Congenital disorder of glycosylation with defective fucosylation 2

Summary

Congenital disorder of glycosylation with defective fucosylation 2 (MONDO:0020777) is a disease caused by FCSK (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: FCSK (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 35

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital disorder of glycosylation with defective fucosylation 2
Mondo ID	MONDO:0020777
OMIM	618324
UMLS	C5193028
MedGen	1676187
GARD	0025247
Is cancer (heuristic)	no

Also known as: CDGF2

Data availability: 35 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 2

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

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

35 retrieved; paginated sample, class counts are floors:

21 uncertain significance, 6 likely pathogenic, 5 conflicting classifications of pathogenicity, 1 benign, 1 pathogenic/likely pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
3065568	NM_145059.3(FCSK):c.1000_1018del (p.Glu335fs)	FCSK	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3065139	NM_145059.3(FCSK):c.956-1G>A	FCSK	Likely pathogenic	criteria provided, single submitter
3779649	NM_145059.3(FCSK):c.412-2A>G	FCSK	Likely pathogenic	criteria provided, single submitter
3779650	NM_145059.3(FCSK):c.503_527dup (p.Pro180fs)	FCSK	Likely pathogenic	criteria provided, single submitter
4529498	NM_145059.3(FCSK):c.3255A>G (p.Ter1085Trp)	FCSK	Likely pathogenic	criteria provided, single submitter
4845770	NM_145059.3(FCSK):c.860del (p.Pro287fs)	FCSK	Likely pathogenic	criteria provided, single submitter
4845771	NM_145059.3(FCSK):c.1197C>A (p.Cys399Ter)	FCSK	Likely pathogenic	criteria provided, single submitter
1031188	NM_145059.3(FCSK):c.2221C>T (p.Arg741Ter)	FCSK	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1703172	NM_145059.3(FCSK):c.669_670del (p.Val225fs)	FCSK	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1705108	NM_145059.3(FCSK):c.1407-1G>C	FCSK	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2196251	NM_145059.3(FCSK):c.82+8A>G	FCSK	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
619034	NM_145059.3(FCSK):c.2047C>T (p.Arg683Cys)	FCSK	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1031186	NM_145059.3(FCSK):c.1955C>T (p.Ala652Val)	FCSK	Uncertain significance	criteria provided, multiple submitters, no conflicts
1031187	NM_145059.3(FCSK):c.2186A>G (p.Tyr729Cys)	FCSK	Uncertain significance	criteria provided, single submitter
1050807	NM_145059.3(FCSK):c.394G>C (p.Asp132His)	FCSK	Uncertain significance	criteria provided, single submitter
1050808	NM_145059.3(FCSK):c.379C>A (p.Leu127Met)	FCSK	Uncertain significance	criteria provided, single submitter
1334068	NM_145059.3(FCSK):c.1640G>A (p.Arg547Gln)	FCSK	Uncertain significance	criteria provided, multiple submitters, no conflicts
1682403	NM_145059.3(FCSK):c.2987T>C (p.Met996Thr)	FCSK	Uncertain significance	criteria provided, multiple submitters, no conflicts
1683401	NM_145059.3(FCSK):c.2068C>T (p.Gln690Ter)	FCSK	Uncertain significance	criteria provided, multiple submitters, no conflicts
1985410	NM_145059.3(FCSK):c.221G>A (p.Arg74Gln)	FCSK	Uncertain significance	criteria provided, multiple submitters, no conflicts
2174337	NM_145059.3(FCSK):c.1669A>G (p.Lys557Glu)	FCSK	Uncertain significance	criteria provided, multiple submitters, no conflicts
2196252	NM_145059.3(FCSK):c.1673C>T (p.Ala558Val)	FCSK	Uncertain significance	criteria provided, multiple submitters, no conflicts
2591646	NM_145059.3(FCSK):c.1813C>T (p.Arg605Trp)	FCSK	Uncertain significance	criteria provided, multiple submitters, no conflicts
2689062	NM_145059.3(FCSK):c.1892A>G (p.Asn631Ser)	FCSK	Uncertain significance	criteria provided, multiple submitters, no conflicts
2773044	NM_145059.3(FCSK):c.1175C>G (p.Pro392Arg)	FCSK	Uncertain significance	criteria provided, multiple submitters, no conflicts
3065033	NM_145059.3(FCSK):c.286G>A (p.Gly96Ser)	FCSK	Uncertain significance	criteria provided, single submitter
3066352	NM_145059.3(FCSK):c.2707C>T (p.Gln903Ter)	FCSK	Uncertain significance	criteria provided, single submitter
3897946	NM_145059.3(FCSK):c.877G>A (p.Asp293Asn)	FCSK	Uncertain significance	criteria provided, single submitter
4024308	NM_145059.3(FCSK):c.94C>T (p.Arg32Trp)	FCSK	Uncertain significance	criteria provided, multiple submitters, no conflicts
4291930	NM_145059.3(FCSK):c.3013G>A (p.Val1005Met)	FCSK	Uncertain significance	criteria provided, single submitter

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
FCSK	Strong	Autosomal recessive	congenital disorder of glycosylation with defective fucosylation 2	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
FCSK	HGNC:29500	ENSG00000157353	Q8N0W3	L-fucose kinase	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FCSK	L-fucose kinase	Takes part in the salvage pathway for reutilization of fucose from the degradation of oligosaccharides.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Kinase	1	27.7×	0.036

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FCSK	Kinase	yes	2.7.1.52	GHMP_kinase_N_dom, GDP_fucose_pyrophosphorylase, GHMP_kinase_C_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
cerebellar hemisphere	1
ileal mucosa	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FCSK	210	ubiquitous	marker	ileal mucosa, right hemisphere of cerebellum, cerebellar hemisphere

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FCSK	699

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FCSK	Q8N0W3	92.20

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
GDP-fucose biosynthesis	1	1903.3×	5e-04	FCSK

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
GDP-L-fucose biosynthetic process	1	4213.0×	4e-04	FCSK
GDP-L-fucose salvage	1	4213.0×	4e-04	FCSK
carbohydrate phosphorylation	1	2106.5×	5e-04	FCSK

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FCSK	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
FCSK	2.7.1.52	fucokinase

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	1	FCSK
E	Difficult family or no structure, no drug	0

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)
FCSK	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.