GFUS

protein-coding

GDP-L-fucose synthase, the group of Short chain dehydrogenase/reductase superfamily

Gene summary

Tissue specific transplantation antigen P35B is a NADP(H)-binding protein. It catalyze the two-step epimerase and the reductase reactions in GDP-D-mannose metabolism, converting GDP-4-keto-6-D-deoxymannose to GDP-L-fucose. GDP-L-fucose is the substrate of several fucosyltransferases involved in the expression of many glycoconjugates, including blood group ABH antigens and developmental adhesion antigens. Mutations in this gene may cause leukocyte adhesion deficiency, type II. [provided by RefSeq, Jul 2008]

Previous symbols:

TSTA3

MANE transcript

NM_003313.4

Inheritance

ClinVar variants

U:79B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.71

Max pathogenic AF

—

Genomic locus

chr8:143,612,618-143,618,048

External References & Databases

Ensembl (ENSG00000104522)

Transcript & Mutation Effects

hg38 • Region Span ~5.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

congenital disorder of glycosylationLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0015286

Submitter: ClinGen

GFUS was first reported in relation to autosomal recessive congenital disorder of glycosylation in 2021 (Feichtinger et al., PMID 34468083). Two variants (missense) that have been reported in a single proband (PMID 34468083) are included in this curation. Symptoms including global developmental delay, mild coarse facial features, and short stature were reported. Evidence supporting this gene-disease relationship includes case-level data and experimental data. This gene-disease relationship is supported by in vitro and in vivo assays showing a defect in fucosylation (PMIDs 34468083) as well as a mouse model (PMID 12186857). In summary, there is limited evidence to support this gene-disease relationship. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship. This classification was approved by the ClinGen Congenital Disorder of Glycosylation Expert Panel on the meeting date 8//7/2025 (SOP Version 11).

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GFUS variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 65

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003313.4. 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			68 clinvar	2 clinvar		70
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			9 clinvar			9
Total	0	0	79	3	0	82

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 58 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003313.4	RefSeq	NP_003304.1	10	MANE Select
ENST00000425753.7	Ensembl	ENSP00000398803.2	10	MANE Select
NM_001317783.2	RefSeq	NP_001304712.1	11	Standard
NM_001413407.1	RefSeq	NP_001400336.1	11	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

T cell mediated cytotoxicity
leukocyte cell-cell adhesion
GDP-mannose metabolic process
electron transport chain
'de novo' GDP-L-fucose biosynthetic process

Molecular Function

electron transfer activity
isomerase activity
GDP-4-dehydro-D-rhamnose reductase activity
identical protein binding
GDP-mannose 3,5-epimerase activity

Cellular Component

cytosol
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000425753
Coding exons: 10
Length: 5431
Individuals with no LoFs: 125686
Homozygous LoFs: 0
Heterozygous LoFs: 56
Defined: 125742
p: 0.000223

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.198	197	205	0.961	0.0000128	2116
Missense (PolyPhen)		55	62.807	0.8757		680
Synonymous	-1.98	113	89.2	1.27	0.00000658	615
Loss of Function	1.15	13	18.3	0.710	9.52e-7	191

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00095	0.00092	rare
Latino/Admixed American	0.00047	0.00046	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00012	0.00011	rare
South Asian	0.00029	0.00029	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Catalyzes the two-step NADP-dependent conversion of GDP- 4-dehydro-6-deoxy-D-mannose to GDP-fucose, involving an epimerase and a reductase reaction. {ECO:0000269|PubMed:8910301}.;

Recessive Scores

pRec: 0.159

Intolerance Scores

LoFtool: 0.247
RVIS EVS: -1.09
RVIS percentile EVS: 7.05

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.151

Gene Damage Prediction

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