GFUS

Chr 8

GDP-L-fucose synthase

Also known as: FX, P35B, SDR4E1, TSTA3

NCBI Gene: 7264 ENSG00000104522 UniProt: Q13630 OMIM: 137020

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).

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.13

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.

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 OE?0.71 (0.46–1.13)

0≤0.351.4

Missense OE?0.96 (0.85–1.08)

0≤0.61.4

Synonymous OE?1.27

0≤1.21.6

LoF obs/exp: 13 / 18.3Missense obs/exp: 197 / 205.0Syn Z: -1.98

This gene — mechanism propensity

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.