FUT5

Summary

FUT5 (fucosyltransferase 5, HGNC:4016) is a protein-coding gene on chromosome 19p13.3, encoding 4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase FUT5 (Q11128). Catalyzes preferentially the transfer of L-fucose, from a guanosine diphosphate-beta-L-fucose, to the N-acetyl-beta-D-glucosamine (GlcNAc) of an N-acetyllactosamine unit (type 2 chain) of an oligosaccharide, or a glycoprotein- and a glycolipid-linked N-acetyllactosamine unit via….

Enables 3-galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferase activity and 4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase activity. Involved in ceramide metabolic process; glycoprotein biosynthetic process; and oligosaccharide metabolic process. Predicted to be located in Golgi membrane.

Source: NCBI Gene 2527 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 113 total
• GTEx eGene: eQTL in 11 tissues, sQTL in 0 (q < 0.05)
• Constraint (gnomAD): pLI 0.11 (intermediate), LOEUF 1.81 (unconstrained)
• MANE Select transcript: NM_002034
• Notable: 113 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4016
Approved symbol	FUT5
Name	fucosyltransferase 5
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	FUC-TV
Ensembl gene	ENSG00000130383
Ensembl biotype	protein_coding
OMIM	136835
Entrez	2527

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

MANE Select: ENST00000588525

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1

ENST00000588525, ENST00000252675

RefSeq mRNA: 1 — MANE Select: NM_002034 NM_002034

CCDS: CCDS12154

Canonical transcript exons

ENST00000588525 — 2 exons

Exon	Start	End
ENSE00002862104	5865826	5867737
ENSE00002879157	5870465	5870540

Expression profiles

Bgee: expression breadth broad, 29 present calls, max score 61.20.

Highest expression (Bgee): lower esophagus mucosa, bone marrow, bone marrow cell, lobe of liver, cortical plate.

Genetic regulation across tissues (GTEx eQTL / sQTL)

FUT5 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 11 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

11 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	eqtl	1.7e-17	-0.62	19:5858784:T:C
Skin Not Sun Exposed Suprapubic	eqtl	1.1e-07	+0.33	19:5895347:C:T
Brain Spinal cord cervical c-1	eqtl	7.1e-06	-0.63	19:5858784:T:C
Skin Sun Exposed Lower leg	eqtl	1.3e-05	+0.21	19:5912319:C:T
Esophagus Mucosa	eqtl	1.0e-03	-0.77	19:5855970:T:C
Brain Substantia nigra	eqtl	5.7e-03	-0.47	19:5866574:C:T
Liver	eqtl	1.7e-02	+0.49	19:5870593:C:A
Minor Salivary Gland	eqtl	2.8e-02	+1.73	19:6541731:C:T
Nerve Tibial	eqtl	3.5e-02	+0.21	19:5895347:C:T
Brain Hippocampus	eqtl	3.9e-02	+0.48	19:5871769:AAAG:A
Brain Amygdala	eqtl	4.7e-02	-0.53	19:5866725:T:C

Top tissues by expression

showing 100 of 112 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	61.20	gold quality
bone marrow	UBERON:0002371	50.23	gold quality
bone marrow cell	CL:0002092	44.63	gold quality
right lobe of liver	UBERON:0001114	41.73	silver quality
cortical plate	UBERON:0005343	40.49	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
tonsil	UBERON:0002372	36.43	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
calcaneal tendon	UBERON:0003701	35.24	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	34.17	silver quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
mucosa of stomach	UBERON:0001199	32.53	gold quality
lymph node	UBERON:0000029	32.35	gold quality
right uterine tube	UBERON:0001302	32.35	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
prefrontal cortex	UBERON:0000451	30.20	gold quality
adenohypophysis	UBERON:0002196	30.01	silver quality
skin of leg	UBERON:0001511	30.00	gold quality
urinary bladder	UBERON:0001255	29.91	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
fallopian tube	UBERON:0003889	29.70	gold quality
zone of skin	UBERON:0000014	28.84	gold quality
testis	UBERON:0000473	28.66	silver quality
islet of Langerhans	UBERON:0000006	28.62	gold quality
gall bladder	UBERON:0002110	28.52	gold quality
left testis	UBERON:0004533	28.15	silver quality
duodenum	UBERON:0002114	28.14	gold quality
Brodmann (1909) area 9	UBERON:0013540	28.05	gold quality
left uterine tube	UBERON:0001303	27.98	gold quality
primary visual cortex	UBERON:0002436	27.42	gold quality
right testis	UBERON:0004534	27.40	silver quality
pancreas	UBERON:0001264	27.37	gold quality
placenta	UBERON:0001987	27.36	gold quality
skin of abdomen	UBERON:0001416	26.82	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	26.65	gold quality
substantia nigra	UBERON:0002038	26.59	silver quality
muscle of leg	UBERON:0001383	26.44	silver quality
leukocyte	CL:0000738	26.42	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
fundus of stomach	UBERON:0001160	26.35	gold quality
monocyte	CL:0000576	26.30	gold quality
Ammon’s horn	UBERON:0001954	25.84	gold quality
saliva-secreting gland	UBERON:0001044	25.68	gold quality
multicellular organism	UBERON:0000468	25.55	gold quality
endometrium	UBERON:0001295	25.43	gold quality
subcutaneous adipose tissue	UBERON:0002190	25.39	silver quality
body of pancreas	UBERON:0001150	25.38	gold quality
esophagus mucosa	UBERON:0002469	25.23	gold quality
small intestine	UBERON:0002108	25.15	gold quality
gastrocnemius	UBERON:0001388	25.09	silver quality
esophagogastric junction muscularis propria	UBERON:0035841	24.88	gold quality
esophagus	UBERON:0001043	24.82	gold quality
nucleus accumbens	UBERON:0001882	24.70	gold quality
cerebellum	UBERON:0002037	24.70	gold quality
cerebellar cortex	UBERON:0002129	24.47	gold quality
cerebellar hemisphere	UBERON:0002245	24.44	gold quality
myometrium	UBERON:0001296	24.24	gold quality
uterine cervix	UBERON:0000002	24.09	gold quality
superior frontal gyrus	UBERON:0002661	24.08	gold quality
right frontal lobe	UBERON:0002810	24.08	silver quality
putamen	UBERON:0001874	24.04	gold quality
cortex of kidney	UBERON:0001225	23.94	gold quality
intestine	UBERON:0000160	23.81	gold quality
lower esophagus	UBERON:0013473	23.59	silver quality
tibial artery	UBERON:0007610	23.55	gold quality
minor salivary gland	UBERON:0001830	23.53	gold quality
popliteal artery	UBERON:0002250	23.52	gold quality
small intestine Peyer’s patch	UBERON:0003454	23.49	gold quality
colon	UBERON:0001155	23.43	gold quality
thoracic mammary gland	UBERON:0005200	23.41	gold quality
adipose tissue	UBERON:0001013	23.15	silver quality
transverse colon	UBERON:0001157	23.15	gold quality
heart	UBERON:0000948	23.01	gold quality
heart left ventricle	UBERON:0002084	22.66	gold quality
right hemisphere of cerebellum	UBERON:0014890	22.56	gold quality
left coronary artery	UBERON:0001626	22.44	gold quality
right atrium auricular region	UBERON:0006631	22.41	gold quality
spleen	UBERON:0002106	22.22	gold quality
smooth muscle tissue	UBERON:0001135	22.15	gold quality
rectum	UBERON:0001052	22.11	gold quality
lung	UBERON:0002048	22.01	silver quality
vagina	UBERON:0000996	21.79	gold quality
right ovary	UBERON:0002118	21.79	gold quality
adrenal gland	UBERON:0002369	21.77	gold quality
ascending aorta	UBERON:0001496	21.62	gold quality
right adrenal gland cortex	UBERON:0035827	21.49	gold quality
thoracic aorta	UBERON:0001515	21.45	gold quality
ovary	UBERON:0000992	21.34	gold quality
right adrenal gland	UBERON:0001233	21.30	gold quality
descending thoracic aorta	UBERON:0002345	21.17	gold quality
corpus callosum	UBERON:0002336	20.84	gold quality
body of uterus	UBERON:0009853	20.65	gold quality
granulocyte	CL:0000094	20.63	gold quality
upper lobe of left lung	UBERON:0008952	20.57	silver quality
left adrenal gland cortex	UBERON:0035825	20.48	gold quality
apex of heart	UBERON:0002098	20.28	gold quality
omental fat pad	UBERON:0010414	20.14	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.65

HPA expression

RNA tissue specificity: Not detected

12 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Medulla oblongata	tissue	0.5
Bone marrow	tissue	0.5
Testis	tissue	0.2
Cerebral cortex	tissue	0.2
Pons	tissue	0.1
Salivary gland	tissue	0.1
Amygdala	tissue	0.1
Midbrain	tissue	0.1
Thalamus	tissue	0.1
Cerebellum	tissue	0.1
Spinal cord	tissue	0.1
Retrosplenial cortex	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 62; highest nTPM — Nucleus raphe obscurus (0.5), Nucleus ambiguus (0.3), Cerebellar white matter (0.2), Corpus callosum, genu (white matter) (0.2), Inferior parietal lobule (0.2).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting FUT5 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

23 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-7157-5P	99.66	69.33	1829
HSA-MIR-497-3P	99.61	69.71	1990
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-4710	98.61	65.96	1048
HSA-MIR-4290	98.51	65.17	907
HSA-MIR-4726-3P	98.49	63.89	1385
HSA-MIR-5008-5P	98.42	65.87	1019
HSA-MIR-4483	98.09	64.12	1642
HSA-MIR-3665	97.73	65.08	975
HSA-MIR-2467-5P	97.36	67.71	991
HSA-MIR-874-5P	96.93	63.92	1014
HSA-MIR-1293	96.16	64.69	916

Functional genomics

gnomAD constraint: pLI 0.109, LOEUF 1.81, missense Z 1.28 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000588525 splits into 2 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
19:5,866,604–5,867,205	176 / 275.2	0.64	no
19:5,867,206–5,867,725	261 / 242.6	1.08	no

Literature-anchored findings (GeneRIF, showing 7)

• Prostatic cancer cell transfected with this enzyme adhered to prostatic stromal cells in vitro with higher affinity than mock-transfected cancer cells. (PMID:14601054)
• FUT5 is a receptor of glycodelin-A and zona pellucida proteins, and glycodelin-A inhibits spermatozoa-zona binding by blocking the binding of sperm FUT5 to the zona pellucida (PMID:17148576)
• results suggested that PKR is the primary target for HSV-1 early RNA during induction of FUT3, FUT5, and FUT6 (PMID:19349624)
• 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)
• FUT5 was expressed on spermatid membranes and in serum, but not in seminal plasma, vaginal fluid and saliva. Expression was localized on head of spermatids. (PMID:22619806)
• 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)
• 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)

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): FUT6 (ENSG00000156413), FUT3 (ENSG00000171124), FUT9 (ENSG00000172461), POFUT3 (ENSG00000172728), FUT7 (ENSG00000180549), FUT4 (ENSG00000196371), POFUT4 (ENSG00000196968)

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pan troglodytes	Q659L0	100.0%	Diamond
Mus musculus	O88819	99.4%	Diamond
Canis lupus familiaris	Q659L1	99.4%	Diamond
Rattus norvegicus	Q99JB3	99.2%	Diamond
Cricetulus griseus	Q9JIG1	98.9%	Diamond
Bos taurus	Q8HZR2	97.8%	Diamond
Gorilla gorilla gorilla	Q8HYJ6	96.9%	Diamond
Hylobates lar	Q8HYJ3	96.5%	Diamond
Pongo pygmaeus	Q8HYJ4	96.3%	Diamond
Oryzias latipes	Q5F2N2	84.7%	Diamond
Takifugu rubripes	Q70AG8	84.7%	Diamond
Xenopus tropicalis	Q6A1G3	84.4%	Diamond
Xenopus laevis	Q6NTZ6	84.3%	Diamond
Arabidopsis thaliana	Q9FX97	77.4%	Diamond
Gallus gallus	Q8AWC7	74.2%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
NDUFA11	protein-coding	126328
FUT3	protein-coding	2525
FUT6	protein-coding	2528
NRTN	protein-coding	4902
VMAC	protein-coding	400673
CAPS	protein-coding	828
RANBP3	protein-coding	8498
RANBP3-DT	ncRNA	100128568
RFX2	protein-coding	5990
DUS3L	protein-coding	56931

Protein

Protein identifiers

4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase FUT5 — Q11128 (reviewed: Q11128)

Alternative names: 3-galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferase FUT5, Fucosyltransferase 5, Fucosyltransferase V, Galactoside 3-L-fucosyltransferase

All UniProt accessions (1): Q11128

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes preferentially the transfer of L-fucose, from a guanosine diphosphate-beta-L-fucose, to the N-acetyl-beta-D-glucosamine (GlcNAc) of an N-acetyllactosamine unit (type 2 chain) of an oligosaccharide, or a glycoprotein- and a glycolipid-linked N-acetyllactosamine unit via an alpha (1,3) linkage and participates in the surface expression of VIM-2, Lewis X/SSEA-1 and sialyl Lewis X antigens. Preferentially transfers fucose to the GlcNAc of an internal N-acetyllactosamine unit of a poly-N-acetyllactosamine chain acceptor substrate. Also catalyzes to a lesser extend the transfer of L-fucose to the GlcNAc of a type 1 (beta-D-galactosyl-(1->3)-N-acetyl-beta-D-glucosaminyl) or H-type 1 (alpha-L-Fuc-(1->2)-beta-D-Gal-(1->3)-D-GlcNAc) chain oligosaccharide via an alpha (1,4) linkage. Preferentially catalyzes sialylated type 2 oligosaccharide acceptors over neutral type 2 or H type 2 (alpha-L-Fuc-(1->2)-beta-D-Gal-(1->4)-D-GlcNAc) oligosaccharide acceptors. Lactose-based structures are also acceptor substrates.

Subcellular location. Golgi apparatus. Golgi stack membrane.

Tissue specificity. Liver, colon and testis and trace amounts in T-cells and brain.

Pathway. Protein modification; protein glycosylation.

Similarity. Belongs to the glycosyltransferase 10 family.

RefSeq proteins (1): NP_002025* (*=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)

• 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)
• a neolactoside nLc4Cer(d18:1(4E)) + GDP-beta-L-fucose = a neolactoside III(3)-alpha-Fuc-nLc4Cer(d18:1(4E)) + GDP + H(+) (RHEA:48332)
• a neolactoside nLc6Cer(d18:1(4E)) + GDP-beta-L-fucose = a neolactoside III(3)-alpha-Fuc-nLc6Cer(d18:1(4E)) + GDP + H(+) (RHEA:48336)
• a neolactoside VI(3)-alpha-NeuNAc-nLc6Cer + GDP-beta-L-fucose = a neolactoside VI(3)-alpha-NeuAc,III(3)-alphaFuc-nLc6Cer + GDP + H(+) (RHEA:48352)
• 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 nLc4Cer + GDP-beta-L-fucose = a neolactoside III(3)-alpha-Fuc-nLc4Cer + GDP + H(+) (RHEA:48376)
• 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)
• alpha-L-Fuc-(1->2)-beta-D-Gal-(1->4)-D-GlcNAc + GDP-beta-L-fucose = alpha-L-Fuc-(1->2)-beta-D-Gal-(1->4)-[alpha-L-Fuc-(1->3)]-D-GlcNAc + GDP + H(+) (RHEA:62900)

UniProt features (25 total): mutagenesis site 14, glycosylation site 4, topological domain 2, sequence variant 2, chain 1, transmembrane region 1, sequence conflict 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q11128-F1	88.70	0.79

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Metabolic proteins, Predicted membrane proteins

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH uncertain

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)

Type	Positions
N-linked (glcnac…) asparagine	60, 105, 167, 198

Mutagenesis-validated functional residues (14)

Position	Phenotype
86	does not affect 4-galactosyl-n-acetylglucosaminide 3-alpha-l-fucosyltransferase activity with type 2 oligosaccharide acceptor; when …
87	does not affect 4-galactosyl-n-acetylglucosaminide 3-alpha-l-fucosyltransferase activity; when associated with h-86 and s-92. increases …
87	reverses the preferential fucosylation properties leading to production of 72% of sialyl-lewis x; when associated with r-124; e-125 and …
92	does not affect 4-galactosyl-n-acetylglucosaminide 3-alpha-l-fucosyltransferase activity; when associated with h-86 and i-87. increases …
101	does not affect 4-galactosyl-n-acetylglucosaminide 3-alpha-l- and 3-galactosyl-n-acetylglucosaminide 4-alpha-l-fucosyltransferase activity …
105	does not affect 4-galactosyl-n-acetylglucosaminide 3-alpha-l- and 3-galactosyl-n-acetylglucosaminide 4-alpha-l-fucosyltransferase activity …
110	does not affect 4-galactosyl-n-acetylglucosaminide 3-alpha-l- and 3-galactosyl-n-acetylglucosaminide 4-alpha-l-fucosyltransferase activity …
111	does not affect 4-galactosyl-n-acetylglucosaminide 3-alpha-l- and 3-galactosyl-n-acetylglucosaminide 4-alpha-l-fucosyltransferase activity …
118	does not affect 4-galactosyl-n-acetylglucosaminide 3-alpha-l- and 3-galactosyl-n-acetylglucosaminide 4-alpha-l-fucosyltransferase activity …
124	decreases both alpha-(1,3)-fucosyltransferase and alpha-(1,4)-fucosyltransferase activity of 50%.
124	increases alpha-(1,3)-fucosyltransferase activity. loss of alpha-(1,4)-fucosyltransferase activity. loss of site-specific fucosylation …
124	does not affect alpha-(1,3)-fucosyltransferase activity. loss of alpha-(1,4)-fucosyltransferase activity.
125	loss of site-specific fucosylation; when associated with r-124 and v-126. reverses the preferential fucosylation properties leading to …
126	loss of site-specific fucosylation; when associated with r-124 and e-125. reverses the preferential fucosylation properties leading to …

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 4; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

4 pathways:

ID	Pathway	Evidence
R-HSA-9037629	Lewis blood group biosynthesis	curated
R-HSA-9033658	Blood group systems biosynthesis	—
R-HSA-1430728	Metabolism	—
R-HSA-71387	Metabolism of carbohydrates and carbohydrate derivatives	—

MSigDB gene sets: 76 (showing top): GOBP_OLIGOSACCHARIDE_METABOLIC_PROCESS, GOBP_PROTEIN_N_LINKED_GLYCOSYLATION, GOBP_MONOSACCHARIDE_CATABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_SPHINGOLIPID_METABOLIC_PROCESS, GOBP_AMIDE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, WAGNER_APO2_SENSITIVITY, MODULE_99, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_SMALL_MOLECULE_CATABOLIC_PROCESS, GOBP_OLIGOSACCHARIDE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_CATABOLIC_PROCESS, GOBP_FUCOSE_METABOLIC_PROCESS

GO Biological Process (10): carbohydrate metabolic process (GO:0005975), protein N-linked glycosylation (GO:0006487), protein O-linked glycosylation (GO:0006493), ceramide metabolic process (GO:0006672), glycoprotein biosynthetic process (GO:0009101), oligosaccharide metabolic process (GO:0009311), oligosaccharide biosynthetic process (GO:0009312), L-fucose catabolic process (GO:0042355), lipid metabolic process (GO:0006629), sphingolipid metabolic process (GO:0006665)

GO Molecular Function (6): 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), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757)

GO Cellular Component (4): Golgi membrane (GO:0000139), Golgi apparatus (GO:0005794), Golgi cisterna membrane (GO:0032580), membrane (GO:0016020)

Reactome top-level categories

3 top-level categories:

Category	Pathways
Blood group systems biosynthesis	1
Metabolism	1
Metabolism of carbohydrates and carbohydrate derivatives	1

GO top-level categories

25 GO namespaces:

Category	Terms
primary metabolic process	2
glycoprotein biosynthetic process	2
fucosyltransferase activity	2
sphingolipid metabolic process	1
macromolecule biosynthetic process	1
glycoprotein metabolic process	1
carbohydrate derivative biosynthetic process	1
carbohydrate metabolic process	1
oligosaccharide metabolic process	1
carbohydrate biosynthetic process	1
hexose catabolic process	1
L-fucose metabolic process	1
lipid metabolic process	1
hexosyltransferase activity	1
alpha-(1->3)-fucosyltransferase activity	1
catalytic activity	1
transferase activity	1
Golgi apparatus	1
bounding membrane of organelle	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
Golgi cisterna	1
cellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 7 of 21 annotations. The rest are phylogenetic / computational / electronic (IEA).

7 experimentally-supported GO terms:

GO term	NS	Evidence
ceramide metabolic process	BP	direct assay
oligosaccharide metabolic process	BP	direct assay
protein N-linked glycosylation	BP	direct assay
protein O-linked glycosylation	BP	direct assay
3-galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferase activity	MF	direct assay
4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase activity	MF	direct assay
fucosyltransferase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 376 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FUT5	FUT1	P19526	893
FUT5	FUT2	Q10981	863
FUT5	B4GALT1	P15291	699
FUT5	RPL30	P04645	650
FUT5	FUT8	Q9BYC5	641
FUT5	RFX3	P48380	639
FUT5	POFUT1	Q9H488	577
FUT5	ORM2	P19652	553
FUT5	ORM1	P02763	545
FUT5	ST3GAL3	Q11203	510
FUT5	RFX2	P48378	499
FUT5	ST3GAL4	Q11206	496
FUT5	MLLT1	Q03111	490
FUT5	RFX1	P22670	490
FUT5	ST6GAL1	P15907	441

Disease & clinical

Genetic variants

Variant evidence for FUT5: 113 ClinVar records (0 pathogenic / likely pathogenic); 6 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	96
Likely benign	13
Benign	2

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 19 predictions of 35):

Position(s)	Effect	Δscore	Sites
19:5867738–5867739	acceptor_loss	0.9900	6
19:5870501	donor_gain	0.9700
19:5870463–5870464	donor_loss	0.9600	5
19:5870468	donor_gain	0.9500
19:5870463	donor_loss	0.9400
19:5867734	acceptor_gain	0.9100
19:5870428	donor_gain	0.8300
19:5870465	donor_loss	0.8200
19:5870465	donor_loss	0.7600
19:5870432	donor_gain	0.6600

AlphaMissense

624 missense substitutions predicted likely pathogenic (of 2,440 scored), across 156 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
F256	8	0.933	0.994
N262	8	0.913	0.970
F303	8	0.889	0.989
F260	8	0.884	0.932
D267	8	0.754	0.849
W335	7	0.943	0.982
K272	7	0.929	0.963
W274	7	0.927	0.975
F309	7	0.924	0.981
W208	7	0.914	0.981
E261	7	0.914	0.985
C351	7	0.910	0.954
C354	7	0.898	0.942
W145	7	0.883	0.951
C104	7	0.877	0.946
F333	7	0.874	0.930
F373	7	0.863	0.966
F85	7	0.859	0.965
R219	7	0.859	0.946
E271	7	0.854	0.967

HPA cancer prognostics

RNA cancer specificity: Not detected

Disease associations

OMIM: gene MIM:136835 | disease phenotypes:

GWAS associations

6 associations:

Study	Trait	p-value
GCST006585_1324	Blood protein levels	2e-91
GCST004714_1	Heart rate variability traits (SDNN)	7e-16
GCST005850_14	Heart rate response to recovery post exercise (30 sec)	4e-10
GCST005849_8	Heart rate response to recovery post exercise (40 sec)	9e-10
GCST005848_17	Heart rate response to recovery post exercise (50 sec)	2e-9
GCST005847_13	Heart rate response to recovery post exercise (20 sec)	7e-9

EFO canonical traits (from GWAS)

2 canonical traits:

EFO ID	Trait name
EFO:0008003	heart rate variability measurement
EFO:0009185	heart rate response to recovery post exercise

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3146 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

3 measured of 5 human assays (6 total across all organisms); most potent 3 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
GDP-Azasugar analogue	IC50	45000 nM
CHEMBL609638	KI	67100 nM
CHEMBL610712	KI	889000 nM

ChEMBL bioactivities

1 potent at pChembl≥5 of 7 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.01	Ki	9700	nM	CHEMBL1170899

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
benzo(e)pyrene	decreases methylation	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Diethylstilbestrol	increases expression	1
Estradiol	increases expression	1
Methapyrilene	decreases methylation	1
Plant Oils	decreases expression	1
Dronabinol	decreases expression	1
Tobacco Smoke Pollution	affects expression	1
Valproic Acid	increases methylation	1
Copper Sulfate	decreases expression	1
Genistein	increases expression	1

ChEMBL screening assays

9 unique, capped per target: 9 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3598444	Binding	Uncompetitive inhibition of FucT-5 (unknown origin) using GDP-fucose as donor substrate	Beyond substrate analogues: new inhibitor chemotypes for glycosyltransferases — *Medchemcomm*

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for FUT5 across ~30M SureChEMBL compounds — explore on Sugi Predict.