GFUS

Chr 8

GDP-L-fucose synthase

Also known as: FX, P35B, SDR4E1, TSTA3

NCBI Gene: 7264ENSG00000104522UniProt: Q13630

The GDP-fucose synthase enzyme catalyzes the NADP-dependent conversion of GDP-4-dehydro-6-deoxy-D-mannose to GDP-fucose, which is essential for fucosylation of glycoproteins including blood group antigens and cell adhesion molecules. Mutations cause leukocyte adhesion deficiency type II, characterized by defective neutrophil adhesion and recurrent bacterial infections, with autosomal recessive inheritance. The gene shows minimal constraint against loss-of-function variants (pLI near zero, LOEUF 1.13).

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
2
Pubs (1 yr)
61
P/LP submissions
0%
P/LP missense
1.13
LOEUF
DN
Mechanism· predicted
Clinical Summary— GFUS
🧬
Gene-Disease Validity (ClinGen)
congenital disorder of glycosylation · ARLimited

Limited evidence — not for standalone diagnostic reporting

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
60 unique Pathogenic / Likely Pathogenic· 67 VUS of 166 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.13LOEUF
pLI 0.000
Z-score 1.15
OE 0.71 (0.46–1.13)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.20Z-score
OE missense 0.96 (0.85–1.08)
197 obs / 205.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.71 (0.46–1.13)
0≤0.351.4
Missense OE0.96 (0.85–1.08)
0≤0.61.4
Synonymous OE1.27
0≤1.21.6
LoF obs/exp: 13 / 18.3Missense obs/exp: 197 / 205.0Syn Z: -1.98
DN
0.79top 25%
GOF
0.5464th %ile
LOF
0.3258th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

166 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic55
Likely Pathogenic5
VUS67
Likely Benign3
Benign11
55
Pathogenic
5
Likely Pathogenic
67
VUS
3
Likely Benign
11
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
55
0
55
Likely Pathogenic
0
0
5
0
5
VUS
0
62
5
0
67
Likely Benign
0
2
0
1
3
Benign
0
1
9
1
11
Total065742141

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

GFUS · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients