Glucose-galactose malabsorption

Summary

Glucose-galactose malabsorption (MONDO:0011731) is a disease caused by SLC5A1 (GenCC Definitive), with 1 cohort gene and 2 clinical trials.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Causal gene: SLC5A1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 490
• Phenotypes (HPO): 15
• Clinical trials: 2

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Prevalence at birth	1-9 / 1 000 000	0.22	France	Validated

Signs & symptoms

Clinical features (HPO)

15 HPO clinical features (Orphanet curated; top 15 by frequency):

HPO ID	Term	Frequency
HP:0001508	Failure to thrive	Very frequent (80-99%)
HP:0001824	Weight loss	Very frequent (80-99%)
HP:0001944	Dehydration	Very frequent (80-99%)
HP:0002014	Diarrhea	Very frequent (80-99%)
HP:0033310	Osmotic diarrhea	Very frequent (80-99%)
HP:0003228	Hypernatremia	Frequent (30-79%)
HP:0003270	Abdominal distention	Frequent (30-79%)
HP:0004395	Malnutrition	Frequent (30-79%)
HP:0000083	Renal insufficiency	Occasional (5-29%)
HP:0000787	Nephrolithiasis	Occasional (5-29%)
HP:0002013	Vomiting	Occasional (5-29%)
HP:0003072	Hypercalcemia	Occasional (5-29%)
HP:0030143	Hyperactive bowel sounds	Occasional (5-29%)
HP:0000790	Hematuria	Very rare (<1-4%)
HP:0001945	Fever	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	glucose-galactose malabsorption
Mondo ID	MONDO:0011731
MeSH	C562602
OMIM	606824
Orphanet	35710
DOID	DOID:0070563
ICD-11	2108415931
SNOMED CT	190749000
UMLS	C0268186
MedGen	78647
GARD	0006521
MedDRA	10066388
NORD	1190
Is cancer (heuristic)	no

Also known as: carbohydrate intolerance of glucose galactose · Complex carbohydrate intolerance · GGM · glucose galactose malabsorption deficiency · glucose-galactose malabsorption · glucose/galactose malabsorption · SGLT1 deficiency

Data availability: 490 ClinVar variants · 4 GenCC gene-disease records.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › digestive system disorder › intestinal disorder › glucose-galactose malabsorption

Related subtypes (57): intestinal atresia, steatorrhea, angiodysplasia of intestine, endometriosis of intestine, hypertrophic pyloric stenosis, mucocele of appendix, gastroenteritis, diverticulitis, intestinal obstruction, postgastrectomy syndrome, chronic intestinal vascular insufficiency, bowel dysfunction, irritable bowel syndrome, Whipple disease, inflammatory bowel disease, intestinal polyp, necrotizing enterocolitis, intestinal perforation, neurogenic bowel, pneumatosis cystoides intestinalis, volvulus of midgut, abetalipoproteinemia, aplasia cutis congenita-intestinal lymphangiectasia syndrome, trichohepatoenteric syndrome, protein-losing enteropathy, chronic diarrhea with villous atrophy, Satoyoshi syndrome, congenital diarrhea 7 with exudative enteropathy, chronic atrial and intestinal dysrhythmia, congenital enterocyte heparan sulfate deficiency, short bowel syndrome, intractable diarrhea-choanal atresia-eye anomalies syndrome, solitary rectal ulcer syndrome, NK-cell enteropathy, chronic intestinal failure, intestinal lymphangiectasia, refractory celiac disease, eosinophilic gastrointestinal disease, cryptogenic multifocal ulcerous stenosing enteritis, chronic enteropathy associated with SLCO2A1 gene, cytosolic phospholipase-A2 alpha deficiency associated bleeding disorder, malakoplakia, malabsorption syndrome, ischemic bowel disorder, intestinal neoplasm, intestinal motility disease, 4-hydroxyphenylacetic aciduria, parasitic intestinal disorder, Aeromonas hydrophila intestinal disease, large intestine disorder, small intestine disorder, primary desmosis coli, isolated mesenteric vein thrombosis, collagenous sprue, visceral leiomyopathy, African degenerative, intestinal dysmotility syndrome, intestinal fistula

Subtypes (1): glucose intolerance

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

490 retrieved; paginated sample, class counts are floors:

193 uncertain significance, 193 likely benign, 31 benign, 26 conflicting classifications of pathogenicity, 21 likely pathogenic, 20 pathogenic, 5 benign/likely benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1407543	NM_000343.4(SLC5A1):c.875G>A (p.Cys292Tyr)	SLC5A1	Pathogenic	criteria provided, single submitter
1425355	NM_000343.4(SLC5A1):c.1394_1395insT (p.Pro466fs)	SLC5A1	Pathogenic	criteria provided, single submitter
1686213	NM_000343.4(SLC5A1):c.1496G>C (p.Arg499Pro)	SLC5A1	Pathogenic	criteria provided, single submitter
2016672	NM_000343.4(SLC5A1):c.824del (p.Pro275fs)	SLC5A1	Pathogenic	criteria provided, single submitter
2103820	NM_000343.4(SLC5A1):c.1388T>A (p.Leu463Ter)	SLC5A1	Pathogenic	criteria provided, single submitter
2431781	NM_000343.4(SLC5A1):c.1666-2del	SLC5A1	Pathogenic	criteria provided, single submitter
2812666	NM_000343.4(SLC5A1):c.673G>T (p.Glu225Ter)	SLC5A1	Pathogenic	criteria provided, single submitter
2820703	NM_000343.4(SLC5A1):c.1683G>A (p.Trp561Ter)	SLC5A1	Pathogenic	criteria provided, single submitter
341251	NM_000343.4(SLC5A1):c.1230C>G (p.Tyr410Ter)	SLC5A1	Pathogenic	criteria provided, single submitter
3587889	NM_000343.4(SLC5A1):c.372+2_372+8delinsCTTATATTAAGG	SLC5A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3587897	NM_000343.4(SLC5A1):c.866G>A (p.Trp289Ter)	SLC5A1	Pathogenic	criteria provided, single submitter
3661475	NM_000343.4(SLC5A1):c.1151C>G (p.Ser384Ter)	SLC5A1	Pathogenic	criteria provided, single submitter
3729850	NM_000343.4(SLC5A1):c.259del (p.Leu87fs)	SLC5A1	Pathogenic	criteria provided, single submitter
4725887	NM_000343.4(SLC5A1):c.1065C>A (p.Cys355Ter)	SLC5A1	Pathogenic	criteria provided, single submitter
4730057	NM_000343.4(SLC5A1):c.1566del (p.Cys522fs)	SLC5A1	Pathogenic	criteria provided, single submitter
4734011	NM_000343.4(SLC5A1):c.1613_1614insTTTTTTTTTTTTTTTTTTTTNNNNNNNNNNGTCTCGATCTCCTGACCTCGTGATCCGCCCGCCTCGGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCACCGCCATTTCTTT (p.Phe538_Ile539insPhePhePhePhePhePheXaaXaaXaaXaaSerArgSerProAspLeuValIleArgProProArgProProLysValLeuGlyLeuGlnAlaTer)	SLC5A1	Pathogenic	criteria provided, single submitter
529229	NM_000343.4(SLC5A1):c.1370A>G (p.Gln457Arg)	SLC5A1	Pathogenic	criteria provided, multiple submitters, no conflicts
803681	NM_000343.4(SLC5A1):c.799C>T (p.Arg267Ter)	SLC5A1	Pathogenic	criteria provided, multiple submitters, no conflicts
803683	NM_000343.4(SLC5A1):c.1695del (p.Asn565fs)	SLC5A1	Pathogenic	criteria provided, single submitter
973540	NM_000343.4(SLC5A1):c.187C>T (p.Arg63Ter)	SLC5A1	Pathogenic	criteria provided, multiple submitters, no conflicts
992967	NM_000343.4(SLC5A1):c.765C>G (p.Cys255Trp)	SLC5A1	Pathogenic	criteria provided, multiple submitters, no conflicts
12907	NM_000343.4(SLC5A1):c.82G>A (p.Asp28Asn)	SLC5A1	Likely pathogenic	criteria provided, single submitter
1325095	NM_000343.4(SLC5A1):c.226del (p.Ala76fs)	SLC5A1	Likely pathogenic	criteria provided, single submitter
1514148	NM_000343.4(SLC5A1):c.372+1_372+2insCTTATAT	SLC5A1	Likely pathogenic	criteria provided, single submitter
1522161	NM_000343.4(SLC5A1):c.1021+1G>A	SLC5A1	Likely pathogenic	criteria provided, single submitter
2138439	NM_000343.4(SLC5A1):c.1496G>A (p.Arg499His)	SLC5A1	Likely pathogenic	criteria provided, single submitter
2631995	NM_000343.4(SLC5A1):c.475T>C (p.Ser159Pro)	SLC5A1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2633895	NM_000343.4(SLC5A1):c.200G>A (p.Trp67Ter)	SLC5A1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2800411	NM_000343.4(SLC5A1):c.665-2A>G	SLC5A1	Likely pathogenic	criteria provided, single submitter
3255338	NM_000343.4(SLC5A1):c.947T>C (p.Leu316Pro)	SLC5A1	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
SLC5A1	Definitive	Autosomal recessive	glucose-galactose malabsorption	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC5A1	Orphanet:35710	Glucose-galactose malabsorption

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
SLC5A1	HGNC:11036	ENSG00000100170	P13866	Sodium/glucose cotransporter 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC5A1	Sodium/glucose cotransporter 1	Electrogenic Na(+)-coupled sugar symporter that actively transports D-glucose or D-galactose at the plasma membrane, with a Na(+) to sugar coupling ratio of 2:1.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLC5A1	Other/Unknown	no		Na/solute_symporter, Na/solute_symporter_CS, Na/Glc_symporter_sf

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
ileal mucosa	1
jejunal mucosa	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC5A1	168	tissue_specific	marker	jejunal mucosa, ileal mucosa, duodenum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SLC5A1	1,793

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SLC5A1	P13866	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. 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
Defective SLC5A1 causes congenital glucose/galactose malabsorption (GGM)	1	11420.0×	4e-04	SLC5A1
Intestinal absorption	1	11420.0×	4e-04	SLC5A1
Intestinal hexose absorption	1	3806.7×	9e-04	SLC5A1
Digestion and absorption	1	761.3×	0.003	SLC5A1
Cellular hexose transport	1	543.8×	0.004	SLC5A1
SLC transporter disorders	1	203.9×	0.008	SLC5A1
Disorders of transmembrane transporters	1	139.3×	0.010	SLC5A1
SLC-mediated transmembrane transport	1	59.2×	0.021	SLC5A1
Transport of small molecules	1	25.1×	0.044	SLC5A1
Disease	1	13.1×	0.076	SLC5A1

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
alpha-glucoside transport	1	8426.0×	4e-04	SLC5A1
pentose transmembrane transport	1	8426.0×	4e-04	SLC5A1
fucose transmembrane transport	1	8426.0×	4e-04	SLC5A1
intestinal hexose absorption	1	8426.0×	4e-04	SLC5A1
renal D-glucose absorption	1	5617.3×	5e-04	SLC5A1
intestinal D-glucose absorption	1	4213.0×	5e-04	SLC5A1
myo-inositol transport	1	4213.0×	5e-04	SLC5A1
galactose transmembrane transport	1	3370.4×	5e-04	SLC5A1
transepithelial water transport	1	3370.4×	5e-04	SLC5A1
D-glucose import across plasma membrane	1	2808.7×	5e-04	SLC5A1
D-glucose transmembrane transport	1	936.2×	0.001	SLC5A1
sodium ion import across plasma membrane	1	624.1×	0.002	SLC5A1
sodium ion transport	1	271.8×	0.004	SLC5A1
transport across blood-brain barrier	1	179.3×	0.006	SLC5A1

Therapeutics

Drug target analysis

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

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

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
SLC5A1	ERTUGLIFLOZIN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SLC5A1	15	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
ERTUGLIFLOZIN	4	SLC5A1
BEXAGLIFLOZIN	4	SLC5A1
IPRAGLIFLOZIN	4	SLC5A1
CANAGLIFLOZIN ANHYDROUS	4	SLC5A1
EMPAGLIFLOZIN	4	SLC5A1
TOFOGLIFLOZIN ANHYDROUS	4	SLC5A1
SOTAGLIFLOZIN	4	SLC5A1
DAPAGLIFLOZIN	4	SLC5A1
ENAVOGLIFLOZIN	3	SLC5A1
HENAGLIFLOZIN	3	SLC5A1
LUSEOGLIFLOZIN	2	SLC5A1
REMOGLIFLOZIN ETABONATE	2	SLC5A1
LICOGLIFLOZIN	2	SLC5A1
SERGLIFLOZIN ETABONATE	2	SLC5A1
MIZAGLIFLOZIN	2	SLC5A1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SLC5A1	132	Binding:124, ADMET:6, Functional:2

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
SLC5A1	132

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

15 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.

Compound	Max phase	Cohort target (bioactivity)
ERTUGLIFLOZIN	4	SLC5A1
BEXAGLIFLOZIN	4	SLC5A1
IPRAGLIFLOZIN	4	SLC5A1
CANAGLIFLOZIN ANHYDROUS	4	SLC5A1
EMPAGLIFLOZIN	4	SLC5A1
TOFOGLIFLOZIN ANHYDROUS	4	SLC5A1
SOTAGLIFLOZIN	4	SLC5A1
DAPAGLIFLOZIN	4	SLC5A1
ENAVOGLIFLOZIN	3	SLC5A1
HENAGLIFLOZIN	3	SLC5A1
LUSEOGLIFLOZIN	2	SLC5A1
REMOGLIFLOZIN ETABONATE	2	SLC5A1
LICOGLIFLOZIN	2	SLC5A1
SERGLIFLOZIN ETABONATE	2	SLC5A1
MIZAGLIFLOZIN	2	SLC5A1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	SLC5A1
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04109352	Not specified	UNKNOWN	Labelled Carbon Sucrose Breath Test (13C-SBT) as a Marker of Environmental Enteropathy
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening