glycogen storage disease type 1 due to SLC37A4 mutation

Summary

glycogen storage disease type 1 due to SLC37A4 mutation (MONDO:0023258) 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: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	glycogen storage disease type 1 due to SLC37A4 mutation
Mondo ID	MONDO:0023258
MeSH	C536831
UMLS	C2931345
MedGen	419390
GARD	0002501
Is cancer (heuristic)	no

Also known as: G6P translocase deficiency · glucose-6-phosphate translocase deficiency · glycogen storage disease I caused by mutation in SLC37A4 · SLC37A4 glycogen storage disease I

Data availability: 2 ClinVar variants · 1 GenCC gene-disease record.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › inborn carbohydrate metabolic disorder › disorder of glycogen metabolism › glycogen storage disease I › glycogen storage disease type 1 due to SLC37A4 mutation

Related subtypes (2): glycogen storage disease due to glucose-6-phosphatase deficiency type IA, glycogen storage disease Id

Subtypes (1): glycogen storage disease Ib

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

2 retrieved; paginated sample, class counts are floors:

1 conflicting classifications of pathogenicity, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
68294	NM_001164277.2(SLC37A4):c.899G>A (p.Arg300His)	SLC37A4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
652090	NM_001164277.2(SLC37A4):c.1286A>C (p.Glu429Ala)	SLC37A4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

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 recessive	glycogen storage disease type 1 due to SLC37A4 mutation	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.