FUT3

Summary

FUT3 (fucosyltransferase 3 (Lewis blood group), HGNC:4014) is a protein-coding gene on chromosome 19p13.3, encoding 3-galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferase FUT3 (P21217). Catalyzes the transfer of L-fucose, from a guanosine diphosphate-beta-L-fucose, to both the subterminal N-acetyl glucosamine (GlcNAc) of type 1 chain (beta-D-Gal-(1->3)-beta-D-GlcNAc) glycolipids and oligosaccharides via an alpha(1,4) linkage, and the subterminal glucose (Glc) o….

The Lewis histo-blood group system comprises a set of fucosylated glycosphingolipids that are synthesized by exocrine epithelial cells and circulate in body fluids. The glycosphingolipids function in embryogenesis, tissue differentiation, tumor metastasis, inflammation, and bacterial adhesion. They are secondarily absorbed to red blood cells giving rise to their Lewis phenotype. This gene is a member of the fucosyltransferase family, which catalyzes the addition of fucose to precursor polysaccharides in the last step of Lewis antigen biosynthesis. It encodes an enzyme with alpha(1,3)-fucosyltransferase and alpha(1,4)-fucosyltransferase activities. Mutations in this gene are responsible for the majority of Lewis antigen-negative phenotypes. Differences in the expression of this gene are associated with host susceptibility to viral infection.

Source: NCBI Gene 2525 — RefSeq curated summary.

At a glance

• GWAS associations: 23
• Clinical variants (ClinVar): 86 total
• Druggable target: yes
• MANE Select transcript: NM_001097639

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4014
Approved symbol	FUT3
Name	fucosyltransferase 3 (Lewis blood group)
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	CD174
Ensembl gene	ENSG00000171124
Ensembl biotype	protein_coding
OMIM	111100
Entrez	2525

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 8 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000303225, ENST00000458379, ENST00000585715, ENST00000587048, ENST00000587183, ENST00000588539, ENST00000589620, ENST00000589714, ENST00000589918, ENST00000593144

RefSeq mRNA: 12 — MANE Select: NM_001097639 NM_000149, NM_001097639, NM_001097640, NM_001097641, NM_001374740, NM_001382744, NM_001382745, NM_001382746, NM_001382747, NM_001382748, NM_001382749, NM_001382750

CCDS: CCDS12153

Canonical transcript exons

ENST00000589620 — 3 exons

Exon	Start	End
ENSE00002852263	5846426	5846618
ENSE00002886157	5842888	5844851
ENSE00002917594	5851390	5851449

Expression profiles

Bgee: expression breadth ubiquitous, 193 present calls, max score 98.92.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.6505 / max 129.3567, expressed in 156 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
178574	1.5461	152
178575	0.0808	40
178569	0.0181	7
178570	0.0056	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	98.92	gold quality
mucosa of transverse colon	UBERON:0004991	98.05	gold quality
esophagus mucosa	UBERON:0002469	96.29	gold quality
nasal cavity epithelium	UBERON:0005384	95.60	gold quality
ileal mucosa	UBERON:0000331	94.25	gold quality
esophagus squamous epithelium	UBERON:0006920	94.07	gold quality
epithelium of esophagus	UBERON:0001976	93.90	gold quality
oral cavity	UBERON:0000167	93.60	gold quality
rectum	UBERON:0001052	93.30	gold quality
minor salivary gland	UBERON:0001830	93.26	gold quality
olfactory bulb	UBERON:0002264	92.91	gold quality
tongue squamous epithelium	UBERON:0006919	92.79	gold quality
mouth mucosa	UBERON:0003729	92.76	gold quality
pharyngeal mucosa	UBERON:0000355	92.71	gold quality
type B pancreatic cell	CL:0000169	91.73	gold quality
buccal mucosa cell	CL:0002336	91.59	gold quality
squamous epithelium	UBERON:0006914	91.54	gold quality
duodenum	UBERON:0002114	91.26	gold quality
amniotic fluid	UBERON:0000173	90.58	gold quality
colonic mucosa	UBERON:0000317	90.37	gold quality
mucosa of sigmoid colon	UBERON:0004993	89.25	gold quality
cervix squamous epithelium	UBERON:0006922	89.17	gold quality
body of tongue	UBERON:0011876	88.90	gold quality
saliva-secreting gland	UBERON:0001044	88.88	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	88.68	gold quality
transverse colon	UBERON:0001157	88.26	gold quality
tongue	UBERON:0001723	88.16	gold quality
gall bladder	UBERON:0002110	87.98	gold quality
small intestine Peyer’s patch	UBERON:0003454	87.64	gold quality
cervix epithelium	UBERON:0004801	87.30	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-3929	yes	186.74
E-CURD-114	yes	53.00
E-ANND-3	yes	9.66

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

miRNA regulators (miRDB)

30 targeting FUT3, 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-6778-3P	99.96	67.29	2693
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-1303	99.65	69.77	1662
HSA-MIR-4690-5P	99.65	66.24	813
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-766-3P	99.47	65.24	1811
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-6878-3P	99.24	64.23	920
HSA-MIR-499A-3P	99.18	69.20	1392
HSA-MIR-499B-3P	99.18	69.27	1391
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-1294	98.91	69.26	1030
HSA-MIR-9986	98.91	69.28	1024
HSA-MIR-2355-5P	98.83	65.51	1589
HSA-MIR-4539	98.78	67.18	888
HSA-MIR-502-5P	98.77	66.51	906
HSA-MIR-589-5P	98.72	66.96	927
HSA-MIR-214-3P	98.71	68.12	2128
HSA-MIR-761	98.71	68.07	2051
HSA-MIR-4710	98.61	65.96	1048
HSA-MIR-4726-3P	98.49	63.89	1385
HSA-MIR-6841-3P	98.08	66.54	604
HSA-MIR-3665	97.73	65.08	975
HSA-MIR-4701-5P	96.45	68.41	1121
HSA-MIR-588	96.45	68.36	1127

Literature-anchored findings (GeneRIF, showing 40)

• PCR using sequence-specific primers DNA enables efficient genotyping of clinical samples (PMID:11668626)
• Sialy Lewis-X antigens play an important role liver metastases of colon carcinoma. (PMID:11819805)
• Distribution of Lewis (FUT3)genotype and allele frequencies by ethnicity in a United States population. (PMID:12424536)
• Cys, Gln, and Tyr residues are important for FT3wt sorting into the transport vesicles possibly due to interactions with other membrane proteins (PMID:12493760)
• study of the Lewis gene polymorphisms in a Caucasian Portuguese population with a high rate of H. pylori infection, and evaluation of the implications of mutant enzymes in Le(b) expression in the gastric mucosa (PMID:12730721)
• results indicated that Mn2+ bound the enzyme and increased its affinity for the acceptor (PMID:14977360)
• The heterologous enzyme hFUT3 was strongly expressed and fully functional in transgenic tobacco, which showed a delay in growth linked to a reduction of internode length. (PMID:15331092)
• Higher expression of Lewis y/b was more often found in high grade and poor prognosis tumours compared to good prognosis breast cancers. (PMID:16168124)
• cloning and characterization of the promoter; strong correlation between the promoter activity and high expression of sialyl Le(a) observed in colon carcinoma cell lines seem to confirm the important regulatory role of FUT3 in synthesis of sialyl Le(a) (PMID:16199102)
• LeX motif present in human milk can bind to dendritic cell-specific ICAM3-grabbing non-integrin (DC-SIGN), thereby preventing the capture and subsequent transfer of HIV-1 to CD4+ T lymphocytes. (PMID:16239964)
• T3 overexpression in gastric cells depends upon promoter hypomethylation and FUT3 is responsible for overexpression of Le(a) in gastric cells, in vitro (PMID:16427187)
• functional mutations of the FUT3 gene may be associated with an increased atherothrombotic disease prevalence, especially among abstainers (PMID:17383304)
• These observations point to a tumor induced transcription of endothelial FUT1 and consequently an enhanced expression of CD174 which is involved in migration and early cell-cell contacts during tumor associated angiogenesis. (PMID:18205178)
• increased CD15 expression is not due to de novo biosynthesis of CD15, but results predominantly from induction of alpha(2-3)-sialidase activity (PMID:18953356)
• Expression of sLex antigen in breast cancer is not associated with breast cancer survival. (PMID:18977761)
• These findings indicate that Lewis y antigen have the ability to enhance the proliferation and elevate the survival rates of RMG-I cells, which can promote the genesis and development of ovarian carcinoma (PMID:19137814)
• Sequence analysis of FUT3 identified many SNPs, but most of them are in complete linkage disequilibrium with previously reported SNPs responsible for the Lewis-negative phenotype. (PMID:19175549)
• results suggested that PKR is the primary target for HSV-1 early RNA during induction of FUT3, FUT5, and FUT6 (PMID:19349624)
• Multiple common and sporadic sequence variations including 14 new alleles at FUT1, FUT2, and FUT3 loci were identified. (PMID:19572973)
• in breast cancer there was a limited humoral immune response through Lewis y/IgM/CIC levels detection which correlated with MUC1/IgM/CIC (PMID:19715603)
• Increased expression of Lewis y antigen plays an important role in promoting cell proliferation through activating PI3K/Akt signaling pathway in ovarian carcinoma-derived RMG-I cells. (PMID:20003467)
• GALNT14 and FUT3/6 H-scores were significantly higher in non-small cell lung cancer cell lines sensitive to dulanermin and drozitumab versus resistant cell lines (PMID:20179215)
• Lewis-negative genotype was associated with invasive ductal breast carcinoma but not with anatomoclinical parameters (PMID:20514537)
• LeY is carried by integrin alphavbeta3 and plays a critical role in attachment to cultured cells. LeY activates integrin alphavbeta3/focal adhesion kinase (FAK) signaling. (PMID:20605574)
• At physiological levels of wall shear stress, the number of flowing cancer cells recruited to the microtube surface was dramatically reduced by FUT3 knockdown (PMID:20833389)
• Elevated expression of Topo-I and Topo-II beta is found in Lewis(y) antigen-overexpressing ovarian cancer cells. (PMID:21542140)
• down-regulation of FUT3 and FUT5 reduces the expression of sialyl-Lewis antigens and the adhesion capacities of gastric cancer cells and allows to identify the specific alpha1-3,4 fucosyltransferases implicated in the Lewis antigens synthesis (PMID:21978830)
• Obtained FST values reveal distinct frequencies of the FUT3 SNPs between the present sample and its representative ancestral populations. (PMID:23922852)
• Use of FUT2/3 genotype-dependent cut-off values for CA19-9 improved sensitivity and reduced the number of false positive results (PMID:23958938)
• Mutations of FUT3 (rs28362459) and (rs3745635) might influence the lesion locations in CD patients. (PMID:24720527)
• that the absence of alpha1,3/4-fucosyltransferase enzyme is related to breast’s invasive breast carcinoma (PMID:26321244)
• Data suggest that fucosyltransferase 3 (FUT3) gene rs28362459 and rs3745635 single nucleotide polymorphisms (SNPs) may engender the increased risk of ileocolonic and ileal Crohn’s disease (CD). (PMID:26663064)
• Polymorphisms in FUT3 and its intestinal expression might be associated with ulcerative colitis pathogenesis. (PMID:26766790)
• High FUT3 expression is associated with breast cancer. (PMID:26908442)
• the miRNA expression vector which targets the FUT3 gene can effectively inhibit the proliferation, migration and invasion abilities of KATO-III cells. (PMID:27453266)
• the high expressions of BCL6 and Lewis y antigen are associated with development, high tumor burden, and worse prognosis of ovarian cancer and targeting BCL6 could be a novel therapeutic strategy for ovarian cancer treatment. (PMID:28671040)
• Overexpressed N-fucosylation on cell surface promotes the migration and invasion of metastatic pancreatic cancer cells. Overexpressed N-fucosylation is driven by gene FUT3, 5, and 6 in metastatic pancreatic cancer cells. (PMID:30808544)
• FUT3 and FUT2 genotyping is associated with infection by T. gondii in pregnant women and the Leb profile appears to protect the infection by this parasite. (PMID:30831115)
• Rs2306969 did not modulate FUT3 expression in breast tumors under non-stimulated conditions. (PMID:30929162)
• Regulation of FUT3 expression under hypoxic and serum deprivation conditions may be involved in the acquisition of advantages related to apoptosis resistance and metastasis promotion, according to the intrinsic differences presented by T47D and MCF7 cells. (PMID:31868335)

Cross-species orthologs

22 orthologs

Organism	Symbol	Gene ID
danio_rerio	fut9b.3	ENSDARG00000027699
danio_rerio	fut9d	ENSDARG00000028098
danio_rerio	fut7	ENSDARG00000044775
danio_rerio	fut9b.2	ENSDARG00000058299
danio_rerio	fut9b.1	ENSDARG00000067524
danio_rerio	fut9b.4	ENSDARG00000086603
danio_rerio		ENSDARG00000100247
danio_rerio	fut9b.5	ENSDARG00000102426
danio_rerio	fut9b.6	ENSDARG00000102554
drosophila_melanogaster	FucTD	FBGN0035217
caenorhabditis_elegans		WBGENE00001505
caenorhabditis_elegans		WBGENE00001507
caenorhabditis_elegans		WBGENE00004010
caenorhabditis_elegans		WBGENE00006402
caenorhabditis_elegans		WBGENE00007211
caenorhabditis_elegans		WBGENE00012922
caenorhabditis_elegans		WBGENE00016163
caenorhabditis_elegans		WBGENE00017343
caenorhabditis_elegans		WBGENE00043986
caenorhabditis_elegans		WBGENE00044383
caenorhabditis_elegans		WBGENE00194870
caenorhabditis_elegans		WBGENE00206359

Paralogs (7): FUT5 (ENSG00000130383), FUT6 (ENSG00000156413), FUT9 (ENSG00000172461), FUT10 (ENSG00000172728), FUT7 (ENSG00000180549), FUT4 (ENSG00000196371), FUT11 (ENSG00000196968)

Protein

Protein identifiers

3-galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferase FUT3 — P21217 (reviewed: P21217)

Alternative names: 4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase, Alpha-3-fucosyltransferase FUT3, Blood group Lewis alpha-4-fucosyltransferase, Fucosyltransferase 3, Fucosyltransferase III

All UniProt accessions (4): P21217, K7ENT3, K7EQ20, K7ES24

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the transfer of L-fucose, from a guanosine diphosphate-beta-L-fucose, to both the subterminal N-acetyl glucosamine (GlcNAc) of type 1 chain (beta-D-Gal-(1->3)-beta-D-GlcNAc) glycolipids and oligosaccharides via an alpha(1,4) linkage, and the subterminal glucose (Glc) or GlcNAc of type 2 chain (beta-D-Gal-(1->4)-beta-D-GlcNAc) oligosaccharides via an alpha(1,3) linkage, independently of the presence of terminal alpha-L-fucosyl-(1,2) moieties on the terminal galactose of these acceptors. Through its catalytic activity, participates in the synthesis of antigens of the Lewis blood group system, i.e. Lewis a (Le(a)), lewis b (Le(b)), Lewis x/SSEA-1 (Le(x)) and lewis y (Le(y)) antigens. Also catalyzes the transfer of L-fucose to subterminal GlcNAc of sialyl- and disialyl-lactotetraosylceramide to produce sialyl Lewis a (sLe(a)) and disialyl Lewis a via an alpha(1,4) linkage and therefore may regulate cell surface sLe(a) expression and consequently regulates adhesive properties to E-selectin, cell proliferation and migration. Catalyzes the transfer of an L-fucose to 3’-sialyl-N-acetyllactosamine by an alpha(1,3) linkage, which allows the formation of sialyl-Lewis x structure and therefore may regulate the sialyl-Lewis x surface antigen expression and consequently adhesive properties to E-selectin. Prefers type 1 chain over type 2 acceptors. Type 1 tetrasaccharide is a better acceptor than type 1 disaccharide suggesting that a beta anomeric configuration of GlcNAc in the substrate is preferred. Lewis-positive (Le(+)) individuals have an active enzyme while Lewis-negative (Le(-)) individuals have an inactive enzyme.

Subcellular location. Golgi apparatus. Golgi stack membrane.

Tissue specificity. Highly expressed in stomach, colon, small intestine, lung and kidney and to a lesser extent in salivary gland, bladder, uterus and liver.

Post-translational modifications. Glycosylated.

Pathway. Protein modification; protein glycosylation.

Polymorphism. Genetic variations in FUT3 define the Lewis blood group system (LE) [MIM:618983]. FUT3 catalyzes the addition of fucose to precursor polysaccharides in the last step of Lewis antigen biosynthesis. Variations in this gene are responsible for the majority of Lewis antigen-negative phenotypes (Le(-)).

Similarity. Belongs to the glycosyltransferase 10 family.

RefSeq proteins (12): NP_000140, NP_001091108, NP_001091109, NP_001091110, NP_001361669, NP_001369673, NP_001369674, NP_001369675, NP_001369676, NP_001369677, NP_001369678, NP_001369679 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001503	Glyco_trans_10	Family
IPR031481	Glyco_tran_10_N	Domain
IPR038577	GT10-like_C_sf	Homologous_superfamily
IPR055270	Glyco_tran_10_C	Domain

Pfam: PF00852, PF17039

Enzyme classification (BRENDA):

• EC 2.4.1.65 — 3-galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferase (BRENDA: 16 organisms, 191 substrates, 64 inhibitors, 119 Km, 15 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
GDP-FUCOSE	0.03–0.244	19
GDP-L-FUCOSE	0.005–0.035	8
GAL-BETA-1,4-GLCNAC-O-(CH2)8CO2CH3	0.17–2.2	6
FUCALPHA(1,2)GALBETA(1,3)GLCNAC	0.1–3.8	5
FUC-ALPHA-1,2GAL-BETA-1,3GLCNAC-SP-BIOTIN	0.2–2.5	4
GAL-BETA-1,3-GLCNAC-O-(CH2)8CO2CH3	8.4–22.7	4
GAL-BETA-1,3GLCNACO(CH2)3NHCO(CH2)5NH-BIOTIN	0.7–3.3	4
FUC-ALPHA-1,2GAL-BETA-1,4GLCNAC-SP-BIOTIN	0.1–1.3	3
GALBETA(1,3)GLCNAC	0.6–12.7	3
GALBETA(1,4)GLCNAC	0.035–8.1	3
GDP-BETA-L-FUCOSE	0.0057–0.0337	3
(GAL-3-O-ME)BETA(1-3)(GLCNAC-6-O-ME)BETA-O-ME	0.12–2.7	2
2-O-MEGALBETA(1,3)GLCNACBETA-O-BN	0.16–0.4	2
3-O-SULFOGALBETA(1,3)GLCNACBETA-O-AL	0.047–0.1	2
FORMIC ACID (2R,3R,4S,5R,6R)-2-((2R,3R,4R,5R,6R)	0.075–1.3	2

Catalyzed reactions (Rhea), 12 shown:

• a beta-D-galactosyl-(1->4)-N-acetyl-beta-D-glucosaminyl derivative + GDP-beta-L-fucose = a beta-D-galactosyl-(1->4)-[alpha-L-fucosyl-(1->3)]-N-acetyl-beta-D-glucosaminyl derivative + GDP + H(+) (RHEA:14257)
• a beta-D-galactosyl-(1->3)-N-acetyl-beta-D-glucosaminyl derivative + GDP-beta-L-fucose = a beta-D-galactosyl-(1->3)-[alpha-L-fucosyl-(1->4)]-N-acetyl-beta-D-glucosaminyl derivative + GDP + H(+) (RHEA:23628)
• N-acetyl-alpha-neuraminosyl-(2->3)-beta-D-galactosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->3)-beta-D-galactosyl-(1->4)-beta-D-glucosyl-(1<->1’)-N-acyl-sphing-4-enine + GDP-beta-L-fucose = N-acetyl-alpha-neuraminosyl-(2->3)-beta-D-galactosyl-(1->3)-alpha-L-fucosyl-(1->4)-[N-acetyl-beta-D-glucosaminyl-(1->3)]-beta-D-galactosyl-(1->4)-beta-D-glucosyl-(1<->1’)-N-acyl-sphing-4-enine + GDP + H(+) (RHEA:47888)
• N-acetyl-alpha-neuraminosyl-(2->3)-beta-D-galactosyl-(1->3)-[N-acetyl-alpha-neuraminosyl-(2->6)]-N-acetyl-beta-D-glucosaminyl-(1->3)-beta-D-galactosyl-(1->4)-beta-D-glucosyl-(1<->1’)-N-acyl-sphing-4-enine + GDP-beta-L-fucose = N-acetyl-alpha-neuraminosyl-(2->3)-beta-D-galactosyl-(1->3)-alpha-L-fucosyl-(1->4)-[N-acetyl-alpha-neuraminosyl-(2->6)-N-acetyl-beta-D-glucosaminyl-(1->3)]-beta-D-galactosyl-(1->4)-beta-D-glucosyl-(1<->1’)-N-acyl-sphing-4-enine + GDP + H(+) (RHEA:47892)
• a beta-D-Gal-(1->3)-beta-D-GlcNAc-(1->3)-beta-D-Gal-(1->4)-beta-D-Glc-(1<->1’)-Cer(d18:1(4E)) + GDP-beta-L-fucose = a III(4)-a-Fuc-Lc4Cer(d18:1(4E)) + GDP + H(+) (RHEA:48328)
• Lc4Cer + GDP-beta-L-fucose = a lactoside III(4)-a-Fuc-Lc4Cer + GDP + H(+) (RHEA:48824)
• an alpha-Neu5Ac-(2->3)-beta-D-Gal-(1->4)-beta-D-GlcNAc-(1->3)-beta-D-Gal-(1->4)-[alpha-L-Fuc-(1->3)]-beta-D-GlcNAc derivative + GDP-beta-L-fucose = an alpha-Neu5Ac-(2->3)-beta-D-Gal-(1->4)-[alpha-L-Fuc-(1->3)]-beta-D-GlcNAc-(1->3)-beta-D-Gal-(1->4)-[alpha-L-Fuc-(1->3)]-beta-D-GlcNAc derivative + GDP + H(+) (RHEA:52864)
• an N-acetyl-alpha-neuraminyl-(2->3)-beta-D-galactosyl-(1->4)-N-acetyl-beta-D-glucosaminyl derivative + GDP-beta-L-fucose = an alpha-Neu5Ac-(2->3)-beta-D-Gal-(1->4)-[alpha-L-Fuc-(1->3)]-beta-D-GlcNAc derivative + GDP + H(+) (RHEA:56076)
• beta-D-galactosyl-(1->4)-N-acetyl-D-glucosamine + GDP-beta-L-fucose = beta-D-galactosyl-(1->4)-[alpha-L-fucosyl-(1->3)]-N-acetyl-D-glucosamine + GDP + H(+) (RHEA:62824)
• beta-D-galactosyl-(1->3)-N-acetyl-D-glucosamine + GDP-beta-L-fucose = beta-D-galactosyl-(1->3)-[alpha-L-fucosyl-(1->4)]-N-acetyl-D-glucosamine + GDP + H(+) (RHEA:62844)
• lactose + GDP-beta-L-fucose = beta-D-galactosyl-(1->4)-[alpha-L-fucosyl-(1->3)]-D-glucose + GDP + H(+) (RHEA:62888)
• alpha-L-Fuc-(1->2)-beta-D-Gal-(1->3)-D-GlcNAc + GDP-beta-L-fucose = alpha-L-Fuc-(1->2)-beta-D-Gal-(1->3)-[alpha-L-Fuc-(1->4)]-D-GlcNAc + GDP + H(+) (RHEA:62896)

UniProt features (22 total): sequence variant 15, topological domain 2, glycosylation site 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-P21217-F1	90.33	0.81

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 (2): 154, 185

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-9037629	Lewis blood group biosynthesis
R-HSA-975578	Reactions specific to the complex N-glycan synthesis pathway

MSigDB gene sets: 105 (showing top): GOBP_OLIGOSACCHARIDE_METABOLIC_PROCESS, GOBP_POLYSACCHARIDE_BIOSYNTHETIC_PROCESS, GOBP_PROTEIN_N_LINKED_GLYCOSYLATION, BROWNE_HCMV_INFECTION_12HR_UP, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CELL_ADHESION, GOBP_CELL_CELL_ADHESION, GOBP_SPHINGOLIPID_METABOLIC_PROCESS, GOBP_AMIDE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, OUELLET_CULTURED_OVARIAN_CANCER_INVASIVE_VS_LMP_DN, WAGNER_APO2_SENSITIVITY, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, MODULE_157, GOBP_LIPID_METABOLIC_PROCESS

GO Biological Process (16): protein N-linked glycosylation (GO:0006487), protein O-linked glycosylation (GO:0006493), ceramide metabolic process (GO:0006672), oligosaccharide metabolic process (GO:0009311), oligosaccharide biosynthetic process (GO:0009312), cell-cell recognition (GO:0009988), Lewis a epitope biosynthetic process (GO:0010493), positive regulation of cell-cell adhesion (GO:0022409), regulation of cell migration (GO:0030334), regulation of cell population proliferation (GO:0042127), carbohydrate derivative biosynthetic process (GO:1901137), obsolete protein glycosylation (GO:0006486), lipid metabolic process (GO:0006629), sphingolipid metabolic process (GO:0006665), obsolete fucosylation (GO:0036065), obsolete macromolecule glycosylation (GO:0043413)

GO Molecular Function (7): fucosyltransferase activity (GO:0008417), 3-galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferase activity (GO:0017060), 4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase activity (GO:0017083), alpha-(1->3)-fucosyltransferase activity (GO:0046920), protein binding (GO:0005515), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757)

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

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Blood group systems biosynthesis	1
N-glycan antennae elongation in the medial/trans-Golgi	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
glycoprotein biosynthetic process	2
fucosyltransferase activity	2
sphingolipid metabolic process	1
carbohydrate metabolic process	1
oligosaccharide metabolic process	1
carbohydrate biosynthetic process	1
cell recognition	1
polysaccharide biosynthetic process	1
carbohydrate derivative biosynthetic process	1
regulation of cell-cell adhesion	1
positive regulation of cell adhesion	1
cell-cell adhesion	1
cell migration	1
regulation of cell motility	1
cell population proliferation	1
regulation of cellular process	1
biosynthetic process	1
carbohydrate derivative metabolic process	1
primary metabolic process	1
lipid metabolic process	1
hexosyltransferase activity	1
alpha-(1->3)-fucosyltransferase activity	1
binding	1
catalytic activity	1
transferase activity	1
Golgi apparatus	1
bounding membrane of organelle	1
cellular anatomical structure	1
organelle membrane	1
Golgi cisterna	1
extracellular vesicle	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

624 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FUT3	FUT2	Q10981	971
FUT3	FUT1	P19526	949
FUT3	GAL3ST3	Q96A11	791
FUT3	FUT8	Q9BYC5	703
FUT3	GAL3ST2	Q9H3Q3	668
FUT3	SELE	P16111	647
FUT3	A0A0J9YYA3	A0A0J9YYA3	646
FUT3	ST3GAL3	Q11203	640
FUT3	POFUT1	Q9H488	595
FUT3	SELP	P16109	574
FUT3	GAL3ST1	Q99999	554
FUT3	MUC1	P13931	552
FUT3	ST3GAL4	Q11206	548
FUT3	B3GALT5	Q9Y2C3	537
FUT3	ST3GAL6	Q9Y274	536

IntAct

19 interactions, top by confidence:

A	B	Type	Score
FUT3	FAM3B	psi-mi:“MI:0915”(physical association)	0.670
FAM3B	FUT3	psi-mi:“MI:0914”(association)	0.670
FUT3	SLC41A2	psi-mi:“MI:0915”(physical association)	0.560
FUT3	SEC22A	psi-mi:“MI:0915”(physical association)	0.560
FUT3	TTMP	psi-mi:“MI:0915”(physical association)	0.560
TUSC5	FUT3	psi-mi:“MI:0915”(physical association)	0.560
FUT3	C1QL1	psi-mi:“MI:0914”(association)	0.530
FAM3B	FUT3	psi-mi:“MI:0915”(physical association)	0.000
TTMP	FUT3	psi-mi:“MI:0915”(physical association)	0.000
SLC41A2	FUT3	psi-mi:“MI:0915”(physical association)	0.000
SEC22A	FUT3	psi-mi:“MI:0915”(physical association)	0.000
TUSC5	FUT3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (39): HAPLN3 (Affinity Capture-MS), C1QL1 (Affinity Capture-MS), GLB1L2 (Affinity Capture-MS), SLC30A5 (Affinity Capture-MS), HYAL2 (Affinity Capture-MS), ZDHHC17 (Affinity Capture-MS), FKBP14 (Affinity Capture-MS), CNNM1 (Affinity Capture-MS), CACNA2D1 (Affinity Capture-MS), ATP5G1 (Affinity Capture-MS), SLC30A6 (Affinity Capture-MS), GALNT12 (Affinity Capture-MS), ECE1 (Affinity Capture-MS), TXNDC15 (Affinity Capture-MS), FAM8A1 (Affinity Capture-MS)

ESM2 similar proteins: A0JND9, D3YTS9, O19058, O35795, O55026, O75173, P08648, P11117, P17405, P20611, P21217, P24638, P29376, P56433, Q04519, Q0P5F0, Q0V8G3, Q0VD19, Q11128, Q11131, Q32M88, Q4R5N9, Q4R942, Q5MY95, Q5NVF6, Q5RFQ8, Q62994, Q63148, Q6IY74, Q8BH73, Q8HYJ3, Q8HYJ4, Q8HYJ5, Q8HYJ7, Q8HZR3, Q8K1S1, Q8N135, Q923W9, Q9BZG2, Q9H3T2

Diamond homologs: G3MZR2, G5EDR5, O19058, O88819, P21217, P22083, P51993, P56433, P56434, P83088, Q11126, Q11127, Q11128, Q11130, Q11131, Q62994, Q659K9, Q659L0, Q659L1, Q712G6, Q8HYJ3, Q8HYJ4, Q8HYJ5, Q8HYJ6, Q8HYJ7, Q8HZR2, Q8HZR3, Q99JB3, Q9FX97, Q9GKU6, Q9JIG1, Q9LJK1, Q9VUL9, Q9Y231, G5EE06, G5EEE1, G5EFP5, O30511, Q495W5, Q70AG8

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MYC	“up-regulates quantity by expression”	FUT3	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	70
Likely benign	11
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

370 predictions. Top by Δscore:

Variant	Effect	Δscore
19:5844847:AGTAT:A	acceptor_gain	0.9900
19:5844848:GTAT:G	acceptor_gain	0.9900
19:5844849:TAT:T	acceptor_gain	0.9900
19:5844849:TATC:T	acceptor_loss	0.9900
19:5844850:AT:A	acceptor_gain	0.9900
19:5844850:ATCTG:A	acceptor_loss	0.9900
19:5844851:TC:T	acceptor_loss	0.9900
19:5844852:C:CA	acceptor_loss	0.9900
19:5844852:C:CC	acceptor_gain	0.9900
19:5844853:T:A	acceptor_loss	0.9900
19:5851387:TACCT:T	donor_loss	0.9900
19:5851388:A:AC	donor_gain	0.9900
19:5851388:AC:A	donor_gain	0.9900
19:5851389:C:CC	donor_gain	0.9900
19:5851389:CC:C	donor_gain	0.9900
19:5846421:CACA:C	donor_gain	0.9800
19:5851389:CCT:C	donor_gain	0.9800
19:5851389:CCTG:C	donor_gain	0.9800
19:5851389:CCTGG:C	donor_gain	0.9800
19:5846421:CA:C	donor_gain	0.9400
19:5851386:TTA:T	donor_gain	0.9100
19:5851387:TAC:T	donor_gain	0.9100
19:5851385:CTTA:C	donor_gain	0.8900
19:5851388:ACC:A	donor_gain	0.8900
19:5846773:A:AC	donor_gain	0.8800
19:5846420:A:AC	donor_gain	0.8700
19:5846421:C:CC	donor_gain	0.8700
19:5850095:C:CT	donor_gain	0.8400
19:5844844:CAGAG:C	acceptor_gain	0.8300
19:5844848:G:C	acceptor_gain	0.8300

AlphaMissense

2343 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:5844111:G:C	F243L	0.991
19:5844111:G:T	F243L	0.991
19:5844113:A:G	F243L	0.991
19:5843970:G:C	F290L	0.988
19:5843970:G:T	F290L	0.988
19:5843972:A:G	F290L	0.988
19:5844112:A:G	F243S	0.981
19:5843874:C:A	W322C	0.979
19:5843874:C:G	W322C	0.979
19:5843876:A:G	W322R	0.977
19:5843876:A:T	W322R	0.977
19:5843952:G:C	F296L	0.977
19:5843952:G:T	F296L	0.977
19:5843954:A:G	F296L	0.977
19:5844070:G:A	T257I	0.968
19:5844097:T:A	E248V	0.966
19:5844028:G:T	P271H	0.965
19:5843968:A:T	I291N	0.964
19:5844257:A:G	W195R	0.963
19:5844257:A:T	W195R	0.963
19:5844273:C:A	K189N	0.961
19:5844273:C:G	K189N	0.961
19:5843971:A:G	F290S	0.959
19:5844031:A:T	V270E	0.951
19:5844112:A:C	F243C	0.951
19:5844028:G:C	P271R	0.948
19:5843760:G:C	F360L	0.947
19:5843760:G:T	F360L	0.947
19:5843762:A:G	F360L	0.947
19:5844096:C:A	E248D	0.947

dbSNP variants (sampled 300 via entrez): RS1000000270 (19:5855991 T>C), RS1000036269 (19:5857432 TC>T), RS1000273296 (19:5845033 A>G), RS1000408635 (19:5857535 C>G), RS1000820395 (19:5852261 G>A), RS1000897292 (19:5853464 A>C), RS1000932444 (19:5847016 A>T), RS1001183183 (19:5851041 G>T), RS1001279156 (19:5846383 A>AATAC), RS1001360402 (19:5846202 T>C), RS1001465862 (19:5854964 C>T), RS1001803101 (19:5854068 C>T), RS1001822254 (19:5851185 C>T), RS1001834289 (19:5853846 G>C,T), RS1001854575 (19:5858305 C>G)

Disease associations

OMIM: gene MIM:111100 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

23 associations (top):

Study	Trait	p-value
GCST000925_3	N-glycan levels	4.000000e-17
GCST000925_4	N-glycan levels	9.000000e-10
GCST000925_5	N-glycan levels	1.000000e-12
GCST000925_7	N-glycan levels	3.000000e-12
GCST002485_13	Elevated serum carcinoembryonic antigen levels	3.000000e-08
GCST004161_1	Vitamin B12 levels	1.000000e-23
GCST005046_10	N-glycan levels	3.000000e-29
GCST005046_11	N-glycan levels	5.000000e-19
GCST005046_12	N-glycan levels	3.000000e-20
GCST005046_27	N-glycan levels	1.000000e-08
GCST005046_28	N-glycan levels	8.000000e-10
GCST005046_29	N-glycan levels	1.000000e-16
GCST005046_30	N-glycan levels	2.000000e-13
GCST005046_31	N-glycan levels	2.000000e-09
GCST005046_37	N-glycan levels	4.000000e-09
GCST005046_38	N-glycan levels	4.000000e-13
GCST005046_39	N-glycan levels	3.000000e-14
GCST005046_40	N-glycan levels	3.000000e-12
GCST005046_8	N-glycan levels	9.000000e-17
GCST005046_9	N-glycan levels	1.000000e-21
GCST006585_154	Blood protein levels	3.000000e-126
GCST009648_4	Serum cancer antigen 19.9 levels	4.000000e-10
GCST90011900_169	Serum alkaline phosphatase levels	2.000000e-13

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004999	N-glycan measurement
EFO:0005760	serum carcinoembryonic antigen measurement
EFO:0004620	vitamin B12 measurement
EFO:0010584	cancer antigen 19.9 measurement
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3269 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

36 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
Estradiol	affects cotreatment, decreases expression, increases expression	2
Formaldehyde	increases expression, decreases expression	2
Silicon Dioxide	decreases expression, increases expression	2
Testosterone	increases expression, decreases expression, affects cotreatment	2
3,19-(2-bromobenzylidene)andrographolide	decreases response to substance, increases expression	1
propionaldehyde	increases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
hydroquinone	increases expression	1
avobenzone	decreases expression	1
ICG 001	decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Decitabine	affects activity, affects expression	1
Arsenic Trioxide	decreases response to substance	1
Leflunomide	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	decreases methylation	1
Cadmium	increases expression	1
Calcitriol	increases expression, affects cotreatment	1
Catechin	affects cotreatment, decreases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Drugs, Chinese Herbal	increases expression	1
Folic Acid	decreases expression	1
Mustard Gas	increases expression	1
Naphthoquinones	increases expression	1
Nickel	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Plant Oils	decreases expression	1
Smoke	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL681262	Binding	In vitro inhibition of Fucosyltransferase 3	Enzymatic fucosylations with purine-diphosphate-fucoses (PDP-Fucoses) — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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