congenital disorder of glycosylation, type IIw

Summary

congenital disorder of glycosylation, type IIw (MONDO:0030437) is a disease caused by SLC37A4 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: SLC37A4 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 75

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital disorder of glycosylation, type IIw
Mondo ID	MONDO:0030437
OMIM	619525
DOID	DOID:0051051
UMLS	C5561986
MedGen	1794196
GARD	0025560
Is cancer (heuristic)	no

Also known as: CDG2W

Data availability: 75 ClinVar variants · 3 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 type II › congenital disorder of glycosylation, type IIw

Related subtypes (25): MGAT2-congenital disorder of glycosylation, leukocyte adhesion deficiency type II, SLC35A2-congenital disorder of glycosylation, SLC35A1-congenital disorder of glycosylation, MOGS-congenital disorder of glycosylation, B4GALT1-congenital disorder of glycosylation, COG7-congenital disorder of glycosylation, COG8-congenital disorder of glycosylation, COG1-congenital disorder of glycosylation, COG4-congenital disorder of glycosylation, COG5-congenital disorder of glycosylation, COG6-congenital disorder of glycosylation, TMEM165-congenital disorder of glycosylation, SLC39A8-CDG, CCDC115-CDG, TMEM199-CDG, congenital disorder of glycosylation, type IIr, congenital disorder of glycosylation, type iit, congenital disorder of glycosylation, type 2v, congenital disorder of glycosylation, type IIq, congenital disorder of glycosylation, type IIy, congenital disorder of glycosylation, type IIz, congenital disorder of glycosylation, type IIaa, congenital disorder of glycosylation, type IIbb, congenital disorder of glycosylation, type IIcc

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

75 retrieved; paginated sample, class counts are floors:

46 uncertain significance, 8 pathogenic/likely pathogenic, 7 likely benign, 6 conflicting classifications of pathogenicity, 5 pathogenic, 2 likely pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1184845	NM_001164277.2(SLC37A4):c.1267C>T (p.Arg423Ter)	SLC37A4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
557015	NM_001164277.2(SLC37A4):c.74_77del (p.Tyr25fs)	SLC37A4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
633417	NM_001164277.2(SLC37A4):c.359dup (p.Cys121fs)	SLC37A4	Pathogenic	criteria provided, multiple submitters, no conflicts
68281	NM_001164277.2(SLC37A4):c.448G>A (p.Gly150Arg)	SLC37A4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
68284	NM_001164277.2(SLC37A4):c.547T>C (p.Cys183Arg)	SLC37A4	Pathogenic	criteria provided, multiple submitters, no conflicts
68286	NM_001164277.2(SLC37A4):c.59G>A (p.Gly20Asp)	SLC37A4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
68291	NM_001164277.2(SLC37A4):c.82C>T (p.Arg28Cys)	SLC37A4	Pathogenic	criteria provided, multiple submitters, no conflicts
68294	NM_001164277.2(SLC37A4):c.899G>A (p.Arg300His)	SLC37A4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
6926	NM_001164277.2(SLC37A4):c.1042_1043del (p.Leu348fs)	SLC37A4	Pathogenic	criteria provided, multiple submitters, no conflicts
6932	NM_001164277.2(SLC37A4):c.148+1G>A	SLC37A4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
6933	NM_001164277.2(SLC37A4):c.83G>A (p.Arg28His)	SLC37A4	Pathogenic	criteria provided, multiple submitters, no conflicts
6934	NM_001164277.2(SLC37A4):c.1243C>T (p.Arg415Ter)	SLC37A4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
6935	NM_001164277.2(SLC37A4):c.1016G>A (p.Gly339Asp)	SLC37A4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3362565	NM_001164277.2(SLC37A4):c.744_745del (p.Gln248fs)	SLC37A4	Likely pathogenic	criteria provided, single submitter
4279891	NM_001164277.2(SLC37A4):c.980_981delinsG (p.Pro327fs)	SLC37A4	Likely pathogenic	criteria provided, single submitter
1020290	NM_001164277.2(SLC37A4):c.264C>T (p.Gly88=)	SLC37A4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
215178	NM_001164277.2(SLC37A4):c.497G>A (p.Arg166His)	SLC37A4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
302706	NM_001164277.2(SLC37A4):c.492C>T (p.Ser164=)	SLC37A4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
652090	NM_001164277.2(SLC37A4):c.1286A>C (p.Glu429Ala)	SLC37A4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
68272	NM_001164277.2(SLC37A4):c.149G>A (p.Gly50Glu)	SLC37A4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
969047	NM_001164277.2(SLC37A4):c.872C>G (p.Ala291Gly)	SLC37A4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1015427	NM_001164277.2(SLC37A4):c.944T>C (p.Met315Thr)	SLC37A4	Uncertain significance	criteria provided, multiple submitters, no conflicts
1038940	NM_001164277.2(SLC37A4):c.943A>G (p.Met315Val)	SLC37A4	Uncertain significance	criteria provided, multiple submitters, no conflicts
1044548	NM_001164277.2(SLC37A4):c.13G>C (p.Gly5Arg)	SLC37A4	Uncertain significance	criteria provided, multiple submitters, no conflicts
1055149	NM_001164277.2(SLC37A4):c.68T>A (p.Leu23Gln)	SLC37A4	Uncertain significance	criteria provided, multiple submitters, no conflicts
1063134	NM_001164277.2(SLC37A4):c.230G>T (p.Arg77Leu)	SLC37A4	Uncertain significance	criteria provided, multiple submitters, no conflicts
1366825	NM_001164277.2(SLC37A4):c.1176T>G (p.Ser392Arg)	SLC37A4	Uncertain significance	criteria provided, multiple submitters, no conflicts
1383252	NM_001164277.2(SLC37A4):c.503C>T (p.Thr168Met)	SLC37A4	Uncertain significance	criteria provided, multiple submitters, no conflicts
1411318	NM_001164277.2(SLC37A4):c.1287G>C (p.Glu429Asp)	SLC37A4	Uncertain significance	criteria provided, multiple submitters, no conflicts
1434384	NM_001164277.2(SLC37A4):c.1129G>A (p.Gly377Ser)	SLC37A4	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 1 · 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
SLC37A4	Definitive	Autosomal dominant	congenital disorder of glycosylation, type IIw	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC37A4	Orphanet:79259	Glycogen storage disease due to glucose-6-phosphatase deficiency type Ib

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
SLC37A4	HGNC:4061	ENSG00000137700	O43826	Glucose-6-phosphate exchanger SLC37A4	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC37A4	Glucose-6-phosphate exchanger SLC37A4	Inorganic phosphate and glucose-6-phosphate antiporter of the endoplasmic reticulum.

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
Transporter	1	77.8×	0.013

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLC37A4	Transporter	yes		Sugar_P_transporter, MFS, MFS_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
duodenum	1
liver	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC37A4	134	ubiquitous	marker	right lobe of liver, liver, duodenum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SLC37A4	1,242

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SLC37A4	O43826	25

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
glucose-6-phosphate transport	1	2808.7×	0.002	SLC37A4
phosphate ion transmembrane transport	1	1203.7×	0.002	SLC37A4
gluconeogenesis	1	324.1×	0.005	SLC37A4
glucose metabolic process	1	255.3×	0.005	SLC37A4
glucose homeostasis	1	130.6×	0.008	SLC37A4

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
SLC37A4	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SLC37A4	5	Binding:5

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	1	SLC37A4
D	Druggable family + AlphaFold only, no drug	0
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)
SLC37A4	5	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.