GAL3ST4

Summary

GAL3ST4 (galactose-3-O-sulfotransferase 4, HGNC:24145) is a protein-coding gene on chromosome 7q22.1, encoding Galactose-3-O-sulfotransferase 4 (Q96RP7). Catalyzes the transfer of a sulfate group from 3’-phosphoadenylyl sulfate (PAPS) to the C-3 hydroxyl group of terminal non-reducing beta-1,3-linked galactose residues, exclusively in O-linked glycoproteins.

This gene encodes a member of the galactose-3-O-sulfotransferase protein family. The product of this gene catalyzes sulfonation by transferring a sulfate to the C-3’ position of galactose residues in O-linked glycoproteins. This enzyme is highly specific for core 1 structures, with asialofetuin, Gal-beta-1,3-GalNAc and Gal-beta-1,3 (GlcNAc-beta-1,6)GalNAc being good substrates.

Source: NCBI Gene 79690 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 115 total
• MANE Select transcript: NM_024637

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24145
Approved symbol	GAL3ST4
Name	galactose-3-O-sulfotransferase 4
Location	7q22.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ12116
Ensembl gene	ENSG00000197093
Ensembl biotype	protein_coding
OMIM	608235
Entrez	79690

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 9 protein_coding, 1 retained_intron

ENST00000360039, ENST00000411994, ENST00000413800, ENST00000423751, ENST00000460995, ENST00000482469, ENST00000495882, ENST00000498000, ENST00000866493, ENST00000965762

RefSeq mRNA: 1 — MANE Select: NM_024637 NM_024637

CCDS: CCDS5688

Canonical transcript exons

ENST00000360039 — 4 exons

Exon	Start	End
ENSE00001181067	100168546	100168617
ENSE00003524290	100166502	100166805
ENSE00003621641	100159244	100160959
ENSE00003782737	100166971	100167283

Expression profiles

Bgee: expression breadth ubiquitous, 208 present calls, max score 91.21.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.3828 / max 89.7740, expressed in 1037 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
85172	1.8682	920
85168	0.8004	204
85167	0.2117	109
85169	0.1974	107
85166	0.1139	49
85170	0.0910	51
85171	0.0534	18
204541	0.0468	20

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	91.21	gold quality
skin of abdomen	UBERON:0001416	87.85	gold quality
mammalian vulva	UBERON:0000997	86.07	silver quality
zone of skin	UBERON:0000014	85.84	gold quality
cervix squamous epithelium	UBERON:0006922	85.82	gold quality
skin of leg	UBERON:0001511	85.62	gold quality
upper leg skin	UBERON:0004262	84.79	gold quality
gingival epithelium	UBERON:0001949	84.61	silver quality
thymus	UBERON:0002370	84.35	silver quality
nipple	UBERON:0002030	83.75	silver quality
germinal epithelium of ovary	UBERON:0001304	83.26	gold quality
ganglionic eminence	UBERON:0004023	82.82	gold quality
layer of synovial tissue	UBERON:0007616	82.43	silver quality
cortical plate	UBERON:0005343	82.19	gold quality
endothelial cell	CL:0000115	81.67	silver quality
hair follicle	UBERON:0002073	81.60	silver quality
inferior vagus X ganglion	UBERON:0005363	81.51	silver quality
descending thoracic aorta	UBERON:0002345	81.41	gold quality
thoracic aorta	UBERON:0001515	81.26	gold quality
vagina	UBERON:0000996	81.13	gold quality
ascending aorta	UBERON:0001496	81.10	gold quality
subthalamic nucleus	UBERON:0001906	80.92	silver quality
ventral tegmental area	UBERON:0002691	80.54	silver quality
right coronary artery	UBERON:0001625	80.24	gold quality
vena cava	UBERON:0004087	80.13	gold quality
ectocervix	UBERON:0012249	79.82	gold quality
saliva-secreting gland	UBERON:0001044	79.81	gold quality
upper arm skin	UBERON:0004263	79.27	silver quality
mucosa of sigmoid colon	UBERON:0004993	79.23	silver quality
colonic mucosa	UBERON:0000317	79.01	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

49 targeting GAL3ST4, 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-3613-3P	100.00	76.36	7965
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-6751-5P	99.56	64.99	1145
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-650	99.45	65.77	1309
HSA-MIR-520F-5P	99.34	70.40	1632
HSA-MIR-664A-3P	99.22	71.08	2696
HSA-MIR-6803-5P	99.19	63.90	1026
HSA-MIR-7109-5P	99.18	66.13	1057
HSA-MIR-6799-5P	99.14	65.72	2093
HSA-MIR-376A-3P	99.06	69.17	1128

Literature-anchored findings (GeneRIF, showing 4)

• Gal3ST-4 is a substrate for the mucin core-2 trisaccharide (PMID:14701868)
• The genetic mutation of GAL3ST4 affects the functions of the encoded protein. (PMID:23147795)
• we found that loss of Gpr126 upregulated the expression of Gal3st4, a gene implicated in human PE, encoding Galactose-3-O-sulfotransferase 4 (PMID:25954032)
• the GAL3ST4 and the CHGB allele variants 23 and 48 are novel genetic loci involved in susceptibility to leprosy among female and male population, respectively (PMID:29180661)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	gal3st4	ENSDARG00000079712
mus_musculus	Gal3st4	ENSMUSG00000075593
rattus_norvegicus	Gal3st4	ENSRNOG00000001375

Paralogs (3): GAL3ST1 (ENSG00000128242), GAL3ST2 (ENSG00000154252), GAL3ST3 (ENSG00000175229)

Protein

Protein identifiers

Galactose-3-O-sulfotransferase 4 — Q96RP7 (reviewed: Q96RP7)

Alternative names: Beta-galactose-3-O-sulfotransferase 4, Gal-beta-1,3-GalNAc 3’-sulfotransferase

All UniProt accessions (5): A0A0J9YVN4, A0A0J9YXX0, A0A0J9YYD8, C9IZ77, Q96RP7

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-1,3-linked galactose residues, exclusively in O-linked glycoproteins. Participates in galactose sulfation and acts on core 1 (Gal-beta-1,3-GalNAc-R) structures. In vitro, also recognizes Gal-beta-1,3 (GlcNAc-beta-1,6)GalNAc-R, asialofetuin, the Globo H precursor and Gal-beta-1,3(6-O-sulfo)GalNAc-R structures as good substrates.

Subcellular location. Golgi apparatus. Golgi stack membrane.

Tissue specificity. Expressed mainly in placenta, thymus, testis, ovary, spinal cord, trachea and adrenal gland and at low levels in brain, lung, spleen, prostate, small intestine, colon, stomach thyroid and lymph node.

Activity regulation. Inhibition by Mn(2+) at high Mn(2+) concentrations.

Pathway. Protein modification; carbohydrate sulfation.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q96RP7-1	1	yes
Q96RP7-2	2

RefSeq proteins (1): NP_078913* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF06990

UniProt features (12 total): sequence conflict 3, topological domain 2, splice variant 2, sequence variant 2, chain 1, transmembrane region 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96RP7-F1	80.30	0.66

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 (1): 374

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 154 (showing top): GOBP_OLIGOSACCHARIDE_METABOLIC_PROCESS, HNF3ALPHA_Q6, WHITEHURST_PACLITAXEL_SENSITIVITY, GOBP_GLYCOLIPID_BIOSYNTHETIC_PROCESS, GAUSSMANN_MLL_AF4_FUSION_TARGETS_E_UP, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_CELL_CELL_SIGNALING, NKX62_Q2, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, HFH3_01, GOBP_LIPID_METABOLIC_PROCESS, GOBP_LIPID_BIOSYNTHETIC_PROCESS, CDPCR3HD_01, GOBP_LIPOSACCHARIDE_METABOLIC_PROCESS

GO Biological Process (7): sulfur compound metabolic process (GO:0006790), cell-cell signaling (GO:0007267), glycoprotein metabolic process (GO:0009100), glycoprotein biosynthetic process (GO:0009101), glycolipid biosynthetic process (GO:0009247), oligosaccharide metabolic process (GO:0009311), proteoglycan biosynthetic process (GO:0030166)

GO Molecular Function (6): galactosylceramide sulfotransferase activity (GO:0001733), 3’-phosphoadenosine 5’-phosphosulfate binding (GO:0050656), galactose 3-O-sulfotransferase activity (GO:0050694), proteoglycan sulfotransferase activity (GO:0050698), sulfotransferase activity (GO:0008146), transferase activity (GO:0016740)

GO Cellular Component (5): membrane (GO:0016020), Golgi cisterna membrane (GO:0032580), extracellular exosome (GO:0070062), Golgi membrane (GO:0000139), Golgi apparatus (GO:0005794)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
carbohydrate derivative biosynthetic process	2
sulfotransferase activity	2
metabolic process	1
cell communication	1
signaling	1
protein metabolic process	1
carbohydrate derivative metabolic process	1
macromolecule biosynthetic process	1
glycoprotein metabolic process	1
glycolipid metabolic process	1
lipid biosynthetic process	1
carbohydrate metabolic process	1
proteoglycan metabolic process	1
glycoprotein biosynthetic 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
extracellular vesicle	1
Golgi apparatus	1
bounding membrane of organelle	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

426 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GAL3ST4	ABI3	Q9P2A4	514
GAL3ST4	SBNO2	Q9Y2G9	504
GAL3ST4	TINAG	Q9UJW2	485
GAL3ST4	SRPX2	O60687	470
GAL3ST4	SYT14	Q8NB59	465
GAL3ST4	LRRC25	Q8N386	459
GAL3ST4	GCNT4	Q9P109	457
GAL3ST4	INPP5D	Q92835	454
GAL3ST4	LRRN1	Q6UXK5	452
GAL3ST4	TAFA5	Q7Z5A7	428
GAL3ST4	PPA1	Q15181	423
GAL3ST4	HOXA13	P31271	416
GAL3ST4	SMIM2	Q9BVW6	400
GAL3ST4	DHRS13	Q6UX07	397
GAL3ST4	CFAP144	A6NL82	392

IntAct

2 interactions, top by confidence:

A	B	Type	Score
ESR2	PSMD11	psi-mi:“MI:0914”(association)	0.350

BioGRID (3): GAL3ST4 (Proximity Label-MS), XRCC6 (Two-hybrid), GAL3ST4 (Affinity Capture-MS)

ESM2 similar proteins: A6QNK1, O14792, O19058, O35310, O43916, O88199, Q10979, Q11127, Q29043, Q5E9W5, Q5RJQ0, Q5XPT3, Q6P7A1, Q6XQG8, Q6XQG9, Q6XQH0, Q712G6, Q7LGC8, Q7T3S3, Q800H9, Q80WV3, Q866C5, Q866C7, Q866D2, Q866D6, Q866D9, Q866E1, Q866E6, Q866E7, Q866E8, Q866F0, Q866F1, Q8HYJ3, Q8HYJ4, Q8HYJ7, Q8N3Y3, Q8NET6, Q92179, Q96RP7, Q99999

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	95
Likely benign	8
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

258 predictions. Top by Δscore:

Variant	Effect	Δscore
7:100166496:CCTTA:C	donor_loss	0.9900
7:100166497:CTTAC:C	donor_loss	0.9900
7:100166498:TTA:T	donor_loss	0.9900
7:100166499:TACCT:T	donor_loss	0.9900
7:100166501:C:CT	donor_loss	0.9900
7:100166501:CCT:C	donor_gain	0.9900
7:100160958:ACC:A	acceptor_loss	0.9800
7:100160959:CCT:C	acceptor_loss	0.9800
7:100160961:T:A	acceptor_loss	0.9800
7:100166806:C:CC	acceptor_gain	0.9800
7:100166500:A:AC	donor_gain	0.9700
7:100166501:C:CC	donor_gain	0.9700
7:100166964:AACTC:A	donor_loss	0.9700
7:100166965:ACTC:A	donor_loss	0.9700
7:100166966:CTCA:C	donor_loss	0.9700
7:100166967:TCA:T	donor_loss	0.9700
7:100166968:CAC:C	donor_loss	0.9700
7:100160912:TCGG:T	acceptor_gain	0.9600
7:100166802:TAGCC:T	acceptor_loss	0.9600
7:100166804:GCCTG:G	acceptor_loss	0.9600
7:100166806:C:CA	acceptor_loss	0.9600
7:100166807:T:A	acceptor_loss	0.9600
7:100166969:ACCT:A	donor_gain	0.9600
7:100166970:CCTC:C	donor_gain	0.9600
7:100166816:A:C	acceptor_loss	0.9500
7:100166963:GAACT:G	donor_loss	0.9500
7:100166589:AGAGG:A	donor_gain	0.9400
7:100166970:CCT:C	donor_gain	0.9400
7:100160913:C:A	acceptor_gain	0.9300
7:100166808:G:C	acceptor_loss	0.9100

AlphaMissense

3105 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:100166704:T:A	K76I	0.999
7:100166529:A:C	C134W	0.997
7:100166703:T:A	K76N	0.997
7:100166703:T:G	K76N	0.997
7:100166712:C:A	K73N	0.997
7:100166712:C:G	K73N	0.997
7:100160003:C:A	K462N	0.996
7:100160003:C:G	K462N	0.996
7:100160292:T:A	D366V	0.996
7:100160293:C:G	D366H	0.996
7:100166694:G:C	S79R	0.996
7:100166694:G:T	S79R	0.996
7:100166696:T:G	S79R	0.996
7:100166719:A:G	F71S	0.996
7:100160454:A:T	V312D	0.995
7:100160825:G:C	F188L	0.995
7:100160825:G:T	F188L	0.995
7:100160826:A:G	F188S	0.995
7:100160827:A:G	F188L	0.995
7:100166641:A:G	F97S	0.995
7:100160852:G:C	F179L	0.994
7:100160852:G:T	F179L	0.994
7:100160854:A:G	F179L	0.994
7:100166530:C:T	C134Y	0.994
7:100166531:A:G	C134R	0.994
7:100166663:C:A	G90W	0.994
7:100166705:T:C	K76E	0.994
7:100160169:C:G	C407S	0.993
7:100160170:A:T	C407S	0.993
7:100160202:A:G	L396P	0.993

dbSNP variants (sampled 300 via entrez): RS1000518460 (7:100162630 A>C,G,T), RS1000622990 (7:100159645 G>T), RS1000700344 (7:100166132 C>G), RS1000731078 (7:100168954 A>G,T), RS1001184521 (7:100169262 GCCATTGCACT>G), RS1001218834 (7:100166470 C>T), RS1001502653 (7:100162040 T>A,G), RS1001569500 (7:100161326 C>A,T), RS1001695813 (7:100167617 C>G,T), RS1002405255 (7:100167771 C>T), RS1002698598 (7:100169236 C>T), RS1002742109 (7:100166235 G>A), RS1002812191 (7:100169634 T>G), RS1003580768 (7:100164038 G>A,C), RS1003959439 (7:100158832 C>G)

Disease associations

OMIM: gene MIM:608235 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST010002_259	Refractive error	3.000000e-16
GCST010702_48	Subcortical volume (MOSTest)	6.000000e-10
GCST010703_289	Brain morphology (MOSTest)	6.000000e-15

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases methylation	3
bisphenol A	affects cotreatment, increases methylation, increases expression	2
Benzo(a)pyrene	increases expression, increases methylation, affects methylation	2
Cadmium Chloride	decreases expression, increases abundance	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	increases expression	1
sulindac sulfide	decreases expression	1
nickel sulfate	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1
MT19c compound	decreases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	increases expression	1
Arsenic	affects methylation	1
Cadmium	decreases expression, increases abundance	1
Calcitriol	decreases expression	1
Doxorubicin	increases expression	1
Lipopolysaccharides	increases expression, affects cotreatment, decreases expression, affects response to substance	1
Phthalic Acids	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Rotenone	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Aflatoxin B1	increases expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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