Congenital lactase deficiency

Summary

Congenital lactase deficiency (MONDO:0009115) is a disease caused by LCT (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: LCT (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 97

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital lactase deficiency
Mondo ID	MONDO:0009115
MeSH	C562600
OMIM	223000
Orphanet	53690
DOID	DOID:0111646
ICD-10-CM	E73.0
ICD-11	2109252471
SNOMED CT	5388008
UMLS	C0268179
MedGen	120617
GARD	0012311
Is cancer (heuristic)	no

Also known as: congenital lactase deficiency

Data availability: 97 ClinVar variants · 4 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 › inborn carbohydrate metabolic disorder › disorder of carbohydrate transmembrane transport and absorption › congenital lactase deficiency

Related subtypes (13): congenital sucrase-isomaltase 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, diarrhea-vomiting due to trehalase deficiency, 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

97 retrieved; paginated sample, class counts are floors:

37 uncertain significance, 27 conflicting classifications of pathogenicity, 11 benign, 8 likely pathogenic, 8 benign/likely benign, 3 pathogenic, 2 pathogenic/likely pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1379572	NM_002299.4(LCT):c.3535C>T (p.Gln1179Ter)	LCT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
56387	NM_002299.4(LCT):c.1692_1696del (p.Val565fs)	LCT	Pathogenic	criteria provided, single submitter
56391	NM_002299.4(LCT):c.4998_5001del (p.Ser1666fs)	LCT	Pathogenic/Likely pathogenic	no assertion criteria provided
6586	NM_002299.4(LCT):c.4170T>A (p.Tyr1390Ter)	LCT	Pathogenic	criteria provided, single submitter
6588	NM_002299.4(LCT):c.804G>C (p.Gln268His)	LCT	Pathogenic	no assertion criteria provided
2584498	NM_002299.4(LCT):c.4866+2T>G	LCT	Likely pathogenic	criteria provided, multiple submitters, no conflicts
56388	NM_002299.4(LCT):c.4087G>A (p.Gly1363Ser)	LCT	Likely pathogenic	no assertion criteria provided
56389	NM_002299.4(LCT):c.4419C>G (p.Tyr1473Ter)	LCT	Likely pathogenic	no assertion criteria provided
56390	NM_002299.4(LCT):c.4834G>T (p.Glu1612Ter)	LCT	Likely pathogenic	no assertion criteria provided
56392	NM_002299.4(LCT):c.5387del (p.Asp1796fs)	LCT	Likely pathogenic	no assertion criteria provided
56393	NM_002299.4(LCT):c.653_654del (p.Ser218fs)	LCT	Likely pathogenic	no assertion criteria provided
982557	NM_002299.4(LCT):c.4950C>A (p.Ser1650Arg)	LCT	Likely pathogenic	criteria provided, single submitter
982558	NM_002299.4(LCT):c.4363C>T (p.Arg1455Cys)	LCT	Likely pathogenic	criteria provided, single submitter
1025930	NM_002299.4(LCT):c.5722C>T (p.Arg1908Cys)	LCT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1480641	NM_002299.4(LCT):c.3947G>C (p.Trp1316Ser)	LCT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
331165	NM_002299.4(LCT):c.5529C>T (p.Pro1843=)	LCT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
331166	NM_002299.4(LCT):c.5493C>T (p.Tyr1831=)	LCT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
331170	NM_002299.4(LCT):c.4695C>T (p.Tyr1565=)	LCT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
331174	NM_002299.4(LCT):c.4434T>C (p.Asp1478=)	LCT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
331190	NM_002299.4(LCT):c.3285C>T (p.His1095=)	LCT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
331192	NM_002299.4(LCT):c.2883C>T (p.Ala961=)	LCT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
729578	NM_002299.4(LCT):c.1113G>A (p.Arg371=)	LCT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
892984	NM_002299.4(LCT):c.5391T>C (p.Asn1797=)	LCT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
892987	NM_002299.4(LCT):c.4776C>T (p.Gly1592=)	LCT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
893034	NM_002299.4(LCT):c.3483C>T (p.Asn1161=)	LCT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
893035	NM_002299.4(LCT):c.3450C>T (p.Ser1150=)	LCT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
893076	NM_002299.4(LCT):c.1539G>A (p.Glu513=)	LCT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
893077	NM_002299.4(LCT):c.1116G>A (p.Ala372=)	LCT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
893213	NM_002299.4(LCT):c.4761C>T (p.Arg1587=)	LCT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
893215	NM_002299.4(LCT):c.4664-10A>G	LCT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

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
LCT	Strong	Autosomal recessive	congenital lactase deficiency	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
LCT	Orphanet:53690	Congenital lactase 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
LCT	HGNC:6530	ENSG00000115850	P09848	Lactase/phlorizin hydrolase	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
LCT	Lactase/phlorizin hydrolase	Broad specificity glycosidase of the intestinal brush border membrane that hydrolyzes lactose, the main sugar in mammalian milk, to produce D-glucose and D-galactose.

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)
LCT	Enzyme (other)	yes	3.2.1.108	Glyco_hydro_1, GH_hydrolase_sf, Glyco_hydro_1_AS

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
jejunum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LCT	26	tissue_specific	marker	jejunal mucosa, duodenum, jejunum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LCT	763

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
LCT	P09848	86.63

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. 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
Intestinal saccharidase deficiencies	1	5710.0×	0.001	LCT
Digestion of dietary carbohydrate	1	951.7×	0.002	LCT
Diseases of carbohydrate metabolism	1	815.7×	0.002	LCT
Digestion and absorption	1	761.3×	0.002	LCT
Digestion	1	571.0×	0.002	LCT
Diseases of metabolism	1	80.4×	0.015	LCT
Disease	1	13.1×	0.076	LCT

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
lactose catabolic process	1	16852.0×	8e-05	LCT
quercetin catabolic process	1	16852.0×	8e-05	LCT
cellobiose catabolic process	1	16852.0×	8e-05	LCT
glycosylceramide catabolic process	1	5617.3×	2e-04	LCT

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
LCT	MIGALASTAT

Top cohort targets by molecule count

Symbol	Molecules	Max phase
LCT	4	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MIGALASTAT	4	LCT
MIGLITOL	4	LCT
DUVOGLUSTAT	2	LCT
NIZUBAGLUSTAT	2	LCT

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
LCT	2	Binding:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
LCT	3.2.1.108, 3.2.1.62, 3.7.1.4	lactase, glycosylceramidase, phloretin hydrolase

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

4 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)
MIGALASTAT	4	LCT
MIGLITOL	4	LCT
DUVOGLUSTAT	2	LCT
NIZUBAGLUSTAT	2	LCT

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	LCT
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: 0.