Congenital disorder of glycosylation with defective fucosylation 1

Summary

Congenital disorder of glycosylation with defective fucosylation 1 (MONDO:0020775) is a disease caused by FUT8 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: FUT8 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 15

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital disorder of glycosylation with defective fucosylation 1
Mondo ID	MONDO:0020775
OMIM	618005
GARD	0025246
Is cancer (heuristic)	no

Also known as: CDGF1

Data availability: 15 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › congenital disorder of glycosylation › congenital disorder of glycosylation with defective fucosylation › congenital disorder of glycosylation with defective fucosylation 1

Related subtypes (1): congenital disorder of glycosylation with defective fucosylation 2

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

15 retrieved; paginated sample, class counts are floors:

6 uncertain significance, 4 pathogenic, 2 benign, 2 likely pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
545465	NM_001371533.1(FUT8):c.715C>T (p.Arg239Ter)	FUT8	Pathogenic	criteria provided, multiple submitters, no conflicts
545466	NM_001371533.1(FUT8):c.1009C>G (p.Arg337Gly)	FUT8	Pathogenic	no assertion criteria provided
545467	NM_001371533.1(FUT8):c.1259+5G>T	FUT8	Pathogenic	no assertion criteria provided
545468	NM_001371533.1(FUT8):c.943C>T (p.Arg315Ter)	FUT8	Pathogenic	no assertion criteria provided
1687283	NM_001371533.1(FUT8):c.952C>T (p.Arg318Ter)	FUT8	Likely pathogenic	criteria provided, single submitter
982408	NM_001371533.1(FUT8):c.12G>A (p.Trp4Ter)	FUT8	Likely pathogenic	no assertion criteria provided
2888926	NM_001371533.1(FUT8):c.1649C>T (p.Thr550Met)	FUT8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1031304	NM_001371533.1(FUT8):c.1675C>T (p.Arg559Ter)	FUT8	Uncertain significance	criteria provided, multiple submitters, no conflicts
1687228	NM_001371533.1(FUT8):c.1406C>T (p.Ser469Phe)	FUT8	Uncertain significance	criteria provided, single submitter
2441638	NM_001371533.1(FUT8):c.1691C>T (p.Thr564Met)	FUT8	Uncertain significance	criteria provided, single submitter
3280223	NM_001371533.1(FUT8):c.20C>T (p.Ser7Phe)	FUT8	Uncertain significance	criteria provided, multiple submitters, no conflicts
3576661	NM_001371533.1(FUT8):c.320G>A (p.Gly107Asp)	FUT8	Uncertain significance	criteria provided, multiple submitters, no conflicts
916157	NM_001371533.1(FUT8):c.222T>G (p.Ile74Met)	FUT8	Uncertain significance	criteria provided, multiple submitters, no conflicts
1285286	NM_001371533.1(FUT8):c.800C>A (p.Thr267Lys)	FUT8	Benign	criteria provided, multiple submitters, no conflicts
402887	NM_001371533.1(FUT8):c.165A>G (p.Gln55=)	FUT8	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 0 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
FUT8	Definitive	Autosomal recessive	congenital disorder of glycosylation with defective fucosylation 1	5

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
FUT8	HGNC:4019	ENSG00000033170	Q9BYC5	Alpha-(1,6)-fucosyltransferase	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FUT8	Alpha-(1,6)-fucosyltransferase	Catalyzes the addition of fucose in alpha 1-6 linkage to the first GlcNAc residue, next to the peptide chains in N-glycans.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FUT8	Scaffold/PPI	no	2.4.1.68	SH3_domain, Fut8, GT23_dom

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
corpus callosum	1
male germ line stem cell (sensu Vertebrata) in testis	1
olfactory bulb	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FUT8	279	ubiquitous	marker	corpus callosum, olfactory bulb, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FUT8	1,447

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FUT8	Q9BYC5	14

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Reactions specific to the complex N-glycan synthesis pathway	1	1142.0×	0.002	FUT8
Maturation of spike protein	1	265.6×	0.004	FUT8

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
receptor metabolic process	1	16852.0×	4e-04	FUT8
GDP-L-fucose metabolic process	1	16852.0×	4e-04	FUT8
L-fucose catabolic process	1	1685.2×	0.003	FUT8
regulation of cellular response to oxidative stress	1	1296.3×	0.003	FUT8
fibroblast migration	1	842.6×	0.003	FUT8
N-glycan processing	1	732.7×	0.003	FUT8
obsolete protein N-linked glycosylation via asparagine	1	674.1×	0.003	FUT8
oligosaccharide biosynthetic process	1	648.1×	0.003	FUT8
respiratory gaseous exchange by respiratory system	1	624.1×	0.003	FUT8
viral protein processing	1	543.6×	0.003	FUT8
protein N-linked glycosylation	1	263.3×	0.005	FUT8
integrin-mediated signaling pathway	1	160.5×	0.007	FUT8
transforming growth factor beta receptor signaling pathway	1	159.0×	0.007	FUT8
regulation of gene expression	1	83.4×	0.013	FUT8
in utero embryonic development	1	72.0×	0.014	FUT8

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FUT8	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
FUT8	2	Binding:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
FUT8	2.4.1.68	glycoprotein 6-alpha-L-fucosyltransferase

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	FUT8

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
FUT8	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.