Diarrhea-vomiting due to trehalase deficiency

Summary

Diarrhea-vomiting due to trehalase deficiency (MONDO:0012803) is a disease with 1 cohort gene.

At a glance

• Prevalence: >1 / 1000 (Greenland) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 2
• Phenotypes (HPO): 6

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Annual incidence	>1 / 1000	7700	Greenland	Validated

Signs & symptoms

Clinical features (HPO)

6 HPO clinical features (Orphanet curated; top 6 by frequency):

HPO ID	Term	Frequency
HP:0012379	Abnormal enzyme/coenzyme activity	Very frequent (80-99%)
HP:0002013	Vomiting	Occasional (5-29%)
HP:0002014	Diarrhea	Occasional (5-29%)
HP:0002024	Malabsorption	Occasional (5-29%)
HP:0002027	Abdominal pain	Occasional (5-29%)
HP:0003270	Abdominal distention	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	diarrhea-vomiting due to trehalase deficiency
Mondo ID	MONDO:0012803
MeSH	C562603
OMIM	612119
Orphanet	103909
ICD-11	2025219157
SNOMED CT	84193000
UMLS	C0268187
MedGen	75660
GARD	0010372
Is cancer (heuristic)	no

Also known as: isolated trehalose intolerance

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

Disease family

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 carbohydrate transmembrane transport and absorption › diarrhea-vomiting due to trehalase deficiency

Related subtypes (13): congenital sucrase-isomaltase deficiency, congenital lactase deficiency, free sialic acid storage disease, infantile form, dystonia 9, Salla disease, hereditary cryohydrocytosis with reduced stomatin, exercise-induced hyperinsulinism, juvenile cataract-microcornea-renal glucosuria syndrome, childhood onset GLUT1 deficiency syndrome 2, chronic diarrhea due to glucoamylase deficiency, intermediate severe Salla disease, glucose transport disorder, autosomal recessive non-syndromic intellectual disability

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 uncertain significance, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
488190	NM_007180.3(TREH):c.90-9_106del	TREH	Conflicting classifications of pathogenicity	no assertion criteria provided
2302191	NM_007180.3(TREH):c.259C>A (p.Gln87Lys)	TREH	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 1 · 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
TREH	Supportive	Autosomal dominant	diarrhea-vomiting due to trehalase deficiency

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TREH	Orphanet:103909	Trehalase deficiency

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
TREH	HGNC:12266	ENSG00000118094	O43280	Trehalase	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TREH	Trehalase	Intestinal trehalase is probably involved in the hydrolysis of ingested trehalose.

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TREH	Enzyme (other)	yes	3.2.1.28	Glyco_hydro_37, 6-hairpin_glycosidase_sf, 6hp_glycosidase-like_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
jejunal mucosa	1
small intestine	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TREH	162	tissue_specific	marker	jejunal mucosa, duodenum, small intestine

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TREH	1,889

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TREH	O43280	92.80

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
Digestion of dietary carbohydrate	1	951.7×	0.001	TREH

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
trehalose metabolic process	1	16852.0×	9e-05	TREH
trehalose catabolic process	1	16852.0×	9e-05	TREH
animal organ morphogenesis	1	191.5×	0.005	TREH

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · 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).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TREH	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
DUVOGLUSTAT	2	TREH

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
TREH	4	Binding:4

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
TREH	3.2.1.28	alpha,alpha-trehalase

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

1 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)
DUVOGLUSTAT	2	TREH

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	1	TREH
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: 0.