FUT8

Chr 14

fucosyltransferase 8

Also known as: CDGF, CDGF1

NCBI Gene: 2530 ENSG00000033170 UniProt: Q9BYC5

This gene encodes a fucosyltransferase that catalyzes the addition of fucose in alpha 1-6 linkage to the first GlcNAc residue in N-linked glycans, including fucosylation of immunoglobulin G Fc regions. Mutations cause congenital disorder of glycosylation with defective fucosylation 1, inherited in an autosomal recessive pattern. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.509).

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes an enzyme belonging to the family of fucosyltransferases. The product of this gene catalyzes the transfer of fucose from GDP-fucose to N-linked type complex glycopeptides. This enzyme is distinct from other fucosyltransferases which catalyze alpha1-2, alpha1-3, and alpha1-4 fucose addition. The expression of this gene may contribute to the malignancy of cancer cells and to their invasive and metastatic capabilities. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2011]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtCongenital disorder of glycosylation with defective fucosylation 1

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · congenital disorder of glycosylation with defective fucosylation 1 · AR · ClinGen 2024

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.51

LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.51LOEUF

pLI 0.010

Z-score 3.75

OE 0.30 (0.18–0.51)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.20Z-score

OE missense 0.65 (0.58–0.73)

206 obs / 316.1 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.30 (0.18–0.51)

0≤0.351.4

Missense OE?0.65 (0.58–0.73)

0≤0.61.4

Synonymous OE?1.22

0≤1.21.6

LoF obs/exp: 10 / 33.3Missense obs/exp: 206 / 316.1Syn Z: -1.79

Background carrier burden — how many people carry a rare variant somewhere in FUT8?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

638 rare PASS variants

Rare truncating (LoF)

1 in 2,500

76 rare PASS variants

Rare synonymous (reference)

1 in 210

266 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for FUT8. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 170	1 in 2,000
South Asian	~43k	1 in 120	1 in 1,700
Remaining (unassigned)	~30k	1 in 120	1 in 5,000
European (Finnish)	~27k	1 in 810	1 in 5,300
Admixed American	~22k	1 in 95	≈ 1 in 7,400
African / African American	~21k	1 in 150	1 in 3,400
East Asian	~20k	1 in 150	1 in 3,300
Ashkenazi Jewish	~13k	1 in 250	none seen
Middle Eastern	~2,884	1 in 93	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 8 of 9 coding exons well covered in gnomAD exomes; exon 10 marginal. Genomes: all 9.? see exons ↓