mg(2+).

Pathway. Protein modification; carbohydrate sulfation.

Similarity. Belongs to the galactose-3-O-sulfotransferase family.

RefSeq proteins (1): NP_149025* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009729	Gal-3-0_sulfotransfrase	Family
IPR027417	P-loop_NTPase	Homologous_superfamily

Pfam: PF06990

UniProt features (11 total): glycosylation site 4, topological domain 2, sequence variant 2, chain 1, transmembrane region 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96A11-F1	86.94	0.73

Functional residue map

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

Glycosylation sites (4): 91, 110, 177, 302

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 111 (showing top): GOBP_OLIGOSACCHARIDE_METABOLIC_PROCESS, GOBP_GLYCOLIPID_BIOSYNTHETIC_PROCESS, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, chr11q13, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, MYOD_01, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_AMINOGLYCAN_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_LIPID_BIOSYNTHETIC_PROCESS, CCAGGTT_MIR490, GOBP_LIPOSACCHARIDE_METABOLIC_PROCESS, GOBP_MONOSACCHARIDE_METABOLIC_PROCESS, GOBP_MEMBRANE_LIPID_METABOLIC_PROCESS

GO Biological Process (6): monosaccharide metabolic process (GO:0005996), sulfur compound metabolic process (GO:0006790), glycolipid biosynthetic process (GO:0009247), oligosaccharide metabolic process (GO:0009311), proteoglycan biosynthetic process (GO:0030166), poly-N-acetyllactosamine metabolic process (GO:0030309)

GO Molecular Function (8): galactosylceramide sulfotransferase activity (GO:0001733), carbohydrate binding (GO:0030246), 3’-phosphoadenosine 5’-phosphosulfate binding (GO:0050656), galactose 3-O-sulfotransferase activity (GO:0050694), proteoglycan sulfotransferase activity (GO:0050698), protein binding (GO:0005515), sulfotransferase activity (GO:0008146), transferase activity (GO:0016740)

GO Cellular Component (3): membrane (GO:0016020), Golgi cisterna membrane (GO:0032580), Golgi apparatus (GO:0005794)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
carbohydrate metabolic process	2
binding	2
sulfotransferase activity	2
small molecule metabolic process	1
metabolic process	1
glycolipid metabolic process	1
lipid biosynthetic process	1
carbohydrate derivative biosynthetic process	1
proteoglycan metabolic process	1
glycoprotein biosynthetic process	1
aminoglycan metabolic process	1
galactose 3-O-sulfotransferase activity	1
adenyl ribonucleotide binding	1
anion binding	1
sulfur compound binding	1
transferase activity, transferring sulphur-containing groups	1
catalytic activity	1
cellular anatomical structure	1
organelle membrane	1
Golgi cisterna	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

384 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GAL3ST3	FUT3	P21217	791
GAL3ST3	SPN	P16150	597
GAL3ST3	CHST5	Q9GZS9	432
GAL3ST3	OR13F1	Q8NGS4	419
GAL3ST3	CHST1	O43916	400
GAL3ST3	CHST4	Q8NCG5	400
GAL3ST3	OR10G4	Q8NGN3	400
GAL3ST3	CHST2	Q9Y4C5	377
GAL3ST3	PIGS	Q96S52	377
GAL3ST3	OR2C1	O95371	370
GAL3ST3	CHST7	Q9NS84	366
GAL3ST3	OR4C3	Q8NH37	359
GAL3ST3	MRPL15	Q9P015	349
GAL3ST3	ZNF813	Q6ZN06	349
GAL3ST3	PSMG1	O95456	329
GAL3ST3	CCDC120	Q96HB5	329

IntAct

4 interactions, top by confidence:

A	B	Type	Score
RHBDD2	GAL3ST3	psi-mi:“MI:0915”(physical association)	0.560
GAL3ST3	RHBDD2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (1): GAL3ST3 (Two-hybrid)

ESM2 similar proteins: A0MGZ5, A0MGZ7, A5D7I4, A5PK45, A9X1C8, B1ATG9, O09010, O12971, O12972, O15399, O60243, O97583, P52848, P52849, P52850, P61315, P97464, Q02353, Q03391, Q0VCH4, Q16394, Q2KJ92, Q3UHN9, Q56UJ5, Q5IGR7, Q5IGR8, Q5QQ50, Q5RBC3, Q5U4X8, Q62645, Q6GQK9, Q6ZRP7, Q76KB2, Q76LW2, Q800H9, Q80UW0, Q86V40, Q8IZP7, Q8K297, Q8NBJ5

Diamond homologs: A6QNK1, P61315, Q0VCH4, Q5E9W5, Q6XQG9, Q6XQH0, Q96A11, Q96RP7, Q99999, Q9H3Q3, Q9JHE4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	177
Likely benign	6
Benign	14

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
190940	NM_022134.3(GAL3ST2):c.197C>T (p.Thr66Met)	Likely pathogenic

SpliceAI

1601 predictions. Top by Δscore:

Variant	Effect	Δscore
11:66049005:A:AC	donor_gain	1.0000
11:66049006:C:CC	donor_gain	1.0000
11:66049009:A:AC	donor_gain	1.0000
11:66049010:C:CA	donor_gain	1.0000
11:66049010:CA:C	donor_gain	1.0000
11:66049010:CACCG:C	donor_gain	1.0000
2:241799059:CCACA:C	acceptor_loss	1.0000
2:241799060:CACA:C	acceptor_loss	1.0000
2:241799061:ACAG:A	acceptor_loss	1.0000
2:241799062:CA:C	acceptor_loss	1.0000
2:241799063:A:AC	acceptor_loss	1.0000
2:241799063:A:AG	acceptor_gain	1.0000
2:241799064:G:GC	acceptor_gain	1.0000
2:241799064:G:T	acceptor_loss	1.0000
2:241799064:GA:G	acceptor_gain	1.0000
2:241799064:GAT:G	acceptor_gain	1.0000
2:241799064:GATA:G	acceptor_gain	1.0000
2:241799064:GATAC:G	acceptor_gain	1.0000
2:241799151:CACC:C	donor_gain	1.0000
2:241799151:CACCG:C	donor_loss	1.0000
2:241799152:ACC:A	donor_gain	1.0000
2:241799153:CC:C	donor_gain	1.0000
2:241799153:CCGT:C	donor_loss	1.0000
2:241799154:CG:C	donor_loss	1.0000
2:241799155:G:GG	donor_gain	1.0000
2:241801776:CCCA:C	acceptor_loss	1.0000
2:241801778:CA:C	acceptor_loss	1.0000
2:241801779:A:AG	acceptor_gain	1.0000
2:241801779:AGCCT:A	acceptor_gain	1.0000
2:241801780:G:GC	acceptor_gain	1.0000

AlphaMissense

2767 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:66043584:C:A	K73N	1.000
11:66043584:C:G	K73N	1.000
11:66042631:T:C	Y391C	0.999
11:66042735:C:A	W356C	0.999
11:66042735:C:G	W356C	0.999
11:66043194:G:C	N203K	0.999
11:66043194:G:T	N203K	0.999
11:66043195:T:A	N203I	0.999
11:66043254:G:C	F183L	0.999
11:66043254:G:T	F183L	0.999
11:66043255:A:G	F183S	0.999
11:66043256:A:G	F183L	0.999
11:66043288:A:C	F172C	0.999
11:66043317:G:C	F162L	0.999
11:66043317:G:T	F162L	0.999
11:66043319:A:G	F162L	0.999
11:66043560:G:C	N81K	0.999
11:66043560:G:T	N81K	0.999
11:66043585:T:A	K73M	0.999
11:66043585:T:G	K73T	0.999
11:66043589:G:C	H72D	0.999
11:66043593:C:A	K70N	0.999
11:66043593:C:G	K70N	0.999
11:66042632:A:C	Y391D	0.998
11:66042933:C:A	W290C	0.998
11:66042933:C:G	W290C	0.998
11:66043034:A:G	W257R	0.998
11:66043034:A:T	W257R	0.998
11:66043078:T:A	E242V	0.998
11:66043255:A:C	F183C	0.998

dbSNP variants (sampled 300 via entrez): RS1000647311 (11:66048036 G>A), RS1000995568 (11:66044864 C>T), RS1001045099 (11:66044500 A>G), RS1001128804 (11:66046075 G>T), RS1001190855 (11:66044463 C>G,T), RS1001603324 (11:66040273 T>C), RS1002098395 (11:66046472 T>C), RS1002601299 (11:66041899 C>G,T), RS1003006369 (11:66041560 C>T), RS1003069139 (11:66048392 T>C), RS1003168331 (11:66048728 C>T), RS1003449715 (11:66047000 C>T), RS1003776162 (11:66047897 G>A,C), RS1004228842 (11:66046903 G>A,T), RS1004259819 (11:66047112 A>C,G)

Disease associations

OMIM: gene MIM:608234 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

19 associations (top):

Study	Trait	p-value
GCST001241_12	Bipolar disorder	2.000000e-07
GCST002481_8	Acne (severe)	3.000000e-11
GCST005537_10	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	7.000000e-10
GCST007294_7	Body fat distribution (trunk fat ratio)	8.000000e-12
GCST007294_75	Body fat distribution (trunk fat ratio)	1.000000e-07
GCST007295_158	Body fat distribution (leg fat ratio)	8.000000e-06
GCST007295_48	Body fat distribution (leg fat ratio)	3.000000e-09
GCST007563_8	Allergic disease (asthma, hay fever or eczema)	2.000000e-15
GCST007564_30	Asthma or allergic disease (pleiotropy)	5.000000e-17
GCST007993_16	Asthma (adult onset)	2.000000e-11
GCST007995_12	Asthma (childhood onset)	2.000000e-20
GCST008103_21	Bipolar disorder	2.000000e-08
GCST008916_19	Asthma	4.000000e-42
GCST009647_1	Serum cancer antigen 125 (CA 125) levels	3.000000e-57
GCST009647_4	Serum cancer antigen 125 (CA 125) levels	1.000000e-28
GCST009647_5	Serum cancer antigen 125 (CA 125) levels	2.000000e-23
GCST009647_6	Serum cancer antigen 125 (CA 125) levels	8.000000e-16
GCST009731_53	Blood protein levels in cardiovascular risk	3.000000e-75
GCST009798_13	Asthma	5.000000e-36

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004341	body fat distribution
EFO:1002011	adult onset asthma
EFO:0010603	cancer antigen 125 measurement
EFO:0010609	mucin‐16 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases methylation, decreases expression	2
aristolochic acid I	increases expression	1
bisphenol S	increases methylation	1
Sunitinib	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Amiodarone	increases expression	1
Benzo(a)pyrene	increases methylation	1
Aflatoxin B1	increases methylation	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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