Lactose intolerance

Summary

Lactose intolerance (MONDO:0100345) is a disease with 1 cohort gene and 43 clinical trials. Top therapeutic interventions include lactase, lactose, anhydrous, and lactobacillus acidophilus.

At a glance

• Cohort genes: 1
• ClinVar variants: 1
• Clinical trials: 43

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	lactose intolerance
Mondo ID	MONDO:0100345
EFO	EFO:1000062
MeSH	D007787
DOID	DOID:10604
ICD-10-CM	E73
ICD-11	1026224967
NCIT	C3154
SNOMED CT	267425008
UMLS	C0022951
MedGen	6001
Is cancer (heuristic)	no

Also known as: lactose intolerance · lactose intolerance (disease)

Data availability: 1 ClinVar variant · 1 HPO phenotype.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by etiologic mechanism › nutritional disorder › lactose intolerance

Related subtypes (6): potassium deficiency disease, overnutrition, eating disorder, hemorrhagic disease of newborn, nutritional deficiency disease, refeeding syndrome

Subtypes (1): lactose intolerance adult type

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

1 retrieved; paginated sample, class counts are floors:

1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
4076128	NM_005915.6(MCM6):c.1078+40A>C	MCM6	Likely benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 0 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

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
MCM6	HGNC:6949	ENSG00000076003	Q14566	DNA replication licensing factor MCM6	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MCM6	DNA replication licensing factor MCM6	Acts as a component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for ‘once per cell cycle’ DNA replication initiation and elongation in eukaryotic cells.

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)
MCM6	Other/Unknown	no		MCM_dom, MCM6, NA-bd_OB-fold

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
embryo	1
endometrium epithelium	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MCM6	288	ubiquitous	marker	ventricular zone, endometrium epithelium, embryo

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MCM6	3,606

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MCM6	Q14566	30

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 17. 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
DNA strand elongation	1	1142.0×	0.008	MCM6
Unwinding of DNA	1	878.5×	0.008	MCM6
Activation of the pre-replicative complex	1	326.3×	0.008	MCM6
DNA Replication Pre-Initiation	1	317.2×	0.008	MCM6
Activation of ATR in response to replication stress	1	300.5×	0.008	MCM6
Switching of origins to a post-replicative state	1	300.5×	0.008	MCM6
Synthesis of DNA	1	300.5×	0.008	MCM6
DNA Replication	1	237.9×	0.008	MCM6
G1/S Transition	1	233.1×	0.008	MCM6
Mitotic G1 phase and G1/S transition	1	184.2×	0.008	MCM6
S Phase	1	181.3×	0.008	MCM6
Orc1 removal from chromatin	1	178.4×	0.008	MCM6
Assembly of the pre-replicative complex	1	139.3×	0.009	MCM6
G2/M Checkpoints	1	134.3×	0.009	MCM6
Cell Cycle Checkpoints	1	88.5×	0.013	MCM6
Cell Cycle, Mitotic	1	48.2×	0.022	MCM6
Cell Cycle	1	36.0×	0.028	MCM6

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
mitotic DNA replication	1	16852.0×	3e-04	MCM6
double-strand break repair via break-induced replication	1	1296.3×	0.002	MCM6
regulation of DNA-templated DNA replication initiation	1	1053.2×	0.002	MCM6
DNA replication initiation	1	624.1×	0.002	MCM6
DNA replication	1	165.2×	0.006	MCM6

Therapeutics

Drugs indicated for this disease

0 approved, 1 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Lactase	Phase 3 (in late-stage trials)

Drug target analysis

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

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
MCM6	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
MCM6	12	Binding:12

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	0
E	Difficult family or no structure, no drug	1	MCM6

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)
MCM6	12	—

Clinical trials & evidence

Clinical trials

Clinical trials: 43.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	35
PHASE4	3
PHASE3	2
PHASE2/PHASE3	1
PHASE2	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02406469	PHASE4	COMPLETED	Effects Comparison of A1 and A2 Milk on Gastrointestinal Physiology, Symptoms and Cognitive Behavior
NCT02636413	PHASE4	COMPLETED	Evaluation of LacTEST for the Diagnosis of Hypolactasia in Adults and Elderly Patients Presenting With Clinical Symptoms of Lactose Intolerance
NCT02878876	PHASE4	COMPLETED	Incidence of Lactose Intolerance Among Self-reported Lactose Intolerant People
NCT01145586	PHASE3	COMPLETED	A Non-inferiority, Multicenter and Randomized, Multiple-Dose Study About a Treatment to Hypolactasia
NCT02673749	PHASE2/PHASE3	COMPLETED	Efficacy, Safety, and Tolerability Study of RP-G28 in Subjects With Lactose Intolerance
NCT03597516	PHASE3	COMPLETED	Evaluation of the Efficacy, Durability, Safety, and Tolerability of RP-G28 in Patients With Lactose Intolerance
NCT01113619	PHASE2	COMPLETED	Effectiveness, Safety and Tolerability Study of RP-G28 for Symptoms Associated With Lactose Intolerance
NCT03563846	PHASE1	COMPLETED	Effect of a Standard Meal on the Pharmacokinetic Profile of RP-G28 in Healthy Adult Male and Female Subjects
NCT05100719	Not specified	NOT_YET_RECRUITING	The Role of Irritable Bowel Syndrome in Lactose Intolerance (LION)
NCT06177938	Not specified	RECRUITING	Lactobreath: A Study to Diagnose Lactose Intolerance Using Breath Markers
NCT06513026	Not specified	RECRUITING	Milk for Diabetes Prevention
NCT06773650	Not specified	RECRUITING	Proper Dietary Management, Follow-up, and Lactase Enzyme Supplementation for Lactose Intolerance
NCT06931379	Not specified	NOT_YET_RECRUITING	Screening of Lactose Intolerance Among IBS Patients Diarrhea Dominant
NCT00247806	Not specified	TERMINATED	Prevalence of Lactose Intolerance Following Stem Cell Transplantation
NCT00395954	Not specified	COMPLETED	Amount of Lactose Causing Symptoms in Lactose Intolerant People
NCT00403923	Not specified	COMPLETED	Amount of Lactose Causing Symptoms in People With Lactose Intolerance and Ulcerative Colitis
NCT00599859	Not specified	COMPLETED	Effects of Lactose on Fecal Microflora
NCT00844766	Not specified	WITHDRAWN	Validation of a Home-screening Test for Lactose Intolerance
NCT01129791	Not specified	COMPLETED	Effects of Raw Versus Other Milk Sources on Lactose Digestion
NCT01286597	Not specified	UNKNOWN	The Effects of Lactose Intolerance on Gastrointestinal Function and Symptoms in a Chinese Population
NCT01331265	Not specified	COMPLETED	Perceived Lactose Intolerance
NCT01593800	Not specified	COMPLETED	The Effect of Probiotics on Lactose Intolerance
NCT02085889	Not specified	UNKNOWN	Fructose and Lactose Intolerance and Malabsorption in Functional Gastrointestinal Disorders
NCT02171403	Not specified	COMPLETED	Comparison of the Colonic Metabolism in Patients With Lactose Intolerance and Healthy Controls
NCT02518295	Not specified	COMPLETED	β-galactosidase Producing Probiotic Strains to Improve Lactose Digestion
NCT02703987	Not specified	COMPLETED	HYBRID: Hydrogen Breath Test in Lactose Digestion
NCT02902016	Not specified	COMPLETED	Modulation of Lactase Expression by a New PPARgamma Ligand in Duodenal Biopsies
NCT03261856	Not specified	COMPLETED	Clinical Utility of Breath Tests in GI
NCT03814668	Not specified	COMPLETED	Effect of Probiotic Supplementation on Lactose Maldigestion Induced by Lactose Solution
NCT03860051	Not specified	COMPLETED	Association Between Lactase Deficiency, and the Small Intestinal Microbiome in Adults.
NCT03952988	Not specified	UNKNOWN	Effect of B.Bifidum 900791 Intake in Adult With Hypolactasia and Lactose Intolerance
NCT04164394	Not specified	COMPLETED	Effect of I31 Probiotic on Lactose Intolerance
NCT04531033	Not specified	COMPLETED	Does Daily Supplementation of Lactobacillus Acidophilus MPH734, for One Week, Affect Acute (Immediate), Subacute (7 Days), and Post-treatment Discontinuation Lactose Metabolism, Gastrointestinal Symptoms, and Clinical Markers of Inflammation and Safety Compared to a Placebo
NCT04754724	Not specified	COMPLETED	Evaluation of GIMate Handheld Hydrogen Breath Monitor for Diagnosis of Lactose Malabsorption
NCT05367453	Not specified	COMPLETED	Effect of a Probiotic With High Beta-galactosidase Activity on Patients With Lactose Intolerance
NCT05660278	Not specified	UNKNOWN	Comparing the Inflammation, Maldigestion and Symptoms Due to Commercial Milk and A2 Milk
NCT05668468	Not specified	UNKNOWN	A Bifido Bacteria to Improve Lactose Digestion and Tolerance
NCT05669274	Not specified	UNKNOWN	Comparing the Adaptation of Commercial Milk and A2 Milk in Lactose Maldigesters
NCT06107088	Not specified	COMPLETED	Effect of a Combination of Lactase and L. Salivarius DSM 34078 in Individuals With Lactose Intolerance
NCT06617364	Not specified	COMPLETED	MSOT for Assessment of Intestinal Transit Time in Lactose Intolerance Patients

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
LACTASE	3	5
LACTOSE, ANHYDROUS	3	2
LACTOBACILLUS ACIDOPHILUS	3	1
GAXILOSE	2	1
CHEMBL443232	0	1