FPGT

Summary

FPGT (fucose-1-phosphate guanylyltransferase, HGNC:3825) is a protein-coding gene on chromosome 1p31.1, encoding Fucose-1-phosphate guanylyltransferase (O14772). Catalyzes the formation of GDP-L-fucose from GTP and L-fucose-1-phosphate.

L-fucose is a key sugar in glycoproteins and other complex carbohydrates since it may be involved in many of the functional roles of these macromolecules, such as in cell-cell recognition. The fucosyl donor for these fucosylated oligosaccharides is GDP-beta-L-fucose. There are two alternate pathways for the biosynthesis of GDP-fucose; the major pathway converts GDP-alpha-D-mannose to GDP-beta-L-fucose. The protein encoded by this gene participates in an alternate pathway that is present in certain mammalian tissues, such as liver and kidney, and appears to function as a salvage pathway to reutilize L-fucose arising from the turnover of glycoproteins and glycolipids. This pathway involves the phosphorylation of L-fucose to form beta-L-fucose-1-phosphate, and then condensation of the beta-L-fucose-1-phosphate with GTP by fucose-1-phosphate guanylyltransferase to form GDP-beta-L-fucose. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the neighboring downstream TNNI3 interacting kinase (TNNI3K) gene.

Source: NCBI Gene 8790 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 99 total
• MANE Select transcript: NM_003838

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3825
Approved symbol	FPGT
Name	fucose-1-phosphate guanylyltransferase
Location	1p31.1
Locus type	gene with protein product
Status	Approved
Aliases	GFPP
Ensembl gene	ENSG00000254685
Ensembl biotype	protein_coding
OMIM	603609
Entrez	8790

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000370894, ENST00000370898, ENST00000467578, ENST00000472069, ENST00000482102, ENST00000524915, ENST00000529485, ENST00000534056, ENST00000905300

RefSeq mRNA: 3 — MANE Select: NM_003838 NM_001199328, NM_001199329, NM_003838

CCDS: CCDS55606, CCDS55607, CCDS663

Canonical transcript exons

ENST00000370898 — 4 exons

Exon	Start	End
ENSE00001453858	74204391	74208702
ENSE00003702503	74198242	74198360
ENSE00003708758	74199664	74199831
ENSE00003711128	74201318	74201410

Expression profiles

Bgee: expression breadth ubiquitous, 243 present calls, max score 87.60.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3371 / max 10.9284, expressed in 178 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
3506	11.5724	1747
3507	0.3371	178

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	87.60	gold quality
mononuclear cell	CL:0000842	87.00	gold quality
leukocyte	CL:0000738	86.60	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.11	gold quality
calcaneal tendon	UBERON:0003701	85.85	gold quality
gall bladder	UBERON:0002110	85.25	gold quality
secondary oocyte	CL:0000655	84.45	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.05	gold quality
rectum	UBERON:0001052	83.76	gold quality
islet of Langerhans	UBERON:0000006	83.38	gold quality
jejunal mucosa	UBERON:0000399	82.48	gold quality
adrenal tissue	UBERON:0018303	82.45	gold quality
ventricular zone	UBERON:0003053	82.03	gold quality
bronchial epithelial cell	CL:0002328	80.67	gold quality
corpus epididymis	UBERON:0004359	80.29	gold quality
right adrenal gland cortex	UBERON:0035827	80.21	gold quality
ganglionic eminence	UBERON:0004023	80.04	gold quality
body of pancreas	UBERON:0001150	79.99	gold quality
right adrenal gland	UBERON:0001233	79.91	gold quality
colonic epithelium	UBERON:0000397	79.89	gold quality
stromal cell of endometrium	CL:0002255	79.66	gold quality
pancreas	UBERON:0001264	79.64	gold quality
left coronary artery	UBERON:0001626	79.64	gold quality
germinal epithelium of ovary	UBERON:0001304	79.36	gold quality
descending thoracic aorta	UBERON:0002345	79.31	gold quality
left adrenal gland	UBERON:0001234	79.30	gold quality
caput epididymis	UBERON:0004358	79.27	gold quality
left adrenal gland cortex	UBERON:0035825	78.80	gold quality
mucosa of stomach	UBERON:0001199	78.72	gold quality
adrenal gland	UBERON:0002369	78.53	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.40

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

125 targeting FPGT, 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-126-5P	100.00	72.71	3180
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872

Literature-anchored findings (GeneRIF, showing 3)

• the nature of the purine base is the major determinant in substrate specificity, followed by the nature of the hexose-1-P, and finally by the ribose moiety. Binding is enthalpy-driven and does not involve proton transfer (PMID:16086588)
• identified five amino acid residues that are critical for catalysis. (PMID:16185085)
• A complete native data set has been collected as a first step in determining the three-dimensional structure of this enzyme. (PMID:16582493)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	fpgt	ENSDARG00000042139
mus_musculus	Fpgt	ENSMUSG00000053870
rattus_norvegicus	Fpgt	ENSRNOG00000009548
caenorhabditis_elegans		WBGENE00044903

Protein

Protein identifiers

Fucose-1-phosphate guanylyltransferase — O14772 (reviewed: O14772)

Alternative names: GDP-L-fucose diphosphorylase, GDP-L-fucose pyrophosphorylase

All UniProt accessions (8): A0A0S2Z4P4, A0A0S2Z4Z3, A0A0S2Z5C6, E9PK10, E9PMK0, E9PMM4, H0YDF0, O14772

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the formation of GDP-L-fucose from GTP and L-fucose-1-phosphate. Functions as a salvage pathway to reutilize L-fucose arising from the turnover of glycoproteins and glycolipids.

Subcellular location. Cytoplasm.

Tissue specificity. Expressed in many tissues.

Isoforms (6)

UniProt ID	Names	Canonical?
O14772-1	2	yes
Q59H18-1	1
Q59H18-3	3
Q59H18-4	4
O14772-2	5
O14772-3	6

RefSeq proteins (3): NP_001186257, NP_001186258, NP_003829* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011004	Trimer_LpxA-like_sf	Homologous_superfamily
IPR012120	Fucose-1-phosphate_GuaTrfase	Family
IPR012887	GDP_fucose_pyrophosphorylase	Domain

Pfam: PF07959

Enzyme classification (BRENDA):

• EC 2.7.7.30 — fucose-1-phosphate guanylyltransferase (BRENDA: 11 organisms, 50 substrates, 3 inhibitors, 46 Km, 36 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
GTP	0.012–0.633	19
ATP	0.516–0.8	2
BETA-L-FUCOSE 1-PHOSPHATE	0.03–0.075	2
GDP-L-FUCOSE	0.12	2
2-AMINO-6-CHLOROPURINE-BETA-D-RIBOSIDE 5’-TRIPHO	0.163	1
2-AMINOADENOSINE TRIPHOSPHATE	0.21	1
7-DEAZAGUANOSINE TRIPHOSPHATE	0.0754	1
8-OXOGUANOSINE TRIPHOSPHATE	0.0636	1
D-ARABINOSE 1-PHOSPHATE	0.0854	1
D-FRUCTOSE 1-PHOSPHATE	0.823	1
D-GALACTOSE 1-PHOSPHATE	0.677	1
D-GLUCOSAMINE 1-PHOSPHATE	0.828	1
D-GLUCOSE 1,6-DIPHOSPHATE	0.621	1
D-GLUCOSE 1-PHOSPHATE	0.346	1
D-MANNOSE 1-PHOSPHATE	0.542	1

Catalyzed reactions (Rhea), 1 shown:

• beta-L-fucose 1-phosphate + GTP + H(+) = GDP-beta-L-fucose + diphosphate (RHEA:13549)

UniProt features (9 total): splice variant 3, sequence conflict 3, chain 1, region of interest 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14772-F1	90.67	0.84

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6787639	GDP-fucose biosynthesis

MSigDB gene sets: 137 (showing top): BROWNE_HCMV_INFECTION_6HR_DN, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, WANG_ESOPHAGUS_CANCER_VS_NORMAL_DN, LI_WILMS_TUMOR_VS_FETAL_KIDNEY_1_UP, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, GARY_CD5_TARGETS_DN, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, GOBP_FUCOSE_METABOLIC_PROCESS, FLECHNER_BIOPSY_KIDNEY_TRANSPLANT_REJECTED_VS_OK_DN

GO Biological Process (4): fucose metabolic process (GO:0006004), GDP-L-fucose biosynthetic process (GO:0042350), GDP-L-fucose salvage (GO:0042352), L-fucose metabolic process (GO:0042354)

GO Molecular Function (6): GTP binding (GO:0005525), fucose-1-phosphate guanylyltransferase activity (GO:0047341), nucleotide binding (GO:0000166), transferase activity (GO:0016740), transferase activity, transferring phosphorus-containing groups (GO:0016772), nucleotidyltransferase activity (GO:0016779)

GO Cellular Component (2): cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Synthesis of substrates in N-glycan biosythesis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
hexose metabolic process	1
nucleotide-sugar biosynthetic process	1
GDP-L-fucose metabolic process	1
GDP-L-fucose biosynthetic process	1
metabolic compound salvage	1
fucose metabolic process	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
guanylyltransferase activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
catalytic activity	1
transferase activity	1
transferase activity, transferring phosphorus-containing groups	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

1200 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FPGT	GMDS	O60547	715
FPGT	LRRIQ3	A6PVS8	705
FPGT	GFUS	Q13630	672
FPGT	SLC35H1	Q9NQQ7	619
FPGT	FCSK	Q8N0W3	554
FPGT	SLC35C1	Q96A29	546
FPGT	TNNI3K	Q59H18	545
FPGT	GGPS1	O95749	529
FPGT	FAM227B	Q96M60	507
FPGT	RTCA	O00442	423
FPGT	FDPS	P14324	420
FPGT	H7C0V5	H7C0V5	418
FPGT	POFUT2	Q9Y2G5	407
FPGT	POFUT1	Q9H488	391
FPGT	OC90	Q02509	377

IntAct

3 interactions, top by confidence:

A	B	Type	Score
ZNF691	FPGT	psi-mi:“MI:0914”(association)	0.350
SLAMF6	FPGT	psi-mi:“MI:0914”(association)	0.350

BioGRID (4): FPGT (Affinity Capture-MS), FPGT (Affinity Capture-MS), FPGT (Affinity Capture-MS), NLN (Co-fractionation)

ESM2 similar proteins: A2RU49, A3KCL7, A7RDN6, A7YVH9, D3ZDM7, E9PYK3, E9Q5L8, G5E8F4, O14772, O55060, O55239, P13676, P13798, P19205, P25154, P31228, P40261, P50747, P79106, P80227, P83006, Q03426, Q06AV1, Q0V8R7, Q14CH1, Q28IN4, Q5I0K5, Q5REJ2, Q5RFM7, Q5SZD4, Q5U2W9, Q68FS6, Q6DJF8, Q6GQ33, Q6PE15, Q8C1A3, Q8CDZ2, Q8R146, Q8WU10, Q90678

Diamond homologs: G5E8F4, O14772

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	94
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1004 predictions. Top by Δscore:

Variant	Effect	Δscore
1:74198341:G:GT	donor_gain	1.0000
1:74198354:C:G	donor_gain	1.0000
1:74198403:G:T	donor_gain	1.0000
1:74199648:T:A	acceptor_gain	1.0000
1:74199658:A:AG	acceptor_gain	1.0000
1:74199659:A:G	acceptor_gain	1.0000
1:74199661:T:G	acceptor_gain	1.0000
1:74199662:A:AG	acceptor_gain	1.0000
1:74199662:A:G	acceptor_loss	1.0000
1:74199662:AG:A	acceptor_gain	1.0000
1:74199663:G:A	acceptor_loss	1.0000
1:74199663:G:GC	acceptor_gain	1.0000
1:74199663:G:GG	acceptor_gain	1.0000
1:74199663:GG:G	acceptor_gain	1.0000
1:74199663:GGC:G	acceptor_gain	1.0000
1:74199663:GGCA:G	acceptor_gain	1.0000
1:74199663:GGCAA:G	acceptor_gain	1.0000
1:74199829:TTGG:T	donor_loss	1.0000
1:74199832:G:GG	donor_gain	1.0000
1:74201372:A:G	donor_gain	1.0000
1:74201379:G:GT	donor_gain	1.0000
1:74198303:G:GT	donor_gain	0.9900
1:74198356:AAGAG:A	donor_loss	0.9900
1:74198357:AGAGG:A	donor_loss	0.9900
1:74198358:G:GT	donor_gain	0.9900
1:74198358:GAG:G	donor_gain	0.9900
1:74198358:GAGGT:G	donor_loss	0.9900
1:74198359:AG:A	donor_loss	0.9900
1:74198359:AGGTA:A	donor_loss	0.9900
1:74198360:GG:G	donor_loss	0.9900

AlphaMissense

3977 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:74199690:T:A	W50R	0.995
1:74199690:T:C	W50R	0.995
1:74204861:A:C	S285R	0.995
1:74204863:C:A	S285R	0.995
1:74204863:C:G	S285R	0.995
1:74204430:G:T	G141V	0.994
1:74204433:A:T	K142I	0.994
1:74204622:C:A	A205D	0.994
1:74205113:T:C	F369L	0.994
1:74205115:T:A	F369L	0.994
1:74205115:T:G	F369L	0.994
1:74205119:C:G	H371D	0.994
1:74204399:A:C	S131R	0.993
1:74204401:T:A	S131R	0.993
1:74204401:T:G	S131R	0.993
1:74204616:C:A	A203D	0.993
1:74204550:A:T	D181V	0.992
1:74205260:A:C	S418R	0.992
1:74205262:C:A	S418R	0.992
1:74205262:C:G	S418R	0.992
1:74204406:G:C	R133P	0.991
1:74204409:T:C	L134P	0.991
1:74204646:G:A	G213D	0.991
1:74204549:G:C	D181H	0.990
1:74204726:T:C	F240L	0.990
1:74204728:C:A	F240L	0.990
1:74204728:C:G	F240L	0.990
1:74205121:C:A	H371Q	0.990
1:74205121:C:G	H371Q	0.990
1:74204420:A:C	S138R	0.989

dbSNP variants (sampled 300 via entrez): RS1000113417 (1:74206413 A>G), RS1000575833 (1:74205619 T>C,G), RS1000576305 (1:74200511 T>A,C,G), RS1000629671 (1:74204269 A>G), RS1000840670 (1:74206579 A>G,T), RS1000989782 (1:74201468 T>G), RS1001088562 (1:74199744 C>T), RS1001293181 (1:74206948 T>C), RS1001346464 (1:74207131 T>C,G), RS1001850766 (1:74201579 G>A,C), RS1002173814 (1:74201761 A>C,T), RS1002836812 (1:74203997 G>A), RS1003579226 (1:74203144 C>T), RS1003787359 (1:74207144 A>G), RS1004247108 (1:74198948 C>T)

Disease associations

OMIM: gene MIM:603609 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST003993_27	Menarche (age at onset)	2.000000e-12
GCST005950_6	Body mass index x sex x age interaction (4df test)	1.000000e-15
GCST005951_197	Body mass index	4.000000e-13
GCST005953_11	Body mass index (age <50)	3.000000e-15
GCST005954_3	Body mass index x age interaction	3.000000e-06
GCST006702_8	Parental longevity (combined parental age at death)	5.000000e-08
GCST008550_13	Mental health study participation (completed survey)	4.000000e-08
GCST90000047_6	Age at first sexual intercourse	3.000000e-12

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004703	age at menarche
EFO:0004340	body mass index
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0007796	parental longevity
EFO:0010130	health study participation
EFO:0009749	age at first sexual intercourse measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	5
Tobacco Smoke Pollution	decreases expression, increases methylation	2
Cadmium Chloride	decreases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
kojic acid	decreases expression	1
sodium arsenite	decreases expression	1
nickel chloride	decreases expression	1
manganese chloride	increases abundance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Vorinostat	increases expression	1
Air Pollutants, Occupational	decreases expression	1
Arbutin	decreases expression	1
Carbamazepine	affects expression	1
Formaldehyde	decreases expression	1
Hydrogen Peroxide	increases expression	1
Manganese	increases expression, increases abundance	1
Nickel	decreases expression	1
Quercetin	decreases expression	1
Thiram	decreases expression	1
Urethane	decreases expression	1
Cyclosporine	decreases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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