FUT6

Summary

FUT6 (fucosyltransferase 6, HGNC:4017) is a protein-coding gene on chromosome 19p13.3, encoding 4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase FUT6 (P51993). Catalyzes the transfer of L-fucose, from a guanosine diphosphate-beta-L-fucose, to the N-acetyl glucosamine (GlcNAc) of a distal alpha2,3 sialylated lactosamine unit of a glycoprotein- or a glycolipid-linked sialopolylactosamines chain or of a distal or internal lactosamine unit….

The protein encoded by this gene is a Golgi stack membrane protein that is involved in the creation of sialyl-Lewis X, an E-selectin ligand. Mutations in this gene are a cause of fucosyltransferase-6 deficiency. Two transcript variants encoding the same protein have been found for this gene.

Source: NCBI Gene 2528 — RefSeq curated summary.

At a glance

• Gene–disease (curated): fucosyltransferase 6 deficiency (No Known Disease Relationship, GenCC)
• GWAS associations: 46
• Clinical variants (ClinVar): 95 total
• Druggable target: yes
• MANE Select transcript: NM_000150

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4017
Approved symbol	FUT6
Name	fucosyltransferase 6
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	FT1A, FCT3A, FucT-VI, FLJ40754
Ensembl gene	ENSG00000156413
Ensembl biotype	protein_coding
OMIM	136836
Entrez	2528

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 14 protein_coding, 2 retained_intron

ENST00000286955, ENST00000318336, ENST00000524754, ENST00000526499, ENST00000527106, ENST00000528505, ENST00000531085, ENST00000531199, ENST00000532464, ENST00000591079, ENST00000592563, ENST00000850998, ENST00000905019, ENST00000905020, ENST00000905021, ENST00000962499

RefSeq mRNA: 10 — MANE Select: NM_000150 NM_000150, NM_001040701, NM_001369502, NM_001369504, NM_001369505, NM_001381955, NM_001381956, NM_001381957, NM_001381958, NM_001381959

CCDS: CCDS12152

Canonical transcript exons

ENST00000318336 — 3 exons

Exon	Start	End
ENSE00001518735	5834950	5835077
ENSE00002168889	5838677	5839702
ENSE00002186798	5830408	5832579

Expression profiles

Bgee: expression breadth ubiquitous, 205 present calls, max score 97.27.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.9642 / max 126.9678, expressed in 73 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
178565	0.6058	70
178564	0.2572	44
178566	0.0527	14
178567	0.0435	11
178568	0.0050	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	97.27	gold quality
pharyngeal mucosa	UBERON:0000355	97.21	gold quality
olfactory bulb	UBERON:0002264	96.33	silver quality
buccal mucosa cell	CL:0002336	96.04	gold quality
tongue squamous epithelium	UBERON:0006919	95.94	gold quality
pancreatic ductal cell	CL:0002079	95.77	gold quality
nasal cavity epithelium	UBERON:0005384	95.66	gold quality
type B pancreatic cell	CL:0000169	95.52	silver quality
ileal mucosa	UBERON:0000331	95.37	gold quality
esophagus squamous epithelium	UBERON:0006920	95.22	gold quality
epithelium of esophagus	UBERON:0001976	94.86	gold quality
amniotic fluid	UBERON:0000173	94.54	gold quality
trachea	UBERON:0003126	93.77	gold quality
esophagus mucosa	UBERON:0002469	93.73	gold quality
oral cavity	UBERON:0000167	93.53	gold quality
squamous epithelium	UBERON:0006914	93.48	gold quality
cervix squamous epithelium	UBERON:0006922	93.03	silver quality
mucosa of transverse colon	UBERON:0004991	92.91	gold quality
adult mammalian kidney	UBERON:0000082	91.23	gold quality
nephron tubule	UBERON:0001231	90.92	gold quality
body of tongue	UBERON:0011876	90.77	gold quality
cervix epithelium	UBERON:0004801	90.74	gold quality
tongue	UBERON:0001723	90.51	gold quality
superior surface of tongue	UBERON:0007371	90.11	gold quality
jejunal mucosa	UBERON:0000399	90.05	gold quality
saliva-secreting gland	UBERON:0001044	89.65	gold quality
mouth mucosa	UBERON:0003729	89.51	gold quality
parotid gland	UBERON:0001831	89.35	gold quality
minor salivary gland	UBERON:0001830	89.19	gold quality
gingiva	UBERON:0001828	89.01	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-114	yes	57.06
E-ANND-3	yes	6.62

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

33 targeting FUT6, 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-4692	100.00	67.32	2066
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-499A-3P	99.18	69.20	1392
HSA-MIR-499B-3P	99.18	69.27	1391
HSA-MIR-6504-3P	99.17	69.31	2891
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-6506-5P	99.04	65.66	1386
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-4742-5P	98.89	68.41	1542
HSA-MIR-2355-5P	98.83	65.51	1589
HSA-MIR-6840-3P	98.68	65.95	1923
HSA-MIR-7977	98.65	66.18	2590
HSA-MIR-4710	98.61	65.96	1048
HSA-MIR-619-5P	98.57	64.97	1988
HSA-MIR-4290	98.51	65.17	907
HSA-MIR-4726-3P	98.49	63.89	1385
HSA-MIR-5089-5P	98.45	66.06	1388
HSA-MIR-6764-3P	98.44	67.64	1153
HSA-MIR-6824-3P	98.44	67.62	1154
HSA-MIR-5008-5P	98.42	65.87	1019
HSA-MIR-6516-5P	98.42	70.19	1551
HSA-MIR-6831-5P	98.26	67.20	990
HSA-MIR-3665	97.73	65.08	975
HSA-MIR-2467-5P	97.36	67.71	991
HSA-MIR-125A-3P	97.04	66.92	902
HSA-MIR-874-5P	96.93	63.92	1014

Literature-anchored findings (GeneRIF, showing 23)

• endo-beta-galactosidase-sensitive and mAb FH6-reactive carbohydrate chains are generated under the control of expression levels of FUT6 and involved in the adhesion of colon carcinoma cells to liver sections. (PMID:12670495)
• 5’UT-exons A or C have higher expression of FUT8 transcripts and higher alpha6-fucosyltransferase activity (PMID:14514715)
• IL-1 beta-induced sLeX expression on HuH-7 cells was suppressed by transfection of gene-specific small interference RNAs against FUT VI and ST3Gal IV but not against FUT IV and ST3Gal III. (PMID:17054948)
• two defined regions in the 5’-flanking region of the FUT VI transcription start site are critical for FUT VI transcription in HepG2 cells (PMID:18274891)
• results suggested that PKR is the primary target for HSV-1 early RNA during induction of FUT3, FUT5, and FUT6 (PMID:19349624)
• 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)
• The biosynthesis of the selectin-ligand sialyl Lewis x in colorectal cancer tissues is regulated by fucosyltransferase VI and can be inhibited by an RNA interference-based approach. (PMID:20965272)
• these results suggest that FUT6 plays an important role in hepatocellular carcinoma growth by regulating the PI3K/Akt signaling pathway. (PMID:22155250)
• Results suggest that FUT4-, FUT6- or FUT8-mediated MDR in human HCC is associated with the activation of the PI3K/Akt pathway and the expression of MRP1. (PMID:24232099)
• In normal colon samples a significant relationship between sLe(x) expression and the ratio between FUT6/B4GALNT2 activities exists, demonstrating for the first time a role for B4GALNT2 in sLe(x) inhibition in vivo (PMID:24953560)
• The T allele of rs3760776 might repress the transcription of the FUT6 gene. (PMID:25962326)
• There were significant differences between the type 2 diabetes mellitus patients and controls in the risk allele distributions of rs3792267 (CAPN10) (P = 0.002), rs1501299 (APM1) (P = 0.017), and rs3760776 (FUT6) (P = 0.031). (PMID:27374856)
• ur results strongly showed that the low expression of FUT6 regulated by miR-106b contributed to cell migration, invasion, and proliferation in human breast cancer. (PMID:27519168)
• meta-analysis identified new variants, rs3760775 (P = 1.2 x 10-23) and rs78060698 (P = 8.3 x 10-17) in FUT6 to be associated with circulating B12 concentrations. (PMID:28334792)
• data suggest that both FUT5 and FUT6 can promote the development of colorectal cancer (CRC) via the PI3K/Akt signalling pathway, which is regulated by miR-125a-3p. miR-125a-3p may serve as a predictive biomarker and a potential therapeutic target in CRC treatment. (PMID:28771224)
• we identified a novel association of a common loss-of-function, missense variant in Fucosyltransferase 6 (FUT6; rs17855739,p.Glu274Lys, P = 9.02 x 10-24) with higher soluble E-selectin levels. This variant is considerably more common in populations of African ancestry compared to non-African ancestry populations. (PMID:30307499)
• findings indicated that HOTAIR/miR-326/FUT6 axis mediated colorectal cancer (CRC) procession through alpha1, 3-fucosylated CD44 via PI3K/AKT/mTOR pathway. This work rendered new therapeutic targets for CRC. (PMID:30742932)
• 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)
• Using Eukaryotic Expression Systems to Generate Human alpha1,3-Fucosyltransferases That Effectively Create Selectin-Binding Glycans on Stem Cells. (PMID:32901486)
• FUT6 deficiency compromises basophil function by selectively abrogating their sialyl-Lewis x expression. (PMID:34215830)
• FUT6 inhibits the proliferation, migration, invasion, and EGF-induced EMT of head and neck squamous cell carcinoma (HNSCC) by regulating EGFR/ERK/STAT signaling pathway. (PMID:36151332)
• Correlation of FUT3 and FUT6 Gene Polymorphisms With Helicobacter pylori Infection. (PMID:39108208)
• FUT6 Suppresses the Proliferation, Migration, Invasion, and Epithelial-Mesenchymal Transition of Esophageal Carcinoma Cells via the Epidermal Growth Factor Receptor/Extracellular Signal-Regulated Kinase Signaling Pathway. (PMID:39375968)

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), FUT3 (ENSG00000171124), FUT9 (ENSG00000172461), FUT10 (ENSG00000172728), FUT7 (ENSG00000180549), FUT4 (ENSG00000196371), FUT11 (ENSG00000196968)

Protein

Protein identifiers

4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase FUT6 — P51993 (reviewed: P51993)

Alternative names: Fucosyltransferase 6, Fucosyltransferase VI, Galactoside 3-L-fucosyltransferase

All UniProt accessions (5): P51993, E9PJ18, E9PJB4, E9PP56, E9PS22

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the transfer of L-fucose, from a guanosine diphosphate-beta-L-fucose, to the N-acetyl glucosamine (GlcNAc) of a distal alpha2,3 sialylated lactosamine unit of a glycoprotein- or a glycolipid-linked sialopolylactosamines chain or of a distal or internal lactosamine unit of a neutral glycoprotein- or a glycolipid-linked polylactosamines chain through an alpha-1,3 glycosidic linkage and participates in surface expression of the sialyl Lewis X (sLe(x)), Lewis X (Le(x)) and non sialylated VIM2 determinants. Moreover transfers fucose to H-type 2 (Fucalpha1-2Galbeta1-4GlcNAc) chain acceptor substrates and participates in difucosylated sialyl Lewis x determinants. Also fucosylates a polylactosamine substrate having a 6 sulfate modification at the GlcNAc moiety and gives rise to sialyl and non-sialyl 6-sulfo lewis X. Does not have activity towards type 1 ((Galbeta1-3GlcNAc)) and H-type 1 chain (Fucalpha1-2Galbeta1-3GlcNAc) acceptors substrates. Does not have alpha(1,3)-fucosyltransferase activity.

Subunit / interactions. Homodimer and monomer. Monomer (secreted form).

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

Tissue specificity. Kidney, liver, colon, small intestine, bladder, uterus and salivary gland.

Post-translational modifications. N-glycosylated. Proteolytic cleavage releases a secreted glycoform of 43 kDa.

Pathway. Protein modification; protein glycosylation.

Polymorphism. Expression of alpha(1,3)-fucosyltransferase in plasma can vary among different populations. 9% of individuals on the isle of Java (Indonesia) do not express this enzyme. Ninety-five percent of plasma alpha(1,3)-fucosyltransferase-deficient individuals have Lewis negative phenotype on red cells, suggesting strong linkage disequilibrium between these two traits. Variations in FUT6 are responsible for plasma alpha(1,3)-fucosyltransferase deficiency [MIM:613852].

Similarity. Belongs to the glycosyltransferase 10 family.

Isoforms (2)

UniProt ID	Names	Canonical?
P51993-1	1	yes
P51993-2	2

RefSeq proteins (10): NP_000141, NP_001035791, NP_001356431, NP_001356433, NP_001356434, NP_001368884, NP_001368885, NP_001368886, NP_001368887, NP_001368888 (=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 2.4.1.152 — 4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase (BRENDA: 24 organisms, 171 substrates, 55 inhibitors, 103 Km, 24 kcat entries)
• 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)

105 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-BETA-L-FUCOSE	0.0001–1.12	18
N-ACETYLLACTOSAMINE	0.0026–0.61	9
GDP-L-FUCOSE	0.005–0.035	8
D-LACTOSE	72–543	6
GAL-BETA-1,4-GLCNAC-O-(CH2)8CO2CH3	0.17–2.2	6
GDP-FUCOSE	0.0016–0.06	5
GDP-L-FUCOSE	0.0055–0.062	5
FUCALPHA(1,2)GALBETA(1,3)GLCNAC	0.1–3.8	5
FUCALPHA(1,2)GALBETA(1,4)GLCNAC	0.7–3.9	4
GALBETA1,4GLCNAC-O(CH2)8CO2CH3	0.37–1.7	4
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
GALBETA(1,4)GLCNAC	1.4–23	3

Catalyzed reactions (Rhea), 11 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 neolactoside VI(3)-alpha-NeuNAc-nLc6Cer + GDP-beta-L-fucose = a neolactoside VI(3)-alpha-NeuAc,V(3)-alphaFuc-nLc6Cer + GDP + H(+) (RHEA:48356)
• a neolactoside nLc6Cer + GDP-beta-L-fucose = beta-D-galactosyl-(1->4)-N-acetyl-beta-D-glucosaminyl-(1->3)-beta-D-galactosyl-(1->4)-[alpha-L-fucosyl-(1->3)]-N-acetyl-beta-D-glucosaminyl-(1->3)-beta-D-galactosyl-(1->4)-beta-D-glucosyl-(1<->1’)-ceramide + GDP + H(+) (RHEA:48364)
• a neolactoside nLc6Cer + GDP-beta-L-fucose = beta-D-Gal-(1->4)-[alpha-L-Fuc-(1->3)]-beta-D-GlcNAc-(1->3)-beta-D-Gal-(1->4)-beta-D-GlcNAc-(1->3)-beta-D-Gal-(1->4)-beta-D-Glc-(1<->1’)-Cer + GDP + H(+) (RHEA:48368)
• 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)
• N-acetyl-alpha-neuraminosyl-(2->3)-beta-D-galactosyl-(1->4)-N-acetyl-beta-D-glucosamine + GDP-beta-L-fucose = N-acetyl-alpha-neuraminosyl-(2->3)-beta-D-galactosyl-(1->4)-[alpha-L-fucosyl-(1->3)]-N-acetyl-beta-D-glucosamine + GDP + H(+) (RHEA:62836)
• 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->4)-D-Glc + GDP-beta-L-fucose = alpha-L-Fuc-(1->2)-beta-D-Gal-(1->4)-[alpha-L-Fuc-(1->3)]-D-Glc + GDP + H(+) (RHEA:64016)
• a beta-D-galactosyl-(1->4)-N-acetyl-beta-D-6-sulfooxy-glucosaminyl derivative + GDP-beta-L-fucose = a beta-D-galactosyl-(1->4)-[alpha-L-fucosyl-(1->3)]-N-acetyl-beta-D-6-sulfooxy-glucosaminyl derivative + GDP + H(+) (RHEA:64032)

UniProt features (19 total): sequence variant 5, mutagenesis site 4, glycosylation site 4, topological domain 2, chain 1, transmembrane region 1, region of interest 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P51993-F1	89.81	0.79

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): 46, 91, 153, 184

Mutagenesis-validated functional residues (4):

Position	Phenotype
73	loss of site-specific fucosylation leading to generation of approximately equal amounts of vim2 and sialyl-lewis x. reve
110	reduces dramatically alpha(1,3)fucosyltransferase activity towards type 2 chain acceptors. loss of site-specific fucosyl
111	reverse the site-specific fucosylation pattern leading to generation of vim2 predominantly instead of sialyl-lewis x; wh
112	reverse the site-specific fucosylation pattern leading to generation of vim2 predominantly instead of sialyl-lewis x; wh

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9037629	Lewis blood group biosynthesis

MSigDB gene sets: 126 (showing top): GOBP_OLIGOSACCHARIDE_METABOLIC_PROCESS, MORF_FLT1, MORF_MSH3, GOBP_GLYCOLIPID_BIOSYNTHETIC_PROCESS, GOBP_PROTEIN_N_LINKED_GLYCOSYLATION, GOBP_MONOSACCHARIDE_CATABOLIC_PROCESS, MORF_ESR1, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_SPHINGOLIPID_METABOLIC_PROCESS, GOBP_AMIDE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, ODONNELL_TARGETS_OF_MYC_AND_TFRC_UP, WAGNER_APO2_SENSITIVITY, GOBP_GLYCOSPHINGOLIPID_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_METABOLIC_PROCESS

GO Biological Process (13): protein N-linked glycosylation (GO:0006487), protein O-linked glycosylation (GO:0006493), ceramide metabolic process (GO:0006672), glycosphingolipid biosynthetic process (GO:0006688), oocyte axis specification (GO:0007309), glycoprotein biosynthetic process (GO:0009101), oligosaccharide biosynthetic process (GO:0009312), protein O-linked glycosylation via fucose (GO:0036066), L-fucose catabolic process (GO:0042355), obsolete protein glycosylation (GO:0006486), lipid metabolic process (GO:0006629), sphingolipid metabolic process (GO:0006665), obsolete N-glycan fucosylation (GO:0036071)

GO Molecular Function (5): fucosyltransferase activity (GO:0008417), 4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase activity (GO:0017083), alpha-(1->3)-fucosyltransferase activity (GO:0046920), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757)

GO Cellular Component (7): Golgi membrane (GO:0000139), extracellular region (GO:0005576), Golgi apparatus (GO:0005794), Golgi cisterna membrane (GO:0032580), methylosome (GO:0034709), extracellular exosome (GO:0070062), 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
glycoprotein biosynthetic process	2
cellular anatomical structure	2
cytoplasm	2
sphingolipid metabolic process	1
glycosphingolipid metabolic process	1
glycolipid biosynthetic process	1
sphingolipid biosynthetic process	1
developmental process involved in reproduction	1
oocyte construction	1
axis specification	1
macromolecule biosynthetic process	1
glycoprotein metabolic process	1
carbohydrate derivative biosynthetic process	1
oligosaccharide metabolic process	1
carbohydrate biosynthetic process	1
protein O-linked glycosylation	1
hexose catabolic process	1
L-fucose metabolic process	1
primary metabolic process	1
lipid metabolic process	1
hexosyltransferase activity	1
alpha-(1->3)-fucosyltransferase activity	1
fucosyltransferase activity	1
catalytic activity	1
transferase activity	1
Golgi apparatus	1
bounding membrane of organelle	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
Golgi cisterna	1
methyltransferase complex	1
extracellular vesicle	1

Protein interactions and networks

STRING

468 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FUT6	FUT1	P19526	902
FUT6	FUT2	Q10981	888
FUT6	B4GALT1	P15291	865
FUT6	FUT8	Q9BYC5	761
FUT6	SELE	P16111	709
FUT6	B4GALNT2	Q8NHY0	651
FUT6	SELP	P16109	644
FUT6	ST3GAL3	Q11203	612
FUT6	ST3GAL4	Q11206	601
FUT6	MGAT5	Q09328	568
FUT6	ST6GAL1	P15907	556
FUT6	ORM2	P19652	547
FUT6	ORM1	P02763	544
FUT6	ST3GAL1	Q11201	529
FUT6	GCNT1	Q02742	506

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A7MB73, G3MZR2, O00587, O09008, O19058, P17405, P21217, P22083, P51993, P56433, P56434, Q05923, Q0VD19, Q10979, Q11126, Q11127, Q11128, Q11130, Q11131, Q17QZ8, Q32NY4, Q5GFD5, Q5T4B2, Q62994, Q659K9, Q6IQX7, Q6UX72, Q6ZMB0, Q712G6, Q8HYJ3, Q8HYJ4, Q8HYJ5, Q8HYJ6, Q8HYJ7, Q8HZR3, Q8IZ52, Q8N3Y3, Q8NET6, Q8NI29, Q8VD52

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

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	85
Likely benign	6
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

745 predictions. Top by Δscore:

Variant	Effect	Δscore
19:5832587:G:GC	acceptor_gain	0.9900
19:5832587:G:C	acceptor_gain	0.9800
19:5834933:TGG:T	donor_gain	0.9800
19:5832577:TATC:T	acceptor_loss	0.9700
19:5832578:ATCTG:A	acceptor_loss	0.9700
19:5832579:TC:T	acceptor_loss	0.9700
19:5832580:C:CC	acceptor_gain	0.9700
19:5832580:CTGGG:C	acceptor_loss	0.9700
19:5832581:T:G	acceptor_loss	0.9700
19:5832576:GTAT:G	acceptor_gain	0.9500
19:5832577:TAT:T	acceptor_gain	0.9500
19:5834961:C:CA	donor_gain	0.9500
19:5838185:T:A	donor_gain	0.9500
19:5839172:T:TA	donor_gain	0.9500
19:5834050:TGA:T	donor_gain	0.9400
19:5833407:TGA:T	donor_gain	0.9200
19:5832464:C:CT	acceptor_gain	0.9100
19:5834980:TGA:T	donor_gain	0.9100
19:5838273:C:CT	donor_gain	0.9100
19:5832578:AT:A	acceptor_gain	0.9000
19:5834884:C:CT	donor_gain	0.9000
19:5838186:C:A	donor_gain	0.9000
19:5838274:C:CT	donor_gain	0.8900
19:5832575:AGTAT:A	acceptor_gain	0.8700
19:5838671:CCTTA:C	donor_loss	0.8700
19:5838672:CTTA:C	donor_loss	0.8700
19:5838673:TTA:T	donor_loss	0.8700
19:5838674:TACC:T	donor_loss	0.8700
19:5838675:ACCTG:A	donor_loss	0.8700
19:5838676:C:CG	donor_loss	0.8700

AlphaMissense

2345 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:5831842:G:C	F242L	0.996
19:5831842:G:T	F242L	0.996
19:5831844:A:G	F242L	0.996
19:5831701:G:C	F289L	0.993
19:5831701:G:T	F289L	0.993
19:5831703:A:G	F289L	0.993
19:5831828:T:A	E247V	0.992
19:5831843:A:G	F242S	0.992
19:5831801:G:A	T256I	0.991
19:5831683:G:C	F295L	0.988
19:5831683:G:T	F295L	0.988
19:5831685:A:G	F295L	0.988
19:5832083:G:A	S162F	0.987
19:5831605:C:A	W321C	0.986
19:5831605:C:G	W321C	0.986
19:5831494:G:C	F358L	0.985
19:5831494:G:T	F358L	0.985
19:5831496:A:G	F358L	0.985
19:5831607:A:G	W321R	0.985
19:5831607:A:T	W321R	0.985
19:5831699:A:T	I290N	0.984
19:5831790:A:G	W260R	0.984
19:5831790:A:T	W260R	0.984
19:5831827:C:A	E247D	0.984
19:5831827:C:G	E247D	0.984
19:5831759:G:T	P270H	0.982
19:5831824:G:C	N248K	0.982
19:5831824:G:T	N248K	0.982
19:5831988:A:G	W194R	0.982
19:5831988:A:T	W194R	0.982

dbSNP variants (sampled 300 via entrez): RS1000198565 (19:5837157 C>A), RS1000259809 (19:5830306 TCACA>T,TCA,TCACACA,TCACACACACA), RS1000300084 (19:5835123 A>G), RS1000351901 (19:5834786 G>C), RS1000638927 (19:5833924 G>A), RS1000646425 (19:5835406 C>A,T), RS1000818099 (19:5840803 G>A), RS1000883421 (19:5829992 C>A,G,T), RS1001202759 (19:5839293 G>C), RS1001304619 (19:5836701 T>C), RS1001561326 (19:5840621 C>T), RS1001872088 (19:5841641 A>C,G), RS1002286711 (19:5834530 G>T), RS1002558028 (19:5838683 G>A,C), RS1002648578 (19:5832956 G>A,C)

Disease associations

OMIM: gene MIM:136836 | disease phenotypes: MIM:613852

GenCC curated gene-disease

Disease	Classification	Inheritance
fucosyltransferase 6 deficiency	No Known Disease Relationship	Autosomal recessive

Mondo (1): fucosyltransferase 6 deficiency (MONDO:0013462)

Orphanet (0):

HPO phenotypes

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

GWAS associations

46 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
GCST001424_6	Vitamin B12 levels	4.000000e-13
GCST001808_1	Tumor biomarkers	1.000000e-35
GCST001808_3	Tumor biomarkers	5.000000e-132
GCST001808_4	Tumor biomarkers	2.000000e-56
GCST001808_5	Tumor biomarkers	3.000000e-290
GCST002485_6	Elevated serum carcinoembryonic antigen levels	8.000000e-19
GCST003219_40	Advanced age-related macular degeneration	2.000000e-15
GCST004161_1	Vitamin B12 levels	1.000000e-23
GCST004161_4	Vitamin B12 levels	6.000000e-15
GCST004618_45	White blood cell count (basophil)	2.000000e-12
GCST004631_9	Basophil percentage of white cells	2.000000e-12
GCST004634_56	Basophil percentage of granulocytes	2.000000e-09
GCST004861_22	Itch intensity from mosquito bite	9.000000e-16
GCST004862_107	Itch intensity from mosquito bite adjusted by bite size	6.000000e-11
GCST004862_206	Itch intensity from mosquito bite adjusted by bite size	2.000000e-06
GCST004863_87	Mosquito bite size	3.000000e-06
GCST004865_19	Itch intensity from mosquito bite adjusted by bite size	5.000000e-08
GCST004925_7	IgG N-glycosylation phenotypes (multivariate analysis)	2.000000e-13
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

EFO canonical traits (16, from GWAS)

EFO ID	Trait name
EFO:0004999	N-glycan measurement
EFO:0004620	vitamin B12 measurement
EFO:0005127	cancer biomarker measurement
EFO:0005760	serum carcinoembryonic antigen measurement
EFO:1001492	atrophic macular degeneration
EFO:0005090	basophil count
EFO:0007992	basophil percentage of leukocytes
EFO:0007995	basophil percentage of granulocytes
EFO:0008377	mosquito bite reaction itch intensity measurement
EFO:0008378	mosquito bite reaction size measurement
EFO:0005193	serum IgG glycosylation measurement
EFO:0010584	cancer antigen 19.9 measurement
EFO:0004459	ferritin measurement
EFO:0004736	aspartate aminotransferase measurement
EFO:0004533	alkaline phosphatase measurement
EFO:0004532	serum gamma-glutamyl transferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4443 (SINGLE PROTEIN)

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

Binding affinities (BindingDB)

2 measured of 2 human assays (3 total across all organisms); most potent 2 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
Gallic Acid, F	IC50	14000 nM
Guanosine Diphosphate	IC50	24000 nM

ChEMBL bioactivities

11 potent at pChembl≥5 of 12 total, top 11 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.42	Ki	376	nM	CHEMBL610389
6.36	Ki	437	nM	CHEMBL610391
6.29	Ki	511	nM	CHEMBL610390
6.21	IC50	610	nM	CHEMBL6190956
6.04	Ki	901	nM	CHEMBL611881
5.97	Ki	1069	nM	CHEMBL608046
5.86	IC50	1394	nM	CHEMBL610389
5.79	IC50	1618	nM	CHEMBL610391
5.72	IC50	1893	nM	CHEMBL610390
5.48	IC50	3338	nM	CHEMBL611881
5.40	IC50	3957	nM	CHEMBL608046

PubChem BioAssay actives

11 with measured affinity, of 14 total; 6 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
[[(2R,3S,4R)-5-(2-amino-6-oxo-1H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [1-[5-(1,2-diphenylethylamino)-5-oxopentyl]triazol-4-yl]methyl hydrogen phosphate	72095: Compound was tested for binding affinity against Fucosyltransferase 6	ki	0.3760	uM
[[(2R,3S,4R)-5-(2-amino-6-oxo-1H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [1-[2-(1,2-diphenylethylamino)-2-oxoethyl]triazol-4-yl]methyl hydrogen phosphate	72095: Compound was tested for binding affinity against Fucosyltransferase 6	ki	0.4370	uM
[[(2R,3S,4R)-5-(2-amino-6-oxo-1H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [1-[5-[(9,10-dioxo-4a,9a-dihydroanthracen-2-yl)amino]-5-oxopentyl]triazol-4-yl]methyl hydrogen phosphate	72095: Compound was tested for binding affinity against Fucosyltransferase 6	ki	0.5110	uM
[[(2R,3S,4R)-5-(2-amino-6-oxo-1H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [1-[3-(naphthalen-1-ylmethylamino)-3-oxopropyl]triazol-4-yl]methyl hydrogen phosphate	72095: Compound was tested for binding affinity against Fucosyltransferase 6	ki	0.9010	uM
[[(2R,3S,4R)-5-(2-amino-6-oxo-1H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [1-[4-(1,2-diphenylethylamino)-4-oxobutyl]triazol-4-yl]methyl hydrogen phosphate	72095: Compound was tested for binding affinity against Fucosyltransferase 6	ki	1.0690	uM
[(2R,3R)-5,7-dihydroxy-2-(3,4,5-trihydroxyphenyl)-3,4-dihydro-2H-chromen-3-yl] 3,4,5-trihydroxybenzoate	1799773: SPA Assay from Article 10.1016/j.abb.2004.02.039: “Inhibition of fucosyltransferase VII by gallic acid and its derivatives.”	ic50	1.8000	uM

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Valproic Acid	decreases expression, increases methylation	2
OTX015	decreases expression	1
mivebresib	decreases expression	1
methyleugenol	decreases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
ochratoxin A	decreases expression	1
ICG 001	increases expression	1
(+)-JQ1 compound	decreases expression	1
Arsenic Trioxide	increases expression	1
Acetaminophen	decreases expression	1
N-Nitrosopyrrolidine	decreases expression	1
Quercetin	decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	affects expression	1
Urethane	decreases expression	1
Cyclosporine	decreases expression	1
Sodium Selenite	decreases expression	1
Antirheumatic Agents	increases expression	1
Okadaic Acid	decreases expression	1
Acrylamide	increases expression	1
Particulate Matter	decreases 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
CHEMBL3598447	Binding	Inhibition of FucT-6 (unknown origin)	Beyond substrate analogues: new inhibitor chemotypes for glycosyltransferases — Medchemcomm

Clinical trials (associated diseases)

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