FPGT

protein-coding

fucose-1-phosphate guanylyltransferase

Gene summary

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. [provided by RefSeq, Dec 2010]

MANE transcript

NM_003838.5

Inheritance

—

ClinVar variants

U:99B:7

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.85

Max pathogenic AF

—

Genomic locus

chr1:74,198,238-74,234,086

External References & Databases

Ensembl (ENSG00000254685)

Transcript & Mutation Effects

hg38 • Region Span ~35.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FPGT variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 106

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003838.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				1 clinvar		1
missense			99 clinvar	6 clinvar		105
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	99	7	0	106

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 18 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003838.5	RefSeq	NP_003829.4	4	MANE Select
ENST00000370898.9	Ensembl	ENSP00000359935.4	4	MANE Select
NM_001199328.3	RefSeq	NP_001186257.3	5	Standard
NM_001199329.3	RefSeq	NP_001186258.3	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Fructose and mannose metabolism - Homo sapiens (human)
Amino sugar and nucleotide sugar metabolism - Homo sapiens (human)
Fructose intolerance, hereditary
Fructose and Mannose Degradation
Fructosuria

Biological Process

fucose metabolic process

Molecular Function

catalytic activity
GTP binding
fucose-1-phosphate guanylyltransferase activity

Cellular Component

cytoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000609362
Coding exons: 4
Length: 35875
Individuals with no LoFs: 125622
Homozygous LoFs: 1
Heterozygous LoFs: 125
Defined: 125748
p: 0.000501

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.900	348	304	1.15	0.0000142	3880
Missense (PolyPhen)		105	92.678	1.133		1214
Synonymous	-1.12	128	113	1.13	0.00000544	1143
Loss of Function	0.604	17	19.9	0.854	9.18e-7	302

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.0011	0.0010	notable
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.0013	0.0013	notable
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00044	0.00043	rare
South Asian	0.00039	0.00036	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: 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.;

Recessive Scores

pRec: 0.108

Intolerance Scores

LoFtool: 0.913
RVIS EVS: 0.4
RVIS percentile EVS: 76.36

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.813

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium