FUT8

Summary

FUT8 (fucosyltransferase 8, HGNC:4019) is a protein-coding gene on chromosome 14q23.3, encoding Alpha-(1,6)-fucosyltransferase (Q9BYC5). Catalyzes the addition of fucose in alpha 1-6 linkage to the first GlcNAc residue, next to the peptide chains in N-glycans.

This gene encodes an enzyme belonging to the family of fucosyltransferases. The product of this gene catalyzes the transfer of fucose from GDP-fucose to N-linked type complex glycopeptides. This enzyme is distinct from other fucosyltransferases which catalyze alpha1-2, alpha1-3, and alpha1-4 fucose addition. The expression of this gene may contribute to the malignancy of cancer cells and to their invasive and metastatic capabilities. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 2530 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital disorder of glycosylation with defective fucosylation 1 (Definitive, ClinGen)
• GWAS associations: 58
• Clinical variants (ClinVar): 187 total — 4 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 34
• Druggable target: yes
• MANE Select transcript: NM_001371533

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4019
Approved symbol	FUT8
Name	fucosyltransferase 8
Location	14q23.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000033170
Ensembl biotype	protein_coding
OMIM	602589
Entrez	2530

Gene structure

Transcript identifiers

Ensembl transcripts: 35 — 30 protein_coding, 4 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000342677, ENST00000358307, ENST00000360689, ENST00000394586, ENST00000549235, ENST00000553924, ENST00000554610, ENST00000554667, ENST00000554765, ENST00000555559, ENST00000556292, ENST00000556518, ENST00000557164, ENST00000557338, ENST00000557536, ENST00000673929, ENST00000674118, ENST00000859038, ENST00000859039, ENST00000859040, ENST00000859041, ENST00000859042, ENST00000859043, ENST00000859044, ENST00000859045, ENST00000859046, ENST00000859047, ENST00000927586, ENST00000958355, ENST00000958356, ENST00000958357, ENST00000958358, ENST00000958359, ENST00000958360, ENST00000958361

RefSeq mRNA: 6 — MANE Select: NM_001371533 NM_001371533, NM_001371534, NM_001371536, NM_004480, NM_178155, NM_178156

CCDS: CCDS9775, CCDS9776

Canonical transcript exons

ENST00000673929 — 11 exons

Exon	Start	End
ENSE00000658485	65724147	65724323
ENSE00000658486	65721775	65722021
ENSE00001373882	65455621	65455718
ENSE00001383814	65561337	65561766
ENSE00001953869	65742093	65744121
ENSE00003473163	65615978	65616093
ENSE00003528423	65629492	65629606
ENSE00003535052	65669243	65669480
ENSE00003576253	65616211	65616373
ENSE00003664030	65733231	65733381
ENSE00003897036	65412730	65413214

Expression profiles

Bgee: expression breadth ubiquitous, 279 present calls, max score 97.05.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 31.5088 / max 332.2511, expressed in 1781 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
140164	13.1122	1661
140161	9.2628	1658
140167	4.4685	1328
140166	1.8841	808
140168	0.8852	551
140163	0.8083	535
140162	0.6464	410
140165	0.4414	242

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus callosum	UBERON:0002336	97.05	gold quality
olfactory bulb	UBERON:0002264	96.83	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	96.47	gold quality
trigeminal ganglion	UBERON:0001675	94.87	gold quality
inferior vagus X ganglion	UBERON:0005363	94.29	gold quality
pylorus	UBERON:0001166	94.23	gold quality
ventricular zone	UBERON:0003053	94.21	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.06	gold quality
spinal cord	UBERON:0002240	93.66	gold quality
subthalamic nucleus	UBERON:0001906	93.18	gold quality
calcaneal tendon	UBERON:0003701	92.49	gold quality
ganglionic eminence	UBERON:0004023	92.40	gold quality
pons	UBERON:0000988	92.25	gold quality
dorsal root ganglion	UBERON:0000044	91.85	gold quality
sural nerve	UBERON:0015488	91.71	gold quality
medulla oblongata	UBERON:0001896	91.65	gold quality
lateral globus pallidus	UBERON:0002476	90.89	gold quality
inferior olivary complex	UBERON:0002127	90.53	gold quality
superior vestibular nucleus	UBERON:0007227	90.39	gold quality
stromal cell of endometrium	CL:0002255	90.34	gold quality
substantia nigra	UBERON:0002038	90.28	gold quality
CA1 field of hippocampus	UBERON:0003881	90.26	gold quality
midbrain	UBERON:0001891	90.25	gold quality
tibial nerve	UBERON:0001323	90.16	gold quality
stomach	UBERON:0000945	90.10	gold quality
tonsil	UBERON:0002372	89.96	gold quality
cardia of stomach	UBERON:0001162	89.76	gold quality
putamen	UBERON:0001874	89.73	gold quality
body of stomach	UBERON:0001161	89.54	gold quality
ventral tegmental area	UBERON:0002691	89.54	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-CURD-89	yes	511.68
E-HCAD-35	yes	76.33
E-ENAD-20	yes	64.53
E-ANND-3	yes	20.37
E-MTAB-9388	yes	6.08
E-GEOD-111727	no	1347.38
E-ENAD-27	no	388.87

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1

miRNA regulators (miRDB)

136 targeting FUT8, 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-4682	100.00	68.89	1258
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-129-5P	99.88	70.26	3273

Literature-anchored findings (GeneRIF, showing 40)

• Expression of FUT8 is regulated by three different promoters, starting transcription in exons A, B, or C. (PMID:14514715)
• These results suggest that FUT8 expression may be a key factor in the progression of thyroid papillary carcinomas, but not follicular carcinomas, and decreases in FUT8 expression might be linked to anaplastic transformation. (PMID:14568171)
• We investigated mRNA levels of glycosyltransferases, namely N-acetylglucosaminyltransferase a (GnT)-IVb, and found that (GnT)-IVb expression was increased in HLE-cells resistant to Epirubicin (PMID:17488527)
• Vascular endothelial growth factor receptor-2 (VEGFR-2) expression was significantly suppressed in Fut8(-/-) mice, suggesting that Fut8 was required for VEGFR-2 expression. (PMID:19179362)
• in colorectal carcinoma patients with moderate or strong alpha(1,6)fucosyltransferase expression, a significant decrease in the overall (P = .04) and disease-free (P = .03) survival rates was observed (PMID:21652057)
• The FUT8 gene Thr267Lys polymorphism is associated with human pulmonary emphysema (PE). (PMID:22011814)
• alpha 1,6-fucosyltransferase 8 expression might be a good indicator of poor prognosis in hepatocellular carcinoma. High alpha 1,6-fucosyltransferase 8 expression may play an important role in hepatitis B virus-related hepatocellular carcinoma progression (PMID:23352314)
• findings define FUT8 as a novel factor for hemoglobin production and demonstrate that core fucosylation plays an important role in erythroid differentiation (PMID:23609441)
• miR-122 and miR-34a are able to target FUT8 3’UTR (PMID:24130780)
• 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)
• Our results suggest that FUT8 may be associated with aggressive PCa and thus is potentially useful for its prognosis. (PMID:24906821)
• MiR-198 was shown to target the 3’UTR of FUT8 directly to downregulate FUT8 expression. (PMID:25174450)
• High expression of FUT8 is associated with an unfavorable clinical outcome in patients with potentially curatively resected NSCLCs, suggesting that FUT8 can be a prognostic factor. (PMID:25572677)
• Expression of FUT8 can stratify breast cancer tissue and may be considered a prognostic marker for breast cancer patients (PMID:26596733)
• The production of the homogeneous core-fucosylated Man5GlcNAc2 glycoform of EPO in the FUT8-overexpressed HEK293S GnT I(-/-) cell line represents the first example of production of fully core-fucosylated high-mannose glycoforms. (PMID:27008861)
• FUT8 is regulated by microRNAs and has a role in hepatocellular carcinoma progression (PMID:27533464)
• This study demonstrated that the alteration of FTU8 expression in the superior temporal gyrus of elderly patients with schizophrenia. (PMID:27773385)
• We observed a strong correlation between EVI1 and alpha1, 6-fucosyltransferase (FUT8) in the chronic phase of the disease and both of them were found to be up-regulated with the progression of the disease. (PMID:27967290)
• the possibility that the higher fucose levels on cell surface glycans of aggressive anaplastic thyroid cancer samples (ATCs), compared to those of less aggressive papillary thyroid cancer samples(PTC), may be at least in part responsible for the more aggressive and metastatic phenotype of ATCs compared to PTCs, as the expression levels of FUCA1 and FUT8 were inversely related in these two types of cancers. (PMID:28440416)
• FUT8 is a driver of melanoma metastasis which, when silenced, suppresses invasion and tumor dissemination. (PMID:28609658)
• This study thus provides insights into the interplay among FUT8, N-acetylglucosaminyltransferase , and GnT-V in N-linked glycosylation during the assembly of glycoproteins. (PMID:28678517)
• results suggest that an appropriate polypeptide context or other adequate structural elements in the acceptor substrate could facilitate the core fucosylation by FUT8 (PMID:28729420)
• Our results reveal a positive feedback mechanism of FUT8-mediated receptor core fucosylation that promotes TGF-b signaling and EMT, thus stimulating breast cancer cell invasion and metastasis. (PMID:28982386)
• loss of function mutations in FUT8 cause a congenital disorder of glycosylation (FUT8-CDG) characterized by defective core fucosylation. (PMID:29304374)
• we also demonstrated that overexpression of FUT8 might be responsible for the decreased PSA expression in prostate cancer specimens. To our knowledge, this is the first study reporting the functional role of fucosylated enzyme in the development of castration-resistant prostate cancer. (PMID:29339807)
• expression in relation to p53 is a prognostic biomarker for patients with stage II and III colorectal cancer (PMID:29975776)
• critical role in maintaining the normal functions of trophoblastic cells (PMID:30712666)
• HCV-induced FUT8 promotes proliferation and 5-FU resistance of Huh7.5.1 cells. (PMID:31022917)
• MicroRNA-198-5p inhibits the migration and invasion of non-small lung cancer cells by targeting fucosyltransferase 8. (PMID:31381176)
• Expanding the molecular and clinical phenotypes of FUT8-CDG. (PMID:32049367)
• Report the crystal structure of FUT8 complexed with GDP and a biantennary complex N-glycan (G0), which provides insight into both substrate recognition and catalysis. FUT8 follows an SN2 mechanism and deploys a series of loops and an alpha-helix which all contribute in forming the binding site. (PMID:32080177)
• Involvement of the alpha-helical and Src homology 3 domains in the molecular assembly and enzymatic activity of human alpha1,6-fucosyltransferase, FUT8. (PMID:32147455)
• Structural basis of substrate recognition and catalysis by fucosyltransferase 8. (PMID:32220931)
• The SH3 domain in the fucosyltransferase FUT8 controls FUT8 activity and localization and is essential for core fucosylation. (PMID:32350116)
• Impact of Increased FUT8 Expression on the Extracellular Vesicle Proteome in Prostate Cancer Cells. (PMID:32378902)
• A lectin-based glycomic approach identifies FUT8 as a driver of radioresistance in oesophageal squamous cell carcinoma. (PMID:32474852)
• FUT8 Remodeling of EGFR Regulates Epidermal Keratinocyte Proliferation during Psoriasis Development. (PMID:32888953)
• Characterizing human alpha-1,6-fucosyltransferase (FUT8) substrate specificity and structural similarities with related fucosyltransferases. (PMID:33004438)
• Role of FUT8 expression in clinicopathology and patient survival for various malignant tumor types: a systematic review and meta-analysis. (PMID:33323540)
• cFUT8 promotes liver cancer progression by miR-548c/FUT8 axis. (PMID:33500381)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	fut8a	ENSDARG00000015449
danio_rerio	fut8b	ENSDARG00000088117
mus_musculus	Fut8	ENSMUSG00000021065
rattus_norvegicus	Fut8	ENSRNOG00000008451
drosophila_melanogaster	FucT6	FBGN0030327
caenorhabditis_elegans		WBGENE00001508

Protein

Protein identifiers

Alpha-(1,6)-fucosyltransferase — Q9BYC5 (reviewed: Q9BYC5)

Alternative names: Fucosyltransferase 8, GDP-L-Fuc:N-acetyl-beta-D-glucosaminide alpha1,6-fucosyltransferase, GDP-fucose–glycoprotein fucosyltransferase, Glycoprotein 6-alpha-L-fucosyltransferase

All UniProt accessions (10): A0A669KAW1, Q9BYC5, G3V443, G3V4A8, G3V509, G3V530, G3V5E3, G3V5Z4, G3XAD2, Q546E0

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the addition of fucose in alpha 1-6 linkage to the first GlcNAc residue, next to the peptide chains in N-glycans. Fucosylates the reducing GlcNAc residue in complex-type N-glycans attached on the fragment crystallizable (Fc) of IgGs. Fully converts Fc glycoforms containing one or two terminal GlcNAc moieties (G0-GlcNAc and G0).

Subcellular location. Golgi apparatus. Golgi stack membrane.

Post-translational modifications. Tyrosine phosphorylated by PKDCC/VLK.

Disease relevance. Congenital disorder of glycosylation with defective fucosylation 1 (CDGF1) [MIM:618005] A form of congenital disorder of glycosylation, a genetically heterogeneous group of multisystem disorders caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. CDGF1 is an autosomal recessive disorder, apparent from birth, characterized by poor growth, failure to thrive, hypotonia, skeletal anomalies, and delayed psychomotor development with intellectual disability. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Protein modification; protein glycosylation.

Miscellaneous. Seems to be only expressed in retina, inactive as a fucosyltransferase.

Similarity. Belongs to the glycosyltransferase 23 family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9BYC5-1	1	yes
Q9BYC5-2	2, Retinal
Q9BYC5-3	3
Q9BYC5-4	4, Retina-1, Retina-2

RefSeq proteins (6): NP_001358462, NP_001358463, NP_001358465, NP_004471, NP_835368, NP_835369 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001452	SH3_domain	Domain
IPR015827	Fut8	Family
IPR027350	GT23_dom	Domain
IPR035653	Fut8_SH3	Domain
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR045573	Fut8_N_cat	Domain

Pfam: PF14604, PF19745

Enzyme classification (BRENDA):

• EC 2.4.1.68 — glycoprotein 6-alpha-L-fucosyltransferase (BRENDA: 17 organisms, 60 substrates, 48 inhibitors, 17 Km, 1 kcat entries)

Substrate kinetics (BRENDA)

9 substrates with measured Km, best-characterized 9. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
GDP-L-FUCOSE	0.0042–0.046	6
ASIALO-AGALACTO-TRANSFERRIN-GLYCOPEPTIDE	0.029–0.066	2
FACTOR VII EGF-1 DOMAIN	0.011–0.015	2
N4-[N-ACETYL-BETA-D-GLUCOSAMINYL-(1-2)-ALPHA-D-M	0.0174–0.025	2
ASN-LINKED AGALACTO-BIANTENNARY SUGAR CHAIN	0.0129	1
GDP-BETA-L-FUCOSE	0.0193	1
GDP-L-FUC	0.117	1
GDP-L-GAL	0.229	1
N4-[N-ACETYL-BETA-D-GLUCOSAMINYL-(1-2)-ALPHA-D-M	0.012	1

Catalyzed reactions (Rhea), 2 shown:

• N(4)-{beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->3)-[beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-beta-D-GlcNAc}-L-asparaginyl-[protein] + GDP-beta-L-fucose = an N(4)-{beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->3)-[beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-[alpha-L-Fuc-(1->6)]-beta-D-GlcNAc}-L-asparaginyl-[protein] + GDP + H(+) (RHEA:12985)
• an N(4)-{beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->3)-[alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-beta-D-GlcNAc}-L-asparaginyl-[protein] + GDP-beta-L-fucose = an N(4)-{beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->3)-[alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-[alpha-L-Fuc-(1->6)]-beta-D-GlcNAc}-L-asparaginyl-[protein] + GDP + H(+) (RHEA:84135)

UniProt features (74 total): helix 19, strand 16, mutagenesis site 10, sequence variant 6, splice variant 5, disulfide bond 4, turn 4, topological domain 2, domain 2, chain 1, transmembrane region 1, sequence conflict 1, region of interest 1, short sequence motif 1, modified residue 1

Structure

Experimental structures (PDB)

14 structures.

PDB	Method	Resolution (Å)
6TKV	X-RAY DIFFRACTION	1.95
9L65	X-RAY DIFFRACTION	1.99
6X5H	X-RAY DIFFRACTION	2.25
6VLD	X-RAY DIFFRACTION	2.28
6VLE	X-RAY DIFFRACTION	2.28
6X5R	X-RAY DIFFRACTION	2.4
6X5T	X-RAY DIFFRACTION	2.47
9L64	X-RAY DIFFRACTION	2.49
2DE0	X-RAY DIFFRACTION	2.61
9L63	X-RAY DIFFRACTION	2.66
9L62	X-RAY DIFFRACTION	3.04
9L6E	X-RAY DIFFRACTION	3.07
6X5U	X-RAY DIFFRACTION	3.2
6X5S	X-RAY DIFFRACTION	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BYC5-F1	92.03	0.77

Functional residue map

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

Post-translational modifications (1): 278

Disulfide bonds (4): 212–230, 218–222, 465–472, 204–266

Mutagenesis-validated functional residues (10):

Position	Phenotype
365	complete loss of activity.
366	decreases activity to 3%.
368	loss of enzyme activity.
369	loss of enzyme activity.
373	loss of enzyme activity.
382	loss of enzyme activity.
409	loss of enzyme activity.
410	no effect on enzyme activity.
453	loss of enzyme activity.
469	loss of enzyme activity.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-9694548	Maturation of spike protein
R-HSA-975578	Reactions specific to the complex N-glycan synthesis pathway

MSigDB gene sets: 422 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_DN, WENDT_COHESIN_TARGETS_UP, GOBP_OLIGOSACCHARIDE_METABOLIC_PROCESS, GOBP_N_GLYCAN_PROCESSING, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, LEE_NEURAL_CREST_STEM_CELL_DN, GOBP_RESPIRATORY_GASEOUS_EXCHANGE_BY_RESPIRATORY_SYSTEM, GOBP_PROTEIN_N_LINKED_GLYCOSYLATION, GCANCTGNY_MYOD_Q6, SP3_Q3, AREB6_03, GOZGIT_ESR1_TARGETS_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, KEGG_N_GLYCAN_BIOSYNTHESIS, GOBP_MONOSACCHARIDE_CATABOLIC_PROCESS

GO Biological Process (18): in utero embryonic development (GO:0001701), protein N-linked glycosylation (GO:0006487), N-glycan processing (GO:0006491), transforming growth factor beta receptor signaling pathway (GO:0007179), integrin-mediated signaling pathway (GO:0007229), respiratory gaseous exchange by respiratory system (GO:0007585), oligosaccharide biosynthetic process (GO:0009312), regulation of gene expression (GO:0010468), fibroblast migration (GO:0010761), obsolete protein N-linked glycosylation via asparagine (GO:0018279), viral protein processing (GO:0019082), L-fucose catabolic process (GO:0042355), receptor metabolic process (GO:0043112), GDP-L-fucose metabolic process (GO:0046368), regulation of cellular response to oxidative stress (GO:1900407), obsolete protein glycosylation (GO:0006486), cell migration (GO:0016477), obsolete N-glycan fucosylation (GO:0036071)

GO Molecular Function (7): glycoprotein 6-alpha-L-fucosyltransferase activity (GO:0008424), SH3 domain binding (GO:0017124), alpha-(1->6)-fucosyltransferase activity (GO:0046921), protein binding (GO:0005515), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757), hexosyltransferase activity (GO:0016758)

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

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Translation of Structural Proteins	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
chordate embryonic development	1
protein N-linked glycosylation	1
cellular response to transforming growth factor beta stimulus	1
transforming growth factor beta receptor superfamily signaling pathway	1
cell surface receptor signaling pathway	1
multicellular organismal process	1
oligosaccharide metabolic process	1
carbohydrate biosynthetic process	1
gene expression	1
regulation of macromolecule biosynthetic process	1
ameboidal-type cell migration	1
viral process	1
viral gene expression	1
hexose catabolic process	1
L-fucose metabolic process	1
macromolecule metabolic process	1
nucleotide-sugar metabolic process	1
cellular response to oxidative stress	1
regulation of cellular response to stress	1
regulation of response to oxidative stress	1
cell motility	1
protein O-linked glycosylation via fucose	1
alpha-(1->6)-fucosyltransferase activity	1
catalytic activity, acting on a glycoprotein	1
protein domain specific binding	1
fucosyltransferase activity	1
binding	1
catalytic activity	1
transferase activity	1
glycosyltransferase activity	1
Golgi apparatus	1
bounding membrane of organelle	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1
organelle membrane	1
Golgi cisterna	1
extracellular vesicle	1

Protein interactions and networks

STRING

1100 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FUT8	MGAT5	Q09328	773
FUT8	FUT1	P19526	762
FUT8	FUT6	P51993	761
FUT8	ST6GAL1	P15907	732
FUT8	POFUT1	Q9H488	730
FUT8	POFUT4	Q495W5	723
FUT8	FUT9	Q9Y231	721
FUT8	MGAT3	Q09327	720
FUT8	SLC35C1	Q96A29	712
FUT8	FUT3	P21217	703
FUT8	POFUT2	Q9Y2G5	703
FUT8	B4GALT1	P15291	702
FUT8	GMDS	O60547	691
FUT8	FUT7	Q11130	685
FUT8	MGAT2	Q10469	677

IntAct

155 interactions, top by confidence:

A	B	Type	Score
PIK3CA	PIK3R2	psi-mi:“MI:0914”(association)	0.900
STX18	NBAS	psi-mi:“MI:0914”(association)	0.810
NIPAL1	ESYT2	psi-mi:“MI:0914”(association)	0.640
ADCY9	NEMP1	psi-mi:“MI:0914”(association)	0.640
ZBTB10	FUT8	psi-mi:“MI:0915”(physical association)	0.560
TMEM30B	KLRG2	psi-mi:“MI:0914”(association)	0.530
SLC9A6	MAP1LC3B2	psi-mi:“MI:0914”(association)	0.530
PLVAP	SMPD2	psi-mi:“MI:0914”(association)	0.530
B3GALNT1	DUSP14	psi-mi:“MI:0914”(association)	0.530
FGL2	PCNT	psi-mi:“MI:0914”(association)	0.530
GABRD	ATF6	psi-mi:“MI:0914”(association)	0.530
SLC39A4	TMEM120B	psi-mi:“MI:0914”(association)	0.530
PBXIP1	GOLIM4	psi-mi:“MI:0914”(association)	0.530
FAM174A	BLTP3B	psi-mi:“MI:0914”(association)	0.530
CCR6	PODXL	psi-mi:“MI:0914”(association)	0.530
SLC30A4	GOSR2	psi-mi:“MI:0914”(association)	0.530
PBXIP1	KCNN4	psi-mi:“MI:0914”(association)	0.530
SLC9A6	ALDH3A2	psi-mi:“MI:0914”(association)	0.530

BioGRID (192): FUT8 (Affinity Capture-MS), FUT8 (Affinity Capture-MS), FUT8 (Affinity Capture-MS), FUT8 (Affinity Capture-MS), FUT8 (Affinity Capture-MS), FUT8 (Affinity Capture-MS), FUT8 (Affinity Capture-MS), FUT8 (Affinity Capture-MS), FUT8 (Affinity Capture-MS), FUT8 (Affinity Capture-MS), FUT8 (Affinity Capture-MS), FUT8 (Affinity Capture-MS), FUT8 (Affinity Capture-MS), MAN2A2 (Affinity Capture-MS), FUT8 (Affinity Capture-MS)

ESM2 similar proteins: A0A8C2LVE3, A0MGZ5, A0MGZ7, A4IID1, F6PTN1, O08889, O60243, O93336, P0DJQ9, P25722, P69478, P79282, P79948, Q56UJ5, Q5NVB3, Q5QQ57, Q5R621, Q5RBC3, Q659X0, Q6EV76, Q6EV77, Q6GQI7, Q6GQK9, Q6KFX9, Q6NVP8, Q76KB1, Q76KB2, Q7LFX5, Q7LGA3, Q7T3S3, Q800H9, Q80UW0, Q86Y38, Q8CHI9, Q8IZP7, Q8JHF2, Q8R3H7, Q8TDX6, Q91XQ5, Q91ZB4

Diamond homologs: G5EFE7, P79282, Q5NVB3, Q659X0, Q6EV76, Q6EV77, Q6NVP8, Q9BYC5, Q9N0W2, Q9VYV5, Q9WTS2, Q5ZJJ9, Q62422, Q6P686, Q6TGW5, Q6XJU9, Q7ZYG4, Q8MJ49, Q8MJ50, Q92882

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 184 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Lysosphingolipid and LPA receptors	5	32.8×	8e-05
R-HSA-425366	9	14.1×	7e-06
Class A/1 (Rhodopsin-like receptors)	9	5.8×	2e-03
SLC-mediated transmembrane transport	11	5.6×	5e-04
GPCR ligand binding	10	5.5×	1e-03
Signaling by GPCR	11	3.8×	1e-02

GO biological processes:

GO term	Partners	Fold	FDR
zinc ion transmembrane transport	8	36.5×	3e-08
intracellular zinc ion homeostasis	8	25.0×	4e-07
calcium ion transport	7	8.2×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	3
Uncertain significance	85
Likely benign	50
Benign	30

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
545465	NM_001371533.1(FUT8):c.715C>T (p.Arg239Ter)	Pathogenic
545466	NM_001371533.1(FUT8):c.1009C>G (p.Arg337Gly)	Pathogenic
545467	NM_001371533.1(FUT8):c.1259+5G>T	Pathogenic
545468	NM_001371533.1(FUT8):c.943C>T (p.Arg315Ter)	Pathogenic
1687283	NM_001371533.1(FUT8):c.952C>T (p.Arg318Ter)	Likely pathogenic
2631207	NM_001371533.1(FUT8):c.786_789del (p.Ser263fs)	Likely pathogenic
982408	NM_001371533.1(FUT8):c.12G>A (p.Trp4Ter)	Likely pathogenic

SpliceAI

4338 predictions. Top by Δscore:

Variant	Effect	Δscore
14:65449520:A:T	donor_gain	1.0000
14:65449524:G:GT	donor_gain	1.0000
14:65455615:TTTCA:T	acceptor_loss	1.0000
14:65455616:TTCA:T	acceptor_loss	1.0000
14:65455617:TCA:T	acceptor_loss	1.0000
14:65455618:CAGGT:C	acceptor_loss	1.0000
14:65455619:A:AG	acceptor_gain	1.0000
14:65455619:A:AT	acceptor_loss	1.0000
14:65455620:G:GC	acceptor_loss	1.0000
14:65455620:G:GG	acceptor_gain	1.0000
14:65455714:TTCAG:T	donor_loss	1.0000
14:65455715:TCAG:T	donor_loss	1.0000
14:65455716:CAGG:C	donor_loss	1.0000
14:65455717:AGG:A	donor_loss	1.0000
14:65455718:GGT:G	donor_loss	1.0000
14:65455719:G:A	donor_loss	1.0000
14:65455720:T:A	donor_loss	1.0000
14:65561335:A:AG	acceptor_gain	1.0000
14:65561336:G:GG	acceptor_gain	1.0000
14:65561336:GCAT:G	acceptor_gain	1.0000
14:65561763:TCCG:T	donor_loss	1.0000
14:65561766:GGTAG:G	donor_loss	1.0000
14:65561767:GTAG:G	donor_loss	1.0000
14:65561768:T:A	donor_loss	1.0000
14:65615969:A:AG	acceptor_gain	1.0000
14:65615970:A:AG	acceptor_gain	1.0000
14:65615975:CAGGA:C	acceptor_loss	1.0000
14:65615976:A:AG	acceptor_gain	1.0000
14:65615976:AG:A	acceptor_gain	1.0000
14:65615977:G:GA	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000008276 (14:65450947 C>A,G), RS1000009430 (14:65568488 A>T), RS1000017467 (14:65710603 A>G,T), RS1000021919 (14:65624568 C>G,T), RS1000025257 (14:65627105 G>A,T), RS1000025579 (14:65541228 T>C), RS1000031133 (14:65583499 A>G), RS1000038132 (14:65675191 A>C,G), RS1000045882 (14:65437782 G>A), RS1000049773 (14:65438049 C>T), RS1000053532 (14:65652887 T>C), RS1000055133 (14:65480475 C>T), RS1000058746 (14:65695979 TTA>T), RS1000065046 (14:65743953 T>C), RS1000070430 (14:65668059 T>A)

Disease associations

OMIM: gene MIM:602589 | disease phenotypes: MIM:618005

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital disorder of glycosylation with defective fucosylation 1	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
congenital disorder of glycosylation with defective fucosylation 1	Definitive	AR

Mondo (1): congenital disorder of glycosylation with defective fucosylation 1 (MONDO:0020775)

Orphanet (0):

HPO phenotypes

34 total (30 of 34 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000121	Nephrocalcinosis
HP:0000218	High palate
HP:0000252	Microcephaly
HP:0000278	Retrognathia
HP:0000337	Broad forehead
HP:0000341	Narrow forehead
HP:0000348	High forehead
HP:0000431	Wide nasal bridge
HP:0000501	Glaucoma
HP:0000557	Buphthalmos
HP:0000821	Hypothyroidism
HP:0000938	Osteopenia
HP:0001007	Hirsutism
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001508	Failure to thrive
HP:0001511	Intrauterine growth retardation
HP:0001561	Polyhydramnios
HP:0001631	Atrial septal defect
HP:0001643	Patent ductus arteriosus
HP:0001875	Decreased total neutrophil count
HP:0001943	Hypoglycemia
HP:0002751	Kyphoscoliosis
HP:0002783	Recurrent lower respiratory tract infections
HP:0002827	Hip dislocation
HP:0003196	Short nose
HP:0003577	Congenital onset
HP:0004322	Short stature

GWAS associations

58 associations (top):

Study	Trait	p-value
GCST000783_2	Multiple sclerosis–Brain Glutamate Levels	9.000000e-06
GCST000925_1	N-glycan levels	3.000000e-18
GCST000925_8	N-glycan levels	1.000000e-08
GCST001737_19	Chronic obstructive pulmonary disease-related biomarkers	5.000000e-06
GCST001762_53	Obesity-related traits	8.000000e-06
GCST001848_163	IgG glycosylation	8.000000e-20
GCST001848_175	IgG glycosylation	2.000000e-06
GCST001848_178	IgG glycosylation	1.000000e-22
GCST001848_188	IgG glycosylation	5.000000e-15
GCST001848_193	IgG glycosylation	3.000000e-14
GCST001848_199	IgG glycosylation	3.000000e-17
GCST001848_262	IgG glycosylation	2.000000e-19
GCST001848_312	IgG glycosylation	1.000000e-10
GCST001848_345	IgG glycosylation	3.000000e-08
GCST001848_369	IgG glycosylation	6.000000e-06
GCST001848_466	IgG glycosylation	2.000000e-13
GCST001848_559	IgG glycosylation	3.000000e-21
GCST001848_644	IgG glycosylation	7.000000e-14
GCST002541_98	Menarche (age at onset)	4.000000e-08
GCST003264_175	Post bronchodilator FEV1/FVC ratio	2.000000e-06
GCST003264_180	Post bronchodilator FEV1/FVC ratio	3.000000e-06
GCST003324_2	Ischemic stroke	7.000000e-06
GCST003498_2	Verbal-numerical reasoning	2.000000e-08
GCST004924_4	IgG monogalactosylation phenotypes (multivariate analysis)	1.000000e-17
GCST004925_3	IgG N-glycosylation phenotypes (multivariate analysis)	3.000000e-15
GCST004926_3	IgG digalactosylation phenotypes (multivariate analysis)	3.000000e-16
GCST004927_2	IgG galactosylation phenotypes (multivariate analysis)	1.000000e-15
GCST004929_2	IgG fucosylation phenotypes (multivariate analysis)	6.000000e-10
GCST004930_3	IgG sialylation phenotypes (multivariate analysis)	5.000000e-15
GCST004932_3	IgG monosialylation phenotypes (multivariate analysis)	6.000000e-15

EFO canonical traits (18, from GWAS)

EFO ID	Trait name
EFO:0004999	N-glycan measurement
EFO:0005193	serum IgG glycosylation measurement
EFO:0004703	age at menarche
EFO:0004713	FEV/FVC ratio
EFO:0004350	reasoning
EFO:0008423	IgG monogalactosylation measurement
EFO:0008424	IgG digalactosylation measurement
EFO:0008425	IgG galactosylation measurement
EFO:0008427	IgG fucosylation measurement
EFO:0008428	IgG sialylation measurement
EFO:0008430	IgG monosialylation measurement
EFO:0010221	systemising measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0008463	glucagon measurement
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0004527	mean corpuscular hemoglobin
EFO:0004305	erythrocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3596087 (SINGLE PROTEIN)

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

ChEMBL bioactivities

1 potent at pChembl≥5 of 2 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.70	Ki	2000	nM	CHEMBL3596198

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, decreases expression, decreases methylation	7
bisphenol A	decreases methylation, increases expression, affects cotreatment	3
sodium arsenite	decreases expression, increases abundance, increases expression	3
p-Chloromercuribenzoic Acid	decreases activity, decreases reaction, affects cotreatment, decreases expression	3
trichostatin A	affects cotreatment, decreases expression	2
Arsenic	affects methylation, decreases expression, increases abundance	2
Cisplatin	decreases expression, affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tretinoin	decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	affects cotreatment, increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
uranyl acetate	affects expression	1
methyl iodide	decreases activity	1
afimoxifene	decreases expression, decreases reaction	1
cobaltous chloride	decreases expression	1
nickel chloride	increases expression	1
manganese chloride	decreases expression, increases abundance	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
dibenzo(a,l)pyrene	decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	affects cotreatment, increases expression	1
jinfukang	increases expression	1
Temozolomide	affects response to substance	1
Zoledronic Acid	increases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3599367	Binding	Inhibition of FucT-8 in human blood platelets	Beyond substrate analogues: new inhibitor chemotypes for glycosyltransferases — Medchemcomm

Cellosaurus cell lines

5 cell lines: 4 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_C8P6	CL1-5 Fut8-KD	Cancer cell line	Male
CVCL_D7GG	Ubigene HEK293T FUT8 KO	Transformed cell line	Female
CVCL_E1XW	HAP1 FUT8 (-) 1	Cancer cell line	Male
CVCL_E1XX	HAP1 FUT8 (-) 2	Cancer cell line	Male
CVCL_E1XY	HAP1 FUT8 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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