GeneBe

FUT8

protein-coding

fucosyltransferase 8, the group of Fucosyltransferases|MicroRNA protein coding host genes

Gene summary

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]

MANE transcript

NM_001371533.1

Inheritance

AR

ClinVar variants

P:7U:84B:47

Top phenotype

Congenital disorder of glycosylation with defective fucosylation 1

gnomAD constraint

pLI —, LoF o/e 0.3

Max pathogenic AF

—

Genomic locus

chr14:65,410,592-65,744,121

External References & Databases

Ensembl (ENSG00000033170)NCBI Gene (2530)OMIM (602589)HGNC:4019GenCCUniProt (Q9BYC5)AlphaFoldClinVar (FUT8)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~333.5 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

congenital disorder of glycosylation with defective fucosylation 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0020775

Submitter: Labcorp Genetics (formerly Invitae)

congenital disorder of glycosylation with defective fucosylation 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0020775

Submitter: PanelApp Australia

congenital disorder of glycosylation with defective fucosylation 1MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0020775

Submitter: Ambry Genetics

congenital disorder of glycosylation with defective fucosylation 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0020775

Submitter: G2P

congenital disorder of glycosylation with defective fucosylation 1DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0020775

Submitter: ClinGen

FUT8 was first reported in relation to autosomal recessive congenital disorder of glycosylation with defective fucosylation 1 in 2018 (Ng et al., PMID: 29304374). 8 variants (nonsense, frameshift, splice site, and missense) that have been reported in 7 probands in 2 publications (PMIDs: 29304374, 32049367) are included in this curation. The maximum score for genetic evidence (12 pts.) has been reached. The mechanism of pathogenicity is known to be loss of function. This gene-disease relationship is also supported by an animal knockout model (PMID: 16236725) and a cell line knockout model (PMID: 27008861). Both models showed a lack of fucosylated N-glycans, which is also observed in affected patients. In summary, there is definitive evidence supporting the relationship between FUT8 and autosomal recessive congenital disorder of glycosylation with defective fucosylation 1. This has been repeatedly demonstrated in both the research and clinical diagnostic settings and has been upheld over time.

Clinical Genomic Database (CGD)

Congenital disorder of glycosylation with defective fucosylation 1AR

Manifestation: Biochemical; Craniofacial; Musculoskeletal; Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 29304374Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FUT8 variants in ClinVar

6 Conditions Cataloged
not providedTotal: 70
Inborn genetic diseasesTotal: 67
not specifiedTotal: 18
FUT8-related disorderTotal: 17
Congenital disorder of glycosylation with defective fucosylation 1Total: 14
See casesTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001371533.1. 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.

EffectPLPVUSLBBSum
synonymous
1
clinvar
40
clinvar
1
clinvar
 42
missense
1
clinvar
80
clinvar
3
clinvar
3
clinvar
 87
nonsense
2
clinvar
2
clinvar
2
clinvar
 6
start loss
0
frameshift
2
clinvar
 2
splice donor/acceptor (+/-2bp)
1
clinvar
 1
Total3484434138

Highest pathogenic variant AF is 0.0000054735738

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 74 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_001371533.1RefSeqNP_001358462.19MANE Select
ENST00000673929.1EnsemblENSP00000501213.19MANE Select
NM_001371534.1RefSeqNP_001358463.19Standard
NM_001371536.1RefSeqNP_001358465.110Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
fut8aDanio rerio

Structure: retinal ganglion cell

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • N-Glycan biosynthesis - Homo sapiens (human)
  • Transcriptional misregulation in cancer - Homo sapiens (human)
  • Glycosaminoglycan biosynthesis - keratan sulfate - Homo sapiens (human)
  • MECP2 and Associated Rett Syndrome
  • Post-translational protein modification

Biological Process

  • in utero embryonic development
  • protein N-linked glycosylation
  • N-glycan processing
  • transforming growth factor beta receptor signaling pathway
  • integrin-mediated signaling pathway

Molecular Function

  • glycoprotein 6-alpha-L-fucosyltransferase activity
  • SH3 domain binding
  • alpha-(1->6)-fucosyltransferase activity

Cellular Component

  • Golgi membrane
  • Golgi apparatus
  • cytosol
  • membrane
  • integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000360689
Coding exons
9
Length
333530
Individuals with no LoFs
125726
Homozygous LoFs
0
Heterozygous LoFs
21
Defined
125747
p
0.0000835
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense2.202063160.6520.00001713760
Missense (PolyPhen)60133.220.450371573
Synonymous-1.791311071.220.000005251093
Loss of Function3.751033.30.3000.00000215346

Population LoF Frequency

PopulationCAFp-valueStatus
African0.0000620.000062rare
Latino/Admixed American0.0000870.000087rare
Ashkenazi Jewish00.0absent
East Asian0.000110.00011rare
Finnish0.000140.00014rare
European (Non-Finnish)0.0000710.000070rare
South Asian0.000100.000098rare
Other0.000160.00016rare

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Catalyzes the addition of fucose in alpha 1-6 linkage to the first GlcNAc residue, next to the peptide chains in N-glycans. {ECO:0000269|PubMed:17172260, ECO:0000269|PubMed:9133635}.;

Recessive Scores

pRec
0.201

Intolerance Scores

LoFtool
0.298
RVIS EVS
-0.47
RVIS percentile EVS
23.43

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
N
Indispensability score
0.497

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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